MDPI - Publisher of Open Access Journals

20 pages, 1269 KB

Open AccessArticle

Genotype-Specific Amino Acid Signatures in the Gn/Gc Glycoprotein of Severe Fever with Thrombocytopenia Syndrome Virus Associated with Neurological Symptoms

by Qiongbin Mao, Bohan Zhang, Haowen Yuan, Zhongru Zhao, Jingwan Han, Hanping Li, Yongjian Liu, Lei Jia, Xiaolin Wang, Hongling Wen and Lin Li

Pathogens 2026, 15(9), 946; https://doi.org/10.3390/pathogens15090946 (registering DOI) - 6 Sep 2026

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal tick-borne disease caused by SFTS virus (SFTSV). The Gn/Gc glycoprotein plays a critical role in viral entry, but whether its amino acid polymorphisms directly determine neurological symptoms remains unclear. We sequenced the M [...] Read more.

Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal tick-borne disease caused by SFTS virus (SFTSV). The Gn/Gc glycoprotein plays a critical role in viral entry, but whether its amino acid polymorphisms directly determine neurological symptoms remains unclear. We sequenced the M segment from 99 SFTS patients (31 with neurological symptoms, 68 without) in Shandong Province, China. After removing recombinant sequences, 91 non-recombinant sequences were analyzed and genotyped based on M segment phylogeny. Systematic signature screening, phylogenetic reconstruction, genotype-stratified analysis, public database validation, cross-genotype comparison, and selection pressure inference were applied to distinguish functional determinants from genotype-specific markers. M segment-based phylogeny classified the sequences into four genotypes (D, E, F, A), with D accounting for 79.3% of NS cases. Although 10 candidate sites initially distinguished NS from Non-NS, their associations disappeared upon genotype-stratified analysis; all were low-frequency variants (<15%) in public databases. Cross-genotype comparison revealed D-specific (“GERHVGIIFL”) and E/F-specific (“DGKQMRVTSF”) patterns, none of which overlapped with positively selected sites. These findings demonstrate that the apparent NS association reflected genotype confounding rather than functional determinants, identifying the 10 sites as potential genotype D-specific markers with high discriminatory potential, warranting further validation in independent datasets. This study provides a cautionary example for virus–phenotype association studies, emphasizing that genotype stratification is essential before interpreting amino acid differences as functional. Full article

(This article belongs to the Section Ticks)

23 pages, 534 KB

Open AccessSystematic Review

Addictive Potential of Methylphenidate: A Systematic Review of Human and Preclinical Behavioral, Clinical and Neurobiological Evidence

by Rafał Bieś, Adam Chabrzyk, Katarzyna Zborowska, Krzysztof Krysta and Marek Krzystanek

Pharmaceuticals 2026, 19(9), 1409; https://doi.org/10.3390/ph19091409 (registering DOI) - 6 Sep 2026

Abstract

Background/Objectives: Methylphenidate is one of the most widely prescribed psychostimulants for attention-deficit/hyperactivity disorder, with increasing global use. Its pharmacological action on dopaminergic pathways raises concerns regarding its addictive potential. This systematic review aims to synthesize current evidence on the addictive properties of [...] Read more.

Background/Objectives: Methylphenidate is one of the most widely prescribed psychostimulants for attention-deficit/hyperactivity disorder, with increasing global use. Its pharmacological action on dopaminergic pathways raises concerns regarding its addictive potential. This systematic review aims to synthesize current evidence on the addictive properties of methylphenidate, including misuse, abuse, tolerance, craving, and withdrawal symptoms. Methods: This systematic review was conducted in accordance with PRISMA guidelines and registered in the PROSPERO database under registration number CRD420261303803. Literature searches were performed in PubMed, Web of Science, and Google Scholar without time restrictions. Studies assessing behavioral, subjective, or neurobiological indicators of methylphenidate addiction were included. Eligible designs comprised randomized controlled trials, observational studies, neuroimaging studies, case reports, and relevant preclinical models. Study quality was assessed using the EPHPP tool. A total of 35 studies were included in the qualitative synthesis. Results: The evidence demonstrated that methylphenidate produced measurable reinforcing effects and subjective drug liking, which were found to be closely related to craving and to depend on dose, pharmacokinetics, and route of administration. Rapid increases in brain dopamine levels, particularly following non-oral or high-dose administration, were associated with higher abuse potential. Misuse was observed to be more common among individuals without ADHD and was often motivated by cognitive enhancement rather than euphoria. In contrast, appropriately monitored therapeutic use was associated with a low observed risk of substance use disorders. Pharmacodynamic tolerance was identified in a subset of patients, whereas a classical withdrawal syndrome was not consistently observed and was generally limited to symptom recurrence. Conclusions: Methylphenidate exhibits measurable addictive potential. However, its clinical significance is context-dependent. Under therapeutic conditions, the risk of addiction is low, whereas it increases substantially with non-medical use, high doses, and alternative routes of administration. These findings support careful patient selection, preference for extended-release formulations, and monitoring of misuse risk. Full article

(This article belongs to the Special Issue Effects of Drug Abuse and Its Consequences on Health)

27 pages, 4059 KB

Open AccessArticle

From Detoxified Yam to Bioactive Extracts: Integrated Extraction and In Silico Evidence of Anti-Biofilm Activity of Dioscorea hispida Extracts Against Cutibacterium acnes

by Suthinee Sangkanu, Jiraporn Khanansuk, Muhammad Ikhlas Abdjan, Yan Wang, Sathianpong Phoopha, Wandee Udomuksorn, Michael Wink and Sukanya Dej-adisai

Life 2026, 16(9), 1494; https://doi.org/10.3390/life16091494 (registering DOI) - 6 Sep 2026

Abstract

The increasing prevalence of biofilm-associated infections caused by Cutibacterium acnes has stimulated interest in food-derived natural products as alternative sources of anti-biofilm agents. This study investigated the effects of processing and extraction conditions on the phytochemical composition, antibacterial activity, and anti-biofilm properties of [...] Read more.

The increasing prevalence of biofilm-associated infections caused by Cutibacterium acnes has stimulated interest in food-derived natural products as alternative sources of anti-biofilm agents. This study investigated the effects of processing and extraction conditions on the phytochemical composition, antibacterial activity, and anti-biofilm properties of Dioscorea hispida Dennst. Reflux extraction of dried yam with 80% ethanol produced the crude extracts with the highest yields (1.39–1.80%), whereas fresh yam yielded 0.51–0.97% extract. Using Gas–liquid chromatography–mass spectrometry (GLC-MS) analysis, linoleic acid ethyl ester, n-hexadecanoic acid, 9,12-octadecadienoic acid (Z,Z)-, and stigmasterol were identified as the major constituents. Among the tested extracts, DH-W-F-H (D. hispida-water washing-fresh-hexane) and DH-W-F-E (D. hispida-water washing-fresh-ethanol) were extracted from fresh yam using hexane and ethanol, respectively, while DH-W-D-E (D. hispida-water washing-dry-ethanol) was isolated from dried yam using ethanol and exhibited the strongest antibacterial activity, with minimum inhibitory concentrations (MIC) ranging from 64 to 2048 µg/mL. These extracts demonstrated pronounced concentration-dependent inhibition of biofilm formation by Staphylococcus epidermidis, Staphylococcus aureus, and Cutibacterium acnes. The strongest anti-biofilm activity was observed against C. acnes, with biofilm formation nearly eliminated at MIC concentrations. Moreover, all three extracts significantly reduced established C. acnes biofilms, with DH-W-F-H exhibiting greater eradication efficacy than vancomycin under the tested conditions. To elucidate the underlying mechanism, major fatty acid derivatives were evaluated against C. acnes lipase (_CALipase), a virulence factor associated with biofilm development, using molecular docking, molecular dynamics simulations, and the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free-energy calculations. The compounds exhibited favorable interactions with _CALipase, with linoleic acid ethyl ester (FA2) showing the strongest binding affinity, stable protein–ligand interactions throughout a 200 ns simulation, and the most favorable binding free energy. Collectively, the biological and computational findings suggest that fatty acid-rich extracts from processed D. hispida suppress biofilm formation through an antivirulence mechanism involving _CALipase inhibition. These results highlight the potential of D. hispida as a source of metabolites for the development of functional food ingredients and value-added cosmetic and dermatological applications. Full article

(This article belongs to the Special Issue Bioactive Natural Products: From Exploration to Therapeutic Potential)

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11 pages, 2864 KB

Open AccessEditorial

From Models to Hybrid Intelligence: Emerging AI Approaches for Engineering Applications

by Zbigniew Gomolka, Damian Kordos and Ewa Dudek-Dyduch

Appl. Sci. 2026, 16(17), 8864; https://doi.org/10.3390/app16178864 (registering DOI) - 6 Sep 2026

Abstract

Artificial intelligence has become an important component of contemporary engineering systems, supporting tasks ranging from optimization, prediction, and anomaly detection to computer vision, medical image analysis, and decision support [...] Full article

(This article belongs to the Special Issue Engineering Applications of Hybrid Artificial Intelligence Tools)

13 pages, 280 KB

Open AccessArticle

Recycling Workers: Food Insecurity as a Novel Associated Risk Factor for Toxocariasis

by Altina Bruna de Souza Barbosa, Vamilton Alvares Santarém, Cassiana Dahlke Machado, Isabella Braghin Ferreira, Joyce Aparecida da Silva, Susana Angélica Zevallos Lescano, Rogério Giuffrida, Louise Bach Kmetiuk and Alexander Welker Biondo

Pathogens 2026, 15(9), 945; https://doi.org/10.3390/pathogens15090945 (registering DOI) - 6 Sep 2026

Abstract

(1) Background: Brazil features one of the largest recycling workforces worldwide, with around 800,000 informal waste pickers, mostly living in urban areas of major cities and dealing with low income and precarious working conditions. This context of vulnerability may lead to a high [...] Read more.

(1) Background: Brazil features one of the largest recycling workforces worldwide, with around 800,000 informal waste pickers, mostly living in urban areas of major cities and dealing with low income and precarious working conditions. This context of vulnerability may lead to a high risk of food insecurity, which may be associated with infectious diseases, particularly toxocariasis, a cosmopolitan neglected parasitic zoonosis with high seroprevalence in tropical countries. (2) Methods: Accordingly, this study assessed Toxocara spp. seropositivity and associated risk factors (including food insecurity) in recycling workers of Curitiba, a major Brazilian (fully urban) city currently ranked 8th in population with 1.83 million habitants, 7th in Gross Domestic Product (GDP), and 10th in Human Development Index (HDI) with 0.823 (very high), out of 5569 Brazilian cities. Recycling and non-recycling (used as population control) workers living in the same neighborhood were invited, voluntarily signed consent forms, and had blood serum samples collected and tested by ELISA for detecting anti-Toxocara spp. (IgG) antibodies; in addition, an epidemiological questionnaire (socioeconomic characteristics, owning dog/cat, food and hygiene habits) was applied. (3) Results: Overall, 95/177 (53.7%) recycling and 38/100 (38.0%) non-recycling workers tested positive by ELISA, with recycling workers more likely seropositive than non-recycling population (53.7% vs. 38.0%; OR: 1.89; 95% CI: 1.15–3.12%). Food insecurity (OR = 2.01, 95% CI: 1.04–3.91) and low (<1 minimum wage) monthly household income (OR = 3.03, 95% CI: 1.01–9.71) were associated with Toxocara spp. seropositivity by multivariate analysis. As expected, cohabitation with both dogs and cats was also significantly associated with seropositivity (OR = 3.75, 95% CI: 1.48–9.75). However, other assessed variables (gender, age, ethnicity, hygienic habits, contact with soil, raw meat ingestion) were not associated with seropositivity. (4) Conclusions: The study herein has filled a gap regarding toxocariasis in vulnerable populations and suggests food insecurity as a socioeconomic indicator for Toxocara spp. seropositivity in recycling workers. Furthermore, recycling workers are at higher risk of infection and, as such, need to be prioritized in healthcare programs. Full article

17 pages, 421 KB

Open AccessArticle

Prognostic and Treatment-Context Associations of EASIX and IPI in Extensive-Stage Small-Cell Lung Cancer Patients Receiving First-Line Therapy

by Hatice Ayyıldız Sevim, Galip Can Uyar, Güner Akgüner and Hayriye Şahinli

Cancers 2026, 18(17), 2888; https://doi.org/10.3390/cancers18172888 (registering DOI) - 6 Sep 2026

Abstract

Background: The comparative prognostic value of the Endothelial Activation and Stress Index (EASIX) and the Inflammatory Prognostic Index (IPI) in extensive-stage small-cell lung cancer remains unclear. This study aimed to compare the prognostic value of EASIX and IPI and assess their contribution beyond [...] Read more.

Background: The comparative prognostic value of the Endothelial Activation and Stress Index (EASIX) and the Inflammatory Prognostic Index (IPI) in extensive-stage small-cell lung cancer remains unclear. This study aimed to compare the prognostic value of EASIX and IPI and assess their contribution beyond established clinical factors. Methods: This retrospective single-center study included 129 patients with de novo extensive-stage small-cell lung cancer who initiated first-line systemic therapy between December 2022 and October 2025. Pretreatment EASIX and IPI values were analyzed as log₂-transformed continuous variables in multivariable Cox models. Overall survival was the primary outcome, and first-line progression-free survival was the secondary outcome. Results: During a median follow-up of 26.91 months, 116 deaths and 123 progression-or-death events occurred. Each doubling of the EASIX value was independently associated with a higher hazard of death (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01–1.28; p = 0.019), whereas IPI was not independently associated with overall survival. Neither index was independently associated with first-line progression-free survival. Adding EASIX to the clinical model improved model fit and increased the C-index from 0.619 to 0.650, whereas IPI provided no additional prognostic contribution. Conclusions: EASIX may provide prognostic information beyond established clinical factors for overall survival in extensive-stage small-cell lung cancer. These findings warrant validation in larger multicenter cohorts. Full article

(This article belongs to the Section Cancer Biomarkers)

23 pages, 746 KB

Open AccessReview

Artificial Intelligence for Sleep Bruxism Detection: A Technical Pipeline Synthesis

by Özge Çekirge

Diagnostics 2026, 16(17), 2865; https://doi.org/10.3390/diagnostics16172865 (registering DOI) - 6 Sep 2026

Abstract

Sleep bruxism is the rhythmic or nonrhythmic masticatory muscle activity that occurs during sleep. It is conventionally diagnosed by a rule-based algorithm. Candidate muscle bursts are flagged against a fixed electromyographic (EMG) amplitude threshold, classified by duration into phasic, tonic, or mixed episodes, [...] Read more.

Sleep bruxism is the rhythmic or nonrhythmic masticatory muscle activity that occurs during sleep. It is conventionally diagnosed by a rule-based algorithm. Candidate muscle bursts are flagged against a fixed electromyographic (EMG) amplitude threshold, classified by duration into phasic, tonic, or mixed episodes, and counted into an hourly rate compared against a second threshold. These thresholds generalize poorly across individuals and nights. This has motivated a growing body of artificial intelligence (AI) research aimed at replacing one or more stages of this classical algorithm with a learned decision function. This paper synthesizes that literature as a technical pipeline across 28 reviewed AI-based sleep bruxism studies, identified through Web of Science and Google Scholar searches for “sleep bruxism” combined with artificial intelligence terms, conducted in 2026, and screened for a learned, trained classification approach reported in English. These accuracy figures should be read alongside several complicating factors. Ten studies draw on the same subset of two patients from a public polysomnography database. Several studies framed as sleep bruxism detection were validated only on awake, simulated grinding. In addition, the ground-truth labels these classifiers are trained against remain contested within the field’s own consensus literature. The paper’s contribution is therefore twofold. It assembles the pipeline synthesis itself, spanning ground truth, recording modality, preprocessing, feature extraction, and architecture, as a technical reference not previously brought together in this form. It also uses that synthesis to set a concrete research agenda, including validation benchmarks across nights and across subjects, a shift from binary toward continuous severity targets, and an extension of detection into real-time treatment devices and clinical prognosis. Full article

(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)

23 pages, 7373 KB

Open AccessArticle

Vertical Propagation Behavior of Hydraulic Fractures and Fracability Evaluation in Shale Reservoirs: A Case Study of the Yongchuan Block, Sichuan Basin

by Xingxiang Che and Xiangyi Yi

Processes 2026, 14(17), 2855; https://doi.org/10.3390/pr14172855 (registering DOI) - 6 Sep 2026

Abstract

Vertical hydraulic-fracture propagation controls the effective stimulated thickness of deep layered shale, yet conventional fracability indices omit this response. Coupled hydromechanical cohesive-zone models were built for nine sublayers in the northern and southern Yongchuan sub-blocks, Sichuan Basin, using rock-mechanics tests, well logs, in [...] Read more.

Vertical hydraulic-fracture propagation controls the effective stimulated thickness of deep layered shale, yet conventional fracability indices omit this response. Coupled hydromechanical cohesive-zone models were built for nine sublayers in the northern and southern Yongchuan sub-blocks, Sichuan Basin, using rock-mechanics tests, well logs, in situ stress evaluation, and measured layer thicknesses. Increasing bedding dip from 0° to 10° raised fracture height by 19.8% in northern Yongchuan and 41.7% in southern Yongchuan, whereas reducing tensile strength from 8.0 to 6.4 MPa raised it by 31.3% and 33.2%, respectively. These results indicate that, within the investigated parameter ranges, fracture height responded more strongly to tensile-strength variation than to bedding-dip variation, whereas the southern sub-block was more sensitive to bedding orientation. For northern Yongchuan, a 30-case full-factorial dataset was used to train a Gaussian process regression model of fracture height (leave-one-out R² = 0.932, MAE = 0.77 m, RMSE = 0.97 m), and 12 additional off-grid simulations yielded an R² of 0.864, an MAE of 0.93 m, and an RMSE of 1.06 m. The normalized vertical fracture-propagation response was then combined with a baseline fracability index through a weighted geometric mean. At the selected wells, the integrated index showed better agreement with average monthly gas production than the baseline index. The resulting evaluation framework provides a basis for fracturing feasibility screening in the Yongchuan area. Full article

(This article belongs to the Special Issue Advances in Reservoir Development and Enhanced Oil Recovery Techniques)

16 pages, 601 KB

Open AccessArticle

Dietary Chlorogenic Acid-Rich Green Coffee Bean Extract Improves Laying Performance and Antioxidant Status in Heat-Stressed Laying Hens

by Yuqing Mu, Xuezheng Shang, Jie Yang and Xuezhuang Wu

Animals 2026, 16(17), 2801; https://doi.org/10.3390/ani16172801 (registering DOI) - 6 Sep 2026

Abstract

Cyclic heat stress compromises egg production and antioxidant defenses in laying hens. The present study employed a short-term, 14-day cyclic heat-stress model to evaluate whether dietary supplementation with a chlorogenic acid-rich green coffee bean extract could mitigate these effects. Before initiation of the [...] Read more.

Cyclic heat stress compromises egg production and antioxidant defenses in laying hens. The present study employed a short-term, 14-day cyclic heat-stress model to evaluate whether dietary supplementation with a chlorogenic acid-rich green coffee bean extract could mitigate these effects. Before initiation of the heat-stress experiment, all hens were maintained under thermoneutral conditions and received the basal diet without the extract. Following 1 week of adaptation and 4 weeks of thermoneutral feeding, 240 approximately 50-week-old Jingfen No. 8 hens were allocated to a thermoneutral control, a heat-stress control, or heat-stressed groups receiving 100 or 200 mg/kg extract containing 70% chlorogenic acid, with four independent replicates of 15 hens each (60 hens per treatment). Heat-stressed hens were subjected to a 14-day cyclic heat-stress challenge at 32–35 °C for 9 h/day. Heat stress decreased average egg weight and laying rate, increased serum malondialdehyde, and reduced total antioxidant capacity (p < 0.05). Both supplemented groups improved average egg weight and laying rate, reduced malondialdehyde and total cholesterol, and increased total antioxidant capacity relative to heat-stressed controls (p < 0.05). Supplementation altered hepatic expression of genes associated with proliferation, apoptosis, and autophagy. Exploratory metabolomics detected changes in the 100 mg/kg group but not the 200 mg/kg group relative to heat-stressed controls. The extract partially mitigated production and antioxidant impairments during cyclic heat stress. Full article

(This article belongs to the Special Issue Metabolic, Health, and Productivity Challenges in Poultry Production)

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25 pages, 15776 KB

Open AccessArticle

Dihydromyricetin-Loaded In Situ Film-Forming Emulsions: A Eudragit^® RS 100-Based Strategy for Controlled Topical Delivery

by Chatchaya Ponsuremas, Takron Chantadee, Pratchaya Tipduangta, Siriporn Okonogi and Pimpak Phumat

Pharmaceutics 2026, 18(9), 1120; https://doi.org/10.3390/pharmaceutics18091120 (registering DOI) - 6 Sep 2026

Abstract

Background/Objectives: Dihydromyricetin (DHM), a poorly water-soluble flavonoid with potent antioxidant and skin-rejuvenating properties, exhibits limited skin permeation. This study aimed to develop and characterize DHM-loaded in situ film-forming emulsions (FFE) using Eudragit^® RS 100 as the film-forming polymer to enhance skin permeation [...] Read more.

Background/Objectives: Dihydromyricetin (DHM), a poorly water-soluble flavonoid with potent antioxidant and skin-rejuvenating properties, exhibits limited skin permeation. This study aimed to develop and characterize DHM-loaded in situ film-forming emulsions (FFE) using Eudragit^® RS 100 as the film-forming polymer to enhance skin permeation while minimizing systemic absorption. Methods: FFE formulations, comprising a DHM-loaded lipid mixture and a Eudragit^® RS 100 polymer solution, were developed using a full-factorial design of experiments varying poloxamer 407 (P407) and octyl cyanoacrylate (O60/20)/N-methyl-2-pyrrolidone (NMP) concentrations to evaluate drying time, elongation at break, water vapor transmission rate (WVTR), and dermal permeation. The optimized formulation was further characterized for physicochemical properties, chemical integrity, drug loading, and release behaviour. Results: All formulations were homogeneous and physically stable over 24 h. Drying time was positively influenced by P407 but negatively by O60/20/NMP; P407 reduced dermal permeation, while O60/20/NMP had a biphasic effect without significantly affecting elongation at break and WVTR. The optimized FFE (0.079%w/w O60/20/NMP, without P407) showed rapid drying (2.68 min), elongation >10%, and self-formed nanoscale emulsion droplets from the lipid mixture. FTIR confirmed component compatibility; XRD revealed DHM conversion from a crystalline to an amorphous state. Compared with a system without lipid, FFE exhibited significantly higher moisture content (p < 0.001), a lower swelling index (p = 0.021), comparable occlusive factor (p = 0.68), and followed Higuchi kinetic release. Conclusions: The optimized FFE demonstrated desirable film-forming properties and physicochemical compatibility, offering an innovative formulation strategy with translational potential for topical industries. However, substitution of NMP is recommended for cosmetic formulations. Full article

(This article belongs to the Special Issue Biomaterials for Skin Drug Delivery)

8 pages, 248 KB

Open AccessCommunication

Evaluation of Respiratory Syncytial Virus Prefusion F IgG Antibodies in Japanese Mother–Infant Pairs Following Maternal Abrysvo Vaccination and in Infants Hospitalized with RSV Infection

by Tomohiro Oishi and Takashi Nakano

Vaccines 2026, 14(9), 780; https://doi.org/10.3390/vaccines14090780 (registering DOI) - 6 Sep 2026

Abstract

Background/Objectives: The approval of Abrysvo, a maternal bivalent respiratory syncytial virus (RSV) prefusion F (pre-F) vaccine, marked a major milestone in pediatric prophylaxis. However, real-world serological data on transplacental antibody transfer in Asian populations remains limited. This brief report evaluated serum RSV [...] Read more.

Background/Objectives: The approval of Abrysvo, a maternal bivalent respiratory syncytial virus (RSV) prefusion F (pre-F) vaccine, marked a major milestone in pediatric prophylaxis. However, real-world serological data on transplacental antibody transfer in Asian populations remains limited. This brief report evaluated serum RSV pre-F immunoglobulin G (IgG) geometric mean titers (GMTs) across three distinct Japanese cohorts. Methods: This single-center, comparative study analyzed neonates born to Abrysvo-vaccinated mothers (n = 12), neonates born to unvaccinated mothers (n = 40), and infants aged <6 months hospitalized with laboratory-confirmed RSV infection (n = 18) using enzyme-linked immunosorbent assay (ELISA). Results: Neonates of vaccinated mothers exhibited significantly higher pre-F IgG GMTs (4.74; 95% CI: 4.30–5.18) than those of unvaccinated mothers (3.80; 95% CI: 3.50–4.14). Conversely, infants requiring hospitalization for RSV infection demonstrated critically low pre-F IgG GMTs (1.08; 95% CI: 0.65–2.15), revealing statistically significant differences across all three groups (p < 0.001). Conclusions: Maternal immunization with Abrysvo significantly enhances passive humoral immunity in Japanese neonates compared to natural background immunity. Given the severe antibody deficiency observed in hospitalized infants, expanding maternal vaccination coverage is a high-priority public health strategy to mitigate the pediatric RSV burden in the post-pandemic era. Full article

(This article belongs to the Special Issue Recent Progress of Vaccines for Respiratory Syncytial Virus (RSV))

25 pages, 9301 KB

Open AccessArticle

Multilocus DNA Barcoding Resolves Area-Based Genetic Variation in Freshwater Shrimps (Macrobrachium sp. and Caridina sp.) from Saline and Non-Saline Habitats in Northeastern Thailand

by Juthaporn Saengprajak and Noppakun Pakdeenarong

Biology 2026, 15(17), 1559; https://doi.org/10.3390/biology15171559 (registering DOI) - 6 Sep 2026

Abstract

Freshwater prawns are important components of freshwater ecosystems, yet their diversity and genetic structure in northeastern Thailand remain insufficiently documented, particularly across habitats differing in soil salinity. This study assessed freshwater prawn diversity and phylogenetic relationships in saline and non-saline habitats using an [...] Read more.

Freshwater prawns are important components of freshwater ecosystems, yet their diversity and genetic structure in northeastern Thailand remain insufficiently documented, particularly across habitats differing in soil salinity. This study assessed freshwater prawn diversity and phylogenetic relationships in saline and non-saline habitats using an integrative taxonomic approach combining morphological examination with mitochondrial and nuclear DNA barcoding. A total of 225 mature specimens were collected from 15 sampling sites in Maha Sarakham province (saline habitats) and Mukdahan province (non-saline habitats). Representative specimens were examined morphologically and characterized using four barcode loci: cytochrome c oxidase subunit I (COI), 16S ribosomal RNA (16S rRNA), 18S ribosomal RNA (18S rRNA), and the internal transcribed spacer (ITS). Morphological assessment identified three taxa, Macrobrachium lanchesteri, Macrobrachium niphanae and Caridina sp. Molecular analyses recovered three principal lineages broadly corresponding to these taxonomic groups, although the resolution varied among loci. COI provided consistent species-level discrimination, while 16S rRNA revealed additional genetic variation within Macrobrachium. The conserved 18S rRNA marker supported separation of the major taxonomic lineages, whereas ITS contributed complementary sequence variation for lineage assessment. The concatenated multilocus dataset provided the most stable phylogenetic reconstruction, with strong support for the principal lineages. Samples from saline and non-saline habitats were not consistently separated, suggesting that salinity was not the primary factor underlying the observed genetic structure. Overall, integrating morphological and multilocus molecular evidence provided a robust framework for assessing freshwater prawn diversity and phylogenetic relationships and establishes a baseline for future taxonomic, phylogeographic, and conservation studies in the Mekong region. Full article

(This article belongs to the Special Issue Animal Genetic Resources and Characterization of Populations)

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19 pages, 19230 KB

Open AccessArticle

On the Application of Respirometric System on Hazelnut Samples to Predict Aflatoxin Production

by Francesca Bosco, Chiara Mollea, Gabriele Baldissone, Micaela Demichela and Davide Fissore

Toxins 2026, 18(9), 385; https://doi.org/10.3390/toxins18090385 (registering DOI) - 6 Sep 2026

Abstract

In the present work, the correlation between the respirometric activity and the aflatoxin synthesis of the hazelnut microbiota has been investigated. Microcosms containing a monolayer of hazelnuts were maintained at controlled conditions in terms of temperature and humidity. To monitor microbial growth, CO [...] Read more.

In the present work, the correlation between the respirometric activity and the aflatoxin synthesis of the hazelnut microbiota has been investigated. Microcosms containing a monolayer of hazelnuts were maintained at controlled conditions in terms of temperature and humidity. To monitor microbial growth, CO₂ was evaluated along with the specific O₂ uptake rate, RO₂, measured by a respirometric sensor, usually applied in the evaluation of soil microbial activity. The respiratory quotient (RQ) was calculated and a linear relationship between RQ and produced aflatoxins was obtained. Depending on incubation time, four main clusters of RQ values were identified: for higher incubation time (15–40 days) RQ was lower than 2 and an aflatoxin amount of 0.31–0.35 μg/kg was observed. CO₂, O₂, and aflatoxin data have been used to develop an autoregressive model and excellent agreement between measurements and estimations was obtained. In most cases, an error lower than 1% on the estimated value of the mycotoxin amount revealed the accuracy of the evaluation of the RQ. The present work represents the first attempt to develop an effective method, fast and low-cost, for the in-line monitoring of mycotoxin contamination. Full article

(This article belongs to the Section Mycotoxins)

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27 pages, 3349 KB

Open AccessReview

Camelid VHHs as a Versatile Platform for Combating Viral Infections

by Mohammed Mufrrih and Thamir A. Alandijany

Pharmaceuticals 2026, 19(9), 1408; https://doi.org/10.3390/ph19091408 (registering DOI) - 6 Sep 2026

Abstract

Viral infections continue to pose a major global health challenge because of rapid viral evolution, immune escape, and the emergence of novel pathogens. This review examines the biological characteristics, antiviral mechanisms, production strategies, and therapeutic potential of camelid VHH as next-generation antiviral agents. [...] Read more.

Viral infections continue to pose a major global health challenge because of rapid viral evolution, immune escape, and the emergence of novel pathogens. This review examines the biological characteristics, antiviral mechanisms, production strategies, and therapeutic potential of camelid VHH as next-generation antiviral agents. The review synthesizes current evidence on the structural and functional properties of VHH, their methods of generation and engineering, and their applications against a broad range of respiratory and non-respiratory viruses. Camelid VHH nanobodies exhibit high specificity and affinity, exceptional physicochemical stability, efficient tissue penetration, and the unique ability to recognize conserved and cryptic epitopes that are often inaccessible to conventional antibodies. Engineering approaches, including multivalent, bispecific, Fc-fused, and half-life-extended constructs, further enhance their antiviral potency and pharmacokinetic properties. Evidence from preclinical studies demonstrates potent antiviral activity against multiple viral pathogens through mechanisms that include blocking viral attachment and fusion, inhibiting intracellular replication, targeting conserved viral proteins, and reducing the likelihood of viral escape. The review also highlights emerging advances in recombinant production platforms, artificial intelligence-assisted nanobody design, targeted delivery technologies, and One Health applications. Collectively, the available evidence indicates that camelid VHH represent a highly versatile and adaptable platform for antiviral therapeutics and diagnostics, with considerable potential to support pandemic preparedness and the development of broad-spectrum interventions against current and emerging viral diseases. Full article

(This article belongs to the Special Issue Next-Generation Targeted Therapy: vNARs, VHH, and Peptides as Drug Carriers and Intracellular Neutralizing Agents)

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40 pages, 33363 KB

Open AccessReview

Jet Printing of MXene-Based Inks for Micro-Supercapacitors and Emerging Energy-Storage Applications

by Prisca Viviani, Cecilia Testa, Federico Lissandrello and Luca Magagnin

Technologies 2026, 14(9), 554; https://doi.org/10.3390/technologies14090554 (registering DOI) - 6 Sep 2026

Abstract

The increasing demand for miniaturized, flexible and wearable electronics has accelerated the development of printed electrochemical energy-storage devices capable of combining high performance with scalable and cost-effective manufacturing. Among emerging electrode materials, MXenes have attracted significant attention owing to their exceptional electrical conductivity, [...] Read more.

The increasing demand for miniaturized, flexible and wearable electronics has accelerated the development of printed electrochemical energy-storage devices capable of combining high performance with scalable and cost-effective manufacturing. Among emerging electrode materials, MXenes have attracted significant attention owing to their exceptional electrical conductivity, hydrophilic surface chemistry, tunable interlayer structure and excellent solution processability, making them particularly suitable for jet printing technologies. In particular, inkjet printing (IJP) and aerosol jet printing (AJP) enable maskless, high-resolution and material-efficient fabrication of micro-scale energy-storage devices while offering excellent compatibility with flexible substrates. This review provides a comprehensive overview of the use of MXene-based inks in jet-printed energy-storage devices, emphasizing the relationships between MXene physicochemical properties, ink formulation, printing processes and electrochemical performance. First, the structural characteristics, synthesis strategies and electrochemical charge-storage mechanisms of MXenes are discussed, together with the rheological, colloidal and stability requirements governing ink printability. The fundamental principles of IJP and AJP are then critically analyzed, highlighting the influence of solvent systems, printability criteria, processing parameters and deposition conditions. Recent advances in jet-printed MXene-based supercapacitors and micro-supercapacitors are comprehensively and critically reviewed, with particular attention to how material design, ink formulation, and printing strategies affect device performance. Battery-related studies, which remain comparatively limited, are discussed as an emerging application area highlighting the broader potential of jet-printed MXenes for electrochemical energy storage. Finally, the major challenges hindering the large-scale implementation of MXene-based printed energy-storage systems, including oxidation stability, restacking, ink shelf life, and manufacturing scalability, are critically discussed. Full article

(This article belongs to the Special Issue Advanced Manufacturing Technologies: From Material Jetting to 3D Printing)

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20 pages, 2027 KB

Open AccessArticle

Explaining Sustainable Cultural Tourism Intention Through Virtual Reality: An Integrated S–O–R, Technology Acceptance, and Flow Perspective

by Ketwalee Srijun, Itthiphol Eampoonga and Kittipol Wisaeng

Tour. Hosp. 2026, 7(9), 286; https://doi.org/10.3390/tourhosp7090286 (registering DOI) - 6 Sep 2026

Abstract

Virtual Reality (VR) is increasingly used to enhance cultural heritage experiences, yet limited research explains how technological characteristics translate into sustainable cultural tourism intention (SCTI) through cognitive, experiential, and affective processes. This study develops and empirically tests an integrated framework combining the Stimulus–Organism–Response [...] Read more.

Virtual Reality (VR) is increasingly used to enhance cultural heritage experiences, yet limited research explains how technological characteristics translate into sustainable cultural tourism intention (SCTI) through cognitive, experiential, and affective processes. This study develops and empirically tests an integrated framework combining the Stimulus–Organism–Response (S–O–R) framework, the Technology Acceptance Model (TAM), and Flow Experience Theory. Data were collected from 360 Thai and international tourists at UNESCO World Heritage destinations in Thailand and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). The results supported all 14 direct hypotheses. Information Presentation Quality (IPQ) had the strongest effect on Perceived Usefulness (PU), whereas Innovation Factors (IF) had the strongest effect on Flow Experience (FE). PU and FE contributed to Emotional Cultural Attachment (ECA) and Sustainable Cultural Tourism Intention, with ECA also exerting a significant effect on SCTI. Mediation analysis further showed that Perceived Ease of Use (PEOU) transmitted the effects of technological stimuli to subsequent cognitive and experiential responses, while FE and ECA served as complementary mechanisms linking VR experiences to SCTI. The significant FE-specific indirect effects further confirmed the experiential pathway, while IPQ showed a stronger total indirect effect on SCTI than IF. These findings extend VR tourism research by demonstrating an interconnected cognitive–experiential–affective mechanism through which technological characteristics contribute to sustainable cultural tourism intention. The study also provides practical guidance for heritage authorities, destination managers, and VR developers seeking to design informative, immersive, and culturally meaningful VR experiences that support responsible tourism and heritage conservation. Full article

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41 pages, 5708 KB

Open AccessArticle

Real-Time Dynamic Adaptive Test Assembly for Personalized Measurement of Cognitive Abilities Under Continuous Item Bank Growth

by Jiawei Xiong, Cheng Tang, Qidi Liu and Feiming Li

J. Intell. 2026, 14(9), 216; https://doi.org/10.3390/jintelligence14090216 (registering DOI) - 6 Sep 2026

Abstract

The accurate measurement of individual cognitive abilities in educational settings increasingly relies on personalized assessment systems that adapt to the learner’s current standing on the measured ability. These systems generate and use assessment items continuously and in real-time, bypassing the field-test cycle that [...] Read more.

The accurate measurement of individual cognitive abilities in educational settings increasingly relies on personalized assessment systems that adapt to the learner’s current standing on the measured ability. These systems generate and use assessment items continuously and in real-time, bypassing the field-test cycle that traditional calibration requires. Item banks therefore contain a growing share of items whose parameters must be predicted first, and each test form must be assembled in real time to match the learner’s current ability level and content needs for effective personalized instruction. This study proposes an Ising framework that addresses both requirements by predicting item parameters from text with calibrated uncertainty estimates and assembling personalized test forms within the time budget of the assessment loop. This framework is validated through a factorial simulation and an empirical study on state-level English Language Arts items across Grades 3 through 12. In the simulation, the proposed uncertainty-aware method achieves a mean test information function (TIF) gap of 0.226, compared with 1.171 for the conventional baseline that ignores prediction uncertainty. The proposed method also produces feasible forms across the full operational region, whereas the chance-constrained and robust baselines become infeasible at high prediction error combined with a high share of predicted items. In the empirical study, predictive intervals achieve coverage within ten percentage points of the nominal level in the pooled condition, and the uncertainty-aware assembly reduces the TIF gap relative to the baseline, with the largest gains at the extremes of the ability distribution where accurate measurement matters most for instructional placement decisions. By separating prediction uncertainty from true individual differences in ability, this framework preserves the interpretability of cognitive ability estimates and provides a foundation for personalized assessment systems that support differentiated instruction under continuous item bank growth. Full article

(This article belongs to the Special Issue New Advances of Intelligence Measurement in the AI Era: Theory, Methods and Applications)

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17 pages, 1205 KB

Open AccessReview

Cancer Cachexia in Advanced Renal Cell Carcinoma: From Molecular Mechanisms to Prognostic Assessment

by Yushuang Cui, Yudong Cao, Chen Lin, Jinchao Ma, Shuo Wang and Peng Du

Int. J. Mol. Sci. 2026, 27(17), 7944; https://doi.org/10.3390/ijms27177944 (registering DOI) - 6 Sep 2026

Abstract

Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive skeletal muscle loss, affecting 30–60% of patients with advanced renal cell carcinoma (RCC). It significantly impacts treatment tolerance, quality of life, and prognosis, yet its diagnosis and management remain challenging due to fragmented [...] Read more.

Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive skeletal muscle loss, affecting 30–60% of patients with advanced renal cell carcinoma (RCC). It significantly impacts treatment tolerance, quality of life, and prognosis, yet its diagnosis and management remain challenging due to fragmented RCC-specific evidence, particularly in the era of immune checkpoint inhibitor (ICI)-based therapy. The pathogenesis involves persistent systemic inflammation, metabolic reprogramming, and tumor–host interactions. The IL-6/STAT3 and TNF-α/NF-κB pathways are central to muscle catabolism, while tumor-derived mediators such as GDF15 and PTHrP, along with mitochondrial dysfunction, further drive cachexia progression. For prognostic assessment, CT-derived skeletal muscle mass evaluation combined with systemic inflammatory and nutritional biomarkers—including neutrophil-to-lymphocyte ratio (NLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), and cachexia index (CXI)—has improved risk stratification in advanced RCC. Preclinical and emerging clinical data suggest that targeted therapies may partially attenuate cachexia by modulating inflammatory signaling, while multimodal interventions integrating nutritional support and exercise rehabilitation remain the cornerstone of management. Novel strategies, such as inhibition of the GDF15/GFRAL axis, are under active investigation. Future research should prioritize identification of early biomarkers, standardization of cachexia assessment, and prospective evaluation of cachexia-directed interventions in the immunotherapy era. Integrating cachexia assessment into routine practice may ultimately enable personalized treatment and improve long-term outcomes for patients with advanced RCC. Full article

(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Oncology)

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17 pages, 5930 KB

Open AccessArticle

Effects of a Xenogeneic Bone Graft Combined with Platelet-Rich Fibrin Obtained Using Two Distinct Centrifugation Protocols on Critical-Size Rat Calvarial Defects: A Microtomographic, Histomorphometric, and Confocal Laser Scanning Microscopy Analysis

by Ulli da Costa Cunha Martins, Débora de Souza Ferreira Sávio, Roberta Okamoto, Carlos Fernando Mourão, Richard J. Miron, Sérgio Luis Scombatti de Souza, Flávia Aparecida Chaves Furlaneto and Michel Reis Messora

J. Funct. Biomater. 2026, 17(9), 451; https://doi.org/10.3390/jfb17090451 (registering DOI) - 6 Sep 2026

Abstract

This study aimed to evaluate bone regeneration in critical-size rat calvarial defects treated with a xenogeneic bone graft alone or combined with autologous platelet concentrates prepared using two distinct centrifugation protocols, one based on horizontal centrifugation to produce horizontal platelet-rich fibrin (H-PRF) and [...] Read more.

This study aimed to evaluate bone regeneration in critical-size rat calvarial defects treated with a xenogeneic bone graft alone or combined with autologous platelet concentrates prepared using two distinct centrifugation protocols, one based on horizontal centrifugation to produce horizontal platelet-rich fibrin (H-PRF) and the other based on vertical fixed-angle centrifugation to produce leukocyte–platelet-rich fibrin (L-PRF). Calvarial defects were created in 24 rats and allocated to four groups: blood clot (C), xenograft (XEN), xenograft plus L-PRF (XEN+L-PRF), and xenograft plus H-PRF (XEN+H-PRF) (n = 6/group). Calcein and alizarin were administered at 14 and 30 days, respectively. After 35 days, specimens were analyzed by micro-computed tomography, confocal laser scanning microscopy, histomorphometry, and histopathology. Data were analyzed using ANOVA and Tukey’s post hoc test (p < 0.05). All treated groups showed higher bone volume and lower trabecular separation than group C. The XEN+L-PRF group showed significantly higher bone volume than the XEN group. The XEN+H-PRF group showed higher bone volume, connectivity density, alizarin labeling, mineral apposition rate, and newly formed bone area, as well as lower trabecular separation, than the other groups (p < 0.05). Under the experimental conditions evaluated, both PRF protocols improved bone regeneration when combined with a xenogeneic bone graft, whereas the H-PRF protocol was associated with superior structural and histomorphometric bone regeneration outcomes and with more favorable spatiotemporal mineralization kinetics. Full article

(This article belongs to the Special Issue New Trends in Biomaterials and Implants for Dentistry (3rd Edition))

33 pages, 7615 KB

Open AccessArticle

Phase-Selective Volt/VAR Placement and Sizing of Distributed Generation in Unbalanced Medium-Voltage Feeders: A Constructive Method Under Local-Demand Constraints

by Anthony Buezo, Jared Murillo, Osly Rodas, Jonathan Muñoz Tabora and Rafael A. Garcia

Energies 2026, 19(17), 4218; https://doi.org/10.3390/en19174218 (registering DOI) - 6 Sep 2026

Abstract

Inverter-interfaced distributed generation (DG) can provide voltage support in unbalanced distribution feeders; however, sequential, phase-selective siting and sizing under local interconnection constraints have received limited attention. This study proposes a constructive Volt/VAR planning method that allocates DG according to the apparent demand and [...] Read more.

Inverter-interfaced distributed generation (DG) can provide voltage support in unbalanced distribution feeders; however, sequential, phase-selective siting and sizing under local interconnection constraints have received limited attention. This study proposes a constructive Volt/VAR planning method that allocates DG according to the apparent demand and voltage-deficient phases at each candidate bus. A descending reactive power feasibility test rejects solutions that cause non-convergence, overvoltage, or deterioration of the minimum system voltage. The method was implemented through automated unbalanced three-phase power-flow simulations and tested on the IEEE 13-node feeder and the real 3849-bus CHIRIPA medium-voltage network in Honduras, using active power allocation factors of 0.7 and 0.9. The selected configurations were evaluated over 24 h profiles for representative sunny and rainy days, annualized, and assessed economically over a 25-year horizon. Annual energy losses decreased by 25.8% and 26.4% in the IEEE feeder, although local capacity constraints prevented all phase voltages from reaching the 0.95–1.05 p.u. range. In CHIRIPA, all medium-voltage bus-phase voltages satisfied this range at maximum demand, although this improvement persisted only during solar hours; annual losses fell by 15.1% and 18.7%. The economic feasibility threshold in CHIRIPA depended primarily on installed capacity (approximately 6.5–6.6 MW), rather than unit count. These results provide a reproducible framework for prioritizing phase-specific DG investments under technical and economic constraints. Full article

(This article belongs to the Special Issue Planning and Operation of Integrated Renewable Energy Distribution System: 2nd Edition)

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30 pages, 26362 KB

Open AccessArticle

The Vaccine Candidates Against Major Fish Pathogens (Pseudomonas fluorescens and Aeromonas hydrophila) from the Outer Membrane Proteins of P. fluorescens in Fish

by Xiang Liu, Wei Sun, Ling Zhu, Yuhang Zhan, Yixin Yu, Kai Wang, Qinkai Hu, Xuan Huang, Juan Lu and Xianjie Liu

Life 2026, 16(9), 1493; https://doi.org/10.3390/life16091493 (registering DOI) - 6 Sep 2026

Abstract

Vaccines have demonstrated greater efficiency in providing immunoprotection against bacterial species, making them potentially valuable in aquaculture. In this study, twenty-four outer membrane proteins (OMPs) of Pseudomonas fluorescens were cloned, purified, and 16 OMP mouse antisera were prepared, with titers all exceeding 1:3200. [...] Read more.

Vaccines have demonstrated greater efficiency in providing immunoprotection against bacterial species, making them potentially valuable in aquaculture. In this study, twenty-four outer membrane proteins (OMPs) of Pseudomonas fluorescens were cloned, purified, and 16 OMP mouse antisera were prepared, with titers all exceeding 1:3200. Subsequently, these 16 antisera were used to passively immunize crucian carp (Carassius auratus) followed by challenge with the pathogenic bacteria. The results showed that five OMP antisera (PF0542, SurA, PF1798, PF2253, and PF4616), as well as the whole OMP serum, provided immune protection rates exceeding 60% against P. fluorescens and Aeromonas hydrophila infection (p < 0.05). Moreover, these five OMP antisera reduced the mRNA expression of inflammatory cytokines and antioxidant factors (p < 0.05), and exerted protective effects on the structural integrity of the kidney, spleen, and intestinal tissues. In addition, active immunization of crucian carp with these five identified OMPs followed by pathogen challenge demonstrated that these proteins could activate non-specific immune responses in fish, confer immune protection against P. fluorescens and A. hydrophila infection, reduce the mRNA expression of inflammatory cytokines and antioxidant factors (p < 0.05), and protect the tissue structure of the kidney, spleen, and intestine. Collectively, these five OMPs (PF0542, SurA, PF1798, PF2253, and PF4616) can activate immune responses in crucian carp, confer protection against bacterial infection, and exhibit reductions in inflammatory/oxidative responses associated with protection following bacterial challenge, and as well as viscera structure-maintaining effects. Therefore, the five OMPs hold promise as vaccine candidates against bacterial infections (P. fluorescens and A. hydrophila) for both passive and active immunization in fish. Full article

(This article belongs to the Special Issue Molecular Pathogenesis and Resistance Mechanisms of Aquatic Pathogens)

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28 pages, 5425 KB

Open AccessSystematic Review

Heating the Cold: Overcoming Immunotherapy Resistance in Microsatellite-Stable Colorectal Cancer: A Systematic Review

by Dorota Bartusik-Aebisher, Daniel Roshan Justin Raj, Izabella Wilk and David Aebisher

Molecules 2026, 31(17), 3124; https://doi.org/10.3390/molecules31173124 (registering DOI) - 6 Sep 2026

Abstract

Colorectal cancer (CRC) has shown significant heterogeneity regarding its response to immunotherapy. Long-lasting, beneficial effects have been observed in mismatch repair-deficient, microsatellite instability-high (dMMR/MSI-H) tumours, while mismatch repair-proficient, microsatellite stable (pMMR/MSS) tumours have remained resistant. Such differences in results have been studied in [...] Read more.

Colorectal cancer (CRC) has shown significant heterogeneity regarding its response to immunotherapy. Long-lasting, beneficial effects have been observed in mismatch repair-deficient, microsatellite instability-high (dMMR/MSI-H) tumours, while mismatch repair-proficient, microsatellite stable (pMMR/MSS) tumours have remained resistant. Such differences in results have been studied in this review through the “hot” and “cold” tumour concept. It explains how various biological and microenvironmental factors play a role in immune resistance and T-cell priming and infiltration. Key factors include a low neoantigen load and defects in antigen presentation, which reduce the overall immune recognition of tumour cells. The review also studies certain processes such as Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signalling and what input they have in the prevention of effective antitumour immune responses. Conventional treatments like chemotherapy and radiotherapy have been considered alongside more targeted treatments such as the inhibition of vascular endothelial growth factor (VEGF) signalling and the suppression of myeloid-mediated immune evasion, to convert “cold” MSS tumours into immune-responsive lesions. Methods which aim to modify the tumour microenvironment such as metabolic reprogramming and microbiome modulation have also been covered in this review. Artificial intelligence and nanomedicine are new technologies that could provide improved patient stratification and therapeutic precision, although their clinical application in pMMR/MSS CRC remains under investigation. A systematic literature search of PubMed and PubMed Central (PMC) was conducted from 10 June 2026 to 19 August 2026 using predefined eligibility criteria, with study selection reported according to PRISMA 2020. Because of substantial heterogeneity in study design, therapeutic approach and reported outcomes, the included evidence was synthesized narratively rather than by meta-analysis. A total of 158 studies were included. Full article

(This article belongs to the Special Issue New Therapeutic Tools Against MDR Tumors: Discovery, Synthesis and Evaluation of Bioactive Compounds: 2nd Edition)

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23 pages, 23133 KB

Open AccessArticle

Yeast-Mediated Pre-Fermentation Modulates the Fecal Microbiome In Vitro in a Genotype-Dependent Manner

by Tekmile Cankurtaran Kömürcü, Miguel Angel Alvarez Gonzales, İhsan Sarıoğlan, Stephen R. Lindemann and Yunus Emre Tunçil

Fermentation 2026, 12(9), 427; https://doi.org/10.3390/fermentation12090427 (registering DOI) - 6 Sep 2026

Abstract

This study investigated the effects of yeast-mediated pre-fermentation on the composition and functional characteristics of modern and ancient wheat genotypes, and their subsequent impact on gut microbial fermentation. Whole wheat flours were pre-fermented using Saccharomyces cerevisiae (6%, w/w) at 30 [...] Read more.

This study investigated the effects of yeast-mediated pre-fermentation on the composition and functional characteristics of modern and ancient wheat genotypes, and their subsequent impact on gut microbial fermentation. Whole wheat flours were pre-fermented using Saccharomyces cerevisiae (6%, w/w) at 30 °C for 6 h. Raw and pre-fermented whole wheat samples were subjected to in vitro upper gastrointestinal digestion, followed by monosaccharide composition analysis, in vitro fecal fermentation using a pooled inoculum prepared from three healthy donors, microbial profiling, and short-chain fatty acid (SCFA) quantification. Fermentation increased Folin–Ciocalteu-reactive values and antioxidant capacity, while reducing residual starch and protein after digestion, indicating alterations in the composition of digestion-derived residues. After fermentation by S. cerevisiae, monosaccharide analysis revealed a relative enrichment of glucose, accompanied by decreased proportions of arabinose and xylose. Following in vitro fecal fermentation, pre-fermented wheat samples exhibited significantly (p < 0.001, AMOVA) different microbial community structures compared with their raw counterparts, based on Bray–Curtis dissimilarities, whereas differences in α-diversity were comparatively limited. In addition, taxa associated with carbohydrate fermentation and SCFA production, including Parabacteroides distasonis, Butyrivibrio crossotus, and Kineothrix, showed treatment- and genotype-dependent responses. All wheat samples supported SCFA production, although SCFA accumulation was more gradual than with inulin. Overall, yeast-mediated pre-fermentation was associated with changes in wheat composition and subsequent shifts in fecal microbial community structure and fermentation dynamics, with responses varying among wheat genotypes. Full article

(This article belongs to the Special Issue Yeasts as Microbial Cell Factories: Diversity, Biotechnology Potential and Applications)

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23 pages, 6888 KB

Open AccessArticle

Evaluating CORDEX-CORE Regional Climate Models for Precipitation Simulation: A Multi-Criteria Ranking Approach for Agro-Hydrological Applications in the Cauvery Delta, Tamil Nadu

by Gunavathi Sundaram and Selvakumar Radhakrishnan

Meteorology 2026, 5(3), 27; https://doi.org/10.3390/meteorology5030027 (registering DOI) - 6 Sep 2026

Abstract

Climate change has significantly influenced regional precipitation patterns, affecting agricultural productivity and water-resource sustainability in monsoon-dependent regions. Reliable climate projections are therefore essential for climate impact assessment and adaptation planning. However, the performance of Regional Climate Models (RCMs) varies considerably across regions and [...] Read more.

Climate change has significantly influenced regional precipitation patterns, affecting agricultural productivity and water-resource sustainability in monsoon-dependent regions. Reliable climate projections are therefore essential for climate impact assessment and adaptation planning. However, the performance of Regional Climate Models (RCMs) varies considerably across regions and climatic conditions, necessitating rigorous evaluation before their application in local-scale studies. In this study, eight CORDEX-CORE South Asia (0.22°) RCMs were evaluated for their ability to reproduce historical precipitation over Thanjavur district, Tamil Nadu, India, during 1976–2005 using observed rainfall data from 13 rain gauge stations. Model performance was assessed using seven statistical metrics integrated through the Compromise Programming Index (CPI), together with evaluations of precipitation occurrence, rainfall intensity occurrence, and cumulative precipitation distribution. The results revealed considerable variability among the RCMs. RegCM-based models generally exhibited wet biases, whereas REMO and CCLIM tended to underestimate seasonal rainfall. Based on the selected metrics and CPI framework, NorESM–RegCM, NorESM-CCLIM, and NorESM-REMO demonstrated comparatively better overall performance. However, analyses of precipitation occurrence and distribution showed that model performance depended on the precipitation characteristic considered, with no single RCM consistently outperforming the others across all evaluation criteria. These findings demonstrate that a multi-criteria evaluation framework provides a more comprehensive assessment of RCM performance than conventional statistical metrics alone and offers a robust basis for selecting suitable RCMs for future climate projections and agro-hydrological applications in the Cauvery Delta region. Full article

33 pages, 8313 KB

Open AccessReview

Chitosan-Based Functional Films and Nanocomposites for Sustainable Electronics: A Structure–Property–Function Systematic Review

by Muhammad Rif’an, Arie Aryanto, Karlisa Priandana and Waras Nurcholis

Int. J. Mol. Sci. 2026, 27(17), 7942; https://doi.org/10.3390/ijms27177942 (registering DOI) - 6 Sep 2026

Abstract

Chitosan-based films and nanocomposites have attracted growing attention as renewable, biodegradable, and chemically adaptable materials for sustainable electronics. This systematic review synthesizes evidence on chitosan-containing functional films, membranes, polymer electrolytes, dielectric substrates, optoelectronic nanocomposites, electrochemical sensors, impedance sensors, and smart-device interfaces. This review [...] Read more.

Chitosan-based films and nanocomposites have attracted growing attention as renewable, biodegradable, and chemically adaptable materials for sustainable electronics. This systematic review synthesizes evidence on chitosan-containing functional films, membranes, polymer electrolytes, dielectric substrates, optoelectronic nanocomposites, electrochemical sensors, impedance sensors, and smart-device interfaces. This review adopts a structure–property–function perspective, examining molecular interactions, crystallinity, amorphous fraction, morphology, filler dispersion, processing routes, and interfacial architecture in relation to optical, electrical, dielectric, electrochemical, and sensing performance. The literature was identified using Scopus-oriented Boolean searches combining chitosan/chitin terms with thin-film or membrane descriptors, electronic-function terms, and structure–property terminology. Relevant studies were grouped into four themes: structural engineering and processing, dielectric/electrical/impedance properties, optoelectronic and band-gap engineering, and electrochemical/impedance-sensing applications. The synthesis shows that chitosan becomes electronically functional when its semi-crystalline, hydrogen-bonded matrix is modified through salt doping, plasticization, blending, conductive polymers, carbon materials, metal oxides, metal–organic frameworks, or noble metal nanoparticles. Reported advances include ionic conductivities up to 10⁻³ S/cm, improved dielectric behavior, band-gap reduction, and low detection limits. However, inconsistent reporting of material source, molecular weight, degree of deacetylation, film thickness, humidity, stability, and sustainability metrics limits comparability. Full article

(This article belongs to the Section Materials Science)

28 pages, 2102 KB

Open AccessArticle

Distributed Mixed-Power Fixed-Time Cooperative Guidance for Multiple Aircraft with Terminal Line-of-Sight Angle Constraints

by Yu Zhang, Huimin Zhu, Shiyan Sun, Likun Han, Chi Li and Weige Liang

Appl. Sci. 2026, 16(17), 8863; https://doi.org/10.3390/app16178863 (registering DOI) - 6 Sep 2026

Abstract

Cooperative interception by multiple aircraft requires coordination of physical event times and terminal line-of-sight (LOS) directions under strongly coupled three-dimensional motion. A limitation of predictor-based designs is that agreement of estimated terminal times is often interpreted as simultaneous interception without an explicit predictor-to-event [...] Read more.

Cooperative interception by multiple aircraft requires coordination of physical event times and terminal line-of-sight (LOS) directions under strongly coupled three-dimensional motion. A limitation of predictor-based designs is that agreement of estimated terminal times is often interpreted as simultaneous interception without an explicit predictor-to-event error bound. This paper develops a distributed mixed-power fixed-time guidance framework that comprises point-mass kinematics and ideal inner-loop tracking. An exact spherical-coordinate model retains the azimuth–elevation coupling terms. The radial predicted terminal time (RPTT) is used as the distributed coordination state, and a local bound links RPTT to independently detected interception events. A mixed-power consensus protocol is analyzed for a fixed graph and a finite set of connected undirected switching graphs using a common Lyapunov function. An inertial-frame fixed-time observer estimates the unmeasured target acceleration, while a C²-regularized nonsingular fast terminal sliding-mode law regulates the terminal LOS azimuth and elevation. The analysis distinguishes nominal exact fixed-time consensus, perturbed practical fixed-time reachability, and exponential convergence inside the regularization layer. Four-aircraft simulations produced a 0.435 ms independent event-time spread and terminal LOS errors below 0.046°. Relative to a peak-matched single-power protocol, the RPTT agreement time was reduced by 34.3%, with a 0.58% increase in total control effort. The results support the method’s use as a guidance-layer coordination design within the stated sensing, communication, and inner-loop assumptions. Full article

16 pages, 327 KB

Open AccessArticle

An Upwind Interior Penalty DG Scheme for Solute Transport in 2D Variable-Order Mobile–Immobile Model

by Leilei Wei, Lijie Liu and Xindong Zhang

Entropy 2026, 28(9), 997; https://doi.org/10.3390/e28090997 (registering DOI) - 6 Sep 2026

Abstract

This paper develops and rigorously analyzes a fully discrete upwind interior penalty discontinuous Galerkin (IPDG) scheme for simulating solute transport in two-dimensional variable-order fractional mobile–immobile media. The temporal variable-order Caputo derivative is discretized via a Grünwald–Letnikov approximation in conjunction with a first-order backward [...] Read more.

This paper develops and rigorously analyzes a fully discrete upwind interior penalty discontinuous Galerkin (IPDG) scheme for simulating solute transport in two-dimensional variable-order fractional mobile–immobile media. The temporal variable-order Caputo derivative is discretized via a Grünwald–Letnikov approximation in conjunction with a first-order backward difference, while the spatial discretization employs an IPDG method featuring an upwind numerical flux for the convection term and a penalty formulation for the diffusion operator. Under the physically relevant assumption of a divergence-free velocity field, we establish the unconditional stability of the proposed scheme. A comprehensive error analysis in the

L^{2}

norm yields a convergence rate of

O (Δ t + h^{min (k + 1, s) - χ - 1 / 2})

, explicitly linking the polynomial degree k, solution regularity s, and the penalty variant

χ

. Numerical experiments in two dimensions are conducted to verify the accuracy and robustness of the proposed scheme in simulating anomalous transport phenomena in subsurface environments. Full article

(This article belongs to the Section Statistical Physics)

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