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Metabolomics and pharmacometabolomics are at the forefront of precision medicine, serving as powerful tools in drug discovery and development. These approaches help address critical challenges in the field, including high clinical trial failure rates, adverse drug reactions, and interindividual variability in drug response. Comprehensive metabolome profiling enables the elucidation of disease mechanisms, identification of drug targets, optimization of therapeutic strategies, and assessment of drug safety and efficacy. It also supports more informed clinical trial design. This review highlights the pivotal role of metabolomics in advancing precision medicine and aims to broaden the perspectives of emerging scientists entering this complex field. Key analytical techniques–namely mass spectrometry and nuclear magnetic resonance spectroscopy–are discussed for their respective strengths and limitations in metabolite identification, quantitation, and structural elucidation. Additionally, analytical separation technologies such as liquid and gas chromatography, ion mobility spectrometry, capillary electrophoresis, and supercritical fluid chromatography are explored for their potential to enhance metabolome coverage, improve analytical efficiency, and reduce costs. Ongoing advancements in instrumentation and computational tools are helping to overcome major challenges in metabolomics, including metabolome complexity, data analysis and integration, and biomarker validation. These developments continue to expand the applications of metabolomics and pharmacometabolomics in both preclinical and clinical research. Ultimately, this review underscores their translational potential in facilitating drug discovery, mitigating risks in clinical trials, and shaping the future of precision medicine. Full article

Understanding asthma’s endotypes is key to advancing precision medicine. Using omics techniques on sputum, bronchial epithelium, and blood have revealed T2 and non-T2 asthma, each which have been further categorized into T2 and non-T2 subgroups. Despite advances in understanding asthma’s molecular complexity, many questions remain. Future research could either enhance current multiomics approaches with sophisticated bioinformatics or integrate hypothesis-driven research. It is now widely accepted that the airway epithelium starts and regulates the inflammatory cascade in asthma. If asthma originates in the altered epithelium, concentrating research on epithelial dysfunction is logical. This approach is likely more straightforward than analyzing the multitude of genes affected by the inflammatory cascade triggered by this disturbed airway epithelium. The airway epithelium comprises various cell types, including basal cells, club cells, ciliated cells, goblet cells, pulmonary neuroendocrine cells, tuft cells, and pulmonary ionocytes, which are connected by junctional complexes including tight junctions, adherens junctions, gap junctions, and desmosomes. The healthy airway epithelium helps support homeostasis, defend against threats, and regulate immunity through innate and adaptive systems. Chronic airway epithelial barrier dysfunction can instigate and propagate excessive immune responses. Knowing the cellular makeup and differentiation of the airway epithelium is vital for creating treatments to restore airway integrity in established asthma. A new consensus highlights focusing research on airway epithelial dysfunction as the main driver of inflammation, marking the start of the “epithelium era” in asthma research. Full article

Background: The minimized pan-coronavirus (CoV) vaccine-1 developed by our laboratory contained pDNA sequences of feline coronavirus serotype-1 (FCoV1) and SARS-CoV2 (SCoV2) spike B-cell epitopes plus FCoV/SCoV2-conserved, CoV-specific polymerase cytotoxic T-lymphocyte (CTL) epitopes formulated in lipid nanoparticle (LNP). Only FCoV2 infects feline cell lines needed for developing native challenge inoculum that causes feline infectious peritonitis (FIP). Hence, Pilot Study 1 evaluated the therapeutic efficacy and safety of the pan-CoV vaccine-1 in feline immunodeficiency virus (FIV)-infected cats, with or without FCoV1 coinfection. Pilot Study 2 evaluated the cross-protective effect of pan-CoV vaccines in specific-pathogen-free (SPF) cats against intranasal challenge with FIP virus serotype 2 (FIPV2). Methods: In Study 1, we vaccinated two FIV-infected cats (one negative and another positive for FCoV1 coinfection) intramuscularly twice with CTL epitopes-LNP vaccine and later twice with pan-CoV vaccine-1. Controls included two unvaccinated FIV-infected cats with or without FCoV1 coinfection. Study 2 assessed the sequential vaccinations of three pan-CoV vaccines in four SPF cats. The first two vaccinations were with pan-CoV vaccine-2, followed by pan-CoV vaccine-3 (twice), and lastly with pan-CoV vaccine-1 (once). Three SPF controls included two cats immunized with LNP and one lacking any immunization. Pan-CoV vaccine-2 contained pDNAs with modified FCoV1/SCoV2 B-cell epitopes plus CTL epitopes in LNP. Pan-CoV vaccine-3 contained only pDNAs with FCoV1 B-cell epitopes plus CTL epitopes in LNP. Results: Study 1 demonstrated no adverse effect with 25 μg and 50 μg CTL epitopes-LNP vaccine and 50 μg pan-CoV vaccine-1. However, 100 μg pan-CoV vaccine-1 caused fever 24 h later, which was resolved by a single Meloxicam treatment. Both vaccinees developed cross-FCoV2 neutralizing antibodies (XNAbs), immunoblot binding antibodies (bAbs) to FCoV1 receptor-binding domain (RBD), and T-cell responses to FCoV1 RBD, whereas one vaccinee also developed bAbs to SCoV2 RBD. Study 2 demonstrated no adverse effects after each vaccination. Three vaccinees developed low-titer XNAbs and bAbs to FCoV2 spike-2 by the fourth vaccination. Upon challenge, all cats developed FCoV2 NAbs and bAbs to FCoV2 nucleocapsid and RBD. High vaccine-induced T-cell responses to FCoV1 RBD and T-cell mitogen responses declined with an increase in responses to FCoV2 RBD at three weeks post-challenge. Two of the three controls died from FIP, whereas one vaccinee, with the lowest vaccine-induced immunity, died from skin vasculitis lesions and detection of FIPV2 infection by semi-nested RT-snPCR in feces. Conclusions: In Pilot Study 1, the pan-CoV vaccine-LNP dose of 50 μg had no adverse effects, but adverse effects were observed at 100 μg dose. In Pilot Study 2, the FCoV1-based B-cell vaccine(s) induced low levels of XNAbs against FIPV2 and delayed challenge infection against high-dose FIPV2. The high-dose FIPV2 infections in the vaccinated and control cats started to clear, by single housing at 23–26 weeks post-challenge, whereas two cats in Pilot Study 1 cleared natural FCoV1 transmission by 26 weeks post-infection. Full article

The clade Gluconacetobacter comprises eleven species originating from various sources such as rhizosphere soil, pink sugarcane mealybug, and vinegar. During sampling of organic vinegars, we isolated strain Hr-1-5, which exhibits high 16S rRNA gene sequence identities (≤98.6%) and low 16S-23S rRNA gene internal transcribed spacer (ITS) sequence identities (≤92.1%) with Gluconacetobacter species. Further genome analysis confirmed that strain Hr-1-5 is a distinct species, supported by an average nucleotide identity (ANIb) of ≤90.6% and an in silico DNA–DNA hybridization (dDDH) value of ≤46% compared with other recognized Gluconacetobacter species. Strain Hr-1-5 darkens the growth medium to a deep brown after 4–5 days of submerged cultivation and similarly colors agar medium after 5–6 days. In silico genome analysis suggests that the strain synthesizes pyomelanin. Phenotypically, it is distinguished from its closest Gluconacetobacter relatives by its ability to produce 5-keto-D-gluconic acid, but not 2-keto-D-gluconic acid, and by its capacity to grow on D-ribose, among other traits. These findings support the classification of strain Hr-1-5 as a novel species, for which we propose the name Gluconacetobacter brunescens sp. nov. Hr-1-5^T (=ZIM B1168^T = LMG 33629^T). Strain Hr-1-5 is of biotechnological interest for its pigment production and enables the in situ production of colored cellulose in a co-culture with a cellulose-producing acetic acid bacterium. Full article

Graph-based Recommender Systems (GRSs) model complex user–item relationships. They offer improved accuracy and personalization in recommendations compared to traditional models. However, GRSs also face severe challenges from novel poisoning attacks. Attackers often manipulate GRS graph structures by injecting attack users and their interaction data. This leads to misleading recommendations. Existing detection methods lack the ability to identify such attacks targeting graph-based systems. To address this, we propose AutoDAP, a novel autoencoder-based detection method for poisoning attacks in GRSs. AutoDAP first extracts key statistical features from user interaction data. It fuses them with original interaction information. Then, an autoencoder architecture processes this data. The encoder extracts deep features and connects to an output layer for classification prediction probabilities. The decoder reconstructs graph structure features. By jointly optimizing classification and reconstruction losses, AutoDAP effectively integrates supervised and unsupervised signals. This enhances the detection of attack users. Evaluations on the MovieLens-10M dataset against various poisoning attacks, and on the Amazon dataset with real attack data, demonstrate AutoDAP’s superiority. It outperforms several representative baseline methods in both simulated (MovieLens) and real-world (Amazon) attack scenarios, demonstrating its effectiveness and robustness. Full article

A model of gene regulatory networks with generalized Caputo fractional derivatives with respect to another function is set up in this paper. The main characteristic of the model is the presence of a switching rule, which changes at certain times at both the lower limit of the applied fractional derivative and the right-side part of the equations. This gives the opportunity for better and more adequate modeling of the problem. Mittag–Leffler-type stability is defined for the model and studied with two types of Lyapunov functions. Initially, some properties of absolute value Lyapunov functions and quadratic Lyapunov functions are given, and two types of sufficient conditions are obtained. An example is provided to illustrate our theoretical results and the influences of the type of fractional derivative as well the switching rule on the stability behavior of the equilibrium. Full article

Background/Objectives: Social media has become a key activity in adolescents’ lives, with potential implications for their health and well-being. Because of this, the objective was to examine the influence of social media on the eating behavior and sleep quality of adolescents aged 13 to 18 years. Methods: The PubMed, Scopus, Proquest, Web of Science, and Cochrane Library databases were reviewed following the PRISMA protocol. The inclusion criteria for the studies were as follows: a sample of adolescents aged 13 to 18 years without a baseline clinical diagnosis and research objectives related to social media and its influence on eating behavior or sleep quality. A total of 24 articles were included at the end of the search. Due to heterogeneity in measurement formats, a single pooled analysis was not feasible. Instead, two partial random-effects meta-analyses of continuous outcomes were performed (sleep and eating behaviours). Results: Qualitative synthesis revealed consistent associations between problematic social media use, poor sleep quality, and disordered eating. The meta-analyses showed a small-to-moderate and statistically significant association on sleep quality (r = 0.36) while the pooled estimate for eating behaviours was imprecise and not significant (r = 0.35), reflecting the very limited number of eligible studies. Conclusions: Excessive social media use is associated with poorer sleep and eating outcomes among adolescents. These findings highlight the need for educational and preventive strategies promoting healthy digital habits and psychological well-being. This systematic review elucidates the implications of social media use for health promotion at this development stage. Full article

The active efflux of drugs by adenosine triphosphate (ATP)-binding cassette (ABC) trans-porters, such as multidrug resistance protein 1 (MDR1/ABCB1), multidrug resistance-associated protein 1 and 2 (MRP1/ABCC1; MRP2/ABCC2), and breast cancer resistance protein (BCRP/ABCG2), is a well-established mechanism contributing to multidrug resistance (MDR). Interestingly, various vitamin A-based molecules have been found to influence the expression or function of these transporters. This work investigated the current evidence on the effects of retinoids, rexinoids, and carotenoids on ABC transporters and their potential to reverse MDR. Several studies indicated that these compounds could inhibit ABC transporter activity at non-toxic concentrations, either by downregulating gene/protein expression or by directly blocking efflux function. These effects were often associated with increased chemosensitivity to several conventional anticancer agents. Overall, the degree of inhibition varied depending on several factors, including compound type and their chemical modification, dose, incubation time, treatment timing, the type of target cells, method of transporter overexpression, and coadministration with other compounds. Although particular attention was paid to elucidating the underlying mechanisms, current knowledge in this area remains limited. Moreover, extensive in vivo and clinical studies validating these findings are still lacking, emphasizing the need for further research to evaluate their translational potential. Full article

Objectives: This study aimed to determine whether chromosomal mosaicism in blastocysts is associated with a distinct morphokinetic signature. Methods: Preimplantation genetic testing for aneuploidy (PGT-A) was performed on 182 human embryos via trophectoderm biopsy on day 5 and analyzed by next-generation sequencing. Embryos were classified as euploid (n = 55), mosaic (n = 39: 21 low-grade, 18 high-grade), or aneuploid (n = 88), of which 18 with concurrent mosaicism. Prior to biopsy, embryos were cultured in a time-lapse system (EmbryoScope), and 12 morphokinetic parameters were assessed, including pronuclei fading (tPNf), cleavage times (t2–t9), morula formation (tM), blastulation start (tSB), and full blastocyst formation (tB). These parameters were compared according to ploidy status. Results: Patients with euploid and mosaic embryos were comparable in terms of maternal age, ART indication and embryo quality (p > 0.05). In contrast, aneuploid embryos were obtained from older patients and had lower morphological grades. Mosaic embryos showed delayed tPNf (24.8 ± 6.5 vs. 22.8 ± 2.3 h, p = 0.03) and t2 (27.6 ± 6.6 vs. 25.4 ± 2.5 h, p = 0.02) compared to euploid embryos, mainly attributable to low-grade mosaic embryos. Whole-chromosome mosaicism, but not segmental mosaicism, was associated with delayed embryo development at several intermediate cleavage time points (t3, t4, t6, t7 and t9). Aneuploid embryos showed significant delays at later stages versus euploid embryos, particularly aneuploid embryos with mosaicism at t7 (56.6 ± 8.3 vs. 52 ± 5.6 h, p = 0.02), t8 (59.1 ± 9.6 vs. 54.8 ± 6.7 h, p = 0.04), tM (90.3 ± 7.7 vs. 83.6 ± 8.2 h, p = 0.006) and tB (113.0 ± 11.6 vs. 106.6 ± 8.9 h, p = 0.03). Conclusions: Mosaic embryos exhibit delays in early development (tPNf, t2) but reach later morphokinetic milestones at rates similar to euploid embryos. In contrast, aneuploid embryos, especially those with mosaicism, exhibit marked developmental delays at later stages (t7, t8, tM, tB). Full article

The transportation problem (TP) is a canonical linear programming model for minimizing the cost of distributing goods from multiple sources to multiple destinations. Classical TPs assume deterministic costs, supplies, and demands, whereas real supply chains are affected by volatility in fuel prices, inflation, disruptions, and weather, making such parameters uncertain. Fuzzy sets (FSs) and intuitionistic fuzzy sets (IFSs) have been widely used to handle vagueness; however, while Atanassov’s IFSs incorporate hesitation in addition to membership and non-membership, they remain limited to isotropic representations of uncertainty. This paper introduces an index-matrix interpretation for a two-stage three-dimensional transportation problem (2-S 3-D TP) defined under Elliptic Intuitionistic Fuzzy Quadruples (E-IFQs). Within this framework, transportation costs, supplies, and demands are represented as E-IFQs, allowing the modeling of anisotropic and correlated uncertainty along the membership and non-membership axes. The two-stage formulation extends previous intuitionistic fuzzy approaches by adding a temporal dimension and incorporating practical constraints such as cost thresholds and feasibility checks. The objective is to determine optimal producer–hub–buyer allocations that minimize the total E-IFQ cost while preserving consistency across all stages and time periods. A detailed case study on EV battery module distribution demonstrates the effectiveness of the proposed model. Compared with conventional fuzzy and intuitionistic fuzzy formulations, the 2-S 3-D E-IFTP yields more robust and precise decisions under complex, multidimensional uncertainty, offering improved interpretability and policy integration over time. Full article

In recent decades, accelerated urban growth in Arequipa has led to the loss of more than 40% of riparian vegetation and increased ecological fragmentation in the Chili River valley. This transformation has degraded water quality and limited equitable access to green and public spaces. Therefore, this research aims to design a Green Corridor along the Chili River as an ecosystem-based strategy to enhance social connectivity and ecological resilience in Arequipa, Peru. The methodology combined an extensive literature review, a comparative analysis of international case studies, and a territorial diagnosis supported by geospatial and climatic data. The process is supported by digital tools such as Google Earth Pro 2025, AutoCAD 2024, SketchUp Pro 2023, and solar simulations with Ladybug-Grasshopper, complemented by data from SENAMHI, SINIA, and the Solar Atlas of Peru. The results propose a resilient green corridor integrating passive and active sustainability strategies, including 40 photovoltaic panels, 44 solar luminaires, biodigesters producing between 90 and 150 kWh per month, and phytotechnologies capable of absorbing 75,225 kg of CO₂ annually, based on WHO conversion factors adapted to high-altitude conditions. The proposal employs eco-efficient materials such as reforested eucalyptus wood and volcanic sillar, creating recreational and productive spaces that promote social cohesion and circular economy. In conclusion, this study demonstrates the potential of ecosystem-based design to regenerate arid urban riverbanks, harmonizing environmental sustainability, social inclusion, and cultural identity. Thus, the Chili River corridor is consolidated as a replicable model of green-blue infrastructure for Andean cities, aligned with Sustainable Development Goals 6, 7, 11, 12, 13, and 15. Full article

Organic anion transporting polypeptide 1B1 (OATP1B1) is specifically expressed at the basolateral membrane of human liver cells and transports a wide range of endogenous compounds, toxins, and drugs, making it a crucial factor in determining the pharmacokinetics of many clinically important medications. Triptergium wilfordii Hook. f. (TWHF) is a traditional Chinese medicine known for its long history of therapeutic effects. A previous study conducted in our laboratory found that major components of TWHF, including wilforine (WFR), wilforgine (WFG), celastrol (CL), and triptolide (TPL), directly suppressed the function of OATP1B1. In the current study, we investigated the long-term (24 h) effects of these TWHF components on the transporter. It was found that TPL was the most potent compound exhibiting inhibitory effects. Mechanistically, TPL accelerated the degradation of OATP1B1, which is likely mediated by serum and glucocorticoid-induced kinase 1 (SGK1). TPL downregulated the mRNA expression of SGK1 and reduced the nuclear accumulation of nuclear factor kappa B (NFκB). Further analysis of the upstream sequence of SGK1 identified three potential binding sites for NFκB. Both luciferase activity assays and chromatin immunoprecipitation (ChIP) analyses confirmed the binding of NFκB to two specific sites located at −1015 bp~−1006 bp and −319 bp~−310 bp. Full article

Peatlands store approximately 30% of global terrestrial carbon, and tropical peatlands contribute 10%–30% of the total peatland carbon storage. Indonesia holds approximately 15% of this resource. Given the rapid degradation of these ecosystems, the Indonesian government has promoted revegetation, identifying Calophyllum inophyllum L. (Tamanu) as a promising restoration species. However, long-term studies on Tamanu performance and optimal environmental conditions in actual peatland settings are lacking. This study aimed to identify the environmental characteristics conducive to Tamanu growth. We planted Tamanu at Perigi in South Sumatra and Buntoi in Central Kalimantan and monitored its growth over a five-year period. We assessed the soil properties and hydrological conditions at both sites. Results revealed that Tamanu trees at the Perigi site, with higher soil nutrient levels, initially exhibited greater root collar diameter, height, and stem volume compared to those at Buntoi. However, prolonged flooding in Perigi caused complete mortality at 60 months. In contrast, despite lower soil nutrient levels, the Buntoi site maintained a survival rate of 52% because of the more stable water levels. These findings suggest that hydrological management is more critical than soil nutrient conditions for the long-term survival of Tamanu in tropical peatlands, informing effective peatland restoration strategies. Full article

Free water surface constructed wetlands are widely used for phosphorus removal from polluted waters, yet their effectiveness varies across wetland types, designs, and environmental conditions, creating uncertainty about their broader application. Building on prior reviews, this study applies stricter screening criteria and includes the literature until 2023 to deliver a more robust and updated global assessment of phosphorus retention performance. From 71 peer-reviewed studies, statistical analysis and models are applied to identify the principal design and loading parameters governing phosphorus retention. Notably, 90% of the wetlands included exhibited net retention, efficiencies ranged from −245% to 99% (median of 43.9%). Wetland area, hydraulic loading rate, hydraulic retention time, and phosphorus loading rate significantly influenced retention. Larger wetlands (>10 ha) and those with low hydraulic loadings (<10 m/year) displayed higher and more consistent efficiencies, whereas high phosphorus loads and short retention times reduced retention and increased variability. Models indicate wetland area and phosphorus loading as key predictors of efficiency, while hydraulic and phosphorus loading are critical in driving retention rates. By integrating an updated global evidence base with robust study selection and modelling, this review demonstrates the effectiveness of well-designed wetlands, supporting their role as valuable tools for water treatment and ecosystem management. Full article