Search Results (119,603)

The spatial variability of soil shear wave velocity (V_s) significantly influences the results of site seismic response analysis. Based on the collected measured V_s values of silty clay in a certain sea area in China, this study divides the V_s data into one set of on-site sample data and six sets of historical data. A power function is used to establish the regression equation between V_s and depth h, and the joint prior distribution of the mean and variance for parameters a and b in the power function is derived using historical data. The joint posterior distribution of parameters a and b is obtained by applying the Bayesian formula to the on-site sample data. Using the maximum a posteriori mean values of a and b combined with the point estimation method, the mean and standard deviation of the predicted V_s values as functions of depth h are derived. The accuracy of the point estimation results is verified using Monte Carlo simulation. Compared to the V_s values predicted using only the mean values of a and b derived from on-site sample data, the V_s values predicted based on the maximum a posteriori mean values of a and b are closer to the measured V_s values. Accordingly, the results of the site seismic response analysis also align more closely with those calculated using the true V_s values. Full article

MicroRNA (miRNA), as a key post-transcriptional regulatory factor, plays a crucial role in embryonic development. The coordination of endoderm cell convergence and cardiac precursor cell (CPC) migration is critical for cardiac tube fusion. Defects in endoderm can impair the normal migration of CPCs towards the midline, leading to cardia bifida. Although the role of the microRNA-183 family (miR-183, miR-96 and miR-182) in cardiovascular diseases has been reported, the mechanism by which they regulate early heart development remains unclear. In this study, we used zebrafish as a model to elucidate the roles of the microRNA-183 family in early heart development. miRNA mimics were injected into Tg (cmlc2: eGFP) and Tg (sox17: eGFP) transgenic embryos to overexpress the miR-183 family. The results showed that, at 36 hpf, single or co-injection of miR-183/96/182 mimics caused defects in endoderm convergence, with a hole in the endoderm, and a significant down-regulation of the endoderm marker gene sox32. Additionally, embryos with single or co-injection of miR-183/96/182 mimics exhibited cardia bifida and tail blisters, with significantly down-regulated expression levels of genes related to heart development, including cmlc2, vmhc, amhc, nppa, gata4, gata5, nkx2.5, bmp2b, and bmp4. The phenotype caused by overexpression of the miR-183 family is highly consistent with loss of the sphingosine 1-phosphate receptor S1Pr2. Bioinformatics analysis result found that miR-183 can bind to 3′-UTR of the s1pr2 to regulate its expression; overexpression of miR-183 led to a significant decrease in the expression of the s1pr2 gene. Dual luciferase assay results suggest that s1pr2 is a bona fide target of miR-183. In summary, the miR-183 family regulates endoderm convergence and cardiac precursor cell migration via the S1Pr2 signaling pathway. This study reveals that the miR-183 family is a key regulatory factor in endoderm convergence and cardiac precursor cell migration during the early zebrafish development, elucidating the molecular mechanisms underlying early cardiac precursor cell and endoderm cell movement. Full article

Microbial safety in low-moisture foods (LMFs) has attracted widespread public attention due to the multiple outbreaks and recalls in recent years. Dry cleaning methods are typically used in LMFs production environments. However, there is no standardized and consistent method for controlling normal force and measuring the shear force of cleaning tool applied on food contact surfaces during dry cleaning. A dry-cleaning platform with the normal force controllable feature was custom-designed, and its performance was evaluated as the primary objective of the study. Effects of various factors (bacterial type, surface material, surface roughness, and normal force) on the shear force and removal of Salmonella enterica Enteritidis PT 30 (S. PT 30) and Enterococcus faecium NRRL B2354 (E. faecium) during dry wiping were investigated using the developed platform. The performance evaluation indicated that the platform was adequately stable during standardized and consistent dry cleaning. Surface roughness, normal force, and surface material significantly affected shear force (p < 0.05) applied on food contact surfaces. The bacterial type significantly affected the shear force on stainless steel (p < 0.05). No significant difference (p > 0.05) was observed in removing S. PT 30 from inoculated surfaces after dry wiping under all investigated conditions. Surface material significantly affected the removal of E. faecium (p < 0.05). The removal of E. faecium was numerically higher than that of Salmonella under the same conditions. Thus, E. faecium may not be a suitable surrogate for S. PT 30 removal at the end of dry cleaning under the wiping conditions tested. The potential applications of the platform were also discussed for future studies on how to enhance dry cleaning efficiency. Shear force can guide the disruption of cohesion and adhesion in surface microorganisms/residues, thereby enhancing cleaning efficiency. The custom-designed dry-cleaning platform with the controllable normal force feature has potential applications in further laboratory dry cleaning studies. Full article

There is increasing evidence on the occurrence of Crithidia spp. in patients presenting either cutaneous or visceral leishmaniasis, solely or associated with Leishmania. We analyzed growth, morphology, and temperature tolerance of two C. fasciculata strains, the reference strain COLPROT048 and patient isolate COLPROT606. We also evaluated their co-cultivation with L. braziliensis, macrophage infectivity, and infections in hamsters, BALB/c mice, and sandflies. In culture, both Crithidia strains survived at 32 °C for 96 h, showing major morphological alterations and decreased mitochondrial membrane potential, with ΔΨm reducing to 52% in COLPROT606. At 34 °C, the patient isolate showed an 80% reduction in cell number. Mixed cultivation of Crithidia-Leishmania led to recovery of only Crithidia. In macrophages, C. fasciculata alone was virtually eliminated, and in co-infection only Leishmania was detected. No Crithidia lesion or RNA were found in infected mice or hamsters, while L. braziliensis reached 1145–1625 parasites/mg of tissue. In sandflies, C. fasciculata successfully established infection for up to 7 days, both alone and in coinfections. Amphotericin B IC₅₀ values at 72 h were 4- to 5-fold higher in C. fasciculata strains compared to L. braziliensis. Our results indicate that both C. fasciculata strains are unable to reproduce the pathogenic effect in vitro and in vivo models. Full article

On-demand urban delivery increasingly relies on electric delivery bicycles (EDBs), yet their limited battery capacity creates coupled challenges of routing efficiency and energy replenishment. We study a novel battery swapping cabinet location-routing problem (BSC-LRP) with multiple depots, which jointly optimizes routing and modular energy infrastructure deployment under time-window and battery constraints. To address the problem’s complexity, we design an improved branch-and-price algorithm enhanced with adaptive heuristic-exact labeling (IBP-HL) and a robust arc-based branching scheme. This hybrid framework accelerates column generation while preserving exactness, representing a methodological advancement over standard B&P approaches. Computational experiments on modified Solomon instances show that IBP-HL consistently outperforms Gurobi in both runtime and solution quality on small cases, and achieves substantial speedups and improved bounds over baseline B&P on medium and large cases. These results demonstrate not only the scalability of IBP-HL but also its practical relevance: the framework provides decision support for operators and planners in designing cost-efficient, reliable, and sustainable last-mile delivery systems with battery-swapping infrastructure. Full article

Pipelines are critical infrastructure for energy transportation, but long-term service under complex loading can cause local buckling failures. This study investigates the wrinkle behavior of API-X80 pipelines under combined internal pressure and bending using finite element analysis. The results show that increasing internal pressure significantly improves structural stability and delays wrinkle formation by suppressing cross-sectional ovalization. Wrinkle growth and protrusion height were quantified under various geometric and load conditions. Furthermore, a convex B-type sleeve repair method was modeled and optimized using response surface methodology and genetic algorithms. The optimized sleeve design effectively mitigates stress concentration around the defect area. This work provides a theoretical foundation for understanding wrinkle mechanisms and enhancing pipeline integrity under complex loads. Full article

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has emerged as a candidate for therapeutic repurposing due to its reported antifungal activity. We systematically reviewed in vitro, in vivo, and clinical evidence up to July 2025 (PubMed, Scopus, Web of Science). As a result, 322 records were screened and 63 studies were found to meet the inclusion criteria (PRISMA 2020). We close a critical gap by consolidating relevant evidence on Candida auris, including preclinical in vivo models, which have been under-represented in previous summaries. Outcomes included minimum inhibitory and fungicidal concentrations (MIC/MFC), biofilm inhibition, fungal burden, survival, and pharmacokinetic/pharmacodynamic parameters. Preclinical data indicate its activity against clinically relevant fungi—particularly Cryptococcus neoformans and Candida spp., including C. auris—as well as consistent anti-biofilm effects and synergy with amphotericin B, fluconazole, micafungin, or voriconazole. Mechanistic evidence implicates mitochondrial dysfunction, membrane perturbation, impaired protein synthesis, and calcium homeostasis disruption. However, its potential for clinical translation remains uncertain: in cryptococcal meningitis, small phase II studies suggested improved early fungicidal activity, whereas a phase III randomized trial did not demonstrate a benefit regarding survival. Pharmacokinetic constraints at conventional doses, the absence of an intravenous formulation, and safety considerations at higher doses further limit its immediate applicability. Overall, the available evidence supports sertraline as a promising adjuvant candidate, rather than a stand-alone antifungal. Future research should define PK/PD targets, optimize doses and formulations, and evaluate rational combinations through rigorously designed trials, particularly for multidrug-resistant and biofilm-associated infections. Full article

This study evaluates the environmental impacts of shipbuilding materials through life cycle assessment (LCA) and assesses potential exposure under the EU Carbon Border Adjustment Mechanism (CBAM). Three representative vessel types, a pure car and truck carrier (PCTC), a bulk carrier, and a container ship, were analyzed across scenarios reflecting different steelmaking routes, recycling rates, and regional energy mixes. Results show that structural steel (AH36, EH36, DH36, A/B grades) overwhelmingly dominates embedded emissions, while aluminium and copper contribute secondarily but with high sensitivity to recycling and energy pathways. Coatings, polymers, and yard processes add smaller but non-negligible effects. Scenario-based CBAM cost estimates for 2026–2030 indicate rising liabilities, with container vessels facing the highest exposure, followed by bulk carriers and PCTCs. The findings highlight the strategic importance of steel sourcing, recycling strategies, and verifiable supply chain data for reducing embedded emissions and mitigating financial risks. While operational emissions still dominate the life cycle, the relative importance of construction-phase emissions will grow as shipping decarbonizes. Current EU-level discussions on extending CBAM to maritime services, together with recognition of domestic carbon pricing as a potential pathway to reduce liabilities, underscore regulatory uncertainty and emphasize the need for harmonized methods, transparent datasets, and digital integration to support decarbonization. Full article

Objectives: Shen-Ling-Bai-Zhu-San (SLBZS) is a classical traditional Chinese herbal formula with spleen-invigorating and dampness-resolving properties. Recent pharmacological studies suggest its potential to regulate immune and metabolic disorders. Type 2 diabetes mellitus (T2D) and ulcerative colitis (UC) often coexist as comorbidities characterized by chronic inflammation, microbial imbalance, and insulin dysregulation, yet effective therapies remain limited. This study aimed to investigate the molecular mechanisms through which SLBZS may benefit T2D–UC comorbidity. Methods: An integrative multi-omics strategy was applied, combining network pharmacology, structural bioinformatics, and ensemble molecular docking–dynamics simulations. These complementary approaches were used to identify SLBZS bioactive compounds, predict their putative targets, and examine their interactions with disease-related biological networks. Results: The analyses revealed that flavonoids in SLBZS act on the SLC6A14/PI3K–AKT signaling axis, thereby modulating immune responses and improving insulin sensitivity. In addition, SLBZS was predicted to regulate the NF-$\kappa$B/MAPK signaling pathways, key hubs linking inflammation and metabolic dysfunction in T2D–UC. These dual actions suggest that SLBZS can intervene in both inflammatory and metabolic processes. Conclusions: SLBZS demonstrates promising therapeutic potential for T2D–UC by targeting interconnected immune–metabolic networks. These findings not only provide mechanistic insights bridging traditional therapeutic concepts with modern pharmacology but also establish a theoretical basis for future experimental validation and clinical application. Full article

Postharvest fungal rot causes significant economic losses in the agroindustry. Current control methods involving the use of synthetic fungicides are becoming increasingly ineffective and pose environmental risks. This necessitates exploring sustainable alternatives, such as essential oils derived from medicinal plants, to achieve safer and effective disease control. This research examined the chemical composition and efficacy of essential oils from Aloysia citriodora, Aloysia polystachya and their compounds against the postharvest rot fungi Monilinia fructicola, Monilinia laxa, and Botrytis cinerea. The main compounds of essential oils were analyzed by GC/MS and revealed differences in their composition. A. citriodora is characterized by the presence of spathulenol and caryophyllene oxide. In contrast, A. polystachya is characterized by the predominance of carvone. The results show that the essential oil of A. citriodora and the compound farnesol are able to inhibit the three pathogens. Notably, against M. fructicola, the EC₅₀ values were 61.89 μg/mL and 72.18 μg/mL, respectively. Against B. cinerea, the EC₅₀ values were 85.34 μg/mL and 47.6 μg/mL. Molecular docking also showed that farnesol has affinity for the enzyme succinate dehydrogenase suggesting a possible mechanism of action. This compound and A. citriodora essential oil show potential in the control of phytopathogens. Full article

Defensins are a class of small cysteine-rich cationic antimicrobial peptides (AMPs) that play vital roles in immune-regulating insect–microbe interaction, offering great potential for developing pest control approaches using RNA interference (RNAi) and insect pathogens. However, the biocontrol potential of defensins from the destructive rice pest Nilaparvata lugens (brown planthopper, BPH) remains largely unexplored. Here, we identified and functionally characterized a defensin-encoding gene NldefB in BPH. The open reading frame (ORF) of NldefB is 315 bp in length, encoding 104 amino acids with a conserved Knot1 domain. The qRT-PCR results showed that the transcription level of NldefB went upward with the increasing developmental stages, with the highest expressions in the female adults and their fat body. The expression of NldefB was continuously induced by bacterial pathogens but exhibited a pattern of initial increase followed by a decrease when challenged by a fungal pathogen Metarhizium anisopliae. RNAi-mediated silencing of NldefB significantly decreased the host survival rate, egg production and hatchability, as well as the capability to resist fungal infection. Additionally, NldefB suppression resulted in a significant increase in microbial loads. Our findings underscored that NldefB plays essential roles in regulating host development, pathogen defense, and microbial maintenance, providing a potential target for RNAi- and microbe-mediated BPH biocontrol. Full article

Transmembrane proteins (TMPs) constitute approximately 30% of the mammalian proteome and are critical targets in biomedical research due to their involvement in signaling, transport, and drug interactions. However, their unique structural characteristics pose significant challenges for conventional multiple sequence alignment (MSA) methods, which are typically optimized for soluble proteins. In this paper, we propose TMP-M2Align, a novel topology-aware multiobjective algorithm specifically designed for the multiple alignment of TMPs. The method simultaneously optimizes two complementary objectives: (i) a topology-aware Sum-of-Pairs (SPs) score that integrates region-specific substitution matrices and gap penalties, and (ii) an Aligned Regions (ARs) score that rewards consistent alignment of functional and topological domains. By combining these objectives, TMP-M2Align generates Pareto front approximations of alignment solutions, enabling researchers to select trade-offs that best suit their biological questions. We evaluated TMP-M2Align on BAliBASE Reference Set 7 and on complete datasets of human G protein-coupled receptors (GPCRs) from classes A, B1, and C. Experimental results demonstrate that TMP-M2Align consistently outperforms both traditional alignment tools and specialized TM-specific methods in terms of SPs and Total Column metrics. Moreover, qualitative topological analyses confirm that TMP-M2Align preserves the integrity of transmembrane helices and loop boundaries more effectively than competing approaches. These findings highlight the effectiveness of integrating topology-aware scoring with multiobjective optimization for achieving accurate and biologically meaningful alignments of TMPs. Full article

Background/Objectives: The global dissemination of tet(X) variants critically threatens tigecycline efficacy as a last-resort antibiotic. The aim of this study was to characterize a tet(X6)-carrying integrative and conjugative element (ICE) in a multidrug-resistant Chryseobacterium lecithinasegens strain, SHZ29, isolated from Shanghai, China. Methods: Minimum inhibitory concentrations (MICs) were determined by broth microdilution for SHZ29. Whole genomic sequencing and bioinformatic analysis were performed to depict the structure of the novel tet(X6)-carrying ICE. Inverse PCR and conjugation experiments were conducted to investigate the transfer ability of the ICE. Results: We depicted a novel tet(X6)-carrying ICE, named ICECleSHZ29, which is 74,906 bp in size and inserted into the 3′ end of tRNA-Met-CAT gene of the C. lecithinasegens strain SHZ29, with 17 bp direct repeats (5′-tcccgtcttcgctacaa-3′). This ICE possesses a 38 kb conserved backbone and four variable regions (VR1-4), with VR3 aggregating multiple resistance genes, including tet(X6), tet(X2), erm(F), ere(D), floR, catB, sul2, ant(6)-I and bla_OXA-1327. NCBI database searching identified 13 additional ICEs sharing a similar backbone to ICECleSHZ29. These ICECleSHZ29-like ICEs could be classified into two types based on their distinct insertion sites: Type I, inserted at the tRNA-Met-CAT gene; and Type II, inserted at the tRNA-Glu-TTC gene. Phylogenetic analysis indicated that differences in integrases may result in differences in the insertion site among these ICEs. A circular intermediate form of ICECleSHZ29 was detected by inverse PCR. However, the conjugation experiments using Escherichia coli EC600 as recipients failed. Conclusions: To our knowledge, this study provides the first report of tet(X6) in C. lecithinasegens and characterizes its carrier, a novel ICE: ICECleSHZ29. Full article

Grazing systems’ production efficiency is a dynamic interaction between soil, pasture, livestock, and climate. The magnitude of the changes is related to the mechanical stress applied by the livestock and their feeding behaviour. In Southern Chile, dairy cattle present a high heterogeneity in breeds, size, live weight, and milk production. This study investigated whether cows of contrasting size/live weight can improve degraded pasture and positively modify soil (Andosol-Duric Hapludand) physical features. Three pasture types were used as follows: (i) cultivated fertilised Lolium perenne L. (perennial ryegrass) and Trifolium repens L. (white clover) mixture (BM); (ii) cultivated fertilised L. perenne, T. repens, Bromus valdivianus Phil. (pasture brome), Holcus lanatus L. (Yorkshire fog), and Dactylis glomerata L. (cocksfoot) mixture (MSM); and (iii) naturalised fertilised pasture Agrostis capillaris L. (browntop), B. valdivianus, and T. repens (NFP). Pastures were grazed with two groups of dairy cows of contrasting size and live weight: light cows (LC) [live weight: 464 ± 5.4 kg; height at the withers: 132 ± 0.6 cm (average ± s.e.m.)] and heavy cows (HC) [live weight: 600 ± 8.7 kg; height at the withers: 141 ± 0.9 cm (average ± s.e.m.)]. Hoof area was measured, and the pressure applied by cows on the soil was calculated. Soil differences in penetration resistance (PR) and macro-porosity (wCP > 50 μm) between pastures were explained by tillage and seeding, rather than as a result of livestock presence and movement (animal trampling). The PR variation during the year was associated with the soil water content (SWC). Grazing dairy cows of contrasting live weight caused changes in soil and pasture attributes, and they behaved differently during grazing. Light cows were linked to more intense grazing, a stable soil structure, and pastures with competitive species and greater tiller density. In MSM, pasture consumption increased, and the soil was more resilient to hoof compression. In general, grazing with heavy cows in these three different pasture systems did not negatively impact soil physical properties. These findings indicate that volcanic soils are resilient and that during renovation, the choice of pasture type has a greater initial impact on soil structure than the selection of cow size, but incorporating lighter cows can be a strategy to promote denser pasture swards in these grazing systems. Full article

Autoimmune gastritis (AIG) is a chronic, organ-specific autoimmune disease characterized by progressive destruction of gastric parietal cells driven by autoreactive CD4⁺ T-cells, epithelial stress pathways, and microbial factors. Parietal cell loss results in achlorhydria, intrinsic factor deficiency, and vitamin B12 malabsorption, ultimately leading to pernicious anemia. Compensatory hypergastrinemia promotes enterochromaffin-like (ECL) cell hyperplasia and contributes to the development of type 1 gastric neuroendocrine neoplasms (gNENs). These clinical consequences are well recognized, yet the cellular and molecular mechanisms driving mucosal atrophy and neoplastic transformation remain incompletely defined. Recent advances highlight the role of endoplasmic reticulum stress, impaired autophagy, innate immune effectors, and dysbiosis in perpetuating inflammation and epithelial injury. The frequent coexistence of AIG with other autoimmune disorders further adds to its clinical complexity. Therapeutic options remain limited, spanning vitamin B12 replacement and endoscopic management to emerging targeted approaches. Netazepide, a gastrin/CCK2 receptor antagonist, is the only agent tested in clinical trials, whereas interventions targeting ER stress, autophagy, immune tolerance, or microbiome composition are still in the preclinical stage. Clarifying these mechanisms is crucial to improve biomarker development, optimize surveillance, and identify targeted therapies to prevent neoplastic transformation. Full article