Search Results (1,738)

Molecular trajectory prediction is fundamental to computational chemistry, drug discovery, and materials simulation, enabling insights into dynamics, reaction pathways, and conformational stability. Its natural alignment with graph-structured spatiotemporal data has made it a key frontier in GNN research. However, current mainstream spatiotemporal GNNs, while enforcing E(3)-equivariance, treat atoms as unconstrained point masses and lack explicit rigid geometric constraints, often yielding unphysical deformations that compromise predictive interpretability. To address this challenge, we propose STEGMN—the first spatiotemporal graph architecture for molecular trajectory prediction that explicitly encodes rigid constraints. Inspired by Graph Mechanics Networks, we design a constraint-preserving equivariant spatiotemporal attention mechanism that captures temporal dependencies while rigorously maintaining both E(3)-equivariance and rigid-body constraints. Additionally, we introduce a constraint-preserving equivariant pooling module that generates future states by performing a learnable weighted aggregation of historical angular velocities, followed by forward kinematics mapping. This ensures that all outputs simultaneously satisfy E(3)-equivariance and strict bond-length conservation. Evaluated on real-world molecular dynamics datasets, STEGMN consistently outperforms strong baselines. On the rMD17 benchmark, it achieves an average ∼40% reduction in prediction MSE relative to representative spatiotemporal graph models (ST-GNN, ST-GCN, and ST-EGNN) across eight small-molecule systems, highlighting the critical value of explicit constraint modeling for physically stable trajectory prediction. Full article

High-throughput sequencing and multi-omics are transforming Traditional Chinese Medicine (TCM) research from empirical descriptions toward data-driven mechanistic analyses. Unlike earlier systems pharmacology frameworks that relied primarily on static network topology and docking-based target prediction, current multi-omics approaches integrate genomic, transcriptomic, proteomic, and metabolomic data to capture dynamic, multi-scale biological responses. This review summarizes recent progress in four related areas: (i) genomic and epigenomic dissection of geo-authentic (Daodi) medicinal materials; (ii) biosynthetic pathway elucidation for major bioactive compound classes; (iii) synthetic biology platforms for heterologous production; and (iv) systems pharmacology integration for mechanism-of-action studies. We identify a central, recurrent gap: most published multi-omics analyses remain at the level of statistical association, and the biosynthetic and pharmacological pathways inferred from such data have not been validated at the causal level. To address this, we propose a tiered experimental validation framework—from biochemical target engagement through genetic perturbation to in vivo functional confirmation—and an iterative computational–experimental feedback loop. We further outline practical priorities for future work, including standardized data formats, community-endorsed metadata checklists, and coordinated DBTL pilot projects. By connecting descriptive multi-omics patterns to experimentally testable mechanistic models, TCM research can move toward precision-oriented medicine while preserving the multi-component character of traditional formulations. Full article

Objective: Diabetes mellitus is closely associated with mitochondrial dysfunction, which disrupts cellular energy metabolism and perturbs hormonal homeostasis. Humanin (HN), a 24-amino acid peptide encoded within the mitochondrial genome, has attracted considerable attention due to its cytoprotective and metabolic regulatory properties. Despite its recognized biological potential, the role of HN in coordinating key metabolic hormone networks under diabetic conditions remains poorly understood. This study aimed to investigate the integrative effects of repeated humanin administration on key metabolic hormones leptin, ghrelin, irisin, and asprosin and its potential role in restoring hormonal homeostasis in a streptozotocin (STZ)-induced diabetic mouse model. Materials and Methods: Forty male mice were randomly assigned to four groups (n = 10 for each group): control, HN (4 mg/kg/day), STZ (150 mg/kg), and STZ + HN. Humanin was administered intraperitoneally for 15 consecutive days. Serum levels of leptin, asprosin, irisin, and ghrelin were measured using enzyme-linked immunosorbent assay (ELISA), and data were analyzed using one-way ANOVA followed by Tukey’s post hoc test. Results: STZ-induced diabetes markedly disrupted metabolic hormone balance, as indicated by decreased leptin and irisin levels and increased asprosin concentrations. Repeated HN treatment effectively restored leptin levels and suppressed asprosin concentrations, while irisin levels showed a relative increase compared to the STZ animals. In addition, ghrelin levels were significantly elevated in HN-treated diabetic mice compared to untreated STZ animals. Conclusions: These findings indicate that humanin exerts an integrative, multi-hormonal regulatory effect, supporting the restoration of metabolic and endocrine homeostasis under diabetic conditions. Full article

Background/Objectives: Traditionally, Sanger sequencing was used to characterize reference materials and confirm discordant allele calls from different STR typing kits at the National Institute of Standards and Technology (NIST). Sequencing can also identify genomic variations within polymerase chain reaction (PCR) amplicons containing STRs, particularly variants that result in null alleles and alleles that do not migrate within allele sizing bins provided by kit manufacturers. Methods: Sanger methods are low-throughput, time- and labor-intensive, and require additional procedures for analysis of heterozygous alleles. To address these limitations, a quicker, more straightforward protocol that uses next-generation sequencing (NGS) was developed. Results: This research provides the criteria used to individually sequence thirty-five autosomal STR loci, with PCR primer locations chosen to increase amplicon length and maximize the likelihood of detecting variants in the flanking region. The list of targeted sequences, associated primers, and chromosomal coordinates is also included. Conclusions: By applying NGS technology to forensic samples containing variant alleles, additional information can be obtained about their molecular basis, and this information can be published and shared across the forensic community. The development of this protocol can increase awareness and encourage the integration of NGS technology into forensic laboratories to improve forensic DNA typing for human identification. Full article

Purpose: Obesity is a global public health issue, and natural products that promote white fat browning and enhance thermogenesis to consume energy represent promising strategy for addressing this problem. Forsythoside A (FTA) is key bioactive constituent isolated from the fruit of Forsythia suspensa. It has been reported that FTA can alleviate metabolic disorders such as hepatic lipid accumulation induced by high-fat diet (HFD). However, research on the role of FTA in alleviating obesity by promoting white fat browning remains scarce. Materials and Methods: We intervened in diet-induced obesity (DIO) mice and differentiated 3T3-L1 cells with FTA and detected thermogenic indices and the expression of thermogenesis-related genes under the guidance of network pharmacology. Mechanistically, molecular docking combined with molecular biology techniques was employed to verify the affinity of pathway-related proteins, and the AMPK inhibitor (BML-275) was used to intervene in 3T3-L1 cells to assist in demonstrating the main pathway through which FTA stimulates white fat browning. Results: FTA significantly attenuated lipid accumulation in both in vivo and in vitro models. Gene Ontology (GO) enrichment analysis revealed that FTA may promote white adipocyte browning and mitochondrial thermogenesis. Consistent with improved energy metabolism, FTA treatment increased oxygen consumption and carbon dioxide production in mice, while maintaining the respiratory exchange ratio (RER) at approximately 0.7. In vitro, FTA enhanced cellular oxygen consumption rate (OCR) and mitochondrial density. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis combined with molecular docking identified the AMPK signaling cascade as a key potential pathway mediating FTA action. Molecular biology assays further confirmed that FTA promotes AMPK phosphorylation and activates the canonical thermogenic downstream PGC-1α/UCP1 pathway. Consistently, inhibition of AMPK with BML-275 abolished the beneficial effects of FTA in 3T3-L1 adipocytes. Conclusions: This study reveals that FTA enhances white fat browning via the AMPK pathway while increasing thermogenesis in adipose tissue. Full article

As pressures from climate change and global trade increase, developing cost-effective tools for origin tracking becomes essential to ensure the traceability and adaptability of forest reproductive material (FRM). Our objectives were (a) to test the efficiency of a set of nuclear microsatellite loci (nSSR) for revealing the genetic structures identified by high-input sequencing studies and (b) to verify this set of nSSR loci for genetic assignment of commercial seed lots into reference regions. We used 12 nSSR markers to genotype 220 trees from 11 populations representing the eastern Baltic, Scandinavian and southern European ranges of Norway spruce. The results showed that the populations from the eastern Baltic range had relatively higher allelic diversity parameters. The Bayesian clustering revealed a geographically consistent genetic structuring of Norway spruce populations by distinguishing the eastern Baltic from southern European and Scandinavian populations. GENECLASS analysis correctly assigned Lithuanian commercial seed lots into the Lithuanian reference region with markedly higher probability than to any other reference regions. Our study demonstrates promising results for origin identification of Norway spruce, particularly in contexts where high-resolution genomic approaches remain financially or logistically inaccessible. Full article

Live virus inoculation (LVI) is widely used for porcine reproductive and respiratory syndrome virus (PRRSV) stabilization, yet preparation practices and pathogen composition remain poorly characterized. This study aimed to evaluate variability in LVI preparation, quantify PRRSV genomic load, and detect additional swine pathogens. A survey was conducted to document LVI preparation methods, and samples were analyzed using reverse-transcription quantitative PCR (RT-qPCR) for PRRSV quantification and next-generation sequencing for PRRSV and the metagenomic characterization of additional pathogens. Among 61 LVI samples, substantial variability was observed in preparation practices and viral composition, with 31 distinct PRRSV variants identified and seven samples containing multiple strains. PRRSV RNA concentrations ranged from 10^1.69 to 2.52 × 10⁸ copies/mL. Metagenomic analysis detected a complete or near-complete genome for PRRSV, porcine parvovirus, and porcine circovirus type 2. Genome fragments of porcine sapovirus, porcine rotavirus, porcine astrovirus, and bacterial genetic material from Salmonella spp., Pseudomonas spp., Streptococcus spp., and Escherichia coli were also detected. These findings highlight substantial heterogeneity in LVI materials and encourage the use of next-generation sequencing to verify LVI PRRSV composition and screen for co-existing pathogens, reinforcing the need for standardized preparation protocols and further investigation into optimal viral dosing for effective immunization. Full article

Heterosis utilization is an effective strategy to improve crop yield, stress resistance, and quality, and has been widely used in crop breeding. Soybean is an important oil and protein crop worldwide with heterosis, but the genetic basis of soybean heterosis remains largely unclear. Whole-transcriptome analysis provides a new technical approach to explore the molecular mechanism of heterosis. In this study, HYBSOY2, a registered soybean hybrid variety with the strongest heterosis in China, together with its female parent JLCMS47A, maintainer line JLCMS47B, and male parent JLR2, were used as experimental material. Whole-transcriptome sequencing was performed using RNA extracted from seedling leaves. After mapping high-quality reads to the soybean reference genome, 57 co-expressed differentially expressed genes (DEGs) were identified in HYBSOY2 compared with both JLCMS47B and JLR2. GO and KEGG enrichment analyses shows that these DEGs were mainly enriched in ADP binding, oxidoreductase activity, fatty acid elongation, and pyruvate metabolism. A total of 787 transcription factors were identified between HYBSOY2 and its parents, most of which shows parental expression-level dominance, with the MYB family accounting for the highest proportion. In addition, 10 differentially expressed lncRNAs were detected between HYBSOY2 and its parents. In the comparison between HYBSOY2 and JLCMS47B, 18 differentially expressed miRNAs were identified, among which up-regulated miR396d functions in promoting leaf development and enhancing drought tolerance. In the comparison between HYBSOY2 and JLR2, 20 differentially expressed miRNAs were found, including down-regulated miR172c which is involved in flowering promotion. A total of 12 DEGs were further verified by qRT-PCR, which may be closely related to soybean heterosis. This study provides a comprehensive transcriptomic profile at the seedling stage of the hybrid soybean and offers valuable information for hybrid soybean breeding. These results lay a foundation for further revealing the molecular mechanism underlying soybean heterosis. Full article

Background and Objectives: Although clinically useful, homologous recombination deficiency (HRD) testing has recently been more broadly adopted in ovarian cancer (OC) management. The VALIDATE study evaluated HRD status and treatment patterns in patients with newly diagnosed advanced OC in Bulgaria to better understand HRD prevalence and disease management. Materials and Methods: This real-world, observational, multi-centre, medical chart review study included 100 adult patients with HRD testing results available at study entry. Data collected at least 30 days after HRD results and 6 months later were descriptively analysed in the full cohort and subgroups (HRD, BRCA mutation, and genomic instability score [GIS]). Results: Mean age at diagnosis: 61.3 years; stage III: 51.0%, prevalence of HRD+ 58.0% (95% confidence intervals [CI] 47.7–67.8%) and HRD− 42.0% (95% CI 32.2–52.3%). Among the 58 HRD+ patients, 20 (34.5%) were BRCA+, whereas 38 (65.5%) were BRCA−, and 52 (89.7%) were GIS+, and 6 (10.3%) GIS−. Overall, platinum–taxane chemotherapy plus antiangiogenics was the most common front-line (FL) treatment (77.0%), regardless of subgroups (range: 66.7–85.0%). Six months later, 81 patients were alive, and 73 (90%) started maintenance therapy (MT). Antiangiogenic monotherapy (32.0%) and antiangiogenic plus PARP inhibitor (34.0%) were the most common MTs. The latter was also common across subgroups (range: 33.3–60.5%), except for HRD− (61.9% received antiangiogenic monotherapy). Conclusions: In this dataset, more than half of advanced OC patients had HRD+ status. Our study provides relevant insights into recent clinical practice patterns in advanced OC in Bulgaria that could serve as an anchor for future, more robust research in this field. Full article

Why do pandemics keep emerging despite decades of surveillance and response? Paleopathology, the study of disease traces in ancient remains, has been revolutionized by ancient DNA (aDNA) analysis and next-generation sequencing (NGS). Reconstructing pathogen genomes from archaeological material enables the identification of extinct lineages, the refinement of disease chronologies, and the characterization of long-term host-pathogen co-evolution. This provides context for public health challenges, including the emergence of pandemics and antimicrobial resistance (AMR). Infectious diseases are increasingly understood as complex phenomena arising from biological, ecological, and sociopolitical forces. Integrating paleopathology, aDNA, and paleomicrobiology supports a deep-time syndemic framework, revealing how recurring biosocial drivers have structured infectious disease risk throughout history. Ancient resistome studies demonstrate that AMR predates modern antibiotic use, reframing resistance as an intrinsic ecological feature rather than solely a modern phenomenon. Coronavirus disease 2019 (COVID-19) reaffirmed how infection intersects with chronic disease, health system fragility, and social inequities. This review highlights how integrating evolutionary perspectives into One Health shifts surveillance from a reactive approach to upstream risk mitigation and spillover prevention. Full article

Background/Objectives: Recombinant adeno-associated virus (AAV) stands at the forefront of gene therapy development, requiring stable formulations to support the expanding therapeutic applications. The growing diversity of serotypes and engineered capsids often creates complex challenges for formulation development, thus demanding innovative formulation development strategies beyond traditional manual approaches to characterize a large formulation design space quickly to discover stable formulations. Methods: Here, we address this critical need through a high-throughput automation platform that dramatically enhances formulation development efficiency and capability through rapid formulation preparation and high-throughput AAV analytics. This system prepares 96 distinct formulations in 40 min and completes AAV compounding in 20 min per plate, with precise control of pH, buffer components, and AAV titers. Results: In a proof-of-concept formulation development study using AAV1, we screened 128 formulations across multiple buffer systems, pH ranges, and excipient combinations. This comprehensive approach successfully identified optimal stable high-titer AAV1 formulations (1.2 × 10¹⁴ vector genome (vg)/mL) that maintained stability under frozen, refrigerated, and room temperature storage conditions. Conclusions: Our study demonstrated that this automation platform combined with high-throughput AAV analytics significantly accelerates formulation development, conserves AAV material, and enables systematic exploration of broader formulation design space. It allows us to achieve identification of robust and stable AAV formulations within a timeframe unmatched by traditional formulation development approaches. Full article

Mycogenic nanomaterials, nanoparticles (NPs) biosynthesized through fungal enzymatic and metabolic activity, have emerged as a compelling alternative to chemically synthesized nanomaterials, offering fundamental biocompatibility, green production conditions, and biologically functional surface coatings. Fungi, acting as natural “nanofactories,” harness reductases, oxidoreductases, secreted proteins, and secondary metabolites to reduce metal ions into stable NPs under ambient conditions, simultaneously capping the particles with biomolecules that enhance colloidal stability, biocompatibility, and secondary biological activity. Unlike previous reviews that have addressed either biosynthesis mechanisms or applications in isolation, this review uniquely adopts a structured “Promise vs. Barrier” framework across six interconnected thematic pillars, offering the first comprehensive critical synthesis that simultaneously maps mechanistic frontiers, biodiversity gaps, and translational barriers within mycogenic nanotechnology. The present review critically examines both the extraordinary promise and the persistent barriers facing mycogenic nanotechnology across biosynthetic mechanisms, fungal biodiversity, nanomaterial portfolio expansion, biomedical applications, environmental and agricultural utility, and industrial scalability. We highlight how emerging multiomics approaches, integrating transcriptomics, proteomics, and metabolomics, are beginning to decode the molecular blueprints of fungal NP synthesis, while acknowledging that mechanistic knowledge gaps, limited genetic toolkits for non-model fungi, and the absence of standardized protocols continue to impede progress. The fungal kingdom represents a vast, underexplored reservoir of nanofactory potential, with fewer than 1% of known species evaluated to date; strategic bioprospecting using genome mining and machine learning is beginning to unlock this diversity. Mycogenic NPs demonstrate broad-spectrum antimicrobial activity against multidrug-resistant pathogens, selective anticancer activity, biosensing capacity, and applications in wound healing, sustainable agriculture, environmental remediation, and smart food packaging. However, critical deficits persist in clinical validation, long-term toxicity data, manufacturing reproducibility, and regulatory clarity. The review concludes with a tiered roadmap, spanning immediate mechanistic priorities through to long-term synthetic biology and AI-integrated commercialization, and calls for coordinated international action on standardization, reference material development, and harmonized regulatory frameworks to bridge the gap between laboratory promise and real-world application. Full article

Viral carcinogenesis as a causative mechanism of breast cancer has been intensively researched during the last decades. The role of Epstein–Barr virus (EBV) and Bovine Leukemia virus (BLV) in breast oncogenesis has been investigated in a plethora of studies, but with conflicting results. The aim of this systematic review and meta-analysis was to compare the frequency of molecular detection of the EBV genome and BLV genome between women with breast cancer and women without malignant breast tumors. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and ClinicalTrials.gov were searched up to 20 May 2024. Included studies were those comparing the frequency of molecular detection of the EBV and/or BLV genome in breast tissue specimens with polymerase chain reaction (PCR) methods between patients with breast cancer and women without breast malignancies. The primary outcomes of the study were the frequency of molecular detection of the EBV genome and BLV genome. Methodological quality of included studies was assessed using the Newcastle–Ottawa Scale. A total of 29 studies met the selection criteria and were included in this meta-analysis; 19 studies reported results for molecular detection of the EBV genome, 9 studies for detection of the BLV genome and 1 study for detection of genomic material of both viruses. The frequency of molecular detection of viral genomes was significantly higher in patients with breast cancer, compared to women with healthy breasts or benign breast diseases, regarding both EBV (OR: 3.041, 95% CI: 1.791 to 5.164, p < 0.0001) and BLV (OR: 3.459, 95% CI: 2.118 to 5.650, p < 0.0001). The frequency of molecular detection of EBV and BLV genomes is higher, in a statistically significant manner, in patients with breast cancer compared to women without breast malignancies. The presence of these viral factors in breast tissue could imply their potential contribution in breast carcinogenesis, but is not sufficient to establish it, and the molecular detection of their genomes could be potentially exploited in the future for preventive, diagnostic and therapeutic purposes. Further studies are required to thoroughly investigate and establish a causal relationship between EBV and BLV infection and breast carcinogenesis, as well as to support the use of viral genome molecular detection in clinical settings for the management of breast cancer patients. Full article

Cancer cells have many derailed processes due to which they have a higher proliferative capacity. The rewiring is continuously taking place to meet their metabolic demands. The demands depend on the stage of cancer, and these differences create challenges in curing them. Nucleotide metabolism plays a pivotal role in shaping cancer fate. DNA repair and other damage pathways also play a key role in cancer progression, genomic instability, errors in genetic material etc. These are discussed in this mini review so that researchers can take the lead to make an effort to combat cancer and design new therapeutics. Full article

Listeria monocytogenes is already a well-known foodborne bacterial pathogen, ubiquitously dispersed not only in the food production environment but also in the primary animal production environment as well. The present study performed whole-genome characterization of the multidrug-resistant (MDR) L. monocytogenes strain BF11, previously isolated from raw pet food and phenotypically described for antimicrobial resistance. To this end, the genomic analysis performed on the isolate confirmed the pathogen’s designation as a serotype 1/2b strain belonging to ST5 and CC5 (Lineage I), carrying multiple MDR genes, stress-related genes, and mobile genetic elements, despite the absence of plasmids. The strain is phylogenetically closely related to Lineage I epidemic strains (e.g., F2365), as it has a full-length inlA and a functional prfA, rendering it capable of invading human cells and marking its high virulence. Overall, this strain may represent a potentially novel genomic profile when core genome multilocus sequence typing (cgMLST) is used, although further data from additional isolates would be required to confirm its classification within a new Complex Type, while displaying a hybrid unique profile. It is an evolved ST5 L. monocytogenes strain that has acquired genetic material conferring a “clinical signature” (Lineage I-like) and an extensive resistance network. Therefore, presence of L. monocytogenes strain BF11 in pet food is alarming, since such hybrid strains often evade surveillance monitoring as they do not fit strictly into classical categories, posing a serious food safety and public health threat in the concept of One Health. Full article