Biology and Life Sciences

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Article
Biology and Life Sciences
Virology

Mohd Yasir Khan

,

Farah Maarfi

,

Abid Ullah Shah

,

Nithyadevi Duraisamy

,

Mohammed Cherkaoui

,

Maged Gomaa Hemida

Abstract: Background. The main protease (MPro) of coronaviruses (CoVs) is an essential enzyme involved in viral replication and represents an attractive target for antiviral drug discovery. Based on the similar binding pocket residues within the MPro of different CoVs, the study aimed to identify potential inhibitors of SARS-CoV-2 MPro from PDB ID 6M2N, using integrated computational approaches. Methods. Interaction-based pharmacophore modeling, virtual screening, molecular docking, MM-GBSA binding energy calculation, and molecular dynamics (MD) simulation were performed using BIOVIA Discovery Studio. The validated pharmacophore model was utilized to screen the ZINC database, followed by docking and 100 ns MD simulation analyses of the top-ranked compounds. Results. The pharmacophore model 01 demonstrated favourable predictive performance (AUC = 0.781). Virtual screening identified 483 compounds, from which 21 compounds were selected for docking studies. Among them, ZINC95473654 (Lig-1), ZINC95473725 (Lig-2), and ZINC08792368 (Lig-3) exhibited strong binding affinity toward MPro. Lig-1 demonstrated the best docking score and binding free energy along with stable interactions with key catalytic residues HIS41, CYS145, and GLU166. MD simulation analyses further confirmed that Lig-1, Lig-2 and Lig-3 maintained stable conformations. The hydrogen bond distance monitoring and post MD-MM-GBSA results suggest Lig-1 followed by Lig-3 as an inhibitor for Mpro and persistent intermolecular interactions throughout the 100 ns simulation period. Conclusion. The findings suggest that Lig-1, followed by Lig-3, may serve as promising computational lead compounds targeting SARS-CoV-2 Mpro, representing promising candidates for further experimental validation.

Review
Biology and Life Sciences
Neuroscience and Neurology

Andrew T. McKenzie

,

Aschwin de Wolf

,

Alexander Grotemeyer

,

Emil Kendziorra

,

Alexander German

Abstract: Perfusion impairment is one of the major barriers to using machine perfusion to prepare brain tissue for research and clinical applications. As ischemia progresses, multiple mechanisms, including intravascular obstructions, perivascular cellular edema, mural cell contraction, and vessel wall breakdown, progressively limit the uniform delivery of preservative solutions. This problem is particularly important for connectomics, wherein successful preservation requires both widespread distribution of preservative chemicals and the maintenance of the cellular ultrastructure needed for circuit reconstruction. We conducted a narrative review of interventions used to ameliorate perfusion impairment across multiple fields, including organ transplantation, resuscitation medicine, forensic pathology, embalming, and neuroscience. We evaluated the evidence for these approaches in their original contexts and considered their potential application for brain banking aimed at preserving tissue for connectome reconstruction. We classify interventions into several categories, including anticoagulants, fibrinolytics, vasodilators, washout solutions, surfactants, osmotic agents, colloids, hypothermia, and perfusion pressure optimization. Many of these interventions have the potential to improve perfusion, but each also carries tradeoffs that may adversely affect tissue preservation. As connectomics advances toward profiling larger volumes of human brain tissue, overcoming perfusion impairment is likely to become an increasingly important challenge. This review provides a mechanistic framework for evaluating existing interventions and guiding the development of future perfusion protocols.

Article
Biology and Life Sciences
Plant Sciences

Xinru Gao

,

Zonghui Wei

,

Yuhan Lin

,

Jundong Rong

,

Tianyou He

,

Yushan Zheng

,

Shuming Liu

,

Lingyan Chen

Abstract: Leaf color variation is an important ornamental trait in bamboo and is closely associated with chlorophyll biosynthesis. However, the molecular mechanism underlying color differentiation in Sinobambusa tootsik f. albostriata remains largely unknown. In this study, fully green (WG) and fully white (WW) leaf buds at three developmental stages (S1–S3) were used to investigate the regulatory mechanism of chlorophyll synthesis and identify key functional genes. Chlorophyll content, coproporphyrinogen III oxidase (CPOX) activity, and comparative transcriptome analyses were integrated to identify candidate genes involved in leaf color formation. Six StaHemF family members were identified, among which StaHemF5 was selected as the core candidate gene based on phylogenetic and expression analyses. WW leaf buds exhibited significantly lower chlorophyll contents and CPOX activities than WG leaf buds throughout development, indicating impaired chlorophyll biosynthesis. StaHemF5 encodes a chloroplast-localized protein and showed distinct expression patterns between transcriptome and qRT-PCR analyses. Functional analysis demonstrated that transient overexpression of StaHemF5 in Nicotiana benthamiana significantly increased CPOX activity and chlorophyll accumulation, supporting its positive role in chlorophyll biosynthesis. These results indicate that StaHemF5 is a conserved regulator associated with chlorophyll synthesis and contributes to leaf color differentiation in S. tootsik f. albostriata. This study provides new insights into the molecular basis of leaf color variation and offers a valuable candidate gene for the genetic improvement of ornamental bamboo.

Article
Biology and Life Sciences
Immunology and Microbiology

Carlos Montero-Palma

,

Antonio López-Martínez

,

Antonio Romero-Salmoral

,

Belén Huerta-Lorenzo

,

Inmaculada Luque-Moreno

,

Carmen Tarradas-Iglesias

,

Alfonso Olaya-Abril

,

Lidia Gómez-Gascón

Abstract: Salmonella Typhimurium is an important pathogen affecting both animal production and public health, with pigs representing a major reservoir. The increasing prevalence of antimicrobial resistance highlights the need for alternative or complementary therapeutic strategies. Carvacrol, a phenolic constituent of Origanum vulgare essential oil, has recognized antimicrobial activity and may contribute to the modulation of antimicrobial resistance mechanisms. The present study investigated the antimicrobial activity of carvacrol and tetracycline, individually and in combination, against swine-derived S. Typhimurium strains. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined by broth microdilution. Interactions between both compounds were assessed by checkerboard assays using the fractional inhibitory concentration index (FICI). Relative expression of tetracycline resistance genes was analysed by quantitative real-time PCR in selected isolates exposed to tetracycline alone or combined with carvacrol. Carvacrol MIC values ranged from 0.5 to 16 mg/mL, with MIC₅₀ and MIC₉₀ values of 2 and 4 mg/mL, respectively. MBC and MIC values were identical in 84.9% of the isolates, indicating a strong bactericidal effect. Tetracycline MIC₅₀ and MIC₉₀ values were 256 and 512 µg/mL, respectively. Checkerboard assays showed synergistic interactions in 14.3% of strains, additive effects in 50.0%, indifferent responses in 28.6%, and antagonism in 1%. Combined exposure reduced tetA and tetB expression in most tested isolates compared with tetracycline alone, although responses were strain dependent. These findings demonstrate that carvacrol exhibits antimicrobial activity against swine-derived multidrug-resistant S. Typhimurium and may enhance tetracycline activity while modulating resistance-associated gene expression. Carvacrol could represent a promising natural adjuvant for antimicrobial control strategies in swine production.

Article
Biology and Life Sciences
Agricultural Science and Agronomy

Viliana Vasileva

,

Emil Vasilev

,

Nataliya Petrovska

Abstract: Improving nitrogen use efficiency while maintaining maize productivity under rainfed conditions is an important objective of sustainable crop management. This study evaluated the residual effects of mineral nitrogen fertilization and pea–oat cover crops on plant height, ear leaf area (ELA), grain yield, and nitrogen use efficiency (NUE) of maize (Zea mays L.). A field experiment was conducted using the maize hybrid Knezha 561 grown under continuous monoculture and monocul-ture following a pea–oat cover crop mixture incorporated into the soil during the previous season. Residual effects of am-monium nitrate and urea previously applied at rates of 60 and 120 kg N ha⁻¹ were assessed. Cover crops significantly im-proved maize performance compared with continuous monoculture. Plant height increased by 5.72%, ear leaf area by 4.33%, grain yield by 16.5%, and nitrogen use efficiency by 13.73%, indicating more efficient utilization of residual nitro-gen. Analysis of variance showed significant effects of the cropping system and nitrogen fertilization on ear leaf area and nitrogen use efficiency, whereas their interaction was not significant. The results demonstrate that integrating pea–oat cov-er crops into maize production can enhance ear leaf development, improve the efficiency of residual nitrogen use, and in-crease grain yield under rainfed conditions, supporting the adoption of cover cropping as a sustainable agronomic practice.

Article
Biology and Life Sciences
Animal Science, Veterinary Science and Zoology

Lajos Molnár

,

Viktor Stéger

,

Petra Zenke

Abstract: African swine fever (ASF) has caused substantial wild boar (Sus scrofa) mortality across Europe and prompted intensive density-reduction measures, yet its long-term effects on population genetics remain poorly understood. To our knowledge, this is the first study to compare the same wild boar population before ASF emergence and after several years of ASF-related management, while simultaneously evaluating the consequences for wildlife forensic STR identification. We examined temporal change in genetic diversity, population structure, and forensic identification parameters in a wild boar population from Nógrád County, northern Hungary, comparing samples collected before ASF emerged in Hungary in 2018 (n = 67) with samples collected after several years of ASF-related management (n = 65). All 132 individuals were genotyped at 13 tetrameric microsatellite loci. Diversity was assessed using allelic richness, allele number, and heterozygosity; differentiation using F-statistics, analysis of molecular variance, and discriminant analysis of principal components; demographic history using a two-phase mutation model; and forensic performance using probability of identity and probability of identity among siblings. The post-ASF sample showed lower genetic diversity and significant temporal differentiation, consistent across methods, but no detectable recent bottleneck. Forensic discrimination power declined modestly while remaining sufficient for individual identification. Because no contemporaneous unaffected reference population was available, these changes cannot be attributed specifically to ASF or management rather than to genetic drift or natural turnover, although they are consistent with sustained demographic disturbance.

Article
Biology and Life Sciences
Agricultural Science and Agronomy

Arlini Rodrigues Fialho

,

Renato Fernando Amabile

,

Juaci Malaquias

,

Marcelo Fagioli

,

Adriano Delly Veiga

,

Sonia Celestino

,

Gustavo Santos

,

Bárbara França

,

Laís Silva

,

Carolaini Campos da Silva

+1 authors

Abstract: The Coffee production in the Brazilian Cerrado has expanded considerably under irrigated conditions, requiring the identification of agronomic and biochemical traits associated with superior genotype performance. This study investigated the relationships among agronomic, morphological, and biochemical characteristics of 35 irrigated Coffea canephora clones cultivated at Embrapa Cerrados, Brazil, during three consecutive crop seasons (2021/2022, 2022/2023, and 2023/2024). Agronomic traits included plant height, canopy projection, coffee yield, and bean size, while biochemical traits comprised caffeine, chlorogenic acid, and soluble solids. Pearson's correlation analysis and principal component analysis (PCA) were applied to characterize trait associations and phenotypic variability. Coffee yield was positively correlated with plant height (r = 0.36), canopy projection (r = 0.25), beans retained above sieve 10 (r = 0.33), and caffeine content (r = 0.26), whereas chlorogenic acid exhibited predominantly negative correlations with agronomic variables, especially plant height (r = −0.50). Bartlett's test of sphericity (χ² = 211.03, p < 0.001) and a Kaiser–Meyer–Olkin index of 0.65 confirmed the suitability of the dataset for PCA. The first three principal components explained 65.52% of the total variation, with the first two accounting for 52.33%. PCA efficiently discriminated crop years and genotypes, revealing contrasting phenotypic groups associated with vegetative vigor, productivity, and biochemical composition. The integration of correlation and multivariate analyses demonstrated that plant height and canopy projection are valuable indirect selection criteria for improving coffee yield, whereas chlorogenic acid represents an independent biochemical attribute. These findings provide useful information for selecting superior Coffea canephora genotypes and support breeding programs targeting high productivity and bean quality under irrigated Cerrado conditions.

Concept Paper
Biology and Life Sciences
Ecology, Evolution, Behavior and Systematics

G. P. Wagner

,

J. Di Frisco

,

M. Pavličev

Abstract: Internal selection is a process of natural selection in which fitness differences between organisms are caused by factors internal to the organism and are invariant across environments. Internal selection has been most successfully applied to explain conserved features such as the phylotypic stage of gnathostomes. In this contribution, we introduce a form of internal selection that can drive evolutionary transformations rather than trait conservation, i.e. directional internal selection. The basic idea is that adaptive evolutionary change of one character can induce directional selection on another trait due to constraints internal to the organism. We provide a formal definition of this concept and discuss examples of directional internal selection as well as its implications.

Article
Biology and Life Sciences
Biology and Biotechnology

Xinchao Yang

,

Chen Li

,

Yuehui Liu

,

Fang Wang

,

Naxin Sun

,

Yuanxiu Wang

,

Chunjiang Ye

,

Zhongzheng Wang

Abstract: To achieve high-value valorization of cold-pressed walnut meal, walnut oligopeptides were prepared using synchronous dual-enzyme hydrolysis coupled with activated carbon decolorization and membrane separation purification. Process optimization was conducted, followed by systematic evaluation of amino acid profile, in vitro antioxidant activity, protective effects against H2O2-induced oxidative injury in PC12 cells, and acetylcholinesterase (AChE) regulatory function. The optimal hydrolysis conditions were determined as pH 10.0, total enzyme dosage 11000 U/g, trypsin/alkaline protease ratio 2.1:1, solid-liquid ratio 1:26, 51℃ for 4 h, yielding a degree of hydrolysis of 33.02%. The optimized decolorization parameters were pH 5.2, activated carbon dosage 2.3%, 58℃ for 43 min, achieving a peptide recovery rate of 83.35%. Walnut meal was abundant in glutamic acid, arginine, and aspartic acid, which served as the molecular basis for its bioactivities. In vitro assays revealed that the oligopeptides exhibited strong scavenging capacities against hydroxyl, DPPH, and superoxide anion radicals (90.18%, 81.72%, and 85.80%, respectively), while retaining 73.21% activity after simulated gastrointestinal digestion. Furthermore, 0.8 mg/mL walnut oligopeptides displayed no cytotoxicity and conferred a 79.88% protection rate against oxidative damage. They significantly elevated SOD and GSH-Px activities, reduced MDA accumulation, and markedly inhibited AChE activity, outperforming donepezil hydrochloride. This efficient and green approach enables the valorization of walnut processing by-products. The resulting oligopeptides show promising potential as natural antioxidant and neuroprotective agents for functional food applications.

Article
Biology and Life Sciences
Cell and Developmental Biology

Fred Y. Ye

Abstract: Background: The mammalian gene encoding OCT4, POU5F1, lies in or immediately adjacent to the major histocompatibility complex (MHC) region. In humans, POU5F1 is located at 6p21.33 within the extended HLA/MHC genomic neighborhood; in mice, Pou5f1 is on chromosome 17 within the homologous MHC-linked region. Marsupial data further suggest that this association belongs to an ancient mammalian immune supercomplex rather than to a lineage-specific accident. Yet birds and teleost fish show divergent arrangements, indicating that OCT4-MHC linkage is not required for all vertebrate zygotic genome activation. Objective: This paper expands a working outline on OCT4-MHC linkage into a formal theoretical article. It asks whether the tight mammalian linkage between a core pluripotency regulator and the principal immune-recognition complex could represent an evo-devo adaptation that coordinates developmental ignition, stress survival, maternal-fetal immune tolerance, chromosome-scale timing, and long-range chromatin topology. Methods: We synthesize comparative genomics, mammalian zygotic genome activation (ZGA), MHC evolution, preimplantation immunology, Hsp70 stress biology, ASAR6 replication-timing literature, 3D genome topology, and fractal genome concepts. We formulate quantitative descriptors for synteny strength, chromatin topological coupling, developmental timing, immune silencing, and evolutionary retention. Representative mammalian and non-mammalian model organisms are summarized, and a falsifiable validation pipeline is proposed. Results/Framework: The OCT4-MHC region is interpreted as a mammalian “start-and-shield” hub. OCT4/POU5F1 provides a developmental ignition module; MHC class III stress-response genes, including Hsp70 family genes, provide early cytoprotection; classical and non-classical MHC genes provide a tunable immune-recognition module; chromosome-scale elements such as ASAR6 suggest autonomous timing control; and 3D genome architecture provides a topological medium through which these modules may be co-regulated. Mathematical formulas define normalized synteny distance, linkage conservation, topological contact kernels, activation-repression coupling, fractal contact scaling, fitness effects, and Bayesian model validation. Conclusions: The OCT4-MHC linkage is best treated neither as a proven universal “origin of life” mechanism nor as a meaningless chromosomal accident. A more defensible hypothesis is that mammals conserved a genomic architecture in which the laws of development and the laws of immune recognition are compressed into a shared chromosomal neighborhood. At the most abstract level, the arrangement may reflect an isomorphic mapping between physical constraints of a genome universe and evolutionary constraints of mammalian life: stable development requires a coordinated geometry of ignition, protection, recognition, timing, and restraint.

Review
Biology and Life Sciences
Neuroscience and Neurology

Amelia Beatson

,

Anna Metzger

,

Matteo Toscani

Abstract: Human vision is profoundly non-uniform. Spatial resolution, contrast sensitivity, colour discrimination decrease, and the appearance of visual features become increasingly distorted with retinal eccentricity, yet visual experience appears remarkably rich and stable across the entire visual field. This apparent paradox has been a central challenge in vision science: how can a perceptually rich world emerge from a sensory system that samples only a small fraction of the environment with high precision? We argue that the apparent richness of peripheral vision cannot be explained solely by cognitive biases. Instead, it reflects genuine perceptual processes. Information sampled in central vision can be extrapolated to peripheral appearance, while prior knowledge and learned regular-ities allow the visual system to infer missing or distorted peripheral information. These processes operate within the constraints of active vision, where eye movements selectively sample task-relevant information rather than building a complete detailed representation of the scene. We propose that rich peripheral experience emerges from the interaction between centre to periphery extrapolation, and learned predictions, allowing the visual system to maintain a coherent and useful representation of the world.

Article
Biology and Life Sciences
Animal Science, Veterinary Science and Zoology

Peter Tually*

,

Jack Meadows

,

Matilda Hathaway

,

Geoffrey Currie

Abstract: Musculoskeletal injury remains a major welfare and performance concern in Thor-oughbred racing, and practical biomarkers for early risk stratification are needed. This multicentre observational cohort study characterised serum concentrations of two bone turnover markers, osteocalcin/BGLAP (OC) and C-terminal telopeptide of type I collagen (CTX-I), in 1,359 fit-to-race Thoroughbred racehorses sampled across New South Wales, Victoria, and Western Australia. Biomarker distributions, reference intervals, demo-graphic and training-related associations, and short-term soundness outcomes were evaluated using non-parametric methods. Both markers were positively skewed, with reference intervals of 0.13–9.44 ng/mL for CTX-I and 0.02–7.25 ng/mL for OC. CTX-I varied significantly by age, jurisdiction, venue, and training surface, with markedly higher concentrations in New South Wales horses and lower concentrations associated with polytrack training, but did not predict lameness outcomes. OC was significantly higher in horses classified as lame at sampling and showed modest but significant dis-criminatory ability for subsequent lameness, with strongest performance for persistent lameness at both 7 and 28 days. At an operational threshold of approximately 1.24 ng/mL, OC achieved high negative predictive value for persistent lameness. These findings support OC as a potential rule-out screening marker for short-term soundness risk, while CTX-I appears more informative for population-level skeletal turnover variation.

Article
Biology and Life Sciences
Biochemistry and Molecular Biology

Nadezhda A Orlova

,

Nadezhda A Potapova

,

Rolan R Shaifutdinov

,

Ivan I Vorobiev

Abstract: Chinese hamster ovary (CHO) producer cells differ in their capacity to accommodate secretory and endoplasmic reticulum (ER) stress, but how engineered survival backgrounds shape ER-proteostasis responses remains poorly understood. We compared 24-h dithiothreitol (DTT)-induced reductive ER stress responses in two clonal producers: CHO-S-derived HB8 secreting human chorionic gonadotropin and apoptosis-resistant CHO-4BGD-derived DUL secreting a GLP-1–Fc fusion protein with similar specific productivities. Responses were analyzed by strand-specific RNA-seq, Xbp1-splicing RT-PCR, immunoblotting, functional enrichment and curated-module analysis. RNA-seq identified 404 differentially expressed genes in HB8 and 1019 in DUL; all 222 genes shared between two producers changed concordantly. Both producers showed ISR/ATF4/CHOP-associated transcriptional activation and Xbp1 mRNA splicing, whereas changes in total Xbp1 and Hspa5/BiP transcript abundance were limited. BiP and CHOP accumulation was detected at the protein level, while phospho-eIF2α and ATF6 responses were variable. Baseline RNA-seq data comparison identified 1879 differentially expressed genes. HB8 showed higher expression of several classical ER folding/redox factors, whereas DUL showed higher expression of selected ISR-, quality-control- and stress-survival-associated genes. DUL additionally displayed broader vesicle/endocytic and amino-acid/glutathione-related remodeling. Thus, the producers occupy distinct ER-proteostasis states, and DUL mounts a broader, but not uniformly stronger canonical UPR, response to reductive ER stress.

Article
Biology and Life Sciences
Neuroscience and Neurology

Mateusz Smolarz

,

Natalia Pondel

,

Gracjana Zając

,

Agata Kurczyk

,

Monika Pietrowska

,

Marta Gawin

,

Magdalena Dębiec

,

Andrzej Małecki

,

Marta Nowacka-Chmielewska

,

Michal Toborek

Abstract: Methamphetamine (METH) is a known proinflammatory agent; however, the impact of inflammasomes on its neurotoxic effects is not fully understood. In the present study, we assessed the impact of a prolonged METH administration on the hippocampal inflammasome profile in male and female mice and determined alterations of inflammasome profile in response to METH. In addition to inflammasome activation, METH induced both systemic and hippocampal-specific inflammatory responses, leading to cognitive impairments, reduced hippocampal cell proliferation, and altered proteomic profiles. Importantly, the responses to METH exposure exhibited important sexual dimorphism. Treatment with inflammasome inhibitor MCC950 attenuated METH-induced inflammatory events; however, we also observed several off-target effects of this inhibitor affecting mouse anxiety-like behavior and cognitive functions. Overall, our results indicate the preventive potential of MCC950 in METH-related neurotoxicity, while underscoring its limitations due to distinct sex-dependent differences in response to both METH and MCC950 and highlighting significant sexual dimorphism.

Article
Biology and Life Sciences
Endocrinology and Metabolism

Karthik Murugadoss

,

A.J. Venkatakrishnan

,

Venky Soundararajan

Abstract: Oral Wegovy (semaglutide weight-loss pill) initiation now spans two clinically distinct real-world entry states: “GLP-starters” without recent GLP-1 receptor agonist (GLP-1RA) prescriptions and “GLP-switchers” with a recent record for a different injectable or oral incretin therapy. Using a large federated U.S. electronic health record network, we studied the five-year history prior to Wegovy pill initiation. Of 891,711 patients with at least one GLP-1RA prescription, 11,215 initiated the Wegovy pill, of whom 6,283 (56.0%) were GLP-starters and 4,932 (44.0%) were GLP-switchers. GLP-starters and -switchers were similar in age (mean 52.4 vs 52.1 years; P=0.21) and sex (75.4% vs 74.4% female; P=0.22). In contrast, GLP-switchers had significantly greater pre-index cardiometabolic and neuropsychiatric burden than GLP-starters (all q<0.001, Benjamini-Hochberg FDR), including type 2 diabetes (Relative Risk [RR] 1.95), obstructive sleep apnea (RR 1.78), heart failure (RR 1.73), atrial fibrillation (RR 1.55), coronary artery disease (RR 1.38), depression (RR 1.32), and migraine (RR 1.25). Of 3,216 disease phenotypes screened, large language model (LLM)-curated clinical notes showed 819 phenotypes significantly higher at baseline in GLP-switchers and none in GLP-starters (all q<0.001), including morbid obesity (RR 1.61), excessive daytime sleepiness (RR 1.56), and fatty liver disease (RR 1.47), with concordantly higher Elixhauser comorbidity index ≥5 (RR 1.47). Among GLP-switchers to Wegovy pill, the most common prior agents in the year before index were injectable Wegovy (40.7%) and Zepbound (36.6%). Among 123 initiators of the recently launched orforglipron pill (Foundayo), only 39.8% had no GLP-1RA exposure in the preceding year, followed by switchers from Zepbound (tirzepatide) injections (31.7%). LLM curation of clinical notes shows the most common reasons for switching to the Wegovy pill include more affordable cost or better insurance coverage (42.7%), oral route or dosing preference (13.1%), and inadequate weight-loss efficacy with prior therapies (10.4%). Studying polypharmacy of Wegovy pill initiators shows significantly larger GLP-switchers (96.9%) than GLP-starters (88.3%) taking other oral medications concomitantly (p<0.001), with GLP-switchers more often taking metformin (RR 1.38), atorvastatin (RR 1.21), losartan (RR 1.28), and insulin glargine (RR 2.60) (all q≤0.001). Consequently, overall polypharmacy was markedly greater in GLP-switchers (mean 13.4 vs 9.7 distinct medications; ≥5 medications 81.6% vs 60.8%; ≥10 medications 48.9% vs 33.1%) (all q<0.001). Medicare-eligible initiators of Wegovy pill (age ≥65 at index, n=2,535) had a substantially greater burden of cardiovascular and renal disease, multimorbidity, and overall polypharmacy than the overall cohort, but less severe obesity (BMI ≥40 in 14.0% vs 23.3%; p<0.001). This study marks the first longitudinal analysis of the incretin care pathway leading up to Wegovy pill initiation and highlights better access and tolerability as leading drivers of patients preferring to switch to Wegovy pill.

Review
Biology and Life Sciences
Biochemistry and Molecular Biology

Thanh Huu Phan Ngo

,

Jiwon Oh

,

Hyeong Jun Kim

,

Wan Lee

Abstract: Skeletal muscle is a continuously load-bearing tissue whose growth, repair, and age-related decline are governed by mechanical signals, and failure of this mechano-regulation underlies disuse atrophy and sarcopenia. Piezo1, a mechanically activated cation channel, has emerged as a tractable transducer of these signals in muscle, contributing to satellite-cell quiescence and senescence, regenerative division, myoblast fusion, and the response to loading and unloading. In parallel, the myogenic noncoding RNA program is among the best defined in any lineage, with the myomiRs miR-1/133/206, the long noncoding RNA LINC-MD1, and the circular RNA circ-ZNF609 as established regulators of the proliferation-to-differentiation transition. These layers are linked because Piezo1-evoked calcium influx feeds the RhoA/ROCK-actin-MRTFA-SRF and YAP/TAZ axis that drives myogenic transcription, yet no direct coupling between Piezo1 and noncoding RNAs has been demonstrated in skeletal myocytes. Drawing on validated precedents from vascular, cardiac, and tendon tissues, this review consolidates the two pillars, frames their convergence as a testable question, distinguishes validated relationships from hypotheses, and proposes three falsifiable predictions using an unbiased candidate-selection strategy. The contribution of this review is this testable framework rather than any specific candidate list. Mechanically tunable noncoding RNAs may thus represent an underexplored node for counteracting disuse atrophy and sarcopenia.

Article
Biology and Life Sciences
Immunology and Microbiology

Michael O. Glocker

,

Manuela Ruß

,

Cornelia Koy

,

Michael Kreutzer

,

Fiona T.I. Melder

,

Yelena Diebler

,

Harald Illges

,

Kwabena F.M. Opuni

Abstract: Studying protein structure dynamics is key to understanding protein function modulation. Alternative protein conformations are well discriminated from each other by nanoESI mass spectrometry. The shapeshifting IgG antibodies and protein G are present as compactly folded native conformations in neutral buffered solution, identified by molecular ions with narrow charge state distributions, relatively few charges, and small collisional cross sections. Simultaneously present extended but nevertheless native conformations produced additional ions with higher charge states, different charge state distributions, and larger collisional cross sections. Computed collisional cross sections from “o-shape” and extended “I-shape” protein G 3D structures match to experimental data, indicating equilibrium, and an “o2I” flip process. Likewise, “m-shape” and “Y-shape” IgGs are two of reversibly adopted antibody conformations which interchange by an “m2Y” flip. Burying Fc receptor binding sites by adopting the m-shape prevents antibody-based initiation of humoral and cellular immune system responses prior to antigen contact. The “m2Y” flip provides robust regulation of opsonophagocytosis, an important immune system mechanism.

Review
Biology and Life Sciences
Agricultural Science and Agronomy

Huajian Liu

,

Yue Wang

,

Fouzia Syeda

,

Haoyu Lou

,

Reddy Pullanagari

Abstract: Plant diseases lead to substantial yield losses and pose a persistent threat to global food security, creating an urgent demand for high-throughput, accurate, scalable, and non-destructive disease monitoring approaches. Remote sensing has emerged as a powerful tool, yet progress in plant disease detection remains fragmented across various disciplines, tasks, sensing methods, and data modalities. This review introduces a hex- view perspective to synthesise remote sensing–based plant disease detection within a cohesive conceptual framework. Instead of treating sensing technologies, algorithms, and datasets independently, the hex-view incorporates six interconnected dimensions that jointly capture how biological processes, measurement scale, and data characteristics constrain disease detectability, including when detection is possible and how reliably it can be achieved. The hex-view framework comprises six interconnected dimensions and forms an integrated framework called BTSCAD: (1) Biology (B): Plant-pathogen interactions constituting the biological foundation of disease development and expression. (2) Task (T): The diverse disease detection tasks and their corresponding research objectives. (3) Sensor (S): The sensing modalities that define the data acquisition type and richness of captured information. (4) Condition (C): The environmental conditions, sensing platforms, and spatial scales that shape disease observations and bridge controlled experiments and real-world deployment across leaf, canopy, plot and regional scales. (5) Algorithm (A): The classical and state-of-the-art data analysis algorithms used to extract disease-related information from sensor data. (6) Dataset (D): The data sources that underpin model development, evaluation, and generalisability. The hex-view perspective provides a clear framework for interpreting previous research and identifying future research directions. This review lays a structured foundation for developing robust, interpretable, and transferable disease detection systems, supporting advancements in precision agriculture, high-throughput phenotyping, and sustainable crop production.

Article
Biology and Life Sciences
Biochemistry and Molecular Biology

Lateef Adegboyega Sulaimon

,

Ayorinde Babatunde James

,

Aishat Abisola Akinbami

,

Oladayo Musa Babalola

,

Grace Folashayo Oni

,

Ganiu Adigun Idris

,

Mayowa Agbi

,

Akintayo Ashraf Akintola

,

Modinat Olawunmi Lawal

,

Adewale Segun James

Abstract: Background/Objectives: Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are highly prevalent among African men. While single-nucleotide polymorphisms (SNPs) in KLK3, HNF1B, and JAZF1 are established risk markers in Western cohorts, their specific allele frequencies and diagnostic utility remain poorly characterized in African populations. This study evaluated the diagnostic accuracy, sensitivity, and cost-effectiveness of High-Resolution Melting (HRM) PCR for germline SNP genotyping in a cohort of Nigerian men. Methods: Peripheral blood buffy coat DNA was extracted from 31 male participants attending the urology clinic at Lagos University Teaching Hospital, classified into PCa (n = 13), BPH (n = 12), and healthy controls (n = 6). Real-time PCR and HRM analysis were optimized to genotype three specific risk variants: rs2735839 (KLK3), rs4430796 (HNF1B), and rs10486567 (JAZF1). Allelic discrimination was validated using sequence-verified, synthetic positive controls for homozygous wild-type and mutant variants. HRM analysis generated reproducible amplification profiles and distinct melting curves that enabled clear discrimination of wild-type, heterozygous, and variant genotypes for all three loci. Results: The risk-associated alleles of KLK3 (G), HNF1B (C), and JAZF1 (T) occurred more frequently among patients with prostate cancer than among those with benign prostatic hyperplasia. Clinically, prostate cancer patients also presented with markedly higher PSA concentrations, older age at diagnosis, and higher Gleason scores, consistent with more aggressive disease. The optimized HRM workflow required less than two hours from amplification to genotype assignment and eliminated the need for post-PCR processing, making it suitable for routine molecular testing in resource-constrained laboratories. Conclusions: HRM-based genotyping of KLK3 (rs2735839), HNF1B (rs4430796), and JAZF1 (rs10486567) provides a highly reproducible, rapid, and low-cost molecular tool for mapping prostate disease risk variants. Because it requires no post-PCR processing, this closed-tube HRM workflow is ideally suited for resource-limited clinical settings to enhance early risk stratification and differentiate malignant PCa from benign BPH.

Review
Biology and Life Sciences
Insect Science

Minghui Zhao

,

Weina Wang

,

Hongyu Lai

,

Lixin Zhou

,

Qi Liao

,

Jinxin Liu

,

Hongning Liu

,

Miao Ouyang

,

Gang Ren

,

Zishu Dong

Abstract: As the global population ages rapidly, demand for safe and effective strategies to promote healthy aging grows markedly. Natural bioactive compounds, with favorable biosafety profiles and multi-target regulatory properties, have become a core focus in developing anti-aging functional foods and nutraceuticals. Amid the search for novel sustainable bioresources, edible insects emerge as promising anti-aging candidates for their rich species diversity, scalable production, low environmental footprint, and abundant unique bioactive components such as functional proteins and bioactive peptides. Based on bibliometric analysis of 500 eligible publications spanning two decades, this review systematically identifies 32 anti-aging insect species across seven orders, classifies their bioactive components into five major categories, summarizes green extraction technologies, and evaluates their in vitro and in vivo anti-aging activities centered on oxidative stress and inflammatory regulation, while outlining the field’s trajectory from basic mechanistic research to functional application. It further highlights core challenges including fragmented research frameworks and insufficient robust in vivo validation. Finally, it recommends integrating established food science and medical methodologies with emerging technologies such as omics, artificial intelligence, and advanced delivery systems to advance future research paradigms. These efforts could provide a strong theoretical foundation for the efficient and sustainable use of insect resources in anti-aging applications.

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