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From population to individual: advocating personalised digital tools for heat-health early warning in a changing climate.

Escalating heat extremes under climate change are imposing substantial health burdens, with 2023 and 2024 consecutively breaking global temperature records. Mounting evidence suggests that heatwaves elevate the risks of hospitalisation and mortality across multiple disease categories, including ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and acute kidney injury. Nonetheless, most existing heat-health warning systems remain primarily reliant on population-level predictions, and considering individual differences and disease-specific considerations when defining warning levels would benefit the effectiveness of early prevention for high-risk groups. In this Viewpoint, which is based on the framework of precision public health-delivering the right intervention to the right population at the right time-we propose a framework for personalised digital heat-health early warning tools comprising three dimensions: individualised, risk-stratified prediction models that generate tiered early warnings; personalised health prompts coupled with theory-informed behavioural interventions; and adaptive, equity-oriented alert delivery mechanisms tailored to diverse populations. Such tools have the potential to bridge precision disease prevention and climate adaptation, thereby helping to mitigate heat exposure risks and disease burdens, particularly among high-risk populations. Future implementation research will be essential to address substantial challenges related to feasibility, validation, and equity.

Journal Article

Flux rewiring enables native D-glucosamine production in Escherichia coli.

D-Glucosamine is an industrially important amino sugar used in pharmaceuticals, nutraceuticals, and functional materials, yet its production remains dominated by chemical extraction from chitinous biomass, raising sustainability and allergen concerns. Escherichia coli natively synthesizes D-glucosamine directly from D-glucose through endogenous metabolism, revealing an underutilized amino sugar biosynthetic capability. Building on this native pathway, D-glucosamine production was enhanced through targeted genetic modifications and systematic optimization of nitrogen metabolism and cultivation conditions, reaching 9.2 g L-1 under shake-flask conditions. This work extends a phosphorylation-dephosphorylation strategy previously developed for neutral rare sugars to amino sugar biosynthesis, demonstrating the broader applicability of this metabolic design principle. Phosphatase identity emerged as a key control point for product formation: YbiV was the most effective phosphatase for selective D-glucosamine production, whereas alternative phosphatases redirected flux toward D-sedoheptulose. This enzyme-dependent flux partitioning further enabled tunable co-production of D-glucosamine and D-sedoheptulose. Native amino sugar biosynthesis in E. coli provides a controllable framework for producing chemically distinct sugars through endogenous metabolism and establishes a generalizable strategy for engineering amino sugar and other nitrogen-containing metabolite biosynthesis.

Escherichia coli

Insights into the regulation of the HOTAIR proximal promoter.

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

Humans

Validation of a Turkish Translation of the Stress in Emergency Healthcare Professionals: The Stress Factors and Manifestations Scale.

AIM: The primary duties of emergency healthcare professionals (EHPs) are to provide emergency patient care to acutely ill and injured individuals. Due to the nature of their work, EHPs operate under constant stress, often requiring rapid decision-making, swift action, and the delivery of necessary medical care in life-or-death situations, sometimes under inadequately safe conditions. Therefore, the aim of this study is to determine the validity and reliability of the Emergency Healthcare Professional Stress Factors and Symptoms (SEHP:SFMS) Scale in Turkish for identifying stress factors and symptoms in emergency medical care professionals providing emergency patient care services. DESIGN: A methodological study design was used in this study. METHODS: The study was conducted with the participation of 211 EHPs from employees working in emergency care institutions affiliated with the Muğla Provincial Health Directorate between November 2023 and June 2024. Data were collected via a face-to-face survey. Data were analysed using Lawshe content validity ratio, Kaiser-Meyer-Olkin coefficient, Bartlett test, exploratory factor analysis, principal component analysis, Varimax factor rotation method, confirmatory factor analysis, Cronbach's α internal consistency coefficient, convergent validity, discriminant validity, test-retest, and Spearman correlation coefficient tests. RESULTS: The linguistic translation and cultural adaptation of the SEHP:SFMS showed strong performance. The scope validity index of the scale is 0.83. The item-total correlation values of the scale were found to be between 0.486 and 0.794, and the factor loadings were between 0.474 and 0.816. Confirmatory factor analysis fit indices: χ2 = 248.727; df = 101; n = 211; p = 0.000; χ2/df = 2.463; RMSEA = 0.083; CFI = 0.914, SRMR = 0.052, which was found to be compatible and acceptable with the proposed 3-factor model. The Cronbach's α reliability coefficient of the scale was 0.931, and the total variance was 61.97%. CONCLUSIONS: SEHP:SFMS is a valid and reliable tool to assess stress factors and symptoms of Turkish emergency healthcare professionals. Its use improves the quality of emergency care. PATIENT OR PUBLIC CONTRIBUTION: These study findings have been used to create a tool with Turkish validity and reliability that allows for the examination of stress factors among healthcare professionals working in emergency and critical services. Identifying and reducing stress factors among healthcare professionals is crucial for the delivery of quality healthcare services. It can also be used to develop targeted interventions and ongoing strategies to facilitate improved clinical supervision and mentoring. IMPLICATION FOR NURSING PRACTICE: Nurses in emergency departments, which are among the most stressful, dynamic, intense, life-saving, and critical environments in healthcare institutions, and where life-saving treatment is administered, are at high risk of experiencing psychological trauma. Trauma experienced in the work environment is a significant problem for nursing. The consequences of trauma negatively affect nurses and institutions. Studies show that post-traumatic stress, anxiety, depression, and burnout are commonly observed in emergency department nurses. In this sense, understanding the stress and stress factors experienced by nurses can guide future interventions. The results of this study are considered important in making visible the stress and stress factors experienced by nurses in the emergency department, and also in guiding managers and nurses working in this field in terms of preventive and protective measures.

Humans

L-glutamine supplementation improves porcine sperm quality and early embryo development during in vitro fertilization.

L-glutamine (Gln), as a key additive in porcine sperm capacitation medium and in vitro fertilization (IVF) systems, has been shown to significantly improve sperm motility and survival rates. However, its precise roles during porcine IVF and subsequent early embryonic development remain elusive. This study utilized an IVF model in pigs to investigate the effects of glutamine on sperm quality and embryonic development. We found that Gln supplementation during sperm treatment significantly improved sperm quality, as evidenced by reduced reactive oxygen species (ROS) production and early apoptosis, while enhancing calcium ion levels and endoplasmic reticulum activity. Supplementing glutamine during embryo culture reduced polyspermy rates, promoted zygotic genome activation (ZGA) and accumulation of 5-ethynyluridine (EU) and histone modifications (H3K4me3 and H3K27ac) at the two-cell and four-cell stages, increased blastocyst formation rates and total cell numbers, while simultaneously reducing DNA damage and early apoptosis during the blastocyst stage. In summary, these findings demonstrate that Gln enhances porcine IVF outcomes by improving sperm quality, reducing polyspermy, and facilitating early embryonic development, thereby providing a basis for optimizing culture systems.

Animals

Morphology-Encoded Colorimetric Hydrogen Sensing Using Embedded Reactive Pd Absorbers in Fabry-Perot Cavities.

Chemical reactions offer a powerful strategy for generating visible optical responses through localized changes in absorption, dielectric environment, and interfacial wetting. A palladium (Pd)-embedded Fabry-Perot cavity is introduced as a reaction-active optical platform in which structural color is governed by intracavity absorption coupled with reaction-induced dielectric perturbation. Positioning Pd within the dielectric spacer creates a spatially controllable reactive absorber whose vertical location relative to the standing-wave field dictates wavelength-selective absorption within the cavity. The morphology of the embedded Pd layer provides an additional design parameter by modulating both optical loss and interfacial wetting. Under hydrogen exposure in the presence of oxygen, catalytic water formation at the Pd/polymer interface generates localized dielectric heterogeneity and interfacial water droplets, thereby perturbing the optical path length and amplifying the visible response. As a result, the cavity exhibits pronounced, morphology-dependent color transitions that are inaccessible through dielectric-layer engineering or Pd/PdH refractive-index changes alone, enabling direct visual hydrogen sensing under ambient light, as well as flexible optical devices capable of large-area patterning. These findings establish a design framework for reaction-active optical cavities that translate localized chemistry into a colorimetric hydrogen sensing mechanism.

Fabry–Perot resonator

Exploring the mechanism of aroma production in fermented cherry juice by L. brevis LD1.0600 using flavomics and whole genome analysis.

This study focused on L.brevis LD1.0600 with excellent fermentation traits: it analyzed genome-wide key regulatory genes for micro-metabolites, combined with fermented cherry juice flavor metabolomics data, and used machine learning to explore correlations between gene regulation, metabolite production, and flavor formation. The SVM model screened and verified fermented cherry juice VOCs; through OAV and flavor wheel analysis, LD1.0600 emerged as the top-performing strain, with a sweet, fruity dominant aroma. Key aroma-active components (OAV > 100) included 2-methoxy-4-vinylphenol, benzaldehyde, 2-methyl-butanoic acid and hexanoic acid, and 2-methoxy-4-vinylphenol and hexanoic acid elevated by LD1.0600-regulated genes (Chrom1-001884, Chrom1-000925, fabF and Chrom1-000199). At the same time, through research, a "strain screening-SVM screening of DVCs-OAV screening of key aroma components-whole genome sequencing of flavor regulatory genes" system was established. This system can not only be applied to the screen fermentation strains, but also can be extended to the application of other fermentation products.

Fermentation

Multiomic insights into fungal polylactic acid degradation: Metabolic adaptation and hydrolytic mechanisms of Sporobolomyces pararoseus.

Polylactic acid (PLA), a biodegradable polyester from renewable resources, is a sustainable alternative to petrochemical plastics. However, its environmental degradation is inefficient naturally, requiring specific microbial activities. While bacterial PLA-degrading mechanisms are well documented, fungal degrading systems-particularly their molecular mechanisms-are underexplored.We isolated Sporobolomyces pararoseus ZRQ01 from the gut microbiota of PLA-fed mealworms. This fungal strain noticeably degraded PLA in PLA-containing medium supplemented with 2% glucose. Biodegradation assays revealed 22.8% loss of the PLA film weight after 35 days of incubation, and scanning electron microscopy confirmed extensive surface erosion and pore formation. Integrated transcriptomic and proteomic analyses, together with the reference genome of S. pararoseus ZRQ01, revealed that S. pararoseus ZRQ01 upregulates hydrolytic enzymes at both transcript and protein levels to cleave PLA into lactic acid. After lactic acid is transferred into S. pararoseus ZRQ01 cells by monocarboxylate transporters with increased abundance, it is assimilated by pathways of pyruvate metabolism and the TCA cycle with increased protein abundance. Intriguingly, upregulation of genes in autophagy-related and MAPK signaling pathways underscores an adaptive stress response potentially supporting cellular homeostasis and degradation-related gene expression. Our results highlight S. pararoseus ZRQ01's metabolic potential for bioremediation and offer insights into fungal bioplastic degradation pathways.

Polyesters

Biological characterization of Candida parapsilosis haploids induced by voriconazole.

OBJECTIVES: Candida parapsilosis is an important opportunistic fungal pathogen causing serious human infections in nosocomial settings. It has long been thought that C. parapsilosis has a diploid genome with a high homozygosity between chromosome homologs. METHODS: In this study, we report the discovery of C. parapsilosis haploids induced by voriconazole, a triazole with broad antifungal activity against fungal pathogens, in an experimental evolutionary assay. RESULTS: The haploid strains were able to undergo auto-diploidization under in vitro culture conditions or during systemic infection at a low frequency. Compared to the progenitor diploid strain, C. parapsilosis haploid and auto-diploid strains exhibited a reduced ability of invasive growth and biofilm formation. Global transcriptional expression analysis indicated that haploid and auto-diploid strains had a similar transcriptomic profile, which showed a remarkable difference from the progenitor diploid strain perhaps due to the loss of chromosome heterozygosity. Moreover, the haploid and diploid strains had distinct fungal burdens in different animal tissues, suggesting the haploid state could have a colonization advantage over the diploids in certain tissues such as the brain and spleen. CONCLUSIONS: The discovery of C. parapsilosis haploids not only sheds lights on the biology of this important fungal pathogen, but also provides a tool for genetic modifications for the field.

Voriconazole

Direct and spillover hospitalisation patterns during climate hazards across regions of different health-system resilience levels in China: a nationwide retrospective analysis.

BACKGROUND: Health-system resilience serves as a key contributor in mitigating adverse health impacts during climate hazards. However, quantitative insights into resilience-associated health-care utilisation patterns and targeted adaptation policies remain scarce. We aimed to capture the spatiotemporal health impacts in disaster-exposed counties and their neighbouring counties in China during storms, floods, tropical cyclones, and blizzards or winter storms; understand the association between health-system resilience metrics and hazard-attributable hospitalisations; and develop evidence-based adaptation policies towards climate extremes. METHODS: In this retrospective, observational analysis of county-level aggregated hospitalisation data, we used a propensity score matching-difference-in-differences framework to assess the spatiotemporal changes of nine types of disease-specific hospitalisations in both disaster-exposed and neighbouring regions during storms, floods, tropical cyclones, and blizzards in China. We quantified the relative importance and health gains of health-system metrics during such hazards through random forest approach with interpretable partial dependence plots to derive evidence-based adaptation recommendations. FINDINGS: We included hospitalisation data from Jan 1, 2016 to Dec 31, 2023. In this period, 3241 county-hazard event combinations and 41 747 482 hospitalisations were recorded across 955 Chinese counties. The disaster-exposed regions experienced an initial decline in hospitalisation rates, followed by admission surges after disasters. For example, infectious disease admissions decreased by 11·92% (95% CI -10·53 to -13·31) during the flood-active period but increased by 7·68% (6·46-8·91) after 1-2 weeks of floods. Neighbouring zones were also affected through spillover effects, with infectious disease admissions increasing by 3·18% (1·76-4·61) after 1-2 weeks of the floods. Cardiovascular disease, injuries, infectious, respiratory, and mental disorders were more sensitive across all regions. Particularly for disaster-exposed counties, cardiovascular hospitalisations increased by 14·31% (7·34-21·29) during the tropical cyclone-active period. Notably, compared with low-resilience counties, high-resilience counties were associated with 19·48-30·03% smaller hazard-related relative changes in hospitalisation rates during the hazard-active period and 27·07-31·08% smaller hazard-related relative changes in hospitalisation rates in post-hazard periods. For instance, during the storm-active period, the increase in respiratory hospitalisations was 7·21% (0·67-13·75) in high-resilience counties versus 12·13% (5·20-19·05) in low-resilience counties. Health workforce (relative importance 14·58% during the hazard-active period and 13·80% during the post-hazard period) and service delivery (14·10% during the hazard-active period and 14·17% during the post-hazard period) were identified as key contributors of health-system resilience. Empirical synergistic effects were observed when combining interventions during the post-hazard period, with the combined effect of service delivery (individual contribution 8%) and workforce (individual contribution 4%) exceeding the sum of their individual contributions (16% reduction in cumulative excess admissions) by 33%. INTERPRETATION: Climate hazards are associated with substantial changes in hospitalisation rates in both disaster-exposed and neighbouring regions. Health-system resilience is essential in addressing disaster-health challenges. Targeted adaptation interventions should be context-appropriate and threshold-aware, thereby maximising the public health benefits relative to resilience-oriented investments in health systems. FUNDING: Gates Foundation and the National Natural Science Foundation of China.

Journal Article

Diving Deeper Into Mechanisms of Acrylamide-Induced Toxicity: RNA Sequencing Reveals Transcriptomic Alteration and Retrotransposon Expression in Drosophila melanogaster.

Given the inevitability of human and animal exposure to acrylamide, there is increasing concern regarding its potential health risks. While a number of molecular mechanisms have been proposed, the complexity of acrylamide toxicological pathways and interactions remains incompletely characterized. In this study, we employed a transcriptomic approach to investigate the transcriptional responses of Drosophila melanogaster following exposure to acrylamide (100 mg/kg). Our analysis identified 634 differentially expressed genes (DEGs), with 362 upregulated and 272 downregulated. Functional analysis revealed these DEGs are enriched in pathways related to reproduction, detoxification, cellular and metabolic processes, signaling, synaptic formation and organization. Notably, acrylamide exposure upregulated the expression of tau and beta-amyloid protein precursor-like genes, both implicated in Alzheimer's disease pathology. An aversive memory test further demonstrated that acrylamide impaired the short-term memory of treated flies. Additionally, acrylamide-induced toxicity altered the expression of nine long terminal repeat retrotransposons, belonging to the gypsy and pao superfamilies. By exploring the potential role of transposable element activity in acrylamide-mediated toxicity, this study provides novel insights into the molecular mechanisms underlying its effects. Collectively, these findings offer a more comprehensive understanding of the mechanisms and pathways associated with the toxic action and detoxification of acrylamide in D. melanogaster.

Animals

Behind the Curtain of Care. Nurses' Experiences Providing Care to Consumers With Alcohol and Other Drug Issues: A Qualitative Scoping Review.

AIM: To scope and synthesise qualitative literature relating to nurses' experiences of providing care to consumers with alcohol and other drug issues and explore how meaning is constructed in practice. DESIGN: Scoping review. METHODS: A scoping review was conducted following Arksey and O'Malley's framework. Findings were analysed using thematic analysis. DATA SOURCES: Systematic searches were conducted between September and November 2025 across Medline, Emcare, CINAHL and Google Scholar, using controlled vocabulary and keywords relevant to nurses' experiences of providing care to consumers with alcohol and other drug issues. RESULTS: Twenty-four studies from 12 countries were included. Seven themes were identified: emotional aspects of care, education, training and skills in practice, the spectrum of stigma, ethical issues in professional practice, navigating pain management, limited support, and how meaning is constructed in practice. CONCLUSION: Nurses' experiences of providing care to consumers with alcohol and other drug issues are shaped by multiple intersecting factors influencing care delivery and professional practice. Further research is needed to examine how workplace culture, language and interpersonal interactions influence healthcare experiences, and inform education, service development and support needs. REPORTING METHOD: Reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

alcohol and other drugs

CNOT1 is a potential YTHDF2 target that orchestrates maternal mRNA decay and zygotic genome activation during goat embryogenesis.

Timely and efficient degradation of maternal mRNA is essential for early embryonic development, which occurs from fertilization through the initiation of zygotic genome activation (ZGA). Yet, the regulatory mechanisms governing this process remain poorly characterized. In the present study, we investigated the function of CCR4-NOT transcription complex subunit 1 (CNOT1) during goat embryogenesis. We found that CNOT1 was upregulated during mammalian ZGA, and that its knockdown led to developmental arrest and a marked reduction in blastocyst formation. Moreover, CNOT1 knockdown impaired nascent RNA activity, resulting in 814 upregulated and 1014 downregulated genes, which were enriched for RNA splicing, regulation of chromosome organization, and RNA localization. RNA splicing analysis revealed differential splicing events in 2959 genes, of which 259 were downregulated following CNOT1 knockdown. Notably, CNOT1 was predicted to crosstalk with the m6A reader YTHDF2. Knockdown of YTHDF2 resulted in CNOT1 downregulation at the 8-cell stage in goats and increased transcription levels around polyadenylation sites during ZGA in mice. Together, these findings indicate that CNOT1 is a potential YTHDF2 target that orchestrates maternal mRNA decay and ZGA during goat embryogenesis. Our work provides new insight into the complex regulatory landscape underlying ZGA and may inform strategies to improve the efficiency of goat embryogenesis.

Animals

Psychological skills training for sport-related outcomes: An umbrella review of evidence credibility and methodological quality.

Psychological skills training (PST) is widely used in sport, but review-level evidence remains fragmented across interventions, populations, outcomes, and methodological standards. This umbrella review synthesized evidence on PST-related interventions for sport-related outcomes, including athletic performance, psychological outcomes, cognitive performance, and sports injury, and evaluated evidence credibility, certainty, and methodological quality. A systematic literature search was conducted on 21 May 2025 in MEDLINE, PsycInfo, PubMed, Scopus, SportDiscus, Web of Science, and CINAHL Complete. Overall, 61 reviews involving 42,106 participants were included; 35 meta-analyses involving 28,076 participants were eligible for quantitative synthesis, and 26 reviews or meta-analyses involving 14,030 participants were summarized qualitatively. Quantitative findings showed generally positive point estimates for mindfulness-based interventions, imagery practice, music-based interventions, neurofeedback, perceptual-cognitive training, and multiple PST interventions, but most findings were weak or non-significant and certainty was generally very low. Qualitative evidence suggested potential benefits, but conclusions varied according to intervention definition, delivery, outcome measurement, and methodological quality. Evidence was more developed for athletic performance and psychological outcomes than for cognitive performance and sports injury. Overall, PST-related interventions may benefit sport-related outcomes, but conclusions should remain cautious because of low certainty, methodological heterogeneity, and limited evidence credibility.

Humans

Genome-wide identification and expression analysis of the CREB/ATF family and its potential role in melanogenesis in the Manila clam (Ruditapes philippinarum).

Ruditapes philippinarum is an economically important bivalve species in China, and shell color is a trait of ecological and commercial significance. Melanin is a key determinant of shell color, and members of the CREB/ATF family have been reported to participate in melanogenesis in other organisms. In this study, members of the CREB/ATF family were systematically identified at the whole-genome level based on genomic and transcriptomic datasets, followed by analyses of their phylogenetic relationships, gene structures, and expression patterns. A total of six CREB/ATF family members were identified and classified into five subfamilies. Expression profiling and RT-qPCR validation revealed that most CREB/ATF genes were highly expressed in the mantle and displayed clear differences among shell-color phenotypes. Except for RpATF4 and RpCREBZF, most members exhibited relatively high expression levels in dark-colored shell strains, particularly in black and zebra-striped clams. Moreover, most genes showed low expression during early embryonic and larval stages but increased expression at the single-siphon spat and juvenile stages. These results suggest that the CREB/ATF family may be involved in melanin-associated shell-color regulation in R. philippinarum, providing important candidate genes and a theoretical basis for further elucidating the molecular mechanisms of shell-color formation in mollusks.

Animals

A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations.

PURPOSE OF REVIEW: Hereditary hearing loss has historically been approached as a diagnostic category rather than a therapeutically modifiable disease. Recent advances in molecular genetics, cochlear gene delivery, and first-in-human clinical trials are changing that. This review summarizes contemporary progress in the genetics of hearing loss, with emphasis on emerging gene-based therapies, clinical trial design, regulatory and ethical considerations, and practical implications for otolaryngologists as biologic treatment enters clinical practice. RECENT FINDINGS: Early clinical trials targeting OTOF -related DFNB9 deafness have demonstrated satisfactory safety profiles and meaningful auditory recovery, establishing the first proof-of-concept for cochlear gene therapy in humans, culminating in the April 2026 FDA approval of Otarmeni. Genetic diagnoses are increasingly informing prognosis, cochlear implant counseling, and therapeutic candidacy. Preclinical research continues to expand toward recessive, dominant, and syndromic hearing loss using gene replacement, antisense, RNA interference, and genome-editing strategies. Substantial challenges remain, including heterogeneous outcome measures, uncertain long-term efficacy, regulatory complexity, and inequitable global access. SUMMARY: The genetics of hearing loss is transitioning from a diagnostic modality to an interventional one. Widespread clinical impact will require advances in vector engineering, equitable implementation, multidisciplinary counseling, and integration with established rehabilitation pathways. For otolaryngologists, genetic literacy is becoming essential to contemporary hearing care.

Humans

The HOXA gene cluster: a critical regulator in bone-related disorders.

BACKGROUND: Skeletal homeostasis relies on the dynamic balance between bone formation and bone resorption. The disruption of this balance acts as the central pathological mechanism of multiple metabolic bone diseases including osteoporosis, and is closely correlated with the progression of various other bone-related disorders. As pivotal transcription factors regulating embryonic development and cell fate, the homeobox A (HOXA) gene family plays an essential role in skeletal physiological and pathological processes. METHODS: This review systematically summarizes recent research advances of the HOXA gene family in bone-related diseases, concludes the evolutionarily conserved regulatory patterns of HOXA members, and clarifies the molecular mechanisms by which HOXA genes mediate bone metabolic disorders and the occurrence as well as development of bone diseases. RESULTS: Accumulating evidence demonstrates that HOXA family members present complex functions and strong heterogeneity in bone-related diseases. They participate in the pathogenesis of bone diseases via three evolutionarily conserved regulatory manners: determining regional patterning, modulating signaling pathways, and integrating epigenetic and non-coding RNA (ncRNA) regulatory networks. CONCLUSION: Further exploring the underlying mechanisms of the HOXA family in bone-related diseases provides novel insights into the pathogenesis of bone disorders. Meanwhile, it also supplies solid theoretical basis and potential therapeutic targets for the development of novel HOXA-targeted therapeutic strategies against bone diseases.

Humans

Mechanistic insights into flavor deterioration in bitter sturgeon caviar: Evidence from lipidomics and metagenomics.

This study systematically compared the flavor and multi-omics differences between normal caviar and bitter caviar based on quantitative descriptive analysis (QDA), volatile compounds (VOCs) analysis, untargeted lipidomics, and metagenomics. The results showed that bitter caviar was characterized not only by increased bitterness, but also by decreased positive sensory attributes, including buttery, nutty, and marine fresh. VOCs analysis indicated that the volatile profile of bitter caviar was reorganized. Compounds such as 3-hydroxy-2-butanone, 1-octen-3-ol, and (E, Z)-2,6-nonadienal showed higher relative odor activity values (rOAVs); however, these changes did not improve its overall sensory experience. Untargeted lipidomics identified 492 differential lipids. These changes were mainly characterized by decreased PC and increased DG and LPC in bitter caviar. KEGG pathways analysis showed that these differential lipids were mainly associated with glycerophospholipid metabolism, choline metabolism in cancer, and retrograde endocannabinoid signaling. Metagenomic analysis showed that bacteria dominated the microbial community of caviar. Among them, Bacillus and Micromonospora showed relatively high abundance in the caviar microbiota. They were also closely associated with lipid metabolic changes involving PC, DG, and LPC, suggesting their potential as candidate targets for future microbiota-directed regulation of caviar quality. These findings provide new insights into the mechanisms underlying sensory deterioration and flavor formation in bitter caviar, and offer a theoretical basis for improving caviar quality in industrial production.

Animals