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Biomedical subjects

Chao Yan

Publications and source records attributed to Chao Yan.

7 recordsLinked to original sources

Transmitochondrial pigs reveal causal effects of mitochondrial DNA on backfat thickness via nuclear epigenetic reprogramming.

Mitochondrial DNA (mtDNA) polymorphisms have been associated with production traits in farm animals, including backfat thickness in pigs, yet direct in vivo evidence establishing a causal link between specific mtDNA haplotypes and fat deposition remains limited. In this study, we generated transmitochondrial pigs (mitopigs) by combining the Dapulian nuclear genome with Wuzhishan mtDNA via somatic cell nuclear transfer, introducing 23 mtDNA mutations relative to controls. Mitopigs exhibited significantly increased backfat thickness at 5 months, a difference that persisted in their offspring, without significant differences in body weight, body size, or litter size. Fibroblasts derived from mitopigs exhibited reduced mtDNA copy numbers, decreased expression of mitochondrial biogenesis genes (PPARA, PPARGC1A, RRM2B, and LRPPRC), impaired mitochondrial respiration, elevated reactive oxygen species (ROS), and upregulated adipogenic transcription factors (CEBPA, CEBPB, and PPARG). Consistent with these fibroblast findings, backfat tissue of mitopigs showed corresponding upregulation of adipogenic transcription factors and downregulation of mitochondrial biogenesis genes. Integrated transcriptomic and whole-genome bisulfite sequencing (WGBS) analyses revealed nuclear transcriptional reprogramming that was closely associated with differential DNA methylation, predominantly affecting mitochondrial function and lipid metabolism pathways. Mitopig fibroblasts also showed a pro-inflammatory response to lipopolysaccharide stimulation, with elevated expression of IL-12, NOS2, RELA, and TNF-α. Our findings provide direct in vivo evidence that mtDNA variants regulate adiposity in pigs through mitochondrial dysfunction, oxidative stress, and nuclear epigenetic modulation, highlighting the potential for incorporating mtDNA haplotype information into pig breeding programs as a complementary strategy to nuclear genomic selection.

Adipogenesis

Family communication patterns and adolescent depressive symptoms: sequential mediating effects of hedonic capacity and anger expression.

OBJECTIVE: Depression is increasingly prevalent among adolescents, highlighting the need to explore its underlying developmental mechanisms to inform effective prevention. This study examined how different family communication patterns longitudinally impact adolescent depressive symptoms, with a focus on the mediating roles of diminished hedonic capacity and anger expression. METHOD: A total of 729 Chinese adolescents from five high schools participated in this two-wave longitudinal study over a six-month period. Participants completed the Family Communication Patterns Scale (FCPS), the Children's Depression Inventory (CDI), the Anhedonia Scale for Adolescents (ASA), and the Children's Inventory of Anger (ChIA). Mediation analyses were conducted using Hayes' PROCESS macro, alongside cross-lagged panel analyses to explore longitudinal effect. RESULTS: Cross-sectional analyses indicated that diminished hedonic capacity and anger experience sequentially mediated the relationship between family communication patterns and adolescent depressive symptoms. Specifically, this mediating effect existed for conversation orientation in junior high school students and female senior high school students, as well as for conformity orientation among female junior and senior high school students. In addition, longitudinal analyses revealed that diminished hedonic capacity mediated the associations at Wave 2. CONCLUSION: Our findings suggest that enhanced hedonic capacity and reduced anger expression may play a key role in the relationship between family communication patterns and adolescent depression, and hedonic capacity should be prioritized in practical interventions. These results support the potential value of interventions that promote positive family communication patterns as a means of mitigating adolescent depression, particularly for families with daughters.

anger expression

Multidrug resistance and genomic characteristics of nontypeable Haemophilus influenzae isolates from the respiratory tract of pediatric patients.

UNLABELLED: Nontypeable Haemophilus influenzae (NTHi) is a common colonizer of the human upper respiratory tract and one of the major pathogens responsible for pediatric respiratory tract infections. Given the increasing severity of its multidrug resistance (MDR), this study comprehensively investigated the genomic characteristics of circulating NTHi isolated from sputum and bronchoalveolar lavage fluid (BALF). A total of 104 H. influenzae isolates (69 from sputum; 35 from BALF) were collected from pediatric patients between January 2024 and January 2025. All isolates underwent whole-genome sequencing and antimicrobial susceptibility testing, followed by core/pan-genome phylogenetic analysis, multilocus sequence typing (MLST), and resistome profiling. Among them, 103 were identified as NTHi. We identified 29 known sequence types (STs) and 10 novel STs, with ST-107 (14.4%), ST-57 (10.6%), and ST-11 (8.7%) being the major circulating lineages. However, core-genome phylogenetic analysis provided a more granular view of the genetic variation within these identical STs. All the isolates showed high resistance to ampicillin (98.1%) and cefuroxime (84.6%). Genomically, the multidrug efflux pump gene hmrM was ubiquitous (100%). Ampicillin resistance was predominantly driven by blaTEM-1 carriage (77.9%), with minor contributions from chromosomal ftsI mutations. Fifteen plasmid replicons were predicted from 25 isolates, which highly coincided with the carriage of blaTEM-1 and other acquired resistance genes. This study demonstrates that MDR in pediatric NTHi is primarily driven by acquired resistance genes and chromosomal mutations, with specific resistant clones persisting and enriching under clinical antibiotic pressures. These findings underscore the importance of continuous high-resolution genomic surveillance in guiding rational antibiotic stewardship. IMPORTANCE: This study highlights the critical importance of high-resolution genomic surveillance in managing pediatric nontypeable Haemophilus influenzae (NTHi) infections. By utilizing whole-genome sequencing, we uncovered the pathogen's highly dynamic population structure and complex multidrug resistance (MDR) mechanisms. Crucially, our findings reveal a strong, non-random coupling between core genomic architectures, virulence factors, and MDR elements, driven by dual environmental and pharmacological pressures. This "virulence-MDR" co-evolutionary trend underscores the persistent clinical threat of locally adapted high-risk clones. These findings provide important insights for guiding rational clinical antibiotic stewardship, optimizing treatment strategies, and improving regional infection control.

Humans

Access to palliative care in rural settings: A mixed-methods systematic review.

BACKGROUND: Rural populations experience persistent inequities in access to palliative care. Existing evidence often describes individual barriers separately, with less attention to how access breaks down across the care pathway or how different service configurations shape access. OBJECTIVES: To synthesise evidence on access to palliative care in rural settings and examine how access barriers, service models, and implementation conditions interact across the care pathway. METHODS: A mixed-methods systematic review using a convergent integrated approach searched nine databases (PubMed, Embase, CINAHL, Web of Science, Scopus, PsycINFO, CNKI, WanFang, SinoMed) from inception to 15 March 2026, supplemented by hand-searching. Eligible studies were primary qualitative, quantitative, and mixed-methods studies on access to palliative care for adults in rural or non-urban settings. Two reviewers independently screened studies, extracted data, and assessed quality using the Mixed Methods Appraisal Tool. Findings were mapped to the Levesque access framework, analysed using the updated Consolidated Framework for Implementation Research, and integrated through mixed-methods synthesis, with additional coding of service models. RESULTS: Thirty-four studies were included, of which 26 were conducted in high-income countries and eight in low- and middle-income countries. Service configurations included specialist or hospice-oriented care, generalist or primary-care-oriented care, mixed specialist-generalist models, home-based and caregiver-centred care, nurse-coordinated services, telehealth-supported care, and community or implementation-oriented approaches. Access broke down cumulatively across four interdependent stages: recognition, entry, reach, and use and continuity, with affordability constraining every stage. Recognition was limited by low awareness, poor service visibility, and delayed identification of need. Entry was shaped by stigma, trust, family expectations, and unclear referral processes. Reach was constrained by distance, transport, workforce shortages, limited specialist capacity, and weak infrastructure. Use and continuity were affected by fragmented coordination, weak transitions, unstable follow-up, and reliance on family caregivers. Access problems varied across service configurations. Evidence on service innovations was methodologically less certain, and the overall evidence base remained concentrated in high-income countries. CONCLUSIONS: Access to palliative care in rural settings is best understood as a pathway and service-configuration problem rather than simply a deficit in service availability. Improving access requires earlier recognition, clearer referral routes, stronger specialist-generalist and nursing links, better support for family caregivers, and greater attention to affordability, continuity, and rural settings with limited resources. REGISTRATION: International Prospective Register of Systematic Reviews: CRD420261340783.

Health Services Accessibility

Macrolide-resistant Mycoplasma pneumoniae resurgence in Chinese children in 2023: a longitudinal, cross-sectional, genomic epidemiology study.

BACKGROUND: After a prolonged period of low detection rates, Mycoplasma pneumoniae resurged in China, during September to November, 2023, raising global concern. This study aims to gain a better understanding of the genetic mechanisms underlying the 2023 increase in cases and the evolutionary dynamics of the epidemic populations, which has been previously hampered due to limited genomic data of this pathogen. METHODS: We sequenced 685 M pneumoniae isolates, including 248 isolates from 11 Chinese provinces and municipalities in 2023 and 437 isolates from Beijing (2013-22). By analysing these isolates and 436 publicly global sequences, we reconstructed the pathogen's evolutionary history using time-calibrated phylogenies and effective population size inference. We investigated potential genomic variations contributing to the 2023 resurgence through genome-wide association study and conducted phylogeographic analysis of the 2023 isolates across China. FINDINGS: Two macrolide-resistant epidemic clusters (T1-2-EC1 and T2-2-EC2) were responsible for the 2023 resurgence in China. Both clusters, having acquired the 23S ribosomal RNA A2063G mutation conferring macrolide resistance, emerged in approximately 1997 and 2014, respectively, and subsequently outcompeted their predecessor populations. This coincided with China's large-scale adoption of azithromycin for paediatric community-acquired pneumonia around the early 2000s. Aside from macrolide resistance, T1-2-EC1 independently acquired 17 clade-specific mutations and T2-2-EC2 four clade-specific mutations, which could further explain their increased competitiveness. Whole-genome analysis revealed no resurgence-specific mutations in the 2023 isolates. Phylogeographic analysis showed rapid mixing of T1-2-EC1 isolates between different sampled regions within China. INTERPRETATION: Our study provides evidence that the 2023 resurgence in China is a continuation of the pre-COVID epidemic, rather than emergence of novel variants. The high prevalence of macrolide resistance and rapid intranational spread emphasise the urgent need for enhanced global surveillance of this pathogen. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China for Key Programs of China Grants, and Beijing High-Level Public Health Technical Talent Project.

Humans

Large-scale analysis of MYB genes in Cucurbitaceae identifies a novel gene regulating plant height.

The MYB transcription factor (TF) family, which is involved in plant growth and development, is large and diverse. Previous studies on MYB family in Cucurbitaceae were mostly based on a single genome or focused on the R2R3 subfamily. Here, we analyzed 91 genomes of 11 Cucurbitaceae species and identified a total of 15 858 MYB genes. According to phylogenetic relationships, these genes were divided into 27 subgroups. The identified MYB genes were further classified into 121 MYB orthologous gene groups (OGGs), including 25 core, 57 softcore, 19 shell and 20 line-specific/cloud groups. Whole-genome duplication was the most common mechanism of MYB genes expansion. In core group, the higher proportions of MYB genes were found to be in the coexpression network constructed by the RNA-seq data. Through the comprehensive analysis including phylogeny and gene expression profile of cucumber MYB genes, as well as genetic variations in 103 cucumber germplasms, we identified a MYB gene CsRAX5, which may be related to cucumber plant height. We used gene editing technology to knockout and overexpress CsRAX5. In the knockout lines, Csrax5, the height was significantly increased compared with wild type (WT), whereas after overexpression the height of CsRAX5-OE plants was significantly decreased compared with WT. These results indicated that MYB gene CsRAX5 negatively regulated cucumber plant height. The large-scale analysis of MYB genes in Cucurbitaceae in this study provides insights for further investigating the evolution and function of MYB genes in Cucurbitaceae crops.

Journal Article

The Relationship Among Range Adaptation, Social Anhedonia, and Social Functioning: A Combined Magnetic Resonance Spectroscopy and Resting-State fMRI Study.

BACKGROUND AND HYPOTHESIS: Social anhedonia is a core feature of schizotypy and correlates significantly with social functioning and range adaptation. Range adaptation refers to representing a stimulus value based on its relative position in the range of pre-experienced values. This study aimed to examine the resting-state neural correlates of range adaptation and its associations with social anhedonia and social functioning. STUDY DESIGN: In study 1, 60 participants completed resting-state magnetic resonance spectroscopy and fMRI scans. Range adaptation was assessed by a valid effort-based decision-making paradigm. Self-reported questionnaires was used to measure social anhedonia and social functioning. Study 2 utilized 26 pairs of participants with high (HSoA) and low levels of social anhedonia (LSoA) to examine the group difference in range adaptation's neural correlates and its relationship with social anhedonia and social functioning. An independent sample of 40 pairs of HSoA and LSoA was used to verify the findings. STUDY RESULTS: Study 1 showed that range adaptation correlated with excitation-inhibition balance (EIB) and ventral prefrontal cortex (vPFC) functional connectivity, which in turn correlating positively with social functioning. Range adaptation was specifically determined by the EIB via mediation of ventral-medial prefrontal cortex functional connectivities. Study 2 found HSoA and LSoA participants exhibiting comparable EIB and vPFC connectivities. However, EIB and vPFC connectivities were negatively correlated with social anhedonia and social functioning in HSoA participants. CONCLUSIONS: EIB and vPFC functional connectivity is putative neural correlates for range adaptation. Such neural correlates are associated with social anhedonia and social functioning.

Humans