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Biomedical subjects

Li Yang

Publications and source records attributed to Li Yang.

14 recordsLinked to original sources

PRDX1 facilitates USP7-dependent stabilization of SCD1 and promotes bladder cancer progression.

Bladder cancer is characterized by redox adaptation and metabolic plasticity, but the mechanisms linking these processes remain incompletely understood. Integrating bulk, single-cell, and spatial transcriptomic analyses, we identified PRDX1 as a malignant epithelial cell-associated factor linked to adverse outcome. Genetic gain- and loss-of-function studies showed that PRDX1 promoted proliferation, motility, and xenograft growth while limiting reactive oxygen species accumulation and mitochondrial apoptosis. Proteomic and biochemical analyses identified an association between PRDX1 and SCD1. PRDX1 prolonged the SCD1 protein half-life without detectably altering SCD1 transcript abundance and increased USP7-SCD1 co-precipitation. USP7 removed K48-linked polyubiquitin chains from SCD1 and prevented its proteasomal degradation, whereas catalytically inactive USP7 failed to deubiquitinate SCD1. Deletion of PRDX1 residues 157-199 weakened its association with SCD1 and reduced USP7-SCD1 co-precipitation. Depletion of SCD1 or USP7 suppressed PRDX1-dependent growth in vitro and in xenografts. These findings support a model in which PRDX1 facilitates USP7-dependent stabilization of SCD1 and promotes bladder cancer progression.

Bladder cancer

Minimal Transport Units Govern Oxygen-Defect Stabilization and Transport for Lightweight Solid Electrolytes.

Solid electrolytes are central to electrochemical energy technologies, including fuel cells, sensors, catalysis, membrane separation, and electrolyser. However, most established oxide-ion solid electrolytes are built around heavy B-site cations embedded in rigid and highly connected coordination frameworks, leading to widespread high-weight and sluggish ionic transport that is strongly coupled to large-amplitude lattice relaxations. This intrinsic challenge hinders further performance optimization and constrains the rational design of lightweight electrolytes. Herein, we propose a minimal transport unit-based design paradigm that combines simplified structural motifs with light-element chemistry, enabled by the exceptional flexibility of B-O polyhedra in coordination, rotation, deformation, and connectivity. As a proof of concept, Sc1- xZnxBO3- x /2, constructed from isolated BO3 units, exhibits high oxide ion conductivity (σ(1000°C) ∼ 1.5 × 10-2 S/cm), alongside excellent thermo-mechanical stability. Oxygen vacancies are stabilized through the formation of B2O5 units rather than isolated BO2 species. Long-range oxide-ion migration is mediated by dynamic oxygen exchange between minimal BO3 and B2O5 units via continuous breaking and reforming of B2O5 units, with transient BO2 configurations as intermediates. This study demonstrates minimal transport units as a governing principle for defect stabilization and ionic conduction in lightweight solid electrolytes, offering a general design framework for portable and scalable high-temperature energy technologies.

NMR spectroscopy and variable‐temperature P

Complete genome characterization, phylogenetic analysis, and capsid P2 variation of a goose astrovirus genotype 2 isolate from Guizhou, China.

Goose astrovirus genotype 2 (GAstV-2) is associated with gout and renal disease in goslings, but its occurrence in Guizhou Province remains poorly documented. We isolated a GAstV-2 strain, designated GZJP2024, from goslings with visceral gout on a farm in Jinping County, Guizhou Province, China. PCR detected GAstV-2 but not goose parvovirus, goose reovirus, Tembusu virus, fowl adenovirus, or goose astrovirus genotype 1. Serial passage in goose embryos produced mortality and hemorrhagic lesions during the third passage. Whole-genome sequencing yielded a 7,251-nt genome containing three overlapping open reading frames (ORF1a, ORF1b, and ORF2). Sequence identity and phylogenetic analyses assigned GZJP2024 to the GAstV-2 lineage. ORF1b was the most conserved coding region, whereas ORF2 was more variable. Comparison with consensus sequences from representative GAstV-2 strains identified five amino acid substitutions in ORF1a and ten in ORF2. Four ORF2 substitutions (E456D, L540Q, S608T, and A614T) occurred in the capsid P2 domain and overlapped or neighbored predicted B-cell epitope-rich regions. Template-based mapping placed E456D, S608T, and A614T on exposed regions of a spike-like capsid structure. These findings document a GAstV-2 isolate from a gout-affected goose farm in Guizhou and provide sequence data for future regional surveillance.

Capsid P2

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count <&#x2009;50 &#xd7;&#x2009;109/L) received rhTPO (n =&#x2009;80) or placebo (n =&#x2009;40) once daily for up to 5 or 7&#x2009;days. The primary endpoint was the proportion of patients with sustained platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L from 24 h before invasive procedure to 7&#x2009;days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p&#x2009;<&#x2009;0.0001). Preoperatively, platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p&#x2009;<&#x2009;0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p&#x2009;<&#x2009;0.0001). The median duration of platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0&#x2009;days, p =&#x2009;0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans

Advancing cancer detection and treatment using longitudinal routine clinical data.

Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.

Humans

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n&#xa0;=&#xa0;65) or routine nursing only (n&#xa0;=&#xa0;65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6&#xa0;months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6&#xa0;months ranged from small for resilience (D&#xa0;=&#xa0;0.28) and avoidance coping (D&#xa0;=&#xa0;0.26) to moderate for confrontation coping (D&#xa0;=&#xa0;0.60) and resignation coping reduction (D&#xa0;=&#xa0;-0.51), and large for attributional style (D&#xa0;=&#xa0;0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans

PRDX1 as a novel urinary biomarker for bladder cancer: Development of an integrated fiber optic sensing platform.

In this study, integrated proteomic and transcriptomic analyses identified peroxiredoxin 1 (PRDX1) as a novel urinary biomarker for bladder cancer (BC). PRDX1 was significantly upregulated in BC tissues and was associated with poorer overall survival. In vitro experiments further demonstrated that PRDX1 promotes malignant phenotypes of BC cells, including proliferation, migration, and invasion. Silencing PRDX1 in BC cells significantly reduced the invasiveness and proliferation ability.To address the clinical need for rapid and non-invasive detection, we developed an innovative optical fiber biosensor based on surface plasmon resonance (SPR) technology for the quantitative detection of urinary PRDX1. The biosensor exhibited excellent analytical performance, including high sensitivity (limit of detection: 0.06&#x202f;ng/mL), a wide linear range (0-25&#x202f;ng/mL), rapid response (&#x223c;14&#x202f;s), as well as good stability and selectivity. In clinical validation involving 97 BC patients and 30 healthy controls, the biosensor demonstrated outstanding diagnostic performance, with an area under the receiver operating characteristic curve (AUC) of 0.91 and an overall diagnostic accuracy of 86.6%, outperforming conventional enzyme-linked immunosorbent assay (ELISA). Collectively, this study not only identifies PRDX1 as a promising biomarker for non-invasive diagnosis and prognostic evaluation of BC, but also establishes an efficient SPR-based optical fiber sensing platform, providing new insights into both clinical detection and the functional role of PRDX1 in BC progression.

Humans

Bacteria and phage consortia modulate cecal SCFA production and host metabolism to enhance feed efficiency in ducks.

BACKGROUND: The gut microbiota influences poultry health, nutrition, feed efficiency (FE), and overall productivity. However, the relationship between gut microbes, including bacteria and phages, and FE in ducks remains underexplored. To address this, we integrated cecal 16S amplicon, metagenome, microbiota-derived short-chain fatty acids (SCFAs) profiling, liver transcriptome, and serum metabolome data to illustrate the contribution of the gut microbiome (bacteria and viruses) to duck FE. RESULTS: We reconstructed viral genomes and prokaryotic metagenome-assembled genomes (MAGs) and annotated their genes using comprehensive databases. Prokaryotic hosts of viruses were also predicted to understand virus-host dynamics within the gut ecosystem. Our results revealed that high-FE ducks have higher concentration of propionate and butyrate in cecum compared with low-FE ducks. The metagenome sequencing revealed distinct cecal microbiota profiles between two groups, with increased relative abundance of representative SCFA producers, especially Paraprevotella sp905215575 and Bacteroides sp944322345, and enhanced SCFA-biosynthesis pathways in high-FE ducks. Virome genome assembly identified two phages encoding auxiliary metabolic genes (AMGs) involved in pyruvate metabolism, enhancing nutrient availability for host bacteria to produce SCFAs (e.g., temperate phage-encoded pyruvate phosphate dikinase) or exploiting host central metabolic pathways for viral replication (e.g., lytic phage-encoded formate C-acetyltransferase). Furthermore, these representative SCFA-producing bacteria and phage consortia were associated with serum metabolites (including L-histidine and 4-hydroxydecanedioylcarnitine) linked to duck FE. CONCLUSION: Collectively, these findings provide novel insights into the gut microbial factors regulating FE in ducks, offering potential strategies to optimize poultry nutrition and productivity. Video Abstract.

Animals

Biallelic FOXRED1 mutations cause infantile mitochondrial encephalopathy with complex I disassembly and basal ganglia degeneration.

Developmental and epileptic encephalopathy (DEE) is a severe neurological disorder. Biallelic mutations in the nuclear-encoded mitochondrial chaperone gene FOXRED1, a specific assembly factor for complex I, cause mitochondrial dysfunction; however, their role in DEE pathogenesis remains unexplored. Clinical data and peripheral blood mononuclear cells (PBMCs) were obtained from two patients with compound heterozygous FOXRED1 mutations (c.850T>C (p.C284R)/c.1054C>T (p.R352W) and c.1054C>T (p.R352W)/c.3dup (p.I2Dfs*35) and age-matched controls. Mitochondrial phenotyping, included complex I activity, mitochondrial respiration stress test, membrane potential, intracellular ROS, and NAD+/NADH ratio, were performed. Both patients exhibited early-onset refractory seizures, basal ganglia lesions, hyperlacticemia, and developmental regression. FOXRED1 mutations resulted in 50% reduction in complex I activity, dissasembly of complex I, mitochondrial depolarization, oxidative stress, and NAD+/NADH imbalance. Niacin restored the NAD+/NADH ratio in vitro, while clinical supplementation reduced blood lactate levels, suggesting it may be a potential therapeutic option.

Humans

Health-associated key gut microbiota drives the variation in community metabolic interactions in non-human primates.

Gut microbiota often undergo metabolic cross-feeding and resource competition. However, our understanding of global variations in these interactions and their implications for host health remain elusive. By analyzing a microbial genome catalog from 841 fecal metagenomes across 53 primate species worldwide, we identified key microbiota assigned to two taxa, i.e., Bacillota_A and Pseudomonadota, which well predicted the trade-off of community-level interaction types between metabolic competition and cooperation. Specifically, Bacillota_A species were inherently competitive and amino acid auxotrophic and typically found in anaerobic habitats. In contrast, members of Pseudomonadota were inherently cooperative, siderophore producers, and more abundant in aerobic conditions. Random forest models successfully distinguished unhealthy gut samples from healthy samples through the key competitive and cooperative microbiota, suggesting potential links between community metabolic interactions and host health. Together, this study enhances our mechanistic understanding of microbial interaction dynamism within complex gut ecosystems, offering new targets for understanding host health.

Animals

Proteomic snapshot of pattern triggered immunity in the Arabidopsis leaf apoplast.

The apoplast is a critical interface in plant-pathogen interactions, particularly in the context of pattern-triggered immunity (PTI), which is initiated by recognition of microbe-associated molecular patterns. Our study characterizes the proteomic profile of the Arabidopsis apoplast during PTI induced by flg22, a 22-amino-acid bacterial flagellin epitope, to elucidate the output of PTI. Apoplastic washing fluid was extracted with minimal cytoplasmic contamination for liquid chromatography-tandem mass spectrometry analysis. By comparing our data to publicly available transcriptome profiles of flg22 treatment from 1 to 18&#x2009;h, we observed that several highly abundant proteins exhibit relatively unchanged gene expression across all time points. We also observed topological bias in peptide recovery of 19 enriched receptor-like kinases with peptides predominantly recovered from their ectodomains. Notably, tetraspanin 8, an exosome marker, was enriched in PTI samples. We additionally confirmed increased concentrations of exosomes during PTI. This study enhances our understanding of the proteomic changes in the apoplast during plant immune responses and lays the groundwork for future investigations into the molecular mechanisms of plant defense under recognition of pathogen molecular patterns.

Arabidopsis

Indel mutation in transcription factor PabHLH2 regulates amygdalin accumulation and kernel bitterness in apricot.

Amygdalin, the phytochemical responsible for the characteristic bitterness of apricot (Prunus armeniaca L.) kernels, also exhibits significant bioactive properties and therapeutic potential. Genetic regulation of amygdalin content is therefore a key objective in apricot breeding programs aimed at quality improvement. In this study, we conducted quantitative trait loci (QTL) mapping to uncover the genetic basis of sweet-bitter differentiation in apricot kernels. We identified a 15-bp insertion/deletion (indel) polymorphism strongly related to kernel bitterness, with marker validation achieving 100% concordance across 601 apricot germplasm accessions. Notably, this polymorphic site is located within the helix-loop-helix (HLH) domain of the basic HLH (bHLH) transcription factor PabHLH2. Protein interaction analyses revealed that the 15-bp deletion variant impaired dimerization capacity, reducing transcriptional activation of downstream targets. Using yeast one-hybrid screening and dual-luciferase reporter assays, we identified PaCYP71AN24 and PaCYP79D16 as direct transcriptional targets of PabHLH2. Functional characterization further indicated that the PabHLH2a variant (harboring the 15-bp insertion) significantly enhanced the promoter activity of these cytochrome P450 genes compared with the deletion variant. Transient overexpression and silencing experiments in apricot kernels further confirmed that the 15-bp insertion positively regulates both PaCYP71AN24/PaCYP79D16 expression and prunasin accumulation, the immediate biosynthetic precursor of amygdalin. Overall, these findings provide mechanistic insights into the allelic variation underlying kernel bitterness and delineate the molecular cascade of amygdalin biosynthesis. The identified molecular markers and functional characterization establish a basis for marker-assisted breeding of low-amygdalin apricot cultivars, supporting the dual-purpose utilization of kernels in food and pharmaceutical industries.

Amygdalin

Genetic analysis of partial duplication of the long arm of chromosome 16.

BACKGROUND: Pure partial trisomy 16q12.1q22.1 is a rare chromosome copy number variant (CNV). The primary clinical phenotypes associated with this syndrome include abnormal facial morphology, global developmental delay (GDD), short stature, and reported predisposing factors for atypical behavior, autism, the development of learning disabilities, and neuropsychiatric disorders. The dosage-sensitive genes associated with partial trisomy are not disclosed preventing to establish a genotype-phenotype correlation. METHODS: We report a case of a Chinese patient diagnosed with GDD and an abnormal facial shape, who was found to have partial trisomy 16 through karyotyping and high-throughput sequencing analysis. Karyotype and CNV tracing analyses were also conducted on the biological parents of the patient to assess for any chromosomal structural abnormalities. Additionally, we included 29 patients with pure partial trisomy 16q, reported in the DECIPHER database and the literature. We and performed a genotype-phenotype correlation analysis. RESULTS: The proband, a 2-year-old female, was found to have a de novo 21.96&#xa0;Mb duplication located between 16q12.1q22.1, with no other deletions observed on other chromosomes, indicating a pure partial trisomy of 16q. Through genotype and phenotype analysis of 29 individuals, we found that patients with the duplicated region located at the distal region of 16q may exhibit more severe symptoms than those with duplication at the proximal region; however, no relationship was identified between phenotype and the size of the duplicated segment. CONCLUSION: We report, for the first time, a patient with partial trisomy 16q validated by multiple genetic tests, including CNV-seq, whole exome sequencing (WES), and karyotyping. It is speculated that partial trisomy of 16q may be associated with continuous gene duplication. However, functional studies are necessary to identify the causative gene or critical region linked to duplication syndrome of chromosome 16q.

Child, Preschool

Single cell RNA sequencing provides novel cellular transcriptional profiles and underlying pathogenesis of presbycusis.

Age-related hearing loss (ARHL) or presbycusis is associated with irreversible progressive damage in the inner ear, where the sound is transduced into electrical signal; but the detailed mechanism remains unclear. Here, we sought to determine the potential molecular mechanism involved in the pathogeneses of ARHL with bioinformatics methods. A single-cell transcriptome sequencing study was performed on the cochlear samples from young and aged mice. Detection of identified cell type marker allowed us to screen 18 transcriptional clusters, including myeloid cells, epithelial cells, B cells, endothelial cells, fibroblasts, T cells, inner pillar cells, neurons, inner phalangeal cells, and red blood cells. Cell-cell communications were analyzed between young and aged cochlear tissue samples by using the latest integration algorithms Cellchat. A total of 56 differentially expressed genes were screened between the two groups. Functional enrichment analysis showed these genes were mainly involved in immune, oxidative stress, apoptosis, and metabolic processes. The expression levels of crucial genes in cochlear tissues were further verified by immunohistochemistry. Overall, this study provides new theoretical support for the development of clinical therapeutic drugs.

Animals