Biomedical subjects

Li Chen

Publications and source records attributed to Li Chen.

9 recordsLinked to original sources

PubMed2026

Timing matters: Impact of covalent BTK inhibitor dose modifications on outcomes in chronic lymphocytic leukemia/small lymphocytic leukemia-A 7-year real-world study.

BACKGROUND: Covalent BTK inhibitors (cBTKis) are the cornerstone of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) therapy, yet real-world data on dose modifications and their differential impact on long-term outcomes remain incompletely defined. This study investigated the incidence, timing, and the effectiveness of drug switching in a real-world CLL cohort. METHODS: In this 7-year retrospective real-world study, 324 CLL/SLL patients treated at a specialized Shanghai outpatient clinic (April 2018-April 2025; median follow-up, 42 months) were analyzed. Dose modifications were classified as dose interruption (DI) or dose reduction (DR). Their prognostic impact on progression-free (PFS) and overall survival (OS) was assessed by Kaplan-Meier analysis and multivariate Cox regression. RESULTS: The 42-month PFS rate was 70.2%. Of 324 patients, 229 (70.7%) experienced dose reductions or interruptions; infections were the predominant cause (61.9%). The full-dose (FD) group (n = 90) demonstrated superior 4-year PFS (93% vs. 58%, p < .001) and OS (98% vs. 76%, p = .007). Early modifications (0-3 months) were independent predictors of inferior PFS (hazard ratio [HR], 3.93, p = .008) and OS (HR, 3.29, p = .014). Prolonged DI (>14 days) was associated with inferior PFS (HR, 2.64) and OS (HR, 2.15), whereas DR and short DI (≤14 days) had negligible impact. Early (0-3 months) prolonged DI was devastating (3-year PFS, 41.2%; HR, 3.84, p < .001). cBTKi switching (n = 82; 100% nonprogression-driven) shortened DI (median, 6 vs. 14 days) and was independently associated with superior OS (HR, 0.34, p = .018) and PFS (HR, 0.36, p = .022). CONCLUSIONS: Early prolonged DI is the dominant adverse prognostic factor in cBTKi-treated CLL/SLL. Proactive switching minimizes treatment gaps and improves survival, supporting a timing-aware, DI- versus DR-informed approach to dose management.

Humans↗

PubMed2026

Functional characterization of lncIMF_17214 in regulating intramuscular fat deposition of yellow-feathered broilers.

Intramuscular fat (IMF) content and lipid composition are key determinants of both the nutritional value and sensory attributes of poultry meat, yet the underlying regulatory mechanisms remain insufficiently elucidated. In this study, triglyceride (TG) content was employed as a quantitative phenotypic proxy to dissect the molecular basis of IMF deposition in yellow-feathered broilers. By integrating TG phenotypic data from 315 individuals with transcriptomic profiles and whole-genome resequencing datasets, a TG-associated long noncoding RNA (lncRNA), lncIMF_17214, was identified. Functional characterization revealed that lncIMF_17214 functions as a negative regulator of lipid deposition. Specifically, its knockdown led to significant increases in TG and total cholesterol concentrations, promoted lipid droplet accumulation, and decreased shear force in breast muscle, whereas its overexpression elicited the opposite effects. Mechanistically, lncIMF_17214 interacts with the RNA-binding protein CNBP, forming a regulatory complex that inhibits lipid accumulation. Furthermore, liver-directed overexpression increased the abundance of lncIMF_17214 in plasma exosomes, while liver-directed manipulation was associated with changes in hepatic and breast-muscle lipid deposition; direct exosome-mediated transfer to intramuscular adipocytes remains to be established. Transcriptomic profiling coupled with pathway enrichment analyses demonstrated that lncIMF_17214 predominantly influences steroid biosynthesis, unsaturated fatty acid metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. This suggests that it may be involved in the regulation of these pathways, although the underlying molecular mechanisms remain to be further elucidated. Collectively, these findings define a lncIMF_17214-centered regulatory axis linking intracellular and systemic lipid metabolism and provide a robust molecular framework for the targeted improvement of meat quality traits in yellow-feathered broilers.

Breast muscle↗

PubMed2026

Clinical and genetic analysis of a family with 16p11.2 microduplication syndrome and variable multisystem manifestations.

16p11.2 microduplication syndrome (OMIM #614671) is a pathogenic recurrent copy-number gain at the 16p11.2 locus and is associated with variable expressivity across neurodevelopmental, growth, and medical phenotypes. Gastrointestinal symptoms have been reported in carrier cohorts, but detailed documentation of gastrointestinal motility and neuromuscular findings remains limited. We performed clinical and genetic analyses in a multigenerational family in which the proband (III1) presented with limb muscle pain, exercise intolerance, and chronic gastrointestinal symptoms. Next-generation sequencing (NGS), low-pass whole-genome sequencing (lpWGS)-based CNV analysis, Sanger sequencing, and qPCR validation identified a 0.8 Mb microduplication at 16p11.2 (BP4-BP5), involving 44 genes including TBX6, inherited from the mother (II2). The proband's clinical manifestations included developmental delay, pointed chin, low body mass index, gastrointestinal dysfunction (chronic abdominal pain, diarrhea, esophageal motility disorder, and rectal prolapse), forward-leaning gait, mild scoliosis, and limb muscle atrophy with inflammatory muscle involvement. Four family members (II2, III1, III2, and III4) carried the microduplication, but their available clinical features varied in severity and system involvement. The proband's twin brother (III2) had left ear deafness and epilepsy, individual II2 had blindness from cone-rod dystrophy, and III4 showed more pronounced scoliosis. This family provides a detailed clinical and genetic description of 16p11.2 microduplication carriers with prominent gastrointestinal motility and neuromuscular manifestations, thereby enriching the clinical characterization of this recurrent CNV and supporting substantial intrafamilial phenotypic heterogeneity.

16p11.2 microduplication syndrome↗

PubMed2026

Integrated analysis reveals the impact of obesity on triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous breast cancer subtype with limited therapeutic options. While the prevalence of overweight/obese (OW/OB) women continues to rise, the impact of obesity on molecular features of TNBC remains incompletely understood. We investigated clinicopathological and molecular data (including genomic, transcriptomic, proteomic and metabolomic profiling) using our original multi-omics database of TNBC (N = 465) for associations with patient body mass index (BMI). Multi-omics profiling revealed that OW/OB patients exhibited worse survival as well as elevated inflammation of tumor microenvironment, higher expression of immune checkpoints, and dysregulated lipid metabolism. Our in vivo experiments demonstrated that tumors in obese mice displayed faster growth rates, a higher proportion of PD-1+CD8+ T cells and enhanced responsiveness to anti-PD-1 treatment. In addition, we analyzed data from four independent clinical trials and discovered that OW/OB patients demonstrated higher pathological complete response rates and longer progression-free survival following anti-PD-1-based immunotherapy. In conclusion, our study systematically revealed that obesity is associated with coordinated immune-metabolic remodeling in TNBC, characterized by checkpoint enrichment and lipid dysregulation, which may help explain the enhanced anti-PD-1 responsiveness and should be taken into account in the field of precision medicine.

Immunity↗

PubMed2026

Trustworthy Agentic AI in Bioinformatics: From Workflow Automation to Traceable and Validated Biological Inference.

Agentic artificial intelligence is extending bioinformatics beyond conversational assistance by enabling systems to select tools, execute code, revise analytical plans, and interpret biological data. These capabilities may accelerate research, but they also redistribute decisions that determine whether biological conclusions are valid. We conducted a targeted, structured PubMed search in July 2026 and identified 11 peer-reviewed agentic bioinformatics systems for descriptive review based on predefined eligibility criteria for analytical decision-making, tool or code execution, iterative evaluation, or coordinated agent activity. The evidence base covered single-cell transcriptomics, microbial genomics, cancer genomics, and omics applications, together with methodological literature on reproducibility and biological validation. We examined how current systems report delegated authority, provenance, validation, evidence, abstention, and human oversight. Existing platforms implement safeguards such as sandboxed execution, restricted commands, interaction logs, evidence identifiers, automated checks, critic agents, quality scores, and expert assessment. However, published reports rarely provide a connected account linking the original biological question to samples, reference resources, analytical decisions, computational actions, statistical results, supporting evidence, validation outcomes, and final claims. We distinguish inherited bioinformatics errors, errors amplified through autonomous action, and emergent failures arising from memory, retrieval, tool interaction, or agent coordination. We further propose a multidimensional decision-rights profile, consequence-sensitive validation gates, and a claim-to-evidence provenance architecture organized through the Traceable History of Research Evidence, Agent Actions, and Decisions in Bioinformatics (THREAD-Bio) framework. Illustrative cases show that technically successful execution may still support misleading inference. Trustworthy agentic bioinformatics therefore requires claims to remain reconstructible, challengeable, validated, and proportionate to the evidence.

accountable autonomy↗

PubMed2026

BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans↗

PubMed2026

Age-stratified associations of glycemia, blood pressure, and cholesterol with mortality in diabetes: A prospective cohort study.

BACKGROUND: Optimization of HbA1c, blood pressure and cholesterol, referred to as the "ABCs", is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients with diabetes remains unclear. METHODS: In this prospective cohort study, 43,732 Chinese adults aged ≥ 40 years with diabetes were included from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Participants were stratified by age (< 55, 55-<65, 65-<75, ≥ 75 years). Cox proportional hazards regression and Fine-Gray competing risk models were employed to estimate the associations of HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with all-cause, cardiovascular, and non-cardiovascular mortality across age groups. Relative importance and population attributable fractions (PAFs) were computed for each metabolic factor. RESULTS: During a median follow-up of 10.1 years, 3,975 deaths were documented. Age significantly modified the associations of HbA1c, SBP, and LDL-C with all mortality outcomes (all P for interaction < 0.05). Among participants aged < 75 years, HbA1c showed graded positive associations with all-cause, cardiovascular, and non-cardiovascular mortality. The SBP thresholds associated with increased mortality risk were 140 mmHg in those aged < 65 years and 160 mmHg in those aged 65-<75 years. Among those aged ≥ 75 years, however, the patterns of these associations differed markedly. Elevated mortality risk was observed only at HbA1c ≥ 9%, with a hazard ratio (HR) of 1.51 (95% confidence interval [CI]: 1.19-1.91) for all-cause mortality and a subdistribution hazard ratio (SHR) of 1.70 (95% CI: 1.23-2.36) for cardiovascular mortality, while SBP showed no significant association with any mortality outcome in this age group. Moreover, LDL-C emerged as a significant risk factor for cardiovascular mortality. Compared with participants with LDL-C < 1.8 mmol/L, those with LDL-C of 1.8-<2.6 mmol/L exhibited a significantly higher risk (SHR: 1.86; 95% CI: 1.11-3.11). Additionally, LDL-C had the largest PAF for cardiovascular mortality (9.6%) within this age group. CONCLUSIONS: The impacts of ABC factors on mortality risk vary substantially by age among adults with diabetes. In patients aged ≥ 75 years, less stringent glycemic and blood pressure targets may be appropriate, whereas lipid management remains critically important for reducing cardiovascular mortality.

Humans↗

PubMed2026

A group of TCP transcription factors is a missing link in strigolactone signaling.

Strigolactones (SLs) are plant-specialized butenolide signaling molecules, recognized as endogenous plant hormones, that control plant development and environmental adaptation. In Arabidopsis (Arabidopsis thaliana), the repressor D53-like SMXLs regulate the expression of a vast number of genes in an EAR-motif-dependent manner to mediate SL signaling. However, it remains unclear how the SMXLs are recruited to specific genes and implement unique functions in vivo. Based on chromatin co-distribution analysis, we constructed a chromatin co-localization map of SMXL6 with 108 transcription factors. Among the candidate transcription factors, the Class II TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) family member TCP4 shows the highest frequency of chromatin co-localization with SMXL6. SMXL6 and TCP4 co‑localize at the promoter regions of 18 SL-induced SMXL6 target genes (SISGs), including BRC1. We confirmed that TCP4 interacts with SMXL6 and can bind directly to these co‑localized sites. The loss of CIN-TCPs function reduces the hormone responsiveness of the SL-induced genes. Introducing the tcp3/4/10 into SL‑deficient mutants restored the BRC1 expression to a level exceeding that of the wild type. However, the branching phenotype of the SL‑deficient mutant was only partially rescued, suggesting a limited role for BRC1 in SL‑mediated branching control and implicating the involvement of additional factors. An unexpected finding was that tcp3/4/10 rescued the dwarf phenotype of the SL‑deficient mutants, providing an opportunity to elucidate the mechanisms underlying SL‑regulated plant height. These findings demonstrate that TCP4 mediates SMXL6 chromatin recruitment during SL signaling, and provide a new understanding of how SMXL6 participates in SL signaling-mediated gene expression and plant development.

Lactones↗

PubMed2025

Deubiquitinase-dependent transcriptional silencing controls inflammation.

Transcriptional control is crucial for the regulation of inflammation. While it is well-established that inducible transcriptional repressors are synthesized de novo through signal-dependent transcriptional upregulation, it remains unclear whether post-translational modification mechanisms, such as deubiquitination, also contribute to this process. We previously identified developmentally silenced sine oculis (SIX) transcription factors that are reactivated to control inflammatory gene transcription in differentiated immune cells under chronic microbial infections. However, the molecular mechanisms by which this transcriptional silencing process is regulated remain unclear. Here, we report that USP2, a deubiquitinase localized in the nucleus and induced by inflammatory signals, stabilizes SIX proteins through deubiquitination under inflammatory conditions. Consequently, the USP2-SIX complex acts in concert to control NF-κB-mediated inflammatory gene transcription by directly targeting gene promoters. Supporting this mechanism, Usp2-/- mice exhibit higher mortality during H1N1 infections, which phenocopies Six1-/- mice, attributed to elevated levels of life-threatening inflammatory mediators and exacerbated pathology. This study establishes a deubiquitinase-dependent transcriptional control of the inflammatory response to prevent immunopathology, offering new therapeutic avenues for combating infectious diseases.

Animals↗