Biology subjects

hu, y.

Publications and source records attributed to hu, y..

6 recordsLinked to original sources

bioRxiv2026

Socio-demographic gradients in traumatic brain injury disability, severity and nutrition: a two-level analysis of the Global Burden of Disease Study 2023 and NHANES 2011-2014

Traumatic brain injury (TBI) is among the most consequential non-fatal outcomes of trauma, yet how its burden, severity and nutritional context are patterned by socio-demographic development remains incompletely characterised. We addressed this question at two levels. Using the Global Burden of Disease (GBD) Study 2023, we quantified the socio-demographic gradients of TBI disability across the five socio-demographic index (SDI) quintiles and characterised the severity composition of the TBI disability burden, its 1990-2023 trend and its cause-specific structure. Using pooled NHANES 2011-2014, we then examined, at the individual level, how reported TBI history among US adults aged 40 years and older varied by income, education, health insurance and food security, and whether dietary differences between adults with and without a TBI history persisted after socio-economic adjustment. The age-standardised TBI disability rate was almost twice as high in the high SDI quintile as in the low SDI quintile (113.68 versus 57.55 per 100,000 in 2023), a gap essentially unchanged since 1990. Moderate or severe injuries accounted for 72.5% of the TBI disability burden in the high SDI quintile versus 84.0-84.6% in the other four quintiles, rising in every quintile between 1990 and 2023. Among US adults, reported TBI history rose with educational attainment (11.9% below high school versus 17.3% above) and was most common in very food-insecure households (23.4%; adjusted odds ratio 1.71, 95% confidence interval 1.39-2.09); income showed no unadjusted gradient but a negative association after mutual adjustment. Unadjusted dietary differences between adults with and without a TBI history largely attenuated after socio-economic adjustment, with only fibre density remaining marginally lower (-0.35 g/1,000 kcal, 95% confidence interval -0.64 to -0.06). The moderate or severe share of the disability burden is a tractable, mortality-free monitoring indicator for injury prevention, and nutritional risk among food-insecure TBI survivors warrants clinical attention.

neuroscience↗

bioRxiv2026

Cerebellar Normative Modeling Identifies Neuroanatomical Biotypes Predicting dTMS Response in Spinocerebellar Ataxia Type 3

BackgroundSpinocerebellar ataxia type 3 (SCA3) presents with significant clinical heterogeneity. Traditional case-control neuroimaging, based on group means, obscures inter-individual anatomical variability, hindering the identification of stratification biomarkers for interventions like Transcranial Magnetic Stimulation (TMS). MethodsTo quantify individual neuroanatomical deviations, we constructed a cerebellar normative model using a multi-center dataset of 2,071 healthy controls with 2,549 MRI scans. Gray matter volume deviations (Z-scores) were mapped across 27 cerebellar lobules in 114 genetically confirmed SCA3 patients, and unsupervised clustering was applied to identify neuroanatomical biotypes. Clinical relevance was assessed by associating biotypes with ataxia severity and deep TMS (dTMS) outcomes in a longitudinal subset . ResultsWe identified two distinct biotypes: Biotype 1 exhibited relative structural preservation (positive deviations) predominantly in the posterior cerebellum (lobules VIIB, VIIIA), whereas Biotype 2 was characterized by extensive atrophy (negative deviations) centered on the anterior motor cerebellum (lobules I-VI). Clinically, Biotype 2 patients presented with significantly more severe baseline ataxia. However, regarding treatment response, an inverse relationship was observed: Biotype 2 patients demonstrated significantly greater symptomatic improvement following dTMS compared to Biotype 1. To further identify the optimal neuromodulatory strategy for each biotype, we compared the therapeutic efficacy of repetitive TMS (rTMS) and dTMS. While both biotypes showed clinical improvement following rTMS, Biotype 1 exhibited a superior therapeutic response to rTMS relative to dTMS. Furthermore, feature weight analysis identified atrophy of the right lobule VIIB as a critical predictor of clinical severity in Biotype 2. ConclusionThis study demonstrates that normative modeling can decode SCA3 heterogeneity. The identification of these biotypes reveals a dissociation between baseline structural integrity and neuromodulatory responsiveness, suggesting that patients with severe anterior cerebellar atrophy may, counterintuitively, derive greater therapeutic benefit from dTMS. Furthermore, by comparing the therapeutic efficacy of rTMS and dTMS, we further clarified biotype-specific treatment responses. These findings support the use of individualized neuroanatomical mapping for patient stratification in precision medicine.

neuroscience↗

bioRxiv2025

Single-Cell Sequencing Identifies the Crucial Role of Mitochondrial Fission-Fusion Balance in Cardiac Hypertrophy Progression

BackgroundThe heart undergoes growth in response to both pathological and physiological stimuli. Pathological hypertrophy often leads to cardiomyocyte loss and heart failure (HF), whereas physiological hypertrophy paradoxically protects the heart and enhances cardiomyogenesis. The molecular mechanisms that distinguish these two forms of hypertrophy remain unclear. MethodsIn this study, we utilized single-cell transcriptomics from transverse aortic constriction (TAC) models at 2, 5, 8, and 11 weeks (GSE120064), along with bulk RNA sequencing from mice subjected to 12 months of exercise-induced physiological hypertrophy and cardiomyogenesis (CRA007207), to investigate the molecular differences between pathological and physiological hypertrophy. ResultsOur results reveal the following. Mitochondrial-related pathways are the primary drivers of the pathological changes that occur following TAC. The mitochondrial fission and fusion pathways exhibited increased activity at 2 weeks but decreased activity at 5, 8, and 11 weeks post TAC. The expression pattern of exercise-induced physiological hypertrophy was similar to that of 2-week TAC-induced changes, indicating that the early stage of TAC represents an adaptive physiological response or physiological hypertrophy. Notably, during HF, the fission genes Fis1 and Dnm1l increase, in contrast to the expected decrease in fusion genes. These findings were experimentally validated, indicating that the mitochondrial fission genes Fis1 and Dnm1l are key promoters of HF. ConclusionsOur data indicate that the balance between mitochondrial fission and fusion plays a critical role in the transition from physiological to pathological hypertrophy. The fission-related genes Fis1 and Dnm1l have emerged as key drivers of pathological hypertrophy and heart failure. These findings suggest that targeting fission genes, particularly Fis1 and Dnm1l, may represent promising therapeutic strategies for managing heart failure.

bioinformatics↗

bioRxiv2022

DrugRepo: A novel approach to repurpose a huge collection of compounds based on chemical and genomic features

The drug development process consumes 9-12 years and approximately one billion US dollars in terms of costs. Due to high finances and time costs required by the traditional drug discovery paradigm, repurposing the old drugs to treat cancer and rare diseases is becoming popular. Computational approaches are mainly data-driven and involve a systematic analysis of different data types leading to the formulation of repurposing hypotheses. This study presents a novel scoring algorithm based on chemical and genomic data types to repurpose vast collection of compounds for 674 cancer types and other diseases. The data types used to design the scoring algorithm are chemical structures, drug-target interactions (DTI), pathways, and disease-gene associations. The repurpose scoring algorithm is strengthened by integrating the most comprehensive manually curated datasets for each data type. More than 100 of our repurposed compounds can be matched with ongoing studies at clinical trials (https://clinicaltrials.gov/). Our analysis is supported by a web tool available at: http://drugrepo.org/.

bioinformatics↗

bioRxiv2020

Combination of ipratropium bromide and salbutamol in children and adolescents with asthma: a meta-analysis

BackgroundA combination of ipratropium bromide (IB) and salbutamol is commonly used to treat asthma in children and adolescents; however, there has been a lack of consistency in its usage in clinical practice. ObjectiveTo evaluate the efficacy and safety of IB + salbutamol in the treatment of asthma in children and adolescents. MethodsThe MEDLINE, Embase, and Cochrane Library as well as other Chinese biomedical databases (including China Biological Medicine Database, Chinese National Knowledge Infrastructure, Chongqing VIP, and Wanfang Chinese language bibliographic database) were systematically searched from the date of database inception to 02/09/2019 for randomized controlled trials in children and adolescents ([≤]18 years) with asthma who received IB + salbutamol or salbutamol alone. The primary outcomes included hospital admission and adverse events. A random effects model with a 95% confidence interval (CI) was used. Subgroup analysis was performed according to age, severity of asthma, and co-interventions with other asthma controllers. This study was registered with PROSPERO. ResultsOf the 637 studies that were identified, 55 met the inclusion criteria and involved 6396 participants. IB + salbutamol significantly reduced the risk of hospital admission compared with salbutamol alone (risk ratio [RR] 0.79; 95% CI 0.66-0.95; p = 0.01; I2 = 40%). Subgroup analysis only showed significant difference in the risk of hospital admission in participants with severe asthma exacerbation (RR 0.71; 95% CI 0.60-0.85; p = 0.0001; I2 = 0%) and moderate-to-severe exacerbation (RR 0.69; 95% CI 0.50-0.96; p = 0.03; I2 = 3%). There were no significant differences in the risk of adverse events between IB + salbutamol group and salbutamol alone group (RR 1.77; 95% CI 0.63-4.98). ConclusionIB + salbutamol may be more effective than salbutamol alone for the treatment of asthma in children and adolescents, especially in those with severe and moderate to severe asthma exacerbation. Future prospective research on these subgroup population are needed.

pharmacology and toxicology↗

bioRxiv2019

scCAT-seq：single-cell identification and quantification of mRNA isoforms by cost-effective short-read sequencing of cap and tail

The differences in transcription start sites (TSS) and transcription end sites (TES) among gene isoforms can affect the stability, localization, and translation efficiency of mRNA. Isoforms also allow a single gene different functions across various tissues and cells However, methods for efficient genome-wide identification and quantification of RNA isoforms in single cells are still lacking. Here, we introduce single cell Cap And Tail sequencing (scCAT-seq). In conjunction with a novel machine learning algorithm developed for TSS/TES characterization, scCAT-seq can demarcate transcript boundaries of RNA transcripts, providing an unprecedented way to identify and quantify single-cell full-length RNA isoforms based on short-read sequencing. Compared with existing long-read sequencing methods, scCAT-seq has higher efficiency with lower cost. Using scCAT-seq, we identified hundreds of previously uncharacterized full-length transcripts and thousands of alternative transcripts for known genes, quantitatively revealed cell-type specific isoforms with alternative TSSs/TESs in dorsal root ganglion (DRG) neurons, mature oocytes and ageing oocytes, and generated the first atlas of the non-human primate cornea. The approach described here can be widely adapted to other short-read or long-read methods to improve accuracy and efficiency in assessing RNA isoform dynamics among single cells.

genomics↗