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Biomedical subjects

Chao Wu

Publications and source records attributed to Chao Wu.

5 recordsLinked to original sources

Unveiling phthalate esters biodegradation from microbial community to Pseudarthrobacter scleromae HL-1: Kinetics, genomic insights, pathways, toxicity assessment and environmental remediation.

Phthalate esters (PAEs) are ubiquitous synthetic plasticizer pollutants posing severe ecological and human health risks. This study compared microbial community structures and dibutyl phthalate (DBP) degradation kinetics of two consortia: 7-day enriched MC1 (50 mg/L DBP) and 6-cycle acclimated MC7 (50-1000 mg/L DBP), demonstrating directional DBP stress selection generated a low-diversity, highly specialized degradative community with a 25.4 mg/L/h maximum degradation rate (Vmax), 1.68-fold higher than MC1. Four dominant DBP-degrading strains were isolated from MC7; Pseudarthrobacter scleromae HL-1 showed the highest efficiency with 17.1 mg/L/h Vmax and complete 500 mg/L DBP removal within 72 h, broad substrate spectrum, and strong adaptability after optimization. Whole-genome sequencing and GC-MS/MS elucidated a dual-parallel DBP mineralization pathway, first reported in Pseudarthrobacter, integrating ester hydrolysis and side-chain β-oxidation. ECOSAR and Chlorella vulgaris bioassays confirmed progressive toxicity attenuation, with > 99% relative toxicity reduction after 72 h and no toxic intermediate accumulation. Natural lake water trials with trace background PAEs showed HL-1 successfully colonized aquatic environments, reshaped indigenous communities into synergistic degradative consortia, and achieved 99.2% DBP removal in 84 h. This work provides comprehensive insights into PAE biodegradation mechanisms from community to single strain and highlights HL-1 as a promising candidate for remediating PAE-polluted aquatic ecosystems.

Genomic analysis

A germline KDM3C polymorphism impairs DNA repair and sensitizes to chemoradiotherapy.

Chemoradiotherapy (CRT) is the standard-of-care therapy for many solid malignancies, yet predictive biomarkers of treatment response remain limited. We identified a germline single nucleotide polymorphism (SNP) in an intrinsically disordered region of the lysine demethylase KDM3C/JMJD1C (p.S464T) that is associated with CRT outcomes in locally advanced rectal cancers (LARC) and head and neck squamous cell carcinoma (LA-HNSCC). In silico modeling with AlphaFold predicted S464T substitution influenced interaction between phosphorylated KDM3C and RNF8 FHA domain. In cellular models, conversion of S464 to T464 increased sensitivity to DNA-damaging agents. S464T substitution impaired damage-induced MDC1-RAP80 signaling and downstream RAP80-BRCA1 colocalization. SNP carrying cells impaired DNA repair causing genotoxic stress that is associated with increased cGAS-cGAMP innate immune signaling and increased apoptosis. Population analyses with the SNP highlighted an increase incidence of UV-induced skin and other cancers, linking inherited variation in the chromatin regulatory gene KDM3C to genome instability, cancer risk, and therapeutic vulnerability.

Journal Article

Long-Term Effectiveness of Tenofovir Alafenamide Versus Entecavir in Treatment-Naive Chronic Hepatitis B: A Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus.

INTRODUCTION: Although both tenofovir alafenamide (TAF) and entecavir (ETV) are recommended first-line treatments for chronic hepatitis B, comparative data on their effectiveness remain limited. We aim to compare their virologic (VR), biochemical (BR), and complete (CR) response rates. METHODS: This retrospective study enrolled treatment-naive chronic hepatitis B patients who initiated either TAF or ETV in 2016 or after across 22 international centers and evaluated their treatment response after balancing their characteristics using inverse probability treatment weighting and through Fine-Gray competing-risks analysis of the balanced cohort. RESULTS: The study included 1,605 patients (784 TAF and 821 ETV patients with significant background differences) of whom 1,553 (96.8%) were from Asia. Inverse probability treatment-weighting analysis yielded a total weighted cohort of 1,660 (822 TAF and 838 ETV patients with balanced characteristics). The 5-year cumulative VRs were high in both groups with a slightly higher rate in TAF patients (98.0% vs 93.9%, P < 0.001), and similar findings were found in a subgroup analysis by median hepatitis B virus (HBV) DNA (5.5 log IU/mL). However, there was no significant difference in the 5-year BR rates overall (93.7 vs 92.8%, P = 0.484) or by alanine aminotransferase (ALT) cutoff of 2&#xd7; upper limit of normal. TAF patients had a slightly higher 5-year cumulative CR overall (94.9% vs 89.4%, P = 0.001) and in high HBV DNA (96.9% vs 87.9%, P < 0.001) or ALT &#x2265;2&#xd7; upper limit of normal patients (97.3% vs 90.6%, P < 0.001), but not in those with lower HBV DNA or ALT. DISCUSSION: BR rates were similar with ETV and TAF, while VR and CR were higher with TAF, although the difference was modest (<5% overall, 7%-9% in high HBV DNA or ALT groups). Antiviral selection between TAF vs ETV should be based mainly on cost, side effect profile, and patient preference.

Adult

Transcriptomic analysis reveals key molecular signatures across recovery phases of hemorrhagic fever with renal syndrome.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS), a life-threatening zoonosis caused by hantavirus, poses significant mortality risks and lacks specific treatments. This study aimed to delineate the transcriptomic alterations during the recovery phases of HFRS. METHODS: RNA sequencing was employed to analyze the transcriptomic alterations in peripheral blood mononuclear cells from HFRS patients across the oliguric phase (OP), diuretic phase (DP), and convalescent phase (CP). Twelve differentially expressed genes (DEGs) were validated using quantitative real-time PCR in larger sample sets. RESULTS: Our analysis revealed pronounced transcriptomic differences between DP and OP, with 38 DEGs showing consistent expression changes across all three phases. Notably, immune checkpoint genes like CD83 and NR4A1 demonstrated a monotonic increase, in contrast to a monotonic decrease observed in antiviral and immunomodulatory genes, including IFI27 and RNASE2. Furthermore, this research elucidates a sustained attenuation of immune responses across three phases, alongside an upregulation of pathways related to tissue repair and regeneration. CONCLUSION: Our research reveals the transcriptomic shifts during the recovery phases of HFRS, illuminating key genes and pathways that may serve as biomarkers for disease progression and recovery.

Hemorrhagic Fever with Renal Syndrome

Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption.

Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity. Megamonas rupellensis possessed genes for myo-inositol degradation, as demonstrated in&#xa0;vitro and in&#xa0;vivo, and the addition of myo-inositol effectively inhibited fatty acid absorption in intestinal organoids. Furthermore, mice colonized with M.&#xa0;rupellensis or E.&#xa0;coli heterologously expressing the myo-inositol-degrading iolG gene exhibited enhanced intestinal lipid absorption, thereby leading to obesity. Altogether, our findings uncover roles for M.&#xa0;rupellensis as a myo-inositol degrader that enhances lipid absorption and obesity, suggesting potential strategies for future obesity management.

Inositol