Biomedical subjects

Zhifeng Wang

Publications and source records attributed to Zhifeng Wang.

3 recordsLinked to original sources

PubMed2026

A Case Report of a Pedigree with Distal Hereditary Motor Neuropathy Caused by a Homozygous c.1124G>A Variant an the /*9Vaccinia-Related Kinase 1 Gene.

This study aimed to analyze the clinical phenotypes, neurophysiological characteristics, and pathogenicity of gene variants in a pedigree with distal hereditary motor neuropathy (dHMN) caused by VRK1 variants, and to provide evidence to support clinical diagnosis and genetic counseling for this disease. We report a Chinese consanguineous family with dHMN caused by a homozygous c.1124G>A variant in the VRK1 gene. Clinical and electrophysiological data of the proband were collected. Whole-exome sequencing (WES) and validation by Sanger sequencing were performed to identify the variant site, and pathogenicity interpretation was conducted in accordance with American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. The proband was a 24-year-old male who presented with 2 years of progressive weakness and atrophy of the distal lower limbs, accompanied by slender upper limbs and no sensory disturbance. Electrophysiological examination showed decreased compound muscle action potential (CMAP) amplitude in motor nerves of both upper and lower limbs, indicating peripheral neurogenic damage, while sensory nerve conduction was normal. Genetic testing detected a homozygous c.1124G>A (p.Trp375Ter) variant in the VRK1 gene. His parents and elder sisters were heterozygous carriers, and the pedigree conformed to autosomal recessive inheritance. According to ACMG guidelines, this variant was classified as pathogenic (evidence: PVS1, PM2, PP1). The homozygous VRK1 c.1124G>A variant causes adult-onset dHMN, rather than pontocerebellar hypoplasia type 1A (PCH1A) as annotated in some genetic databases. This pedigree presents distinctive phenotypes, including slender upper limbs and diffusely decreased CMAP amplitudes in both upper and lower limbs, thereby expanding the clinical and genetic spectrum of VRK1-related dHMN in the Chinese population.

Humans↗

PubMed2025

MetaflowX: a scalable and resource-efficient workflow for multi-strategy metagenomic analysis.

Microbiomes play crucial roles in diverse ecosystems, spanning environmental, agricultural, and human health domains. However, in-depth metagenomic data analysis presents significant technical and resource challenges, particularly at scale. Existing computational pipelines are typically limited to either reference-based or reference-free approaches and exhibit inefficiencies in process large datasets. Here, we introduce MetaflowX (https://github.com/01life/MetaflowX), an open-resource workflow integrating both analytical paradigms for enhanced metagenomic investigations. This modular framework encompasses short-read quality control, rapid microbial profiling, hybrid contig assembly and binning, high-quality metagenome-assembled genome (MAG) identification, as well as bin refinement and reassembly. Benchmarking tests showed that MetaflowX completed full metagenomic analyses up to 14-fold faster and with 38% less disk usage than existing workflows. It also recovered the highest number of high-quality and taxonomically diverse MAGs. A dedicated reassembly module further improved MAG quality, increasing completeness by 5.6% and reducing contamination by 53% on average. Functional annotation modules enable detection of key features, including virulence and antibiotic resistance genes. Designed for extensibility, MetaflowX provides an efficient solution addressing current and emerging demands in large-scale metagenomic research.

Metagenomics↗

PubMed2024

PARP1 UFMylation ensures the stability of stalled replication forks.

The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells. An in vitro study indicated that PARP1 is UFMylated at K548, which enhances its catalytic activity. Correspondingly, a PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromised CHK1 activation, the restart of stalled replication forks following replication blockage, and chromosome stability. Defective PARP1 UFMylation also resulted in excessive nascent DNA degradation at stalled replication forks. Finally, we observed that PARP1 UFMylation-deficient knock-in mice exhibited increased sensitivity to replication stress caused by anticancer treatments. Thus, we demonstrate that PARP1 UFMylation promotes CHK1 activation and replication fork stability during replication stress, thus safeguarding genome integrity.

DNA Replication↗