Biomedical subjects

Bo Xu

Publications and source records attributed to Bo Xu.

6 recordsLinked to original sources

PubMed2026

Directed evolution of Lactiplantibacillus plantarum for utilizing ethanol to produce postbiotics.

Alcohol is a recognized carcinogen worldwide. In this study, we aimed to utilize probiotics to metabolize ethanol and produce postbiotics. Initially, we identified a lactic acid bacteria community in kimchi with excellent probiotic activity. By employing our previously developed directed evolution techniques, a Lactiplantibacillus plantarum mutant with safe characteristics and an ethanol utilization capacity of 40 g/L and 0.15 g/L/OD was obtained. Genome sequencing and RT-qPCR analysis revealed the up-regulated expression of alcohol dehydrogenase and aldehyde dehydrogenase genes greatly contributed to ethanol utilization. Furthermore, the mutant strain demonstrated marked superiority in producing postbiotics, including antimicrobial peptides and beneficial organic acids such as lactic acid, phenyllactic acid, succinic acid, and indole-3-lactic acid. In the ethanol-fed fermentation process, the mutant strain achieved a lactic acid yield of 8.47 g/L and a carbon conversion rate of 21.8%. In vivo testing further validated its safety and ability to assist alcohol metabolism.

Adaptive laboratory evolution↗

PubMed2026

Auxin-induced ARF transcription factor degradation defines tissue boundaries.

How organs partition themselves into discrete domains with distinct functions is a fundamental question in biology. The gynoecium of flowering plants provides an excellent system to address this question. Here, we show that the boundary between the stigma and style at the gynoecium apex is established by the complementary distribution of the phytohormone auxin and the Auxin Response Factor (ARF), ETTIN (ETT). Mechanistically, auxin induces ETT protein destabilization via the ubiquitin-proteasome pathway. A short sequence motif within an intrinsically disordered region is required for this auxin-triggered degradation. Disruption of this motif leads to ectopic ETT accumulation at the gynoecium apex and consequently abolishes stigma-style boundary development. We further demonstrate that this previously unrecognized mode of auxin-induced ARF instability is evolutionarily conserved among ETT orthologs across angiosperms. In summary, this study reveals how graded auxin distribution affects ARF transcription factor activity, contributing to the establishment of the stigma-style boundary, ensuring correct gynoecium formation and reproductive success in flowering plants.

Indoleacetic Acids↗

PubMed2026

A Novel Homozygous Mutation in ARL2BP Causes Multiple Morphological Abnormalities of the Flagella and Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) and multiple morphological abnormalities of the sperm flagella (MMAF) frequently co-occur in male infertility. However, the genetic basis of this syndromic presentation remains unclear. Using whole-exome sequencing, we identified a novel homozygous ARL2BP splice-site mutation (c.294-2A>G) in a 23-year-old infertile male from a consanguineous family who presented with syndromic PCD and MMAF. This variant causes aberrant pre-mRNA splicing and triggers nonsense-mediated mRNA decay, resulting in the complete absence of ARL2BP protein expression. Transmission electron microscopy revealed extensive disorganization of flagellar axonemes with consistent central pair (CP) microtubule depletion and disorganization of peripheral doublets. Immunofluorescence confirmed a severe deficiency of the CP protein SPAG6 in the sperm flagella. Notably, the patient presented without retinal symptoms. Given that ARL2BP-related retinitis pigmentosa generally emerges during the third decade, long-term ophthalmological follow-up is essential to detect delayed-onset retinal degeneration. In conclusion, these findings confirm ARL2BP as a causative gene for both PCD and MMAF, expanding the genotypic and phenotypic spectrum of ciliopathies.

Humans↗

PubMed2026

Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations.

De novo mutations (DNMs) are an important source of congenital diseases. With delayed parenthood and assisted reproductive technology (ART) use increasing, it is essential to elucidate how these reproductive factors influence DNMs and whether resulting mutations influence offspring health. Here we performed whole-genome sequencing of 24,030 individuals from 7,851 parent-offspring families, identifying 390,924 de novo single-nucleotide variants (dnSNVs). Paternal and maternal aging exhibited distinct mutational patterns, with maternal DNM accumulation accelerating at advanced ages. Increased paternal dnSNVs partially accounted for the association between advanced parental age and shorter gestational duration. Moreover, ART showed age-independent, procedure-specific effects: intracytoplasmic sperm injection (ICSI) and ovarian stimulation were associated with increased paternal and maternal dnSNVs, respectively, and ICSI-associated paternal dnSNVs also partially accounted for the association between ICSI and shorter gestational duration. In vitro embryo manipulation was associated with increased early post-zygotic mosaic mutations, particularly C > A substitutions linked to delayed neurocognitive development at 1 year. Collectively, these findings advance understanding of the determinants and consequences of de novo mutagenesis.

Journal Article↗

PubMed2026

EZH2 Suppression Diversifies Prostate Cancer Lineage Variant Evolution and Lacks Efficacy in Inhibiting Disease Progression.

UNLABELLED: Advanced prostate cancer remains a leading cause of cancer-related death among men due to disease progression in nearly all patients on standard-of-care therapy targeting the androgen receptor. An important mechanism driving therapeutic resistance is lineage plasticity, which enables prostate cancer cells to reprogram into lineage variants no longer dependent on androgen receptor signaling. As inhibitors of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) are being evaluated clinically for the treatment of advanced prostate cancer, we investigated in this study how EZH2 affects prostate cancer lineage plasticity. Data from genetically engineered mice and human clinical samples demonstrated that genetic or pharmacologic suppression of EZH2 altered chromatin to expand active transcription factor programs. These changes in gene expression during prostate cancer progression increased the diversity of prostate cancer lineage variants that arose. EZH2 suppression did not inhibit disease progression nor therapeutic resistance in this context. These findings advance the current understanding of prostate cancer lineage plasticity and suggest that EZH2 inhibitors may be less effective in treating prostate cancer prone to lineage plasticity. SIGNIFICANCE: EZH2 suppression diversifies prostate cancer lineage plasticity, which has implications for EZH2-targeted therapies that are being evaluated for prostate cancer treatment. See related commentary by Thienger et al., p. 827.

Enhancer of Zeste Homolog 2 Protein↗

PubMed2025

Genomic analysis of xerophyte Salweenia species provides insights into the alpine dry-warm valleys divergence and survival history.

Salweenia species are evergreen shrubs capable of preventing desertification and maintaining the health of alpine dry-warm ecosystems in the Hengduan Mountains. However, both the narrowly distributed S. bouffordiana and its more widespread close relative S. wardii are endemic and endangered. Furthermore, their small population sizes render each of these species at risk of extinction. To infer how past climate changes have shaped the evolutionary history of these species, we developed a chromosome-level S. bouffordiana genome (788 Mb) and compared the two species' evolutionary histories, genetic loads and the genomic adaptions to local environmental conditions using whole-genome resequencing data. Our findings reveal a sharp population decline from the Pliocene to the Quaternary. However, populations of S. bouffordiana then started to recover before declining further, while S. wardii populations continued to decline until recently. Abundant homozygous-derived variants accumulated in the two species, particularly in S. bouffordiana, while the species with the most heterozygous variants was S. wardii. Accumulated extensive inbreeding effects but possessed few LOF mutations and few highly deleterious variants in the S. bouffordiana that have experienced the most severe demographic bottlenecks, most likely because of purging effects. This accelerating decline cascade will likely be detrimental to the consequences for the species' future viability and adaptive potential. Overall, this study improves our understanding of the evolutionary history of Salweenia shrubs tolerant to extreme environments and offers a genetic resource for future breeding and conservation efforts.

Genome, Plant↗