Reconstruction and Correction of the Rice Mitochondrial Reference Genome.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
Jie Wang
Publications and source records attributed to Jie Wang.
Unraveling the coastal marine plastisphere archaeome.
Plastic pollution has created an expanding anthropogenic microbial niche, the plastisphere, raising questions about microbial ecology and associated impacts. Archaea, the third domain of life with fundamental ecological and evolutionary significance, remain poorly understood in this habitat. Here, using paired plastic debris and bulk-water samples from coastal marine ecosystems, key archaeal habitats increasingly threatened by plastic pollution, we characterize the plastisphere archaeome through archaeal amplicon sequencing and metagenomics. We show that the archaeome is significantly reshaped in the plastisphere, exhibiting higher taxonomic diversity, greater community heterogeneity, and selective enrichment of Euryarchaeota and Crenarchaeota. Archaeal genes involved in methane, nitrogen, and sulfur cycling are enriched in the plastisphere. Taxonomic and functional divergence between the plastisphere and bulk water increases with anthropogenic chemical stress. These findings suggest that plastic pollution could alter marine archaeal diversity, biogeography, and biogeochemical potential, extending understanding of plastisphere impacts to the archaeal domain.
Archaea↗
Genomic Profiling, Risk Stratification, and Post-Transformation Treatment Outcomes in Patients with Transformed Small-Cell Lung Cancer: A Multicenter Analysis.
BACKGROUND: Transformed small-cell lung cancer (T-SCLC) is an increasingly recognized resistance mechanism in EGFR-mutant lung adenocarcinoma. This study aimed to identify early predictors of histologic transformation and evaluate post-transformation treatment outcomes. METHODS: We retrospectively collected 163 T-SCLC patients from five Chinese centers. Next-generation sequencing was performed on 60 EGFR-mutant patients, including 47 paired primary-transformed samples. Integrated genomic and clinical analyses were conducted to delineate molecular features and survival outcomes. RESULTS: Among 150 EGFR-mutant patients, the median time to SCLC transformation was 25.8 months and median post-transformation overall survival (OS) was 14.2 months. Clinical and survival data for the 13 EGFR wild-type patients are reported descriptively given the limited sample size. Among 108 treatment-evaluable patients, first-line EGFR-TKI plus chemotherapy, chemotherapy alone, and immune checkpoint inhibitors (ICIs) plus chemotherapy yielded median progression-free survival (PFS) of 6.2, 5.30, and 4.07 months (P = 0.041) and median OS of 21.2, 27.6, and 13.6 months (P = 0.193). In later-line therapy, taxane-based regimens achieved a median PFS of 6.93 months, outperforming camptothecin-based (1.13 months) and other regimens (1.90 months; P = 0.049). High evolutionary diversity was associated with shorter post-transformation OS (6.77 vs. 11.10 months), with restricted cubic spline analysis showing a nonsignificant trend toward a nonlinear association (P = 0.055).Age, RB1/NTRK1 mutation, and secondary T790M mutation were identified as independent risk factors and integrated into a predictive model with high accuracy. CONCLUSIONS: This study establishes a clinically applicable model for early prediction and risk stratification of SCLC transformation. Taxane-based regimens emerge as a promising later-line therapeutic option for T-SCLC.
Humans↗
Bioinformatic analysis reveals the potential association of ESRP1 with the splicing of cytoskeleton-associated genes in doxorubicin-resistant MCF7 breast cancer cells.
BACKGROUND: Breast cancer remains one of the most prevalent malignancies among women, with doxorubicin resistance posing a significant challenge that undermines treatment success and survival outcomes. Aberrant alternative splicing (AS), driven by dysregulation or mutations in splicing factors (SFs), is implicated in cancer initiation, progression, and drug resistance. This study aims to investigate the association of the epithelial cell-specific splicing factor ESRP1 with doxorubicin resistance in breast cancer, focusing on how ESRP1 deficiency correlates with AS changes that promote chemoresistance. METHODS: We analyzed RNA-sequencing (RNA-seq) data from doxorubicin-resistant (MCF7-DR) and parental (MCF7) breast cancer cell lines to identify enhanced alternative splicing events (ASEs) and changes in ESRP1 expression; we further leveraged The Cancer Genome Atlas (TCGA)-BRCA cohort to construct an SF-RASE correlation network for screening core SFs (including ESRP1). An integrative analysis combining crosslinking immunoprecipitation (CLIP-seq) data and The Cancer Genome Atlas (TCGA) database was performed to validate ESRP1 binding targets and assess the association between ESRP1-related splicing and cytoskeleton organization. RESULTS: We observed extensive AS changes and significantly downregulated ESRP1 expression in MCF7-DR cells. Integrative analysis identified 61 high-confidence ASEs that correlate with ESRP1 expression. Further bioinformatic integration suggests that ESRP1 expression is associated with the splicing patterns of SPTBN1, MAP2K7, FGFR3, and CYB561A3-four genes involved in cytoskeleton organization-though direct experimental verification to confirm a causal regulatory relationship between ESRP1 and the splicing of these genes is still pending. CONCLUSIONS: Our findings suggest that ESRP1 expression is closely associated with doxorubicin resistance in breast cancer cells, with concomitant alterations in key ASEs linked to cytoskeletal remodeling that correlate with ESRP1. Exploring the ESRP1-related splicing network may offer new strategies to overcome chemoresistance and improve patient outcomes. However, the small cell line sample size (n = 2 per group) constrains the robustness of ASE and SF-ASE correlation findings, and these results should be interpreted with caution and require further validation with larger sample cohorts.
Alternative splicing↗
The global potential of freshwater microbes for plastic degradation.
Plastic pollution is becoming increasingly severe on a global scale, and the potential for biodegradation as a treatment method that is environmentally friendly merits greater attention. A significant number of genes that associated the degradation of plastic (PDAGs) have been identified, however, the distribution of these genes among microorganisms in global inland waters remains to be elucidated. A global-scale meta-analysis was conducted, incorporating approximately 1000 metagenome datasets of inland waters across seven continents. A total of 13,109 metagenome-assembled genomes (MAGs) were obtained by means of metagenomics binning, and 22,621 PDAGs were identified from these. Among these recognized PDAGs, phenylacetaldehyde dehydrogenase (PAD) was the most dominant (n = 16,664), followed by catalase (n = 5931). The predominant hosts for PAD and catalase were identified as Gamma-proteobacteria and Bacteroidia, respectively. The largest number of both PAD and catalase was found in MAGs from North America, while the average gene number in single MAG was highest in MAGs from Oceania. In accordance with the prediction of traits, PDAG-carrying MAGs from Europe demonstrated the fastest growth rate and the lowest optimal growth rate. Furthermore, 25 styrene monooxygenase (StyA) enzymes were identified, which were found to cluster into two distinct groups hosted by Alpha-proteobacteria and Gamma-proteobacteria, respectively. Moreover, 11 MAGs were observed to possess the complete pathway of polystyrene degradation. These results explored the potential of inland water microorganisms as a biological resource for plastic degradation and provided valuable microbial reference information that can be used to develop biological treatment technologies for mitigating plastics.
Plastics↗
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↗
Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.
Cell division inevitably shortens telomeric DNA owing to the end-replication problem. Eukaryotic chromosomes possess specialized telomere structures to maintain genomic stability. In most proliferative cells, telomerase adds telomeric repeats during S-phase. In differentiated cells where telomerase is silenced, telomeres shorten progressively, thereby compromising genomic integrity. Consequently, cancer cells universally activate alternative telomere maintenance mechanisms during malignant transformation: ~80% reactivate telomerase, while a portion of the rest rely on BIR (break-induced replication)-mediated homologous recombination-based ALT (alternative lengthening of telomeres). Although these mechanisms are stable once established, the initial determinants influencing a cancer cell's choice remain poorly understood. This review discusses recent molecular insights into how telomeric chromatin properties profoundly impact this choice. After briefly introducing telomere chromatin characteristics and key players in its maintenance and dynamics, we discuss the mechanisms by which cancer cells acquire distinct telomere replication capabilities. In particular, we present an in-depth analysis linking telomere heterochromatin status to ALT. Furthermore, based on recent advances, we propose a coupled feedforward loop model explaining how the ALT state becomes "locked in" once initiated. Finally, we offer novel perspectives on rational, telomere-centric therapeutic interventions for ALT-positive cancers, focusing on strategies designed to disrupt such feedforward loops by manipulating telomeric chromatin structure.
Humans↗
A genome-wide CRISPRi screen identifies homologous recombination pathway as potential target for broad-spectrum antibiotic adjuvants.
INTRODUCTION: The widespread misuse and overuse of antibiotics have driven the emergence of multidrug-resistant and pan drug-resistant bacteria, constituting a formidable global health threat. Antibiotic adjuvants that potentiate the efficacy of existing antibiotics represent a particularly promising avenue to address this challenge. METHODS: We performed a genome-wide CRISPR interference (CRISPRi) screening to identify potential targets for broad-spectrum antibiotic adjuvants, which highlighted the homologous recombination pathway as a promising candidate. To functionally validate this pathway, we employed three strategies to suppress the expression and function of recA, a key component of homologous recombination, including a CRISPRi system delivered via transconjugation, a RecX-derived peptide (RecX-20) fused to a cell-penetrating motif, and a small-molecule inhibitor cisplatin validated by surface plasmon resonance. RESULTS: Disruption of the homologous recombination pathway not only significantly increased bacterial susceptibility to multiple classes of antibiotics, including quinolones, β-lactams, aminoglycosides, and nitrofurantoin, but also reduced horizontal gene transfer of antibiotic resistance. In addition, recA deficiency resulted in a cascade of physiological disruptions, including membrane damage, efflux pump dysfunction, oxidative stress imbalance and metabolic disruption. All three recA-targeting strategies enhanced the antibacterial activity, with cisplatin exhibiting the most pronounced potentiating effect both in vitro and in vivo. CONCLUSIONS: This study reveals that the homologous recombination pathway, particularly RecA, is a viable target for the development of broad-spectrum antibiotic adjuvant. Our findings provide mechanistic insights and practical strategies to restore the effectiveness of existing antibiotics and address the growing threat of antimicrobial resistance.
Anti-Bacterial Agents↗
Integrated 16 S rRNA and transcriptome analysis reveal molecular and microbial mechanisms of cold-tolerant germination in hulless barley.
BACKGROUND: Elucidating the mechanisms underlying cold-tolerant germination is crucial for enhancing crop resilience to low temperatures. Hulless barley (Hordeum vulgare var. coeleste L.), with remarkable natural cold adaptation, serves as an ideal model to study cold stress tolerance mechanisms in gramineous crops. In this study, cold-tolerant variety 37 and cold-sensitive variety 44 were screened and used to investigate the molecular mechanisms of cold-tolerant germination, via seed germination assays, combined with phytohormone determination, transcriptome sequencing and 16 S rRNA amplicon sequencing. RESULTS: Low temperature significantly inhibited hulless barley seed germination: the germination rate of cold-sensitive variety 44 decreased by 69%, while that of cold-tolerant variety 37 only decreased by 2%. Transcriptome analysis identified 2,647 and 2,392 differentially expressed genes (DEGs) in variety 37 and 44, respectively. Weighted gene co-expression network analysis (WGCNA) revealed a green module significantly positively correlated with gibberellic acid (GA) content, containing 10 core genes such as late embryogenesis abundant protein (LEA) and Homeobox genes. 16 S rRNA sequencing showed that the cold-tolerant variety 37 had enriched abundances of dominant endophytes including Sphingomonas and Pelomonas, with correlation coefficients of 0.70 and 0.87 with GA content, respectively. Additionally, exogenous GA treatment significantly increased germination rates under cold stress by 176.67% in cold-sensitive variety 44. CONCLUSIONS: This study confirms that the enhanced cold tolerance of hulless barley during seed germination originates from the synergistic interaction between beneficial endophytes (Sphingomonas, Pelomonas), GA, and core genes (e.g., LEA, Homeobox). Exogenous GA application can significantly restore the germination ability of cold-sensitive varieties. These findings provide a critical theoretical basis for improving cold tolerance in hulless barley germplasm.
Hordeum↗
Adaptive Evolution for Freshwater Adaptation in Coilia nasus by Directional Selection on Osmoregulation Genes.
The molecular mechanisms underlying the adaptation to freshwater habitats in fish of marine origin remain unclear. Grenadier anchovies, such as Coilia nasus, originate from marine environments and include both anadromous and freshwater-resident conspecifics, making them ideal for studying adaptive evolution from marine to freshwater habitats. We conducted a comparative population genomic and transcriptome analysis of two distinct C. nasus lineages, one anadromous and the other freshwater-resident, collected from mainstream and estuarine regions of the Yangtze River, China. By genome-wide genotyping of the anadromous and the freshwater-resident populations, we observed significant divergence in osmoregulation, energy metabolism, and immune response pathways associated with ecological adaptation and energy expenditure for migration. Some ion transport genes such as CAMK1, ATP1α3, KCNJ1 and SLC30A2 were identified that may contribute to freshwater adaptation. Notably, numerous mineralocorticoid signalling genes (e.g., NR3C2, SGK1, ATP1α3, KCNJ1) exhibit dynamic change between the anadromous and freshwater populations, suggesting an important role for the hormone cortisol in regulating salinity acclimation in euryhaline fish. Among these genes, the ion channel ATP1α3 experienced adaptive amino acid substitutions (Val317Ile and Thr329Ser), which appear to be evolutionary hotspots across migratory species based on ortholog comparisons. These variants may facilitate sodium/potassium transport and highlight salinity tolerance as a key driver of divergence in anadromous fish transitioning to freshwater. These results enhance our understanding of the genetic basis underlying freshwater adaptation for an anadromous fish across osmotic boundaries.
Animals↗
Environmental Stresses Constrain Soil Microbial Community Functions by Regulating Deterministic Assembly and Niche Width.
Increasing evidence indicates that the loss of soil microbial α-diversity triggered by environmental stress negatively impacts microbial functions; however, the effects of microbial α-diversity on community functions under environmental stress are poorly understood. Here, we investigated the changes in bacterial and fungal α- diversity along gradients of five natural stressors (temperature, precipitation, plant diversity, soil organic C and pH) across 45 grasslands in China and evaluated their connection with microbial functional traits. By quantifying the five environmental stresses into an integrated stress index, we found that the bacterial and fungal α-diversity declined under high environmental stress across three soil layers (0-20 cm, 20-40 cm and 40-60 cm). Metagenomic-based analyses showed that the diversity of functional genes decreased along the stress gradients. High stress enhanced the abundance of genes associated with broad functional categories (e.g., glycolysis/gluconeogenesis, TCA cycle, DNA replication/repair and cell growth/death) but reduced the abundance of genes linked to specialised functional categories (e.g., C, N, S and methane metabolism). Phylogenetic null models and niche analyses indicated that stochastic assembly processes predominated in high-diversity communities, in which bacterial and fungal taxa had a narrow ecological niche. However, in low-diversity communities, deterministic assembly processes were dominant, and taxa had wide niches, correlating with the reduction in gene abundance observed for broad and specialised functional categories. Given the essential role of the microbiome in regulating ecosystem functions, our findings suggest that low-diversity-induced deterministic community assembly processes and a wide niche under high environmental stress may regulate microbial functions. These findings emphasise the ecological mechanisms through which microbial biodiversity regulates terrestrial ecosystem functioning.
Soil Microbiology↗
Large-scale analysis of MYB genes in Cucurbitaceae identifies a novel gene regulating plant height.
The MYB transcription factor (TF) family, which is involved in plant growth and development, is large and diverse. Previous studies on MYB family in Cucurbitaceae were mostly based on a single genome or focused on the R2R3 subfamily. Here, we analyzed 91 genomes of 11 Cucurbitaceae species and identified a total of 15 858 MYB genes. According to phylogenetic relationships, these genes were divided into 27 subgroups. The identified MYB genes were further classified into 121 MYB orthologous gene groups (OGGs), including 25 core, 57 softcore, 19 shell and 20 line-specific/cloud groups. Whole-genome duplication was the most common mechanism of MYB genes expansion. In core group, the higher proportions of MYB genes were found to be in the coexpression network constructed by the RNA-seq data. Through the comprehensive analysis including phylogeny and gene expression profile of cucumber MYB genes, as well as genetic variations in 103 cucumber germplasms, we identified a MYB gene CsRAX5, which may be related to cucumber plant height. We used gene editing technology to knockout and overexpress CsRAX5. In the knockout lines, Csrax5, the height was significantly increased compared with wild type (WT), whereas after overexpression the height of CsRAX5-OE plants was significantly decreased compared with WT. These results indicated that MYB gene CsRAX5 negatively regulated cucumber plant height. The large-scale analysis of MYB genes in Cucurbitaceae in this study provides insights for further investigating the evolution and function of MYB genes in Cucurbitaceae crops.
Journal Article↗
The Novel HLA-B*46:106 Allele, Identified by Sanger Dideoxy Nucleotide Sequencing in a Chinese Individual.
The HLA-B*46:106 allele differs from HLA-B*46:01:01:01 by one nucleotide substitution in codon 66 in exon 2.
Humans↗
The Novel HLA-C*03:712 Allele, Identified by Sanger Dideoxy Nucleotide Sequencing in a Chinese Individual.
The HLA-C*03:712 allele differs from HLA-C*03:03:01:01 by one nucleotide substitution in codon 61 in exon 2.
Humans↗