Biomedical subjects

Jie Huang

Publications and source records attributed to Jie Huang.

8 recordsLinked to original sources

PubMed2026

Natural variation in SL6 determines fatty acid components and seed longevity in rice.

Seed longevity (SL) is vital for ensuring food security worldwide. However, the genetic basis of SL has been scarcely documented. Here, we report the cloning of a major SL locus, qSL6, encoding a fatty acyl-ACP thioesterase type B. SL6 is functionally conserved in regulating palmitic acid synthesis in seeds, conferring higher oxidation durability and SL in various species. Through the VP1-SL6 module, a seed desiccation-derived ABA signal is transmitted via VP1, which directly activates SL6 transcription to alter the fatty acid composition and elevate SL in seeds. The ancestral elite allele SL6HHZ harbors a virus-derived CT-rich motif cis-element in the 5'UTR, which serves as a universal, bidirectional mRNA stabilizer, contributing to the divergence between indica and japonica in terms of SL. Moreover, manipulating SL6 expression via marker-assisted selection or transgenic approaches notably improved SL in rice cultivars and F1 hybrids without affecting major agronomic traits. Our findings provided a promising genetic locus for improving SL in rice.

Oryza↗

PubMed2026

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans↗

PubMed2026

Genomic and functional characterization of ST11-KL64 hypervirulence-associated carbapenem-resistant Klebsiella pneumoniae co-harboring bla KPC-2 and bla NDM-13.

BACKGROUND: Hypervirulence-associated carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is a major clinical and public health threat. However, ST11-KL64 hv-CRKP co-harboring bla KPC-2 and bla NDM-13 remains poorly characterized, particularly regarding genomic relatedness, plasmid dynamics, and attenuated virulence-associated phenotypes. METHODS: We retrospectively investigated clinical K. pneumoniae isolates collected at a tertiary hospital in Chengdu, China, between January and December 2024. Hypervirulence-associated markers were screened by PCR, followed by antimicrobial susceptibility testing and carbapenemase inhibitor enhancement assay to identify genotype-defined hv-CRKP. All isolates were subjected to molecular typing. ST11-KL64 isolates co-harboring bla KPC-2 and bla NDM-13 were subjected to Illumina sequencing, with the representative isolate K3 undergoing hybrid whole-genome sequencing and functional characterization. RESULTS: Among the 46 hvKP isolates recovered from 43 patients, 35 were identified as hv-CRKP, predominantly ST11-KL64. Three ST11-KL64 hv-CRKP isolates co-harbored bla KPC-2/bla NDM-13, and Illumina sequencing coupled with core-genome SNP (cgSNP) typing revealed minimal genetic variation. The expanded cgSNP analysis supported close relatedness between K3 and Beijing isolate K56649. K3 carried a pLVPK-like virulence plasmid, a bla KPC-2-bearing IncFII/IncR plasmid, and a bla NDM-13-bearing IncI1 plasmid. Relative to pK2044, K3 exhibited an rmpA-proximal ISKpn26-associated insertion and a complex alteration of the 5'-terminal coding region of rmpA. The bla NDM-13 plasmid was conjugatively transferred to Escherichia coli C600 with a mean conjugation frequency of 5.213 × 10-3 transconjugants per recipient cell and bla NDM-13 maintained high stability following approximately 100 generations of antibiotic-free passage, whereas bla KPC-2 was not detected under the tested conditions. Phenotypically, K3 showed a negative string test, low mucoviscosity, and attenuated virulence-associated phenotypes. CONCLUSION: Our results reveal that the three isolates formed a closely related local genomic cluster, among which K3 was closely related to the K56649 clone. In addition, K3 exhibited conjugative transfer capacity of the bla NDM-13-bearing IncI1 plasmid, and alterations at the rmpA locus accompanied by reduced rmpA transcript abundance were associated with low mucoviscosity.

IncI1 plasmid↗

PubMed2026

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↗

PubMed2026

Precisely designed keystone metabolites boost shrimp disease resistance by recruiting symbionts via the lipoxin A4-AP-1 pathway.

BACKGROUND: Gut metabolites and symbionts are indispensable for host health, yet the precise identification of keystone metabolites and construction of synthetic microbial communities (SynComs) to enhance disease resistance remains limited. RESULTS: Using Litopenaeus vannamei as a model, we identified pyruvic acid and DL-glutamine (1:2) as keystone metabolites by borrowing the microbial ecology principles of bio-indicators and driver taxa. Dietary supplementation with these metabolites sufficiently protected shrimp from white feces syndrome (WFS). Multi-omics analyses demonstrated that keystone metabolites exerted positive effects by enriching beneficial Ruegeria lacuscaerulensis, Bacillus subtilis and Nioella nitratireducens, strengthening the gut network stability, and enhancing shrimp immunity, which collectively potentiated WFS resistance. The recruited three strains were consumers and producers of the two keystone metabolites, and discriminative strains between healthy and diseased shrimp across global datasets. A SynCom constructed from the three strains (4:3:2) replicated the efficacy of keystone metabolites. Both keystone metabolites and SynCom elevated shrimp gut and hepatopancreas lipoxin A4 (LXA4) levels, which suppressed the pro-inflammatory transcription factor AP-1, as validated by in vivo inhibition assay. CONCLUSIONS: Our findings demonstrate that precisely designed keystone metabolites enhance shrimp disease resistance through the recruitment of key symbionts-LXA4-AP-1 axis. The rationally designed keystone metabolites and SynCom are compelling biocontrol solutions in improving host disease resistance. Video Abstract.

Animals↗

PubMed2025

Comprehensive assessment of homologous recombination deficiency via simultaneous methylation and mutation analysis in epithelial ovarian cancer: implications for PARP inhibitors efficacy.

BACKGROUND: The advent of poly (ADP-ribose) polymerase inhibitors (PARPi) over the past decade has significantly altered the management of epithelial ovarian cancer (EOC). We proposed that the etiology of homologous recombination deficiency (HRD) might underlie the variable responses to PARPi observed across patient populations. METHODS: As part of the phase 2 study of the Chinese HRD Harmonization Project, we developed a genomic methylation sequencing (GM-seq) pipeline facilitated by the TET enzyme for the simultaneous identification of methylated modifications and genetic variations in EOC tumor samples, and compared with established DNA sequencing-based HRD assays. RESULTS: Somatic mutation and HRD scores were confounded by low tumor purity in our cohort of 98 locally advanced/advanced EOC patients. In samples with tumor purity ≥ 30% (n = 45), the GM-seq pipeline showed high consistency with DNA sequencing-based HRD assay, identifying genetic variations in homologous recombination repair (HRR) genes and HRD score with 92.6% (25/27) and 97.1% (33/34) consistency respectively, in addition to conducting methylation profiling. Moreover, different underlying mechanisms of HRD were associated with varying degrees of PARPi efficacy, with BRCA1/2 LOH group having the best efficacy (median PFS, undefined), followed by BRCA1 methylation group (median PFS, 23.4 months), and those with unknown etiology of HRD having the worst efficacy (median PFS, 8.8 months, p < 0.001). CONCLUSION: Our findings underscore the importance of considering HRD etiology when evaluating PARPi efficacy in EOC patients. The GM-seq pipeline, represents a significant advancement in HRD detection, enabling more accurate predictions of PARPi response.

Epithelial ovarian cancer (EOC)↗

PubMed2025

Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment.

Therapeutic epigenetic modulation is currently being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARP inhibitors. To broaden its clinical applicability and identify more effective combination strategies, we conducted a drug screen combining PARP inhibitors with 74 well-characterized epigenetic modulators targeting five major classes of epigenetic enzymes. Notably, both type I PRMT inhibitors and PRMT5 inhibitors scored highly in combination efficacy and clinical prioritization. PRMT inhibition significantly enhanced PARP inhibitor-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMT suppression downregulates DNA damage repair genes and BRCAness-associated pathways, while also modulating intrinsic innate immune responses within cancer cells. Integrative analysis of large-scale genomic and functional datasets from TCGA and DepMap further supports PRMT1, PRMT4, and PRMT5 as promising therapeutic targets in oncology. Importantly, dual inhibition of PRMT1 and PRMT5 synergistically sensitizes tumors to PARP inhibitors. Collectively, our findings provide strong rationale for the clinical development of PRMT and PARP inhibitor combinations in HR-proficient ovarian and breast cancers.

Journal Article↗

PubMed2025

A positive-sense single-stranded RNA virus acquired a negative-sense open reading frame through recombination.

Although positive- and negative-sense single-stranded RNA viruses are ubiquitous in nature, there is currently no evidence of recombination or reassortment between viruses with these two major forms of genome organization. Here, we describe the discovery of brine shrimp virga-like virus 1 (BSVV1), a novel positive-sense single-stranded RNA virus with a recombinant genome structure derived from two viral phyla with differing genome organizations. The genome of BSVV1 comprises three open reading frames (ORFs). ORF1 resembles the RNA-dependent RNA polymerase of Ips virga-like virus 1 (a positive-sense RNA virus), while ORF2, transcribed in the positive orientation, is related to the glycoprotein of Hubei bunya-like virus 10 and other negative-sense RNA viruses. The predicted ORF3 was unique to BSVV1 without known homologs identified. The presence of the three protein products was verified by mass spectrometry. Notably, our analysis also revealed that BSVV1 is geographically widespread and found in brine shrimp from at least eight countries on four continents. In addition, BSVV1 was successfully cultured and proliferated to high viral loads during brine shrimp development. In sum, we provide compelling evidence of an ancient recombination event between negative- and positive-sense single-stranded RNA viruses, enriching our understanding of the evolution of genome structures in RNA viruses.

Open Reading Frames↗