Biomedical subjects

Kai Jiang

Publications and source records attributed to Kai Jiang.

4 recordsLinked to original sources

PubMed2026

Iterative Enoyl Reduction by a FabV-Family Enzyme Expands the Chemical Landscape of Discrete Polyketide Synthases.

Polyketides are a structurally diverse class of natural products with immense therapeutic potential. However, the biosynthetic output of discrete polyketide synthases (PKSs) has been constrained by a fundamental functional limitation: unlike modular Type I systems, discrete PKS systems typically lack integrated enoyl reductase (ER) activity. This constraint restricts their chemical repertoire primarily to unsaturated polyenes or aromatic scaffolds. Here, we characterize PbrC16, a FabV-family ER from a manumycin-type biosynthetic gene cluster (BGC) in Peterkaempfera bronchialis. This enzyme represents the first experimentally validated ER capable of functioning within discrete PKS architectures. In vitro biochemical reconstitution demonstrates that PbrC16 along with its homologue ScFabV catalyze iterative enoyl reductions in both β-ketoacyl-acyl carrier protein synthase III (KAS III)-dependent and highly reducing (HR) Type II PKS contexts, enabling the complete saturation of long-chain polyketide intermediates. Structural and computational analyses reveal the molecular basis for its exceptional substrate promiscuity and versatile acyl carrier protein (ACP) recognition. These findings resolve a long-standing "reductive gap" in discrete PKS biology and provide a "plug-and-play" module for the rational engineering of saturated polyketide scaffolds.

Polyketide Synthases↗

PubMed2026

Metagenomics indicates new taxa in Candidatus Saccharimonadia and proposal of Parviradicicola hetaonensis gen. nov. sp. nov. and Parviputeicola dengkouensis gen. nov. sp. nov. following the rules of the SeqCode.

Candidatus Saccharimonadia is a core lineage within the phylum Patescibacteriota (formerly the bacterial candidate phyla radiation, CPR), yet the class has long lacked a standardized, complete taxonomic framework. This nomenclatural gap severely hinders consistent academic exchange and global research into its diversity, evolutionary history, and ecological roles. Here, we recovered 29 medium- to high-quality Ca. Saccharimonadia metagenome-assembled genomes (MAGs) from groundwater, rhizosphere soil, and saline-alkali soil in the Hetao Irrigation District, Inner Mongolia, China, and performed integrated phylogenomic, genome size evolution, and metabolic analyses alongside reference genomes from the GTDB r220 database. Based on robust polyphasic taxonomic evidence (multi-dimensional phylogenetic analyses, widely accepted genome-wide ANI/AAI thresholds) and SeqCode rules, we formally propose two novel taxa: Parviradicicola hetaonensis gen. nov., sp. nov. (type material: txb011_bin.8.strictTS) and Parviputeicola dengkouensis gen. nov., sp. nov. (type material: sgl022_bin.19.origTS), plus two novel families and one novel order. We further identified potential drivers and important associations related to Ca. Saccharimonadia genome size evolution and adaptive metabolic traits. This work refines the Ca. Saccharimonadia taxonomic framework, providing critical genomic references for follow-up research.

Phylogeny↗

PubMed2026

High dietary fiber is associated with improved outcomes in patients with melanoma and sarcoma treated with immunotherapy regardless of gut microbiome dysbiosis and social vulnerability.

BACKGROUND: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes. METHODS: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS). RESULTS: SVI percentile was 0.4 (interquartile ratio [IQR], 0.2-0.7), and median dietary fiber intake was 17 (IQR, 15-20) g/day. SVI was inversely correlated with dietary fiber intake (r, -0.18, p = .0398). Gut microbiome analyses revealed community and compositional differences by SVI, including inverse associations with α-diversity and the relative abundance of favorable bacteria such as Bifidobacterium longum (p < .001), contrasting the positive associations observed between fiber and these microbial markers. Increased dietary fiber intake was associated with measurable response to ICB. A difference in OS was not observed in more socially vulnerable patients (SVI, not reached vs. 81.7 months), however, a survival advantage was evident with higher dietary fiber intake (not reached, 58.9 months). CONCLUSIONS: Increased social vulnerability was associated with a less favorable gut microbiome composition but not worse OS among melanoma and sarcoma patients treated with ICB. Consistent with prior findings, high dietary fiber intake emerged as a potentially modifiable pathway to improve outcomes in patients initiating ICB, particularly those with increased SVI.

Humans↗

PubMed2025

Fluorinated Ionizable Lipids for Efficient Spleen-Targeted mRNA Delivery in Cancer Immunotherapy.

Efficient and selective mRNA delivery to immune-related organs, particularly the spleen, remains a major barrier to the broader clinical translation of mRNA therapeutics. Here, leveraging the clinically approved SM-102/ALC-0315 ionizable lipid scaffold, we rationally designed a combinatorial library of fluorinated ionizable lipids (FILs) by systematically modulating hydrophobic tails and fluorine stoichiometry. Through synthesis and evaluation of 74 candidate FILs, we identify SSC6F5 lipid nanoparticles (LNPs) as a lead formulation with exceptional spleen-targeting specificity (>90%) across intravenous, intramuscular, and subcutaneous administrations. Compared to clinically approved SM102 LNPs and spleen-tropic SM102/18PA (SORT) LNPs, intravenously administered SSC6F5 LNPs achieve 10.6-fold and 63.1-fold higher splenic mRNA transfection, respectively. Proteomic analysis of protein corona on SSC6F5 LNPs reveals significant enrichment of apolipoprotein D (Apod) and reduction in apolipoprotein H (Apoh), implicating a novel endogenous recognition pathway driving enhanced spleen targeting. Functionally, SSC6F5 LNPs enable efficient genome editing in splenic macrophages, dendritic cells, T cells, and B cells in Ai9 mice, and elicit potent CD8+ T cell and humoral responses in a B16-OVA murine melanoma model, resulting in significant tumor growth inhibition. These findings establish fluorinated lipids as a mechanistically distinct and translationally versatile platform for precision spleen-targeted mRNA delivery in gene editing and cancer immunotherapy.

Animals↗