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Shuo Yang

Publications and source records attributed to Shuo Yang.

5 recordsLinked to original sources
PubMed2026

Decoding mechanoregulation in immunological synapses using biomimetic artificial cells.

Mechanical force-driven signaling has emerged as a key regulator of cell-cell interactions (CCIs), which can enhance immune cell function. However, current biochemical approaches for studying CCIs offer minimal direct control over cellular bulk phenotypes, while synthetic biomaterial systems fail to mimic the dynamic complexity of cells. Here we introduce kpiCells, a biomaterial-based platform that uses a biomimetic membrane-endoplasmic architecture to enable finely tuned phenocopying of cellular states via modular mechanical, chemical and topographical inputs. We demonstrate that kpiCells can engage in physiological CCIs and reproduce critical subcellular features. In T cell systems, kpiCells enable integrated interrogation of afferent mechanosensing pathways and efferent force-exertion pathways, and support measurement of piconewton-scale forces at individual T cell antigen receptors as well as single cell-cell force fingerprints that define activation thresholds. This work establishes kpiCells as a bionic model that enables synthetic material design with the level of functional complexity approaching living cell systems.

Artificial Cells↗
PubMed2026

Emergence of cefiderocol resistance in carbapenem-resistant Escherichia coli ST167 prior to clinical use: A multifactored resistance landscape.

OBJECTIVES: Cefiderocol is a novel siderophore cephalosporin with potent activity against multidrug-resistant Gram-negative bacteria. Here, we reported the prevalence and mechanisms of cefiderocol resistance in carbapenem-resistant Escherichia coli (CREC) in China before its clinical use. METHODS: A total of 443 non-duplicate CREC isolates collected from 67 hospitals in China (2013-2021) underwent antimicrobial susceptibility testing according to CLSI guidelines. Whole-genome sequencing, transcriptomic analysis, siderophore quantification, and targeted genetic manipulation were performed to investigate the underlying resistance mechanisms. RESULTS: Among the 443 CREC isolates, 102 (23.0%) were resistant to cefiderocol, and 34 (7.6%) showed intermediate susceptibility. Multivariable logistic regression identified ST167 lineage (OR, 3.05; 95% CI, 1.12-8.29; P = 0.028), blaNDM-5 carriage (OR, 9.04; 95% CI, 2.96-27.57; P < 0.001), and cirA truncation (OR, 49.56; 95% CI, 20.33-120.79; P < 0.001) as independent factors associated with cefiderocol resistance. Among ST167 isolates, cefiderocol-resistant isolates showed increased yersiniabactin carriage and siderophore production but comparable TonB-dependent transporter expression profiles. Phylogenetic analysis revealed that cefiderocol-resistant ST167 isolates clustered into a distinct subclade enriched with resistance-associated determinants, including a recurrent FhuA P50S substitution detected in 59/64 (92.2%) resistant isolates. Functional assays showed that the P50S substitution increased cefiderocol minimum inhibitory concentration (0.032-0.125 &#xb5;g/mL), particularly in an NDM-5-producing background (0.032-0.5 &#xb5;g/mL). CONCLUSIONS: Cefiderocol resistance is highly prevalent among high-risk ST167 CREC isolates before the clinical introduction of cefiderocol in China, highlighting the need for continued surveillance of this epidemic lineage. Cefiderocol resistance is mediated by multiple resistance determinants, and we identify the recurrent FhuA P50S substitution as a novel contributor to reduced cefiderocol susceptibility.

Antimicrobial resistance↗
PubMed2026

Epigenetic safety of in vitro maturation in PCOS: genome-wide DNA methylation profiling of cord blood from a randomized controlled trial.

BACKGROUND: In vitro maturation (IVM) provides a safer alternative to conventional in vitro fertilization (IVF) for women with polycystic ovary syndrome (PCOS) by mitigating the risk of ovarian hyperstimulation. However, concerns persist regarding whether IVM perturbs epigenetic reprogramming in the offspring. Current evidence is constrained by candidate-gene approaches or a lack of parental controls. This study aimed to evaluate the genome-wide DNA methylation safety of IVM compared with conventional IVF using a rigorous trio-based design. METHODS: This secondary epigenetic analysis was nested within a randomized controlled trial (RCT) (ClinicalTrials.gov: NCT03463772). We included 10 nuclear families (trios), comprising five IVM-conceived and five IVF-conceived singleton offspring alongside their biological parents. Both groups utilized a uniform freeze-only single-blastocyst transfer strategy to minimize hormonal confounding. Genomic DNA from umbilical cord blood (UCB) and parental peripheral blood was analyzed using reduced representation bisulfite sequencing (RRBS). Genome-wide methylation patterns and differentially methylated regions (DMRs) were subsequently compared between the groups. RESULTS: Clinical characteristics were comparable between the IVM and IVF groups. Genome-wide analyses demonstrated high concordance in UCB methylation patterns, revealing no significant differences in global CpG methylation levels or distributions across key genomic features (promoters, CpG islands, and gene bodies). Only three rare DMRs were identified in UCB (representing&#x2009;~&#x2009;0.0001% of the genome), none of which mapped to imprinted or developmentally critical loci. Furthermore, methylation variability remained consistent between the groups. CONCLUSIONS: Our findings provide robust mechanistic evidence supporting the epigenetic safety of IVM. The remarkable stability of the neonatal methylome confirms that specific IVM conditions do not compromise early developmental programming, thereby endorsing IVM as a safe and viable alternative for women with PCOS. TRIAL REGISTRATION: ClinicalTrials.gov registry, NCT03463772. Registered on March 13, 2018.

Humans↗
PubMed2026

Enzymatic innovations in Angelica pubescens reveal dual coumarin biosynthetic pathways driving metabolic diversification.

Coumarins are structurally diverse phenylpropanoid derivatives with ecological and pharmacological significance, yet the biosynthetic logic underlying their diversification remains incompletely understood in non-model medicinal plants. Angelica pubescens (Apiaceae), widely used in traditional Chinese medicine, accumulates a rich repertoire of furanocoumarins and dihydrofuranocoumarins, making it an ideal system to investigate this metabolic complexity. Here, we combined chromosome-level genome assembly, transcriptome and metabolite profiling, phylogenetics, and heterologous expression assays to dissect coumarin biosynthesis in A. pubescens. We identified two functionally specialized O-methyltransferases, ApOMT1 and ApOMT2, which catalyze regioselective methylation of xanthotoxol and bergaptol to yield the furanocoumarins xanthotoxin and bergapten. We also characterized ApCYP736A121, a cytochrome P450 enzyme that converts osthenol to the dihydrofuranocoumarin columbianetin via a previously unknown mechanism. Gene expression and metabolite accumulation patterns across tissues and developmental stages revealed functional partitioning among pathway branches. Phylogenetic and syntenic analyses indicated that ApOMT1 and ApOMT2 arose through subfunctionalization following gene duplication, whereas ApCYP736A121 evolved via neofunctionalization from a distantly related CYP736 ancestor. Together, our findings uncover dual biosynthetic routes to structurally distinct coumarins in A. pubescens and provide insights into the evolutionary mechanisms contributing to metabolic innovation in Apiaceae. This work lays a foundation for future efforts to engineer coumarin pathways and understand their ecological functions in medicinal plants.

Coumarins↗
PubMed2025

Targeting phagocytosis for amyloid-&#x3b2; clearance: implications of morphology remodeling and microglia activation probed by bifunctional chimaeras.

Amyloid-&#x3b2; (A&#x3b2;), a key driver of Alzheimer's disease (AD) pathogenesis, possesses diverse harmful and clearance-resistant structures that present substantial challenges to therapeutic development. Here, we demonstrate that modulating A&#x3b2; morphology, rather than Toll-like receptor 2 (TLR2)-dependent microglia activation, is essential for effective phagocytosis of A&#x3b2; species by microglia. By developing a bifunctional mechanistic probe (P2CSKn) designed to remodel A&#x3b2; and activate TLR2, we show it restructures soluble A&#x3b2; (sA&#x3b2;) and fibrillar A&#x3b2; (fA&#x3b2;) into less toxic hybrid aggregates (hPA&#x3b2;). Critically, this structural remodeling protects microglia from A&#x3b2; toxicity while enabling robust phagocytosis. Moreover, although TLR2 activation mildly enhances A&#x3b2; uptake, it concurrently triggers detrimental inflammation that negates its benefits. Our findings establish morphological remodeling as the critical determinant of effective A&#x3b2; clearance and suggest a morphology-focused strategy for developing safe therapeutics for A&#x3b2;-related diseases.

Microglia↗