Biomedical subjects

Juan Chen

Publications and source records attributed to Juan Chen.

6 recordsLinked to original sources

PubMed2026

Impaired leptin A signaling disrupts hepatic lipid metabolism and growth in female medaka (Oryzias latipes).

Leptin is a central regulator of appetite and energy metabolism in vertebrates, and its deficiency in mammals typically results in hyperphagia and severe obesity. In fish, however, the physiological roles of leptin remain less clearly defined, partly due to the whole genome duplication (WGD) and divergent expression patterns. In this study, we generated a leptin A (lepa) loss-of-function mutant in medaka (Oryzias latipes) using CRISPR/Cas9 to investigate the function of leptin signaling. Phenotypic analysis revealed that female homozygous mutants exhibited significantly reduced body length and body weight compared with wild-type females, indicating growth impairment. Unexpectedly, despite their lean phenotype, the female mutants developed pronounced hepatic steatosis accompanied by the formation of spongiosis hepatis structures, while no obvious fibrosis was detected. To explore the molecular mechanisms underlying these abnormalities, transcriptomic profiling of mutant livers was performed. Differentially expressed genes were significantly enriched in pathways related to lipid metabolism, including Fatty acid metabolism and PPAR signaling pathway, suggesting a potential reduction in hepatic fatty acid β-oxidation capacity. In addition, genes involved in endoplasmic reticulum stress, autophagy, and apoptosis were altered, indicating transcriptional changes in cellular stress-response pathways under leptin A deficiency. Together, these findings suggest that leptin A may play an important role in coordinating growth and hepatic lipid metabolism in medaka and highlight potential differences in leptin-mediated metabolic regulation between fish and mammals.

Animals↗

PubMed2026

Engineering local nitrogen coordination environments of Palladium subnanometric clusters in metal-organic frameworks for efficient hydrogenation.

Subnanometric clusters (SCs) bridge the gap between single-atom catalysts and nanoparticles by combining high atomic utilization with cooperative multi-atom effects. However, stabilizing low-coordinated SCs while maintaining accessible active sites remains challenging. Here, we introduce pyrazole-3,5-dicarboxylic acid (PZDC), pyridine-3,5-dicarboxylic acid (PDC), and pyrrole-3,5-dicarboxylic acid (PPy) as secondary ligands in metal-organic frameworks to regulate the local nitrogen (N) coordination environment of Pd SCs (∼0.6 nm). Specifically, PZDC provides a chemically differentiated pyrazolic dual-N environment containing formally pyridinic-like and pyrrolic-like N sites. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC HAADF-STEM) and X-ray absorption spectroscopy (XAS) confirm the formation of low-coordinated Pd clusters containing PdN and PdPd interactions, while CO diffuse reflectance infrared Fourier transform spectroscopy (CO-DRIFTS) reveals a distinctive adsorption environment characterized by geminal dicarbonyl species and strongly suppressed bridge-bonded CO adsorption. Within this catalyst series, the PZDC-functionalized material exhibits the highest activity and tetrahydrocyclopentadiene (THDCPD) selectivity in dicyclopentadiene (DCPD) hydrogenation. These results demonstrate that modification of the local N environment can regulate the average coordination structure, adsorption behavior, and catalytic properties of MOF-supported Pd SCs.

Hydrogenation catalysis↗

PubMed2026

Controlled framework nickel exsolution in metal-organic frameworks creates confined active sites for chemoselective citral hydrogenation.

Selective hydrogenation of citral to citronellal over non-noble-metal catalysts remains challenging because highly active metallic Ni simultaneously promotes efficient substrate activation and undesired over‑hydrogenation of the desired product. Herein, we develop a controlled exsolution strategy in waste polyethylene terephthalate (PET)-derived nickel metal-organic frameworks (Ni-MOFs) to transform framework Ni into confined metallic active sites while preserving the porous framework architecture. During reductive treatment, framework Ni2+ species undergo gradual node-to-metal evolution, generating highly dispersed Ni0 sites confined within the partially retained MOF framework. More importantly, the degree of framework Ni exsolution governs the balance between citral activation and citronellal over‑hydrogenation, thereby establishing a distinct chemoselective window. Within the optimal exsolution regime, the framework-confined Ni0 sites enable efficient H2 activation and selective hydrogenation of the CC bond while suppressing the subsequent hydrogenation of citronellal. Consequently, the optimized catalyst achieves ∼99% citral conversion and 100% citronellal selectivity at 90 °C and 2 MPa H2, together with excellent catalytic stability and recyclability. Beyond the sustainable valorization of waste PET, this work establishes controlled framework exsolution as an effective strategy for engineering confined active sites and regulating chemoselectivity in non-noble-metal hydrogenation catalysts.

Chemoselective hydrogenation↗

PubMed2026

hnRNPK condensates facilitate enhancer-promoter looping and RNA polymerase II recruitment.

Enhancer RNAs interact with promoter-derived RNAs to dictate enhancer-promoter looping, but the RNA-binding protein that mediates this process has remained unidentified. Here we identify hnRNPK as a general structural regulator that preferentially binds to nascent RNAs transcribed from enhancer and promoter regions, promoting enhancer-promoter looping and transcriptional activation. We further show that hnRNPK forms phase-separated, cavity-containing condensates that encapsulate RNA polymerase II (Pol II) via its RPB3 subunit, facilitating chromatin looping and potentially enabling recruitment of Pol II from enhancers to promoters through protein dimerization. Notably, a mutation associated with Au-Kline syndrome in hnRNPK (c.953+1dupG) alters its condensates from a liquid-like to a gel-like state, leading to developmental defects in knock-in mice. Fibroblasts derived from these mutants display reduced enhancer-promoter looping and decreased Pol II recruitment at promoters of key developmental genes. These findings suggest that hnRNPK is a structural regulator of enhancer-promoter communication and highlight the importance of RNA-RNA interactions mediated by RNA-binding proteins in transcriptional regulation.

RNA Polymerase II↗

PubMed2026

Current landscape of Cys-OxiPTMs in plants: from hormone signaling to phenotypic control and their potential in sustainable agriculture.

The integration of environmental and developmental cues into coherent physiological responses is fundamental to plant survival. Reactive oxygen, nitrogen, and sulfur species (ROS/RNS/RSS) are now recognized as essential signaling molecules, not merely cytotoxic byproducts. Their specificity is largely achieved through reversible, site-specific cysteine oxidative post-translational modifications (Cys-OxiPTMs), which constitute a dynamic and sophisticated "redox code". This review provides a systematic synthesis of the current landscape of Cys-OxiPTMs in plants, bridging chemistry, hormone biology, agronomy, detection, and engineering. The chemical and enzymatic basis of major Cys-OxiPTMs is detailed, along with a discussion of how their spatiotemporal interplay orchestrates signaling specificity. A critical examination is then presented on how these modifications decode and integrate plant hormone signaling networks to regulate key agronomic traits. Cutting-edge proteomic technologies that have revolutionized the identification of redox-sensitive cysteines are also evaluated. Finally, forward-looking strategies to "write" the redox code are explored. By moving the field from descriptive cataloging to predictive "redox breeding", this review establishes a foundational framework for manipulating Cys-OxiPTMs to develop climate-resilient, high-yielding crops for sustainable agriculture.

Agronomic traits↗

PubMed2026

Fate of antibiotic resistance genes during rural domestic wastewater treatment: Anaerobic unit as enrichment hotspot versus aerobic unit as attenuation zone.

Rural domestic wastewater treatment systems are important but understudied reservoirs for antibiotic resistance genes (ARGs), whose full-process migration mechanisms remain unclear. Herein, the contribution of each treatment unit of ARGs was investigated using metagenomic methods across two seasons in typical rural domestic wastewater treatment systems. Although a removal efficiency (69 % in winter and 22 % in summer) was observed for ARGs, higher antibiotic residues and temperature dramatically induced ARG occurrence in wastewater and horizontal gene transfer (HGT) risk during wastewater treatment. The ARG abundances in the anaerobic unit increased by 1.6-2.1 fold compared to the regulating pool, primarily driven by elevated mobile genetic element (MGE) activity. In sharp contrast, ARG reduction was achieved through ARG host removal and suppressed HGT potential in the aerobic unit. Notably, mobile ARGs were dominated by tetracycline resistance genes in winter and co-dominated by tetracycline and sulfonamide genes in summer, with most flanked by transposases. Key pathogenic hosts, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa carrying ARG-MGE complexes, were primarily concentrated in the regulating pool and the influent, forming high-risk upstream sources of dissemination. Partial least-squares path model highlighted MGEs as the primary drivers, and variance partitioning analysis indicated that MGEs account for 31 % of the explained variation in ARGs during wastewater treatment. In summary, the anaerobic unit was an ARG enrichment hotspot, while the aerobic unit as ARG attenuation zone during wastewater treatment. These findings provide crucial evidence to optimize rural wastewater treatment processes and to target the control of antibiotic resistance.

Wastewater↗