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Science Advances · 2025 ·Vol. 11 ·期 34 · IF 12.5

Plant negative-strand RNA virus phosphoprotein condensates exploit host trafficking and lipid synthesis for viral factory assembly

Zhiyi Wang,Jingyi Zhang,Jilei Huang,Gan Sha,Xinyue Song,Xue Cao,Zhenchen Yan,Chuanhe Liu,Siping Chen,Ziying Li,Xiuqin Huang,Qingjun Xie,Xin Yang,Guohui Zhou,Tong Zhang

RNA viruses often remodel host intracellular membranes to establish specialized replication compartments through viral protein–induced phase separation. However, the mechanisms underlying membrane remodeling and the characteristics that render these sites conducive to replication remain poorly understood, particularly in plant negative-strand RNA viruses. Here, we demonstrate that the phosphoprotein (P) of rice stripe mosaic virus (RSMV) forms biomolecular condensates via liquid-liquid phase separation (LLPS) to recruit essential components for viral replication factories (VFs). We identify a direct interaction between RSMV P and adenosine diphosphate (ADP) ribosylation factor 1 (OsARF1C), a crucial regulator of the coatomer protein I (COP I) vesicle transport pathway that is vital for viral replication. This interaction indirectly recruits OsARF1C’s partner, phosphatidylinositol 4-kinase beta (OsPI4KB), which drives localized phosphatidylinositol-4 phosphate (PI4P) synthesis. Concurrently, the P protein modulates its aggregates and LLPS droplets through PI4P, thereby expanding the replication site and enhancing viral replication.

研究领域: 植物病毒学 · 分子植物病理学 · 病毒复制机制 · 细胞生物学 · 生物大分子相分离
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Scientific Reports · 2023 ·Vol. 13 ·期 1 ·1-12 · IF 4.6

HCG supplement did not accelerate tunica albuginea remodeling to facilitate penile growth

Li Tao,Tian Yuan,Zhong Quliang,Chen Peng,Zhang Junhao,Du Guangshi,Li Lei,Jiang Yiting,Jiang Kehua

Penile size is closely concerned and short penis contributes serious sexual dysfunction and tremendous psychological problems to couples. Androgen is essential for penile development and testosterone replacement is recommended to patients with micropenis. We previously proved that inhibiting activity of lysyl oxidase (Anti-lysyl oxidase, Anti-LOX) combined with vacuum erectile device (VED) lengthened penis by remodeling tunica albuginea. We thus explored whether HCG supplement could accelerate tunica albuginea remodeling (induced by Anti-LOX + VED) to promote penile growth. Forty-two SD male rats (4 weeks old) were purchased and divided into 7 groups: control, Anti-LOX, HCG, VED (with a negative aspirated pressure of − 300 mmHg), Anti-LOX + VED, HCG + VED, and Anti-LOX + HCG + VED. After an intervention for 4 weeks, all rats’ penile length, exposed penile length, and erectile function were measured. Serum samples were collected to detect hormone levels and penile corpus cavernosum were harvested for histo-pathological analysis. All intervention groups showed significantly longer penis than controlled rats. Anti-LOX sharply increased penile length and exposed length by 15% and 9% respectively, this lengthening effect was more obvious in Anti-LOX + VED group (26% and 19%, respectively). Although HCG promoted penile length by 8%, this effect was slight for exposed length (3%). Moreover, Anti-LOX + HCG + VED dramatically increased penile length and exposed length by 22% and 18%, respectively, which was similar with that in Anti-LOX + VED (26% and 19%, respectively). HCG dramatically stimulated testosterone and dihydrotestosterone secretions than control group, whether with or without Anti-LOX and VED; while it induced more AR expression than other groups. Finally, all procedures did not improve or deteriorate normal erectile function. Although we verified that Anti-LOX + VED lengthened penis by inducing tunica albuginea remodeling, however, HCG supplement did not synergize with Anti-LOX + VED to accelerate albuginea remodeling to facilitate penile growth.

研究领域: 泌尿学 · 内分泌学 · 性医学
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Cell Discovery · 2024 ·Vol. 10 ·期 1 ·1-14 · IF 13

Gut microbiota-derived indole-3-acetic acid suppresses high myopia progression by promoting type I collagen synthesis

Li Hao,Du Yu,Cheng Kaiwen,Chen Yuxi,Wei Ling,Pei Yujun,Wang Xiaoyu,Wang Lan,Zhang Ye,Hu Xiaoxin,Lu Yi,Zhu Xiangjia

High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM’s gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.

研究领域: 眼科学 · 微生物学 · 分子生物学 · 遗传学
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Advanced Composites and Hybrid Materials · 2025 ·Vol. 8 ·期 1 ·1-20 · IF 21.8

Metabolic reprogramming of fibroblast-like synoviocytes with a supramolecular nano-drug for osteoarthritis therapy

Ma Yibo,Dong Jiaxing,Zou Xiangqian,Jiang Xiaohua,Liu Linhua,Wang Bing,Mao Xiulin,Gong Liangfeng,Li Guoshu,Chen Changjian

Metabolic reprogramming is fundamental to synovium remodeling with drug delivery for osteoarthritis (OA) therapy. Mitochonic acid 5-MASM7@MnTBAP nanoparticles (MM@MT NPs) with various physicochemical properties and biological activities may be developed as a supramolecular nano-drug delivering to articulus for regulating mitochondrial metabolism of synovium. This study aims to explore the feasibility, efficacy, and mechanism of MM@MT NPs, which possibly excavates a novel perspective for OA therapy. Herein, for feasibility, MM@MT NPs has been indicated to possess excellent photothermal, reactive oxygen species (ROS) response, and oxygen release performances. For efficacy, MM@MT NPs has been confirmed to promote extracellular matrix (ECM) regeneration. For mechanism, MM@MT NPs has been illustrated to restore the mitochondrial membrane potential and recover the mitochondrial dynamics, which is beneficial for maintaining mitochondrial homeostasis. Moreover, MM@MT NPs has been demonstrated to stimulate the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) in mitochondria as well as enhance antioxidant capacity and eliminate oxidative stress, which is reflected in regulating the adenosine triphosphate (ATP) and ROS metabolism. Therefore, MM@MT NPs can remodel the homeostasis of mitochondria via reprogramming metabolism in synovium, which achieves the symptomatic and etiological treatments of OA.

CAS / MDL: 67-56-1
研究领域: 纳米医学 · 风湿病学 · 药物递送系统 · 线粒体生物学 · 骨科
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