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MiR-335-5p Escaped from CircKIAA0586 Adsorption Contributes to Mechanical Overloading-Induced Cartilage Degeneration by Targeting Lymphoid-Specific Helicase. CircKIAA0586中逃逸的MiR-335-5p通过靶向淋巴特异性解旋酶促进机械超载诱导的软骨变性。
IF 11 1区 综合性期刊
Research Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.34133/research.0694
Haoyu Xie, Yuheng Lu, Jianying Pan, Hua Zeng, Zhicheng Zhang, Jianbin Yin, Jinjian Zhu, Bingsheng Luo, Dong Guo, Chunyu Wu, Chun Zeng, Yan Shao, Xiaochun Bai, Daozhang Cai, Haiyan Zhang
{"title":"MiR-335-5p Escaped from CircKIAA0586 Adsorption Contributes to Mechanical Overloading-Induced Cartilage Degeneration by Targeting Lymphoid-Specific Helicase.","authors":"Haoyu Xie, Yuheng Lu, Jianying Pan, Hua Zeng, Zhicheng Zhang, Jianbin Yin, Jinjian Zhu, Bingsheng Luo, Dong Guo, Chunyu Wu, Chun Zeng, Yan Shao, Xiaochun Bai, Daozhang Cai, Haiyan Zhang","doi":"10.34133/research.0694","DOIUrl":"https://doi.org/10.34133/research.0694","url":null,"abstract":"<p><p>Mechanical overload is a critical contributor to cartilage degeneration in osteoarthritis (OA) pathogenesis. Circular RNA (circRNA) is expected to provide a long-lasting therapy for OA. However, the involvement of the circRNA-associated competitive endogenous RNA network in chondrocyte senescence induced by mechanical overloading remains unestablished. A mechanical overloading-induced chondrocyte senescence model in human primary chondrocytes is constructed, and differences in the expression of circRNAs and miRNAs were analyzed. The biological roles of circKIAA0586/miR-335-5p in chondrocyte senescence and OA progression under mechanical overloading and its downstream targets were determined using gain- and loss-of-function experiments in various biochemical assays in human chondrocytes. The in vivo effects of circKIAA0586 overexpression were also determined in destabilization of the medial meniscus (DMM) OA mice and aged spontaneous OA mice. The mechanical overloading-induced chondrocyte senescence was aggravated by miR-335-5p or circKIAA0586 knockdown. Accumulated DNA damage response was observed following mechanical overloading, which reduced after miR-335-5p inhibition or circKIAA0586 supplementation. MiR-335-5p was regulated by circKIA0586 adsorption. HELLS was prominently down-regulated following mechanical overloading treatment. Moreover, miR-335-5p bound to lymphoid-specific helicase (HELLS) mRNA during mechanical overloading was demonstrated to mediate the nonhomologous end joining (NHEJ) pathway, thereby inducing DNA damage and senescence. In addition, the senescence delaying and cartilage protective functions of circKIAA0586 and HELLS were validated in DMM OA mice and aged spontaneous OA mice. Our findings suggest that miR-335-5p, which escapes circKIAA0586 adsorption, facilitates mechanical overloading-induced chondrocyte senescence and OA progression by impairing the NHEJ pathway through HELLS inhibition. Overall, targeting circKIAA0586/miR-335-5p/HELLS signaling provides a novel therapeutic approach for OA.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"9 ","pages":"0694"},"PeriodicalIF":11.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Globally Distributed Cyanobacterial Nitroreductase Capable of Conferring Biodegradation of Chloramphenicol. 一种能够生物降解氯霉素的全球分布的蓝藻硝化还原酶。
IF 11 1区 综合性期刊
Research Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.34133/research.0692
Qiu-Lian Zhong, Jiu-Qiang Xiong
{"title":"A Globally Distributed Cyanobacterial Nitroreductase Capable of Conferring Biodegradation of Chloramphenicol.","authors":"Qiu-Lian Zhong, Jiu-Qiang Xiong","doi":"10.34133/research.0692","DOIUrl":"https://doi.org/10.34133/research.0692","url":null,"abstract":"<p><p>Cyanobacteria play pivotal roles in global biogeochemical cycles and aquatic ecosystems due to their widespread distribution and significant contributions to primary production. Yet, the interactions between cyanobacteria and antibiotics remain unclear. This study revealed that <i>Synechocystis</i> sp., a cyanobacterial species, removed 94.27% of 0.1 mg l<sup>-1</sup> chloramphenicol (CAP) through enzyme-mediated degradation. While cytochrome P450 enzymes (CYP450s) were found unnecessary for CAP removal, a gene encoding cyanobacterial nitroreductase was significantly up-regulated (7.85-fold) under CAP exposure. The purified nitroreductase exhibited strong binding affinity to CAP (<i>K</i> <sub>d</sub> = 2.9 nM) and a Michaelis constant (<i>K</i> <sub>m</sub>) of 104.0 μM. By engineering a bacterial strain with nitroreductase, 94.43% of 0.1 mg l<sup>-1</sup> CAP was removed within 2 h. Metagenomic and metatranscriptomic analyses showed that nitroreductase genes and transcripts are globally distributed across diverse microbial phyla. These findings uncover a novel enzyme for CAP degradation and advance sustainable biotechnologies to mitigate antibiotic pollution, addressing critical environmental challenges in aquaculture and other industries globally.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0692"},"PeriodicalIF":11.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isobutyrate Confers Resistance to Inflammatory Bowel Disease through Host-Microbiota Interactions in Pigs. 异丁酸盐通过猪宿主-微生物群相互作用增强对炎症性肠病的抵抗力。
IF 11 1区 综合性期刊
Research Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.34133/research.0673
Xiuyu Fang, Haiyang Liu, Junling Liu, Yongqing Du, Zihan Chi, Yiqi Bian, Xuan Zhao, Teng Teng, Baoming Shi
{"title":"Isobutyrate Confers Resistance to Inflammatory Bowel Disease through Host-Microbiota Interactions in Pigs.","authors":"Xiuyu Fang, Haiyang Liu, Junling Liu, Yongqing Du, Zihan Chi, Yiqi Bian, Xuan Zhao, Teng Teng, Baoming Shi","doi":"10.34133/research.0673","DOIUrl":"https://doi.org/10.34133/research.0673","url":null,"abstract":"<p><p>Supplementation with short-chain fatty acids (SCFAs) is a potential therapeutic approach for inflammatory bowel disease (IBD). However, the therapeutic effects and mechanisms of action of isobutyrate in IBD remain unclear. Clinical data indicate that the fecal levels of isobutyrate are markedly lower in patients with Crohn's disease than in healthy controls. Compared with healthy mice and healthy pigs, mice and pigs with colitis presented significantly lower isobutyrate levels. Furthermore, the level of isobutyrate in pigs was significantly negatively correlated with the disease activity index. We speculate that isobutyrate may play a crucial role in regulating host gut homeostasis. We established a model of dextran sulfate sodium-induced colitis in pigs, which have gastrointestinal structure and function similar to those of humans; we performed multiomic analysis to investigate the therapeutic effects and potential mechanisms of isobutyrate on IBD at both the animal and cellular levels and validated the results. Phenotypically, isobutyrate can significantly alleviate diarrhea, bloody stools, weight loss, and colon shortening caused by colitis in pigs. Mechanistically, isobutyrate can increase the relative abundance of <i>Lactobacillus reuteri</i>, thereby increasing the production of indole-3-lactic acid, regulating aryl hydrocarbon receptor expression and downstream signaling pathways, and regulating Foxp3<sup>+</sup> CD4<sup>+</sup> T cell recruitment to alleviate colitis. Isobutyrate can directly activate G protein-coupled receptor 109A, promote the expression of Claudin-1, and improve intestinal barrier function. In addition, isobutyrate can increase the production of intestinal SCFAs and 3-hydroxybutyric acid and inhibit the TLR4/MyD88/NF-κB signaling pathway to suppress intestinal inflammation. In conclusion, our findings demonstrate that isobutyrate confers resistance to IBD through host-microbiota interactions, providing a theoretical basis for the use of isobutyrate in alleviating colitis.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0673"},"PeriodicalIF":11.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genome-wide Pleiotropy Analysis Reveals Shared Genetic Associations between Type 2 Diabetes Mellitus and Subcortical Brain Volumes. 全基因组多效性分析揭示2型糖尿病与皮质下脑容量之间的共同遗传关联
IF 11 1区 综合性期刊
Research Pub Date : 2025-05-06 eCollection Date: 2025-01-01 DOI: 10.34133/research.0688
Qiyu Zhao, Jiayuan Xu, Ziqing Shi, Yang Zhang, Xin Du, Ying Zhai, Jinglei Xu, Feng Liu, Quan Zhang
{"title":"Genome-wide Pleiotropy Analysis Reveals Shared Genetic Associations between Type 2 Diabetes Mellitus and Subcortical Brain Volumes.","authors":"Qiyu Zhao, Jiayuan Xu, Ziqing Shi, Yang Zhang, Xin Du, Ying Zhai, Jinglei Xu, Feng Liu, Quan Zhang","doi":"10.34133/research.0688","DOIUrl":"https://doi.org/10.34133/research.0688","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM), a prevalent metabolic disorder marked by insulin resistance and hyperglycemia, has been linked to volumetric changes in subcortical regions, yet the genetic basis of this relationship remains unclear. We analyzed genome-wide association study summary data for T2DM and 14 subcortical volumetric traits, using MiXeR to quantify shared genetic architecture and applying conditional/conjunctional false discovery rate analyses to detect novel and shared genomic loci. Enrichment and gene expression analyses were subsequently performed to explore the biological functions and mechanisms of genes associated with these loci. We observed a substantial proportion of trait-influencing variants shared between T2DM and subcortical structures, with Dice coefficients ranging from 22.4% to 49.6%. Additionally, 70 distinct loci were identified as being jointly associated with T2DM and subcortical volumes, 5 and 22 of which were novel for T2DM and subcortical volumes, respectively. The 769 protein-coding genes mapped to these shared loci are enriched in metabolic and neurodevelopmental pathways and exhibit specific developmental trajectories, with 117 genes showing expression levels linked to both T2DM and subcortical structures. This study uncovered polygenic overlap between T2DM and subcortical structures, deepening our comprehension of the genetic factors linking metabolic disorders and brain health.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0688"},"PeriodicalIF":11.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-Cell RNA Sequencing Analysis Reveals the Role of Macrophage-Mediated CD44-AKT-CCL2 Pathways in Renal Tubule Injury during Calcium Oxalate Crystal Formation. 单细胞RNA测序分析揭示巨噬细胞介导的CD44-AKT-CCL2通路在草酸钙晶体形成过程中肾小管损伤中的作用
IF 11 1区 综合性期刊
Research Pub Date : 2025-05-06 eCollection Date: 2025-01-01 DOI: 10.34133/research.0690
Xi Jin, Zhongyu Jian, Yucheng Ma, Jun Wen, Ningning Chao, Xiaoting Chen, Liyuan Xiang, Yiqiong Yuan, Linhu Liu, Ya Li, Jingwen Wei, Banghua Liao, Li Zhang, Kunjie Wang
{"title":"Single-Cell RNA Sequencing Analysis Reveals the Role of Macrophage-Mediated CD44-AKT-CCL2 Pathways in Renal Tubule Injury during Calcium Oxalate Crystal Formation.","authors":"Xi Jin, Zhongyu Jian, Yucheng Ma, Jun Wen, Ningning Chao, Xiaoting Chen, Liyuan Xiang, Yiqiong Yuan, Linhu Liu, Ya Li, Jingwen Wei, Banghua Liao, Li Zhang, Kunjie Wang","doi":"10.34133/research.0690","DOIUrl":"https://doi.org/10.34133/research.0690","url":null,"abstract":"<p><p>Oxalate-induced crystalline kidney injury is a common form of crystal nephropathy. The accumulation of calcium oxalate (CaOx) crystal could lead to renal epithelium injury and inflammation. The underlying cellular events in kidney after CaOx crystal formation are largely unknown. This study was aimed to gain a better understanding of mouse kidney function in the development of renal CaOx formation. The study utilized a mouse CaOx model to analyze the cellular response at 5 time points using single-cell RNA sequencing and investigate the interaction of different cells during renal CaOx crystal formation. Additionally, the study investigated the communication between these cells and macrophages, as well as the role of chemokines in recruiting infiltrating macrophages. RNA velocity analysis uncovered an alternative differentiation pathway for injured and S1 proximal tubule cells, which mainly communicate with macrophages through the SPP1-CD44 pair, along with the expression of proinflammatory factors and stone matrix genes during renal CaOx crystal formation. Furthermore, resident Fn1 macrophages were found to express chemokines, such as CCL2, which recruited infiltrating macrophages. The CCL2 secretion was mediated by the CD44-AKT pathway. Blocking CCL2 decreased the expression of injury markers in the kidney, including CLU, LCN2, and KIM-1, and inhibited CaOx crystal deposition. The study identified potential cell types and target genes involved in renal tubule injury in oxalate-related crystal nephropathy. The findings shed light on the cellular processes that contribute to the formation and damage caused by CaOx crystals within the kidney, which could lead to the development of potential cell types and target genes for treating this condition.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0690"},"PeriodicalIF":11.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mutation in the Unrearranged PML Allele Confers Resistance to Arsenic Trioxide in Acute Promyelocytic Leukemia. 未重排PML等位基因突变赋予急性早幼粒细胞白血病对三氧化二砷的抗性。
IF 11 1区 综合性期刊
Research Pub Date : 2025-05-06 eCollection Date: 2025-01-01 DOI: 10.34133/research.0696
Pei-Han Yu, Chen-Ying Zhu, Yuan-Yuan Kang, Hua Naranmandura, Chang Yang
{"title":"Mutation in the Unrearranged <i>PML</i> Allele Confers Resistance to Arsenic Trioxide in Acute Promyelocytic Leukemia.","authors":"Pei-Han Yu, Chen-Ying Zhu, Yuan-Yuan Kang, Hua Naranmandura, Chang Yang","doi":"10.34133/research.0696","DOIUrl":"https://doi.org/10.34133/research.0696","url":null,"abstract":"<p><p>Arsenic trioxide (ATO) is able to selectively target and degrade the disease-causing PML::RARα (P/R) oncoprotein in acute promyelocytic leukemia (APL) for curing the disease. However, some relapsed patients develop resistance to ATO due to mutations in the promyelocytic leukemia (PML) part of the <i>PML::RARα</i> fusion gene. A relapsed APL patient had shown resistance to ATO and chemotherapy and was identified to harbor a point mutation (A216V) in the unrearranged <i>PML</i> allele rather than the <i>PML::RARα</i> fusion gene. Here, we report that mutations in the unrearranged <i>PML</i> allele impede the ATO-induced destabilization and degradation of the wild-type P/R oncoprotein. Deletion of the coiled-coil domain in a PML mutant completely reversed wild-type P/R protein resistance to ATO by abolishing the interaction between PML and P/R proteins. Collectively, our findings reveal that a point mutation in the unrearranged <i>PML</i> allele can confer ATO resistance through a protein-protein interaction. Therefore, the unrearranged <i>PML</i> allele should also be screened for drug-resistant mutations in relapsed APL patients.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0696"},"PeriodicalIF":11.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Perfusion Parameter Map Generation from 3 Phases of Computed Tomography Perfusion in Stroke Using Generative Adversarial Networks. 基于生成对抗网络的脑卒中ct灌注3个阶段的灌注参数图生成。
IF 11 1区 综合性期刊
Research Pub Date : 2025-04-30 eCollection Date: 2025-01-01 DOI: 10.34133/research.0689
Cuidie Zeng, Xiaoling Wu, Fusheng Ouyang, Baoliang Guo, Xiao Zhang, Jianghua Ma, Dong Zeng, Bin Zhang
{"title":"Perfusion Parameter Map Generation from 3 Phases of Computed Tomography Perfusion in Stroke Using Generative Adversarial Networks.","authors":"Cuidie Zeng, Xiaoling Wu, Fusheng Ouyang, Baoliang Guo, Xiao Zhang, Jianghua Ma, Dong Zeng, Bin Zhang","doi":"10.34133/research.0689","DOIUrl":"https://doi.org/10.34133/research.0689","url":null,"abstract":"<p><p>Computed tomography perfusion (CTP) plays a crucial role in guiding reperfusion therapy and patient selection for acute ischemic stroke (AIS) through perfusion parameter maps of the brain; however, its widespread use is limited by the complexity of acquisition protocols and high radiation dose. Previous studies have attempted to reduce radiation exposure by equally lowering the temporal sampling rate; however, it may miss the peak of arterial enhancement, leading to underestimation of blood flow parameter. Here, we investigate the feasibility of using a generative adversarial network (GAN) to generate perfusion maps from 3 phases of CTP (mCTP). The three phases were chosen based on the multiphase computed tomography angiography scanning protocol: the peak arterial input function phase, the peak venous output function phase, and the delayed venous output function phase. The findings demonstrate that the GAN model achieved high visual overlap and performance for cerebral blood flow and time-to-maximum maps, with a mean structural similarity index measure of 0.921 to 0.971 and 0.817 to 0.883, a mean normalized root mean squared error of 0.019 to 0.108 and 0.058 to 0.064, and a mean learned perceptual image patch similarity of 0.039 to 0.088 and 0.141 to 0.146, respectively. For the 2 external datasets, the volume agreement between the model- and CTP-derived infarct and hypoperfusion areas was the intraclass correlation coefficient of 0.731 to 0.883 and 0.499 to 0.635, and the Spearman correlation coefficient of 0.720 to 0.808 and 0.533 to 0.6540, respectively. Qualitative assessments of diagnostic quality further confirmed that the mCTP-derived maps were comparable to those obtained from traditional CTP. In conclusion, the GAN-based model is effective in generating perfusion maps from mCTP, which could serve as a viable alternative to traditional CTP in the diagnostic evaluation of AIS.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0689"},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Discovery of Phages in the Substantia Nigra and Its Implication for Parkinson's Disease. 黑质噬菌体的发现及其对帕金森病的意义。
IF 11 1区 综合性期刊
Research Pub Date : 2025-04-30 eCollection Date: 2025-01-01 DOI: 10.34133/research.0657
Yun Zhao, Changxian Xiong, Bingwei Wang, Daotong Li, Jiarui Liu, Shizhang Wei, Yujia Hou, Yuan Zhou, Ruimao Zheng
{"title":"The Discovery of Phages in the Substantia Nigra and Its Implication for Parkinson's Disease.","authors":"Yun Zhao, Changxian Xiong, Bingwei Wang, Daotong Li, Jiarui Liu, Shizhang Wei, Yujia Hou, Yuan Zhou, Ruimao Zheng","doi":"10.34133/research.0657","DOIUrl":"https://doi.org/10.34133/research.0657","url":null,"abstract":"<p><p><b>Background:</b> A century ago, a mystery between a virus and Parkinson's disease (PD) was described. Owing to the limitation of human brain biopsy and the challenge of electron microscopy in observing virions in human brain tissue, it has been difficult to study the viral etiology of PD. Recent discovery of virobiota reveals that viruses coexist with humans as symbionts. Newly developed transcriptomic sequencing and novel bioinformatic approaches for mining the encrypted virome in human transcriptome make it possible to study the relationship between symbiotic viruses and PD. Nevertheless, whether viruses exist in the human substantia nigra (SN) and whether symbiotic viruses underlie PD pathogenesis remain unknown. <b>Methods:</b> We collected current worldwide human SN transcriptomic datasets from the United States, the United Kingdom, the Netherlands, and Switzerland. We used bioinformatic approaches including viruSITE and the Viral-Track to identify the existence of viruses in the SN of patients. The comprehensive RNA sequencing-based virome analysis pipeline was used to characterize the virobiota in the SN. The Pearson's correlation analysis was used to examine the association between the viral RNA fragment counts (VRFCs) and PD-related human gene sequencing reads in the SN. The differentially expressed genes (DEGs) in the SN between PD patients and non-PD individuals were used to examine the molecular signatures of PD and also evaluate the impact of symbiotic viruses on the SN. <b>Findings:</b> We observed the existence of viruses in the human SN. A dysbiosis of virobiota was found in the SN of PD patients. A marked correlation between VRFC and PD-related human gene expression was detected in the SN of PD patients. These PD-related human genes correlated to VRFC were named as the virus-correlated PD-related genes (VPGs). We identified 3 bacteriophages (phages), including the <i>Proteus</i> phage VB_PmiS-Isfahan, the <i>Escherichia</i> phage phiX174, and the <i>Lactobacillus</i> phage Sha1, that might impair the gene expression of neural cells in the SN of PD patients. The <i>Proteus</i> phage VB_PmiS-Isfahan was a common virus in the SN of patients from the United Kingdom, the Netherlands, and Switzerland. VPGs and DEGs together highlighted that the phages might dampen dopamine biosynthesis and weaken the cGAS-STING function. <b>Interpretation:</b> This is the first study to discover the involvement of phages in PD pathogenesis. A lifelong low symbiotic viral load in the SN may be a contributor to PD pathogenesis. Our findings unlocked the black box between brain virobiota and PD, providing a novel insight into PD etiology from the perspective of phage-human symbiosis.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0657"},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum to "Aggravated Ulcerative Colitis via circNlgn-Mediated Suppression of Nuclear Actin Polymerization". “通过环lnn介导的核肌动蛋白聚合抑制加重溃疡性结肠炎”的勘误。
IF 11 1区 综合性期刊
Research Pub Date : 2025-04-29 eCollection Date: 2025-01-01 DOI: 10.34133/research.0684
William W Du, Chi Zhou, Hui Yang, Shuoyang Wen, Yu Chen, Eric X Chen, Xiuwei H Yang, Feiya Li, Kevin Y Du, Hui Yuan, Ting Ye, Javeria Qadir, Burton B Yang
{"title":"Erratum to \"Aggravated Ulcerative Colitis via circNlgn-Mediated Suppression of Nuclear Actin Polymerization\".","authors":"William W Du, Chi Zhou, Hui Yang, Shuoyang Wen, Yu Chen, Eric X Chen, Xiuwei H Yang, Feiya Li, Kevin Y Du, Hui Yuan, Ting Ye, Javeria Qadir, Burton B Yang","doi":"10.34133/research.0684","DOIUrl":"https://doi.org/10.34133/research.0684","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.34133/research.0441.].</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0684"},"PeriodicalIF":11.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microrobotic Swarms for Cancer Therapy. 用于癌症治疗的微型机器人群。
IF 11 1区 综合性期刊
Research Pub Date : 2025-04-29 eCollection Date: 2025-01-01 DOI: 10.34133/research.0686
Leiming Xie, Jinbo Liu, Zhen Yang, Hui Chen, Yibin Wang, Xingzhou Du, Yongping Fu, Peng Song, Jiangfan Yu
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