hLifePub Date : 2024-12-01DOI: 10.1016/j.hlife.2024.07.007
Xiaohong Zhou , Qian Zhu , Anqi Zheng , Boyuan Xue , Qihui Wang , Lip Ket Chin , Jingkun Jiang , Miao He
{"title":"De novo design of covalent bonding peptides for target protein","authors":"Xiaohong Zhou , Qian Zhu , Anqi Zheng , Boyuan Xue , Qihui Wang , Lip Ket Chin , Jingkun Jiang , Miao He","doi":"10.1016/j.hlife.2024.07.007","DOIUrl":"10.1016/j.hlife.2024.07.007","url":null,"abstract":"<div><div>To rapidly develop hyper-stable inhibitors that bind specifically and covalently to functional proteins is critical for diagnostics and therapeutics. Taking targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants as an example, we report a fast and low-cost <em>de novo</em> design strategy on covalent bonding peptides toward the SARS-CoV-2 spike protein receptor-binding domain (RBD), hence blocking its interaction with the human angiotensin-converting enzyme 2 (hACE2). As a proof-of-concept, peptide scaffolds built by ligating the hotspot residues at the hACE2-Omicron RBD interface were docked against RBD, and then the chemically modified peptides were designed by predicting their reactivity against RBD using a modified Amber ff14SB force field. Two peptides (15- and 16-mer peptides) were equipped with sulfonyl fluoride warheads bound with the conserved Y449 residue of RBD <em>via</em> the sulfur (VI) fluoride exchange (SuFEx) click chemistry. With permanent bonding and without dissociation, the two peptides blocked Omicron BA.2 pseudovirus infection with 50% inhibitory concentration (IC<sub>50</sub>) values of 1.07 μM and 1.56 μM, respectively. Our design approach greatly promotes the discovery of hyper-stable inhibitors against SARS-CoV-2 variants and other rapidly evolving viruses, potentially applicable to combat future viral outbreaks efficiently.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 12","pages":"Pages 641-652"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143180726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
hLifePub Date : 2024-11-01DOI: 10.1016/j.hlife.2024.06.004
Qun Yan , Ibrokhim Yulchievich Abdurakhmonov , Jinghua Cao
{"title":"Cooperation and innovation: An interview with Minister Ibrokhim Y. Abdurakhmonov and Professor Jinghua Cao","authors":"Qun Yan , Ibrokhim Yulchievich Abdurakhmonov , Jinghua Cao","doi":"10.1016/j.hlife.2024.06.004","DOIUrl":"10.1016/j.hlife.2024.06.004","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 11","pages":"Pages 547-553"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
hLifePub Date : 2024-11-01DOI: 10.1016/j.hlife.2024.06.006
Guanglin He , Mengge Wang , Lintao Luo , Qiuxia Sun , Haibing Yuan , Hongliang Lv , Yuhang Feng , Xiaojun Liu , Jing Cheng , Fengxiao Bu , Maxat Zhabagin , Huijun Yuan , Chao Liu , Shuhua Xu
{"title":"Population genomics of Central Asian peoples unveil ancient Trans-Eurasian genetic admixture and cultural exchanges","authors":"Guanglin He , Mengge Wang , Lintao Luo , Qiuxia Sun , Haibing Yuan , Hongliang Lv , Yuhang Feng , Xiaojun Liu , Jing Cheng , Fengxiao Bu , Maxat Zhabagin , Huijun Yuan , Chao Liu , Shuhua Xu","doi":"10.1016/j.hlife.2024.06.006","DOIUrl":"10.1016/j.hlife.2024.06.006","url":null,"abstract":"<div><div>Central Asia, a crucible of prehistoric and historical Trans-Eurasian interactions, has been pivotal in shaping cultural exchanges, population dynamics, and genetic admixture. Recent insights from ancient DNA studies have shed light on the extensive population turnover within this region, encompassing a spectrum of groups from Paleolithic hunter-gatherers to Holocene herders and the nomadic pastoralist empires of historical times. The genomic analysis of ancient pathogens across the Eurasian steppe has further deepened our understanding of pathogen origins, clonal expansions, and the intricate processes of host-pathogen coevolution in relation to varying pathogen exposures and their spread. We consolidate the latest findings pertaining to the ancient human and pathogen genomes of Central Asia, elucidating their profound influence on the genomic tapestry of contemporary Central Asians. A notable gap in the current genomic databases for Central Asia is underscored, particularly within the scope of genomics-driven precision medicine. We stress the urgent need for the development of extensive, region-specific genomic resources that hold promise for revealing the genetic blueprints underlying human traits and diseases, refining polygenic scoring models for predictive medicine, and bolstering genomic research endeavors across Central Asia.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 11","pages":"Pages 554-562"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
hLifePub Date : 2024-11-01DOI: 10.1016/j.hlife.2024.08.001
Fengrong Zhang , Yong Fan , Nghi Van Phung , Boyang Ji , Junmiao Chen , Xingyue Xu , Fuli Li , Peifeng Ji , Hongjun Yang , Xianyu Li
{"title":"Nervonic acid alleviates stroke and its associated poststroke depression behaviors","authors":"Fengrong Zhang , Yong Fan , Nghi Van Phung , Boyang Ji , Junmiao Chen , Xingyue Xu , Fuli Li , Peifeng Ji , Hongjun Yang , Xianyu Li","doi":"10.1016/j.hlife.2024.08.001","DOIUrl":"10.1016/j.hlife.2024.08.001","url":null,"abstract":"<div><div>Nervonic acid (NA) is an important long-chain monounsaturated fatty acid found in mammalian nervous tissue. It has recently garnered research attention due to its therapeutic potential in treating psychiatric and neurodegenerative disorders. In this study, we investigated the efficacy of NA in treating ischemia/reperfusion and poststroke events in a rat model. Specifically, there was significant reduction in the infarct area, cell death, and neuronal swelling after NA treatment, and the improvement in cerebral blood flow was also observed on day five after middle cerebral artery occlusion. Moreover, NA treatment led to the upregulation of brain-derived neurotrophic factors and myelin basic protein genes. NA displayed improved effects on depressive-like behavior of rats by three validated assays—the sucrose preference test, open-field test, and forced swim test. Regarding the mechanism of action, direct supplementation of NA in the brain was observed. We also observed the indirect effects of NA on the gut microbiota. Notably, the NA group gradually restored the bacterial diversity and the EGb group exhibited no impact based on observed-out analysis. We found an increase in the abundance of <em>Blautia</em> and <em>Sutterella</em>, which participated in phenylalanine metabolism. The metabolomics of plasma and brain samples revealed a decrease in the levels of phenylalanine-based amino acids, which alleviated the inhibitory effects on glutamine metabolism and promoted the recovery and signaling transmission of neurons after stroke. Altogether, our findings suggest that NA can be a viable treatment option for alleviating stroke and its associated poststroke depressive-like behaviors.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 11","pages":"Pages 592-606"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
hLifePub Date : 2024-11-01DOI: 10.1016/j.hlife.2024.07.006
Sunil Kumar Verma , Renu Khare , Devendra Singh
{"title":"Current perspectives on neuroendocrine tumors","authors":"Sunil Kumar Verma , Renu Khare , Devendra Singh","doi":"10.1016/j.hlife.2024.07.006","DOIUrl":"10.1016/j.hlife.2024.07.006","url":null,"abstract":"<div><div>Neoplasms arising from neuroendocrine cells form a heterogeneous group known as neuroendocrine tumors (NETs), which possess both endocrine and neural characteristics. These tumors can occur in various organs throughout the body, with the most prominent sites being the gastrointestinal tract, pancreas, and lungs. Despite their relatively low incidence, NETs have gained significant attention due to their unique biology and clinical behavior. This review intends to provide a widespread gestalt of the present perception of NETs, including their epidemiology, etiology, pathogenesis, classification, clinical presentation, diagnostic modalities, treatment options, and prognosis. Treatment strategies for NETs depend on tumor grade, stage, location, and functional status. Surgical resection remains the pillar of curative treatment for localized disease; on the other hand, systemic therapies take account of targeted therapies like tyrosine kinase inhibitors (TKIs), peptide receptor radionuclide therapy (PRRT), somatostatin analogs, and immunotherapy have shown promising results in advanced cases. In conclusion, this review provides an up-to-date summary of our current knowledge regarding neuroendocrine tumors. Further research is needed to better understand the underlying molecular mechanisms driving tumor development and progression. This will aid in developing novel therapeutic strategies targeting specific pathways involved in NET pathogenesis to improve patient outcomes.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 11","pages":"Pages 563-575"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
hLifePub Date : 2024-11-01DOI: 10.1016/j.hlife.2024.07.003
Min Wu , Guijie Bai , Ziyi Zhang , Haixia Xiao , Wenliang Sun , Chaoguang Tian
{"title":"Targeted protein editing technique in living mammalian cells by peptide-fused PNGase","authors":"Min Wu , Guijie Bai , Ziyi Zhang , Haixia Xiao , Wenliang Sun , Chaoguang Tian","doi":"10.1016/j.hlife.2024.07.003","DOIUrl":"10.1016/j.hlife.2024.07.003","url":null,"abstract":"<div><div>Various precise gene editing techniques at the DNA/RNA level, driven by clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology, have gained significant prominence. Yet, research on targeted protein editing techniques remains limited. Only a few attempts have been made, including the use of specific proteases and de-O-glycosylating enzymes as editing enzymes. Here, we propose direct editing of N-glycosylated proteins using de-N-glycosylating enzymes to modify N-glycosylation and simultaneously alter the relevant asparagine residue to aspartate in living cells. Selective protein deglycosylation editors were developed by fusing high-affinity protein-targeting peptides with active peptide:N-glycanases (PNGases). Three crucial cell membrane proteins, programmed cell death protein-1 (PD-1), programmed cell death-1 ligand 1 (PD-L1), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein, were chosen to be tested as a proof of concept. N-linked glycans were removed, and the relevant sites were converted from Asn to Asp in living mammalian cells, destabilizing target proteins and accelerating their degradation. Further investigation focused on SARS-CoV-2 spike protein deglycosylation editing. The collaboration of LCB1-PNGase F (PNGF) effectively reduced syncytia formation, inhibited pseudovirus packaging, and significantly hindered virus entry into host cells, which provides insights for coronavirus disease 2019 (COVID-19) treatment. This tool enables editing protein sequences post-de-N-glycosylation in living human cells, shedding light on protein N-glycosylation functions, and Asn to Asp editing in organisms. It also offers the potential for developing protein degradation technologies.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 11","pages":"Pages 576-591"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
hLifePub Date : 2024-10-01DOI: 10.1016/j.hlife.2024.03.004
{"title":"Regulatory functions and mechanisms of human microbiota in infectious diseases","authors":"","doi":"10.1016/j.hlife.2024.03.004","DOIUrl":"10.1016/j.hlife.2024.03.004","url":null,"abstract":"<div><div>The human microbiota, a diverse community of microorganisms living on or within their hosts, play an irreplaceable role in maintaining human health. Dysbiosis of the microbiota is associated with the pathogenesis of diverse human diseases. In recent years, growing evidence has been presented to support the substantial effect of human microbiota on the progression of infectious diseases. In this review, we describe the functional role of human microbiota in infectious diseases by highlighting their Janus-faced effects in the regulation of acute and chronic infections as well as their related co-morbidities. Thereafter, we review the latest advances elucidating the mechanisms underlying tri-directional interactions between the microbiota, hosts, and invading pathogens, with a further discussion on external environmental factors that shape this interconnected regulatory network. A better understanding of the regulatory functions and mechanisms of human microbiota in infectious diseases will facilitate the development of new diagnostic, preventive, and therapeutic approaches for infectious diseases.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 10","pages":"Pages 496-513"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140283515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
hLifePub Date : 2024-10-01DOI: 10.1016/j.hlife.2024.05.003
Qi Pan , Xiaomin Xing , Jianhai Yu , Qiang Chen , Haizhan Jiao , Wanqin Zhang , Yingfen Wen , Ming Gao , Wei Zhao , Lei Yu , Hongli Hu
{"title":"Structural insights into the distinct protective mechanisms of human antibodies targeting ZIKV NS1","authors":"Qi Pan , Xiaomin Xing , Jianhai Yu , Qiang Chen , Haizhan Jiao , Wanqin Zhang , Yingfen Wen , Ming Gao , Wei Zhao , Lei Yu , Hongli Hu","doi":"10.1016/j.hlife.2024.05.003","DOIUrl":"10.1016/j.hlife.2024.05.003","url":null,"abstract":"<div><div>Antibodies targeting non-structural protein 1 (NS1) confer protection against Zika virus (ZIKV). Although monoclonal antibodies (MAbs) 3G2 and 4B8 are more potent than MAb 4F10 in suppressing ZIKV infection in neonatal mice models, the epitopes are unclear. Herein, we determined the Cryo-electron microscopy (Cryo-EM) structures of ZIKV NS1 in complex with five human antibodies at 2.6–2.9 Å resolution. Group I antibodies (3G2 and 4B8) recognize the previously unreported epitopes on the outer surface of the NS1 dimer. The unique binding mode of Group I antibodies led to a stronger recognition of the cell surface form of NS1 and completely inhibited secreted form non-structural protein 1 (sNS1)-induced endothelial permeability <em>via</em> their immunoglobulin G (IgG) and Fab. Group II antibodies (4F10, 2E11, and 14G5) recognize common epitopes in the distal end of the β-ladder domain, with a blockade efficiency that may be related to their affinity for the sNS1 protein and the presence of full-length IgG. These findings elucidate the correlation between epitope recognition and protective efficacy of anti-NS1 antibodies and highlight the diagnostic and therapeutic potential of 3G2 and 4B8.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 10","pages":"Pages 527-541"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142533679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}