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Generation and characterization of nanobodies targeting GPCR. 以 GPCR 为靶标的纳米抗体的生成和表征。
Biophysics reports Pub Date : 2024-02-29 DOI: 10.52601/bpr.2023.230026
Shenglan Zhang, Zhiran Fan, Jianfeng Liu
{"title":"Generation and characterization of nanobodies targeting GPCR.","authors":"Shenglan Zhang, Zhiran Fan, Jianfeng Liu","doi":"10.52601/bpr.2023.230026","DOIUrl":"10.52601/bpr.2023.230026","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are a large family of cell membrane proteins that are important targets for drug discovery. Nanobodies, also known as VHH (variable domains of heavy chain-only antibodies, HcAbs) antibodies, are small antibody fragments derived from camelids that have gained significant attention as potential therapeutics for targeting GPCRs due to their advantages over conventional antibodies. However, there are challenges in developing nanobodies targeting GPCRs, among which epitope accessibility is the most significant because the cell membrane partially shields the GPCR surface. We developed a universal protocol for making nanobodies targeting GPCRs using the cell membrane extract of GPCR-overexpressing HEK293 cells as the llama/alpaca immunization antigen. We constructed an immune VHH library and identified nanobodies by phage display bio-panning. The monoclonal nanobodies were recombinantly expressed in <i>Escherichia coli (E. coli)</i> and purified to characterize their binding potency.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 1","pages":"22-30"},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912684","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}
引用次数: 0
Life under tension: the relevance of force on biological polymers. 张力下的生命：力对生物聚合物的影响。
Biophysics reports Pub Date : 2024-02-29 DOI: 10.52601/bpr.2023.230019
Matthew T J Halma, Longfu Xu
{"title":"Life under tension: the relevance of force on biological polymers.","authors":"Matthew T J Halma, Longfu Xu","doi":"10.52601/bpr.2023.230019","DOIUrl":"10.52601/bpr.2023.230019","url":null,"abstract":"<p><p>Optical tweezers have elucidated numerous biological processes, particularly by enabling the precise manipulation and measurement of tension. One question concerns the biological relevance of these experiments and the generalizability of these experiments to wider biological systems. Here, we categorize the applicability of the information garnered from optical tweezers in two distinct categories: the direct relevance of tension in biological systems, and what experiments under tension can tell us about biological systems, while these systems do not reach the same tension as the experiment, still, these artificial experimental systems reveal insights into the operations of biological machines and life processes.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 1","pages":"48-56"},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912738","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}
引用次数: 0
Catecholaminergic neurons orchestrate fasting-induced immune harmony. 儿茶酚胺能神经元协调空腹诱导的免疫和谐。
Biophysics reports Pub Date : 2024-02-29 DOI: 10.52601/bpr.2024.240901
Mengdi Guo, Weiyan Wang, Xiao Tu, Meiling Jiang, Cun-Jin Zhang
{"title":"Catecholaminergic neurons orchestrate fasting-induced immune harmony.","authors":"Mengdi Guo, Weiyan Wang, Xiao Tu, Meiling Jiang, Cun-Jin Zhang","doi":"10.52601/bpr.2024.240901","DOIUrl":"10.52601/bpr.2024.240901","url":null,"abstract":"","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 1","pages":"57-59"},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912517","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}
引用次数: 0
APTAnet: an atom-level peptide-TCR interaction affinity prediction model. APTAnet：原子级多肽-TCR相互作用亲和力预测模型。
Biophysics reports Pub Date : 2024-02-29 DOI: 10.52601/bpr.2023.230037
Peng Xiong, Anyi Liang, Xunhui Cai, Tian Xia
{"title":"APTAnet: an atom-level peptide-TCR interaction affinity prediction model.","authors":"Peng Xiong, Anyi Liang, Xunhui Cai, Tian Xia","doi":"10.52601/bpr.2023.230037","DOIUrl":"10.52601/bpr.2023.230037","url":null,"abstract":"<p><p>The prediction of affinity between TCRs and peptides is crucial for the further development of TIL (Tumor-Infiltrating Lymphocytes) immunotherapy. Inspired by the broader research of drug-protein interaction (DPI), we propose an atom-level peptide-TCR interaction (PTI) affinity prediction model APTAnet using natural language processing methods. APTAnet model achieved an average ROC-AUC and PR-AUC of 0.893 and 0.877, respectively, in ten-fold cross-validation on 25,675 pairs of PTI data. Furthermore, experimental results on an independent test set from the McPAS database showed that APTAnet outperformed the current mainstream models. Finally, through the validation on 11 cases of real tumor patient data, we found that the APTAnet model can effectively identify tumor peptides and screen tumor-specific TCRs.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912516","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}
引用次数: 0
Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection. 通过连续尾静脉注射筛选小鼠黑色素瘤细胞中的转移相关基因。
Biophysics reports Pub Date : 2024-02-29 DOI: 10.52601/bpr.2023.230043
Qinggang Hao, Rui Dong, Weiyu Bai, Dong Chang, Xinyi Yao, Yingru Zhang, Huangying Xu, Huiyan Li, Xiang Kui, Feng Wang, Yan Wang, Chengqin Wang, Yujie Lei, Yan Chen, Junling Shen, Lei Sang, Yan Bai, Jianwei Sun
{"title":"Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection.","authors":"Qinggang Hao, Rui Dong, Weiyu Bai, Dong Chang, Xinyi Yao, Yingru Zhang, Huangying Xu, Huiyan Li, Xiang Kui, Feng Wang, Yan Wang, Chengqin Wang, Yujie Lei, Yan Chen, Junling Shen, Lei Sang, Yan Bai, Jianwei Sun","doi":"10.52601/bpr.2023.230043","DOIUrl":"10.52601/bpr.2023.230043","url":null,"abstract":"<p><p>Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of <i>in vivo</i> screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 1","pages":"15-21"},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912787","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}
引用次数: 0
Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion. 建立 Fah-LSL 小鼠模型，研究 BEC 向肝细胞的转化。
Biophysics reports Pub Date : 2023-12-31 DOI: 10.52601/bpr.2023.230034
Xingrui Wang, Wenjuan Pu, Huan Zhu, Mingjun Zhang, Bin Zhou
{"title":"Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion.","authors":"Xingrui Wang, Wenjuan Pu, Huan Zhu, Mingjun Zhang, Bin Zhou","doi":"10.52601/bpr.2023.230034","DOIUrl":"10.52601/bpr.2023.230034","url":null,"abstract":"<p><p>The liver consists predominantly of hepatocytes and biliary epithelial cells (BECs), which serve distinct physiological functions. Although hepatocytes primarily replenish their own population during homeostasis and injury repair, recent findings have suggested that BECs can transdifferentiate into hepatocytes when hepatocyte-mediated liver regeneration is impaired. However, the cellular and molecular mechanisms governing this BEC-to-hepatocyte conversion remain poorly understood largely because of the inefficiency of existing methods for inducing lineage conversion. Therefore, this study introduces a novel mouse model engineered by the Zhou's lab, where hepatocyte senescence is induced by the deletion of the fumarylacetoacetate (<i>Fah</i>) gene. This model facilitates the efficient conversion of BECs to hepatocytes and allows for the simultaneous lineage tracing of BECs; consequently, a transitional liver progenitor cell population can be identified during lineage conversion. This study also outlines the technical procedures for utilizing this model to determine the underlying cellular and molecular mechanisms of BEC-to-hepatocyte conversion and provides new insights into liver regeneration and its underlying molecular mechanism.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 6","pages":"309-324"},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10960572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208410","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}
引用次数: 0
Regulation of cellular senescence by innate immunity. 先天性免疫对细胞衰老的调节。
Biophysics reports Pub Date : 2023-12-31 DOI: 10.52601/bpr.2023.230032
Jinxiu Hou, Yi Zheng, Chengjiang Gao
{"title":"Regulation of cellular senescence by innate immunity.","authors":"Jinxiu Hou, Yi Zheng, Chengjiang Gao","doi":"10.52601/bpr.2023.230032","DOIUrl":"10.52601/bpr.2023.230032","url":null,"abstract":"<p><p>During the COVID-19 pandemic, the interplay between the processes of immunity and senescence is drawing more and more intensive attention. SARS-CoV-2 infection induces senescence in lung cells, failure to clear infected cells and increased presence of inflammatory factors could lead to a cytokine storm and acute respiratory disease syndrome (ARDS), which together with aging and age-associated disease lead to 70% of COVID-19-related deaths. Studies on how senescence initiates upon viral infection and how to restrict excessive accumulation of senescent cells to avoid harmful inflammation are crucially important. Senescence can induce innate immune signaling, and innate immunity can engage cell senescence. Here, we mainly review the innate immune pathways, such as cGAS-STING, TLRs, NF-κB, and NLRP3 inflammasome, participating in the senescence process. In these pathways, IFN-I and inflammatory factors play key roles. At the end of the review, we propose the strategies by which we can improve the immune function and reduce inflammation based on these findings.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 6","pages":"338-351"},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10960571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208413","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}
引用次数: 0
Rapid quantification of 50 fatty acids in small amounts of biological samples for population molecular phenotyping. 快速量化少量生物样本中的 50 种脂肪酸，用于群体分子表型分析。
Biophysics reports Pub Date : 2023-12-31 DOI: 10.52601/bpr.2023.230042
Pinghui Liu, Qinsheng Chen, Lianglong Zhang, Chengcheng Ren, Biru Shi, Jingxian Zhang, Shuaiyao Wang, Ziliang Chen, Qi Wang, Hui Xie, Qingxia Huang, Huiru Tang
{"title":"Rapid quantification of 50 fatty acids in small amounts of biological samples for population molecular phenotyping.","authors":"Pinghui Liu, Qinsheng Chen, Lianglong Zhang, Chengcheng Ren, Biru Shi, Jingxian Zhang, Shuaiyao Wang, Ziliang Chen, Qi Wang, Hui Xie, Qingxia Huang, Huiru Tang","doi":"10.52601/bpr.2023.230042","DOIUrl":"10.52601/bpr.2023.230042","url":null,"abstract":"<p><p>Efficient quantification of fatty-acid (FA) composition (fatty-acidome) in biological samples is crucial for understanding physiology and pathophysiology in large population cohorts. Here, we report a rapid GC-FID/MS method for simultaneous quantification of all FAs in numerous biological matrices. Within eight minutes, this method enabled simultaneous quantification of 50 FAs as fatty-acid methyl esters (FAMEs) in femtomole levels following the efficient transformation of FAs in all lipids including FFAs, cholesterol-esters, glycerides, phospholipids and sphingolipids. The method showed satisfactory inter-day and intra-day precision, stability and linearity (R<sup>2</sup> > 0.994) within a concentration range of 2-3 orders of magnitude. FAs were then quantified in typical multiple biological matrices including human biofluids (urine, plasma) and cells, animal intestinal content and tissue samples. We also established a quantitative structure-retention relationship (QSRR) for analytes to accurately predict their retention time and aid their reliable identification. We further developed a novel no-additive retention index (NARI) with endogenous FAMEs reducing inter-batch variations to 15 seconds; such NARI performed better than the alkanes-based classical RI, making meta-analysis possible for data obtained from different batches and platforms. Collectively, this provides an inexpensive high-throughput analytical system for quantitative phenotyping of all FAs in 8-minutes multiple biological matrices in large cohort studies of pathophysiological effects.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 6","pages":"299-308"},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10960574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208412","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}
引用次数: 0
Nucleoside deaminases: the key players in base editing toolkit. 核苷脱氨酶：碱基编辑工具包中的关键角色。
Biophysics reports Pub Date : 2023-12-31 DOI: 10.52601/bpr.2023.230029
Jiangchao Xiang, Wenchao Xu, Jing Wu, Yaxin Luo, Bei Yang, Jia Chen
{"title":"Nucleoside deaminases: the key players in base editing toolkit.","authors":"Jiangchao Xiang, Wenchao Xu, Jing Wu, Yaxin Luo, Bei Yang, Jia Chen","doi":"10.52601/bpr.2023.230029","DOIUrl":"10.52601/bpr.2023.230029","url":null,"abstract":"<p><p>The development of nucleoside deaminase-containing base editors realized targeted single base change with high efficiency and precision. Such nucleoside deaminases include adenosine and cytidine deaminases, which can catalyze adenosine-to-inosine (A-to-I) and cytidine-to-uridine (C-to-U) conversion respectively. These nucleoside deaminases are under the spotlight because of their vast application potential in gene editing. Recent advances in the engineering of current nucleoside deaminases and the discovery of new nucleoside deaminases greatly broaden the application scope and improve the editing specificity of base editors. In this review, we cover current knowledge about the deaminases used in base editors, including their key structural features, working mechanisms, optimization, and evolution.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 6","pages":"325-337"},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10960570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208411","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}
引用次数: 0
An artificial intelligence model for embryo selection in preimplantation DNA methylation screening in assisted reproductive technology. 辅助生殖技术植入前 DNA 甲基化筛查中胚胎选择的人工智能模型。
Biophysics reports Pub Date : 2023-12-31 DOI: 10.52601/bpr.2023.230035
Jianhong Zhan, Chuangqi Chen, Na Zhang, Shuhuai Zhong, Jiaming Wang, Jinzhou Hu, Jiang Liu
{"title":"An artificial intelligence model for embryo selection in preimplantation DNA methylation screening in assisted reproductive technology.","authors":"Jianhong Zhan, Chuangqi Chen, Na Zhang, Shuhuai Zhong, Jiaming Wang, Jinzhou Hu, Jiang Liu","doi":"10.52601/bpr.2023.230035","DOIUrl":"10.52601/bpr.2023.230035","url":null,"abstract":"<p><p>Embryo quality is a critical determinant of clinical outcomes in assisted reproductive technology (ART). A recent clinical trial investigating preimplantation DNA methylation screening (PIMS) revealed that whole genome DNA methylation level is a novel biomarker for assessing ART embryo quality. Here, we reinforced and estimated the clinical efficacy of PIMS. We introduce PIMS-AI, an innovative artificial intelligence (AI) based model, to predict the probability of an embryo producing live birth and subsequently assist ART embryo selection. Our model demonstrated robust performance, achieving an area under the curve (AUC) of 0.90 in cross-validation and 0.80 in independent testing. In simulated embryo selection, PIMS-AI attained an accuracy of 81% in identifying viable embryos for patients. Notably, PIMS-AI offers significant advantages over conventional preimplantation genetic testing for aneuploidy (PGT-A), including enhanced embryo discriminability and the potential to benefit a broader patient population. In conclusion, our approach holds substantial promise for clinical application and has the potential to significantly improve the ART success rate.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 6","pages":"352-361"},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10960573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208409","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}
引用次数: 0
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