Journal of Advanced Research最新文献

{"title":"Mini and enhanced CRISPR activators for cancer therapies","authors":"Meiyu Huang, Keshan Wang, Anshu Li, Xiagu Zhu, Zuping Zhou, Chao Yang, Changhao Bi, Xueli Zhang","doi":"10.1016/j.jare.2024.10.027","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.027","url":null,"abstract":"<h3>Introduction</h3>The RNA-guided nuclease Cas9 can be used as a programmable transcription activator, but there is still room for improvement in its effectiveness in eukaryotes, and its potential in cancer genetic therapy has been poorly investigated.<h3>Objectives</h3>We aim to construct optimized CRISPRa tools and detect their potential role in cancer therapy by screening 9aa-TAD.<h3>Methods</h3>We selected a range of transcriptional coactivators for programmable activation and analyzed their effects on the expression of multiple endogenous genes using Flow cytometry and qRT-PCR. In order to improve the activation capacity of the CRISPRa tool, we fused the coactivators with the efficient dCas9-VPR system to construct a new activation system. Utilize RNA-seq to assess the activation specificity of genome-wide. To evaluate the value of the newly constructed activation system in cancer gene therapy, we activated the expression of the tumor suppressor genes <em>PER2</em> and <em>ZNF382</em>, and performed changes in cancer cell proliferation qRT-PCR and clonal formation analysis.<h3>Results</h3>In this study, we screened the NHR module from C. elegans, which demonstrated a high transcription activation capacity with a compact size compared to VP64. We successfully demonstrated its efficiency in activating endogenous genes in mammalian cells. Furthermore, we developed an enhanced fused variant called NHR-VP64-p65-Rta (NVPR), which showed even higher efficiency compared to the previously established VPR module, making it an effective CRISPRa tool. The dCas9-NVPR complex also exhibited high specificity on a genome-wide scale. Finally, we utilized the dCas9-NVPR tool to restore the expression of tumor suppressor genes <em>PER2</em> and <em>ZNF382</em>, effectively inhibiting the malignant phenotype of cancer cells.<h3>Conclusion</h3>We have successfully developed and demonstrated a breakthrough CRISPRa tool with promising implications for cancer genetic therapy. This innovation expands the range of available gene editing tools and further validates the immense potential of CRISPR-based approaches in precision medicine.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"145 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic associations of metabolic factors and therapeutic drug targets with polycystic ovary syndrome","authors":"Changlong Zhang, Yuxuan Li, Yang Wang, Shourui Hu, Yue Liu, Xiaofan Liang, Zi-Jiang Chen, Yuqing Zhang, Han Zhao","doi":"10.1016/j.jare.2024.10.038","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.038","url":null,"abstract":"<h3>Introduction</h3>Polycystic ovary syndrome (PCOS) is frequently accompanied with metabolic dysfunctions, yet the causal relationships between metabolic factors and PCOS remain to be conclusively established and etiology-based therapies are lacking.<h3>Objectives</h3>To comprehensively identify the metabolic causal factors and potential drug targets for PCOS.<h3>Methods</h3>This genetic association study was conducted using bidirectional two-sample Mendelian Randomization (MR), multivariable MR (MVMR) and drug-target MR. Considering metabolic sexual dimorphism, female-specific genome-wide association studies (GWASs) for metabolic factors were obtained. To ensure the robustness of the findings, an additional independent PCOS GWAS dataset was utilized for replication.<h3>Results</h3>The PCOS cohort included 10,074 PCOS cases (mean age 28 to 45 years) and 103,164 controls (mean age 27 to 60 years) of European ancestry. All participants were female. Employing two-sample MR analysis, we found that genetically proxied body mass index (BMI) (OR = 3.40 [95 % CI, 2.65–4.36]), triglyceride (TG) (OR = 1.54 [95 % CI, 1.17–2.04]), low-density lipoprotein cholesterol (LDL-c) (OR = 1.37 [95 % CI, 1.07–1.76]), and type 2 diabetes (T2D) (OR = 1.24 [95 % CI, 1.09–1.41]) were significantly associated with an increased risk of PCOS, whereas genetically predicted high-density lipoprotein cholesterol (HDL-c) (OR = 0.61 [95 % CI, 0.47–0.80]) decreased the odds of PCOS. Stepwise MVMR established a hierarchy of interactions among these metabolic factors, identifying BMI and HDL-c as the most prominent causal factors. Notably, drug-target MR analysis identified incretin-based therapeutics, PCSK9 inhibitors, LPL gene therapy, sulfonylureas, and thiazolidinediones as potential therapeutics for PCOS. All these findings were validated in an independent dataset.<h3>Conclusion</h3>This study offered insights into the roles of obesity, diabetes, and dyslipidemia in PCOS etiology and therapeutics, underscoring the necessity for managing metabolic health in women and paving the way for tailored therapeutic strategies for PCOS based on its metabolic underpinnings.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"scPerb: Predict single-cell perturbation via style transfer-based variational autoencoder","authors":"Zijia Tang, Minghao Zhou, Kai Zhang, Qianqian Song","doi":"10.1016/j.jare.2024.10.035","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.035","url":null,"abstract":"<h3>Introduction</h3>Traditional methods for obtaining cellular responses after perturbation are usually labor-intensive and costly, especially when working with multiple different experimental conditions. Therefore, accurate prediction of cellular responses to perturbations is of great importance in computational biology. Existing methodologies, such as graph-based approaches, vector arithmetic, and neural networks, either mix perturbation-related variances with cell-type-specific patterns or implicitly distinguish them within black-box models.<h3>Objectives</h3>This study aims to introduce and demonstrate a novel framework, scPerb, which explicitly extracts perturbation-related variances and transfers them from unperturbed to perturbed cells to accurately predict the effect of perturbation in single-cell level.<h3>Methods</h3>scPerb utilizes a style transfer strategy by incorporating a style encoder into the architecture of a variational autoencoder. The style encoder captures the differences in latent representations between unperturbed and perturbed cells, enabling accurate prediction of post-perturbation gene expression data.<h3>Results</h3>Comprehensive comparisons with existing methods demonstrate that scPerb delivers improved performance and higher accuracy in predicting cellular responses to perturbations. Notably, scPerb outperforms other methods across multiple datasets, achieving superior R² values of 0.98, 0.98, and 0.96 on three benchmarking datasets.<h3>Conclusion</h3>scPerb offers a significant advancement in predicting cellular responses by effectively separating and transferring perturbation-related variances. This framework not only enhances prediction accuracy but also provides a robust tool for computational biology, addressing the limitations of current methodologies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"61 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biofortification of potato nutrition","authors":"Linxuan Li, Tingting Zhu, Lina Wen, Tanran Zhang, Maozhi Ren","doi":"10.1016/j.jare.2024.10.033","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.033","url":null,"abstract":"<h3>Background</h3>Potato (<em>Solanum tuberosum</em> L.) is the fourth most important food crop after rice, wheat and maize in the world with the potential to feed the world’s population, and potato is a major staple food in many countries. Currently, potato is grown in more than 100 countries and is consumed by more than 1 billion people worldwide, and the global annual output exceeds 300 million tons. With the rapid increase in the global population, potato will play a key role in food supply. These aspects have driven scientists to genetically engineer potato for yield and nutrition improvement.<h3>Aim of review</h3>Potato is an excellent source of carbohydrates, rich in vitamins, phenols and minerals. At present, the nutritional fortification of potato has made remarkable progress, and the biomass and nutrient compositions of potato have been significantly improved through agronomic operation and genetic improvement. This review aims to summarize recent advances in the nutritional fortification of potato protein, lipid and vitamin, and provides new insights for future potato research.<h3>Key scientific concepts of review</h3>This review comprehensively summarizes the biofortification of potato five nutrients from protein, lipid, starch, vitamin and mineral. Meanwhile, we also discuss the multilayered insights in the prospects of edible potato fruit, vaccines and high-value products synthesis and diploid potato seeds reproduction.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"16 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic potentiation of the anti-metastatic effect of a Ginseng-Salvia miltiorrhiza herbal pair and its biological ingredients via the suppression of CD62E-dependent neutrophil infiltration and NET formation","authors":"Keqin Lu, Yawen Xia, Peng Cheng, Yanan Li, Liang He, Li Tao, Zhonghong Wei, Yin Lu","doi":"10.1016/j.jare.2024.10.036","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.036","url":null,"abstract":"<h3>Introduction</h3>The combination of the roots of <em>ginseng</em> and <em>Salvia miltiorrhiza</em> is an effective approach for treating metastatic cancer in patients with Qi stagnation and blood stasis patterns. However, the molecular mechanism underlying the combined use of <em>ginseng</em> and <em>Salvia miltiorrhiza</em> is unknown.<h3>Objectives</h3>This study unveils the pharmacological foundation of <em>ginseng</em> and <em>Salvia miltiorrhiza</em> by examining the involvement of neutrophils in the critical process of tumor hematogenous metastasis. Additionally, by employing a reverse pharmacology research model (effect–target–constituent), potential potent components were screened, and the dominant component formulations were determined.<h3>Methods</h3>An experimental lung metastatic model was constructed to compare the antitumor effects of <em>ginseng</em> and <em>Salvia miltiorrhiza</em>. RNA sequencing was employed to identify pivotal biological events and key targets, while the detection of CD62E expression and neutrophil extracellular traps (NETs) release was used to screen for effective substances in <em>ginseng</em> and <em>Salvia miltiorrhiza</em>. In addition, a comprehensive array of in vitro and in vivo experiments was conducted to explore the underlying mechanisms and therapeutic significance.<h3>Results</h3>Compared with single-herb use, the use of <em>ginseng</em> or <em>Salvia miltiorrhiza</em> significantly reduced tumor metastasis, which was accompanied by reduced neutrophil infiltration into the lungs. Cryptotanshinone (CPT), an active constituent of <em>Salvia miltiorrhiza</em>, can inhibit neutrophil adhesion and recruitment to lung tissue by downregulating the expression of E-selectin (CD62E) in endothelial cells. Moreover, the <em>ginseng</em> −derived ginsenoside Rg1 mitigated the formation of NETs in lung tissues and reversed the protumor effects of NETs. We further explored the efficacy of combination therapy with Rg1 and CPT, which also reduced tumor metastasis in vivo.<h3>Conclusion</h3><em>Ginseng</em> and <em>Salvia miltiorrhiza</em> exhibited a mutual potentiation of the anti-metastatic effect by suppressing both early and late stages of neutrophil-initiated metastasis cascade. Rg1 and CPT represent the synergistic ingredients from <em>ginseng</em> and <em>Salvia miltiorrhiza</em>, respectively.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"45 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exerkine irisin mitigates cognitive impairment by suppressing gut-brain axis-mediated inflammation","authors":"Hu Zhang, Jiling Liang, Jielun Huang, Minghui Wang, Liangwen Wu, Tong Wu, Ning Chen","doi":"10.1016/j.jare.2024.10.031","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.031","url":null,"abstract":"<h3>Introduction</h3>Exercise has been recognized to improve cognitive performance by optimizing gut flora and up-regulating exerkine irisin.<h3>Objective</h3>Although exercise-induced irisin is beneficial to cognitive improvement, whether this benefit is achieved by optimizing gut microbiota and metabolites is not fully explored.<h3>Methods</h3>After aerobic exercise and exogenous irisin interventions for 12 weeks, the 16S rRNA and metabolites in feces of 21-month-old mice were analyzed. Meanwhile, the differential miRNAs and mRNAs in hippocampal tissues were screened by high-throughput sequencing. Relevant mRNAs and proteins were evaluated by RT-PCR, Western blot, and immunofluorescence.<h3>Results</h3>Compared with the young control mice, irisin levels and cognitive capacity of aged mice revealed a significant reduction, while aerobic exercise and intraperitoneal injection of exogenous irisin reversed aging-induced cognitive impairment. Similarly, 147 up-regulated and 173 down-regulated metabolites were detected in aged mice, while 64 and 45 up-regulated and 225 and 187 down-regulated metabolites were detected in aged mice with exercise and irisin interventions, respectively. Moreover, during hippocampal miRNA and mRNA sequencing analysis, 9 differential gut flora and 35 differential genes were identified to be correlated with the inflammatory signaling mediated by the TLR4/MyD88 signal pathway.<h3>Conclusion</h3>Aging-induced cognitive impairment is due to insulin resistance induced by TLR4/MyD88 signaling activation in hippocampal tissues mediated by gut microbiota and metabolite changes. Myokine irisin may be an important mediator in optimizing gut microbiota and metabolism for an improved understanding of mitigated aging process upon exercise interventions.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"2 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-molecule targeting BCAT1-mediated BCAA metabolism inhibits the activation of SHOC2-RAS-ERK to induce apoptosis of Triple-negative breast cancer cells","authors":"Ling Huang, Guanjun Li, Ying Zhang, Ruishen Zhuge, Shijie Qin, Jinjun Qian, Ruixing Chen, Yin Kwan Wong, Huan Tang, Peili Wang, Wei Xiao, Jigang Wang","doi":"10.1016/j.jare.2024.10.021","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.021","url":null,"abstract":"<h3>Introduction</h3>Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with the worst prognosis. Exploring novel carcinogenic factors and therapeutic drugs for TNBC remains a focus to improve prognosis. Branched-chain amino acid transaminase 1 (BCAT1), a crucial enzyme in branched-chain amino acid (BCAA) metabolism, has been linked to various tumor developments, but its carcinogenic function and mechanism in TNBC remain unclear. Eupalinolide B (EB) is a naturally-derived small-molecule with anti-tumor activity, but its role in TNBC remains unknown.<h3>Objectives</h3>By exploring the targets and pharmacological mechanisms of EB in inhibiting TNBC, this study aimed to discover novel therapeutic targets and potential inhibitors for TNBC, and elucidate novel pathogenic mechanisms of TNBC.<h3>Methods</h3>The inhibitory effect of EB on TNBC was investigated using mouse models and cellular phenotypic experiments. Activity-based protein profiling (ABPP) technology, pull down-WB, CETSA-WB and MST were utilized to discover and validate the targets of EB. The oncogenic role of BCAT1 was determined through clinical data analysis and biochemical experiments. To elucidate the mechanism by which EB inhibited TNBC, many methods, including but not limited to HPLC and proteomic sequencing were used.<h3>Results</h3>We found that EB significantly inhibited TNBC progression. We identified BCAT1 as the direct target of EB and confirmed that BCAT1 was critical for TNBC development. EB inhibited BCAT1-involved BCAA metabolism to reduce the synthesis of BCAAs (including Leu, Ile, and Val), thereby inhibiting SHOC2 (a Leu-rich repeat protein) expression and the downstream SHOC2-participating RAS-ERK signaling pathway, ultimately leading to apoptosis of TNBC cells.<h3>Conclusion</h3>Collectively, this study not only elucidates the oncogenic role of BCAT1 and its downstream SHOC2-RAS-ERK signaling axis in TNBC progression but also opens up avenues for potential therapies targeting BCAT1 or BCAA metabolism (using EB alone or in combination with its inhibitor candesartan) for TNBC treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"61 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, m6A modification and diverse cell death mechanisms","authors":"Xiangyu Wang, Jianhua Yang, Wanting Yang, Haiyang Sheng, Buyun Jia, Peng Cheng, Shanshan Xu, Xinhui Hong, Chuanwei Jiang, Yinfeng Yang, Ziyin Wu, Jinghui Wang","doi":"10.1016/j.jare.2024.10.026","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.026","url":null,"abstract":"<h3>Background</h3>The protein p53, encoded by the most frequently mutated gene TP53 in human cancers, has diverse functions in tumor suppression. As a best known transcription factor, p53 can regulate various fundamental cellular responses, ranging from the cell-cycle arrest, DNA repair, senescence to the programmed cell death (PCD), which includes autophagy, apoptosis, ferroptosis, cuproptosis, pyroptosis and disulfidoptosis. Accumulating evidence has indicated that the tumor microenvironment (TME), N⁶-methyladenosine (m⁶A) modification and diverse PCD are important for the progression, proliferation and metastases of cancers.<h3>Aim of review</h3>This paper aims to systematically and comprehensively summarize the multiple roles of p53 in the development of cancers from the regulation of TME, m⁶A Modification and diverse PCD.<h3>Key scientific concepts of review</h3>TME, a crucial local homeostasis environment, influences every step of tumorigenesis and metastasis. m⁶A, the most prevalent and abundant endogenous modification in eukaryotic RNAs, plays an essential role in various biological processes, containing the progression of cancers. Additionally, PCD is an evolutionarily conserved mechanism of cell suicide and a common process in living organisms. Some forms of PCD contribute to the occurrence and development of cancer. However, the complex roles of p53 within the TME, m⁶A modification and diverse PCD mechanisms are still not completely understood. Presently, the function roles of p53 including the wild-type and mutant p53 in different context are summarized. Additionally, the interaction between the cancer immunity, cancer cell death and RNA m⁶A methylation and the p53 regulation during the development and progress of cancers were discussed. Moreover, the key molecular mechanisms by which p53 participates in the regulation of TME, m⁶A and diverse PCD are also explored. All the findings will facilitate the development of novel therapeutic approaches.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"31 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteomic profiles reveal proteins and three characteristic patterns associated with osteoporosis: A prospective cohort study","authors":"Yi Zheng, Jincheng Li, Yucan Li, Jiacheng Wang, Chen Suo, Yanfeng Jiang, Li Jin, Kelin Xu, Xingdong Chen","doi":"10.1016/j.jare.2024.10.019","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.019","url":null,"abstract":"<h3>Introduction</h3>Exploration of plasma proteins associated with osteoporosis can offer insights into its pathological development, identify novel biomarkers for screening high-risk populations, and facilitate the discovery of effective therapeutic targets.<h3>Objectives</h3>The present study aimed to identify potential proteins associated with osteoporosis and to explore the underlying mechanisms from a proteomic perspective.<h3>Methods</h3>The study included 42,325 participants without osteoporosis in the UK Biobank (UKB), of whom 1,477 developed osteoporosis during the follow-up. We used Cox regression and Mendelian randomization analysis to examine the association between plasma proteins and osteoporosis. Machine learning was utilized to explore proteins with strong predictive power for osteoporosis risk.<h3>Results</h3>Of 2,919 plasma proteins, we identified 134 significantly associated with osteoporosis, with sclerostin (SOST), adiponectin (ADIPOQ), and creatine kinase B-type (CKB) exhibiting strong associations. Twelve of these proteins showed significant associations with bone mineral density (BMD) T-score at the femoral neck, lumbar spine, and total body. Mendelian randomization further supported causal relationships between 17 plasma proteins and osteoporosis. Moreover, follitropin subunit beta (FSHB), SOST, and ADIPOQ demonstrated high importance in predictive modeling. Utilizing a predictive model built with 10 proteins, we achieved relatively accurate prediction of osteoporosis onset up to 5 years in advance (AUC = 0.803). Finally, we identified three osteoporosis-related protein modules associated with immunity, lipid metabolism, and follicle-stimulating hormone (FSH) regulation from a network perspective, elucidating their mediating roles between various risk factors (smoking, sleep, physical activity, polygenic risk score (PRS), and menopause) and osteoporosis.<h3>Conclusion</h3>We identified several proteins associated with osteoporosis and highlighted the role of plasma proteins in influencing its progression through three primary pathways: immunity, lipid metabolism, and FSH regulation. This provides further insights into the distinct molecular patterns and pathogenesis of bone loss and may contribute to strengthening early diagnosis and long-term monitoring of the condition.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"26 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosome-scale assembly with improved annotation provides insights into breed-wide genomic structure and diversity in domestic cats","authors":"Yuki Matsumoto, Claire Yik-Lok Chung, Sachiko Isobe, Mika Sakamoto, Xiao Lin, Ting-Fung Chan, Hideki Hirakawa, Genki Ishihara, Hon-Ming Lam, Shinobu Nakayama, Shigemi Sasamoto, Yasuhiro Tanizawa, Akiko Watanabe, Kei Watanabe, Masaru Yagura, Yoshihito Niimura, Yasukazu Nakamura","doi":"10.1016/j.jare.2024.10.023","DOIUrl":"https://doi.org/10.1016/j.jare.2024.10.023","url":null,"abstract":"<h3>Introduction</h3>Comprehensive genomic resources offer insights into biological features, including traits/disease-related genetic loci. The current reference genome assembly for the domestic cat (<em>Felis catus</em>), Felis_Catus_9.0 (felCat9), derived from sequences of the Abyssinian cat, may inadequately represent the general cat population, limiting the extent of deducible genetic variations.<h3>Objectives</h3>The goal was to develop Anicom American Shorthair 1.0 (AnAms1.0), a reference-grade chromosome-scale cat genome assembly.<h3>Methods</h3>In contrast to prior assemblies relying on Abyssinian cat sequences, AnAms1.0 was constructed from the sequences of the phylogenetically distant and more popular American Shorthair breed, which is related to more breeds than the Abyssinian cat. By combining advanced genomics technologies, including PacBio long-read sequencing and Hi-C- and optical mapping data-based sequence scaffolding, we compared AnAms1.0 to existing Felidae genome assemblies (20 scaffolds, scaffolds N50 &gt; 150 Mbp). Homology-based and <em>ab initio</em> gene annotation through Iso-Seq and RNA-seq was used to identify new coding genes and structural variations.<h3>Results</h3>AnAms1.0 demonstrated superior contiguity and accuracy than existing Felidae genome assemblies. Using AnAms1.0, we identified over 1.5 thousand structural variations and 29 million repetitions compared to felCat9. Additionally, we identified &gt; 1,800 novel protein-coding genes and structural variants. Notably, olfactory receptor structural variants and cardiomyopathy-related variants were identified.<h3>Conclusion</h3>AnAms1.0 facilitates the discovery of novel genes related to normal and disease phenotypes in domestic cats. The analyzed data are publicly accessible on Cats-I (<span><span>https://cat.annotation.jp/</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>), which we established as a platform for accumulating and sharing genomic resources to discover novel genetic traits and advance veterinary medicine.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}