{"title":"Cell-type-specific mRNA m6A landscape and regulatory mechanisms underlying pulmonary injury in COVID-19","authors":"Peidong Zhang, Zhe Wang, Yuling Yang, Songqi Duan, Shengqian Dou, Huiying Sun, Chi Zhang, Xueying Li, Jinpeng Li, Yakun Liu, Mengmeng Sang, Xueqi Lv, Tianli Zhang, Chunxiao Chen, Fengcongzhe Gong, Xiaorui Ping, Wenlu Xing, Wenhao Ju, Yi Ping, Baofa Sun","doi":"10.1002/mef2.94","DOIUrl":"https://doi.org/10.1002/mef2.94","url":null,"abstract":"<p>Coronavirus disease 2019 (COVID-19) pandemic has caused millions of deaths. The risk of COVID-19 spreading still exists after the deconfinement act, Omicron became the dominant variant. Although N6-methyladenosine (m<sup>6</sup>A) regulators has been reported to affect the pathogenicity of COVID-19, their mechanism in the progression of lung injury in COVID-19 patients remain elusive. Here we show the landscape and specific mechanisms of m<sup>6</sup>A regulators in lung tissues through single-nucleus RNA sequencing (snRNA-Seq) data sets of 116,252 cells, and the external validation was performed using data from another snRNA-Seq data. The m<sup>6</sup>A reader <i>IGF2BP2</i> was specifically upregulated in alveolar type I (AT1) cells, resulting in impaired lung regeneration. <i>ALKBH5</i> expression upregulation in macrophages, impairing immune responses. Moreover, <i>WTAP</i> markedly upregulated in fibroblasts, leading to pulmonary fibrosis. In addition, m<sup>6</sup>A regulators dysregulation induced aberrant cell–cell communication in pulmonary tissue and mediated ligand–receptor interactions across diverse cell types in lung tissues by activating the TGF-β signaling pathway. Overall, these results indicated that the upregulation of m<sup>6</sup>A regulators in alveolar cells, myeloid cells, and fibroblasts may induce pulmonary injury in patients. The development of m<sup>6</sup>A-regulator inhibitors could be as one potential antifibrotic drugs for COVID-19.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.94","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077995","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}
{"title":"Comprehensively dissecting onco-microbiome: Intriguing connection of the microbiome to cancer metastasis","authors":"Lan Yang, Hailin Zhang, Min Wu","doi":"10.1002/mef2.93","DOIUrl":"https://doi.org/10.1002/mef2.93","url":null,"abstract":"<p>In a recent paper published in Cell, Battaglia et al. provide a valuable pan-cancer analysis of the microbiome in metastatic cancer,<span><sup>1</sup></span> which identified the specific preferences of microbes for different organs and demonstrated the correlations between diversity of microbes and neutrophils invasive into tumors, the anaerobic bacterial enrichments in hypoxic tumors, and the relationship between Fusobacterium and immune checkpoint blockade resistance in nonsmall cell lung cancer.</p><p>For over a century, researchers have observed the presence of bacteria in human tumors. However, the pathophysiological impact of intratumor microbiomes has been consistently ignored. Because of this overlook, despite our extensive knowledge of cancer and our array of treatment options, the microbiome has just been linked to cancer studies in the recent 20 years. Even though only a small number of bacteria are known to be directly carcinogenic, there has been a consistent rise in the number of bacteria that have an indirect impact on cancer.</p><p>The microbiome has been found to be linked to the tumor microenvironment, the initiation of innate immune sensing pathways, the tumor-infiltrating immune compartment, and the effectiveness of immunotherapy. The presence of microbes in local tissue, adjacent locations, and tumors themselves has been demonstrated to foster and inhibit the onset and growth of cancer. Moreover, these microbes have demonstrated the ability to influence the effectiveness of many cancer treatments, such as radiation, chemotherapy, and immunotherapy, which play a vital part in regulating the host immune system and influencing the body's response to anticancer treatments (Figure 1). Primary tumors contain intricate microbial communities, and current research indicates that certain types of cancer are significantly influenced by these microbes. In our view, it is crucial to comprehend the impact of the bacteria that exist in tumors on tumor biology, immunology, and therapeutic response. However, little is known about the existence and significance of the microbiome in relation to cancer, including the distinction in the microbial composition between the primary tumor and its metastases, the preferential colonization of bacteria in certain tumor types or organs, and the resilience of the microbial population during therapeutic interventions.</p><p>To this end, Battaglia et al. combined metagenomics, genomics, and transcriptomics techniques to examine the microbiota of metastatic tumors and their tumor-resident microbiome. They employed a bioinformatics methodology for data analysis, utilizing computational approaches such as Kraken2 and PathSeq, and also used high-throughput sequencing technology and various bioinformatics analysis approaches, including the STAR RNA-seq comparison tool and MutationalPatterns analysis, to enhance the precision and comprehensiveness of data processing and analysis. They analyzed 4164 samples of ","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.93","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141966475","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}
{"title":"The impact of intestinal microbiota-derived metabolites on cancer and their potential application in tumor immunotherapy","authors":"Mingyan Zhang, Feng Xie, Fangfang Zhou","doi":"10.1002/mef2.92","DOIUrl":"https://doi.org/10.1002/mef2.92","url":null,"abstract":"<p>In recent publications,<span><sup>1, 2</sup></span> the group of Professor Zhu Shu/Pan Wen and the research team of Wang Liangjing/Chen Shujie, respectively investigated two intestinal microbial metabolites: deoxycholic acid (DCA) and indole-3-propionic acid (IPA). DCA acts on the calcium ion channel plasma membrane Ca<sup>2+</sup> ATPase (PMCA), inhibits the effector function of CD8<sup>+</sup> T cells and consequently promotes colorectal cancer (CRC) growth. IPA activates precursor-exhausted T (T<sub>pex</sub>) cells and induces their transformation into effector T (T<sub>eff</sub>) cells, thereby increasing T-cell infiltration into the tumor tissue and enhancing the efficacy of immunotherapy (Figure 1).</p><p>Zhu et al. screened 73 small-molecule compounds derived from microbial sources to examine their effects on CD8<sup>+</sup> T-cell-mediated cytotoxicity or IFN-γ production, and identified DCA. Subsequent experiments using sodium dodecyl sulfate (SDS) or other chemical inhibitors confirmed that DCA does not lead to cell death. In tumor immunity, CD8<sup>+</sup> T cells are crucial in resisting tumors, with cytokines such as IFN-γ and TNF-α playing key roles in killing tumor cells. CD8<sup>+</sup> T-cell activation relies on Ca<sup>2+</sup> as a second messenger and the cytoplasmic Ca<sup>2+</sup> concentration directly affects CD8<sup>+</sup> T-cell activation. The authors found that DCA could inhibit cytoplasmic Ca<sup>2+</sup> accumulation by monitoring the real-time fluorescence intensity of cytoplasmic Ca<sup>2+</sup> in anti-CD3/CD28-activated CD8<sup>+</sup> T cells.</p><p>NFAT2 is an important transcription factor regulating CD8<sup>+</sup> T cells.<span><sup>3</sup></span> According to immunoblotting results, DCA reduced the transcription of this factor. Using NFAT2-luciferase reporter gene assays, the authors observed that PMA/ionomycin stimulation increased the transcriptional activity of NFAT2. Notably, DCA supplementation attenuated this transcriptional activation, indicating that DCA could inhibit the NFAT2-mediated transcription induced by Ca<sup>2+</sup> influx. To further study the specific effects of DCA, the authors examined several key observations. First, DCA did not reduce the levels of free calcium ions in cell-free culture medium, indicating that DCA does not chelate calcium ions. Second, the calcium-release activated channel (CRAC) was the main inward pathway. The immunosuppressive impact of DCA on CD8<sup>+</sup> T cells persisted despite the presence of the selective CRAC channel blocker, BTP2, indicating that DCA did not affect calcium influx. Third, PMA/ionomycin induces Ca<sup>2+</sup> to be released directly from the endoplasmic reticulum without relying on transporter proteins.<span><sup>1, 4</sup></span> However, DCA inhibits Ca<sup>2+</sup> accumulation, indicating that Ca<sup>2+</sup> may flow out of the cell membrane in large quantities or into intracellular stores. Therefore, having blocked various ch","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.92","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968362","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}
{"title":"Cordyceps sinensis ameliorates idiopathic pulmonary fibrosis in mice via inhibiting mitochondrion-mediated oxidative stress","authors":"Ying Zhang, Lirun Zhou, Guangqing Cheng, Yanyan Zhou, Qiuyan Guo, Jiangpeng Wu, Yin K. Wong, Junzhe Zhang, Huan Tang, Jigang Wang","doi":"10.1002/mef2.91","DOIUrl":"https://doi.org/10.1002/mef2.91","url":null,"abstract":"<p>Idiopathic pulmonary fibrosis (IPF) represents a chronic interstitial lung disease with an unclear underlying mechanism and currently lacks a definitive treatment. <i>Cordyceps sinensis</i> (CS), renowned for its pharmacological properties in traditional Chinese medicine and extensive use in lung disease treatment, holds promise as a therapeutic agent for IPF. However, the specific role of CS in treating IPF remains unclear. In this study, we aimed to assess the efficacy of CS in treating IPF and unravel potential underlying mechanisms. Our results demonstrate that CS treatment effectively mitigated pulmonary inflammation and collagen deposition in bleomycin-induced IPF mice. Proteomics analysis revealed that the regulation of mitochondrial oxidative phosphorylation may serve as a potential protective mechanism of CS against IPF in mice. Further investigation unveiled that CS could suppress the excessive production of mitochondrial reactive oxygen species in lung tissues induced by bleomycin through moderating the expression and activity of mitochondrial complexes, thus safeguarding the integrity and function of mitochondria. Overall, our findings not only underscore the effectiveness of CS in preventing bleomycin-induced IPF but also highlight mitochondrial-mediated oxidative stress as a promising therapeutic target for treating IPF.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.91","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732553","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}
{"title":"Unraveling the influence of metabolic signatures on immune dynamics for predicting immunotherapy response and survival in cancer","authors":"Qiyun Ou, Zhiqiang Lu, Gengyi Cai, Zijia Lai, Ruicong Lin, Hong Huang, Dongqiang Zeng, Zehua Wang, Baoming Luo, Wenhao Ouyang, Wangjun Liao","doi":"10.1002/mef2.89","DOIUrl":"https://doi.org/10.1002/mef2.89","url":null,"abstract":"<p>Metabolic reprogramming in cancer significantly impacts immune responses within the tumor microenvironment, but its influence on cancer immunotherapy effectiveness remains uncertain. This study aims to elucidate the prognostic significance of metabolic genes in cancer immunotherapy through a comprehensive analytical approach. Utilizing data from the IMvigor210 trial (<i>n</i> = 348) and validated by retrospective datasets, we performed patient clustering using non-negative matrix factorization based on metabolism-related genes. A metabiotic score was developed using a “DeepSurv” neural network to assess correlations with overall survival (OS), progression-free survival, and immunotherapy response. Validation of the metabolic score and key genes was achieved via comparative gene expression analysis using qPCR. Our analysis identified four distinct metabolic classes with significant variations in OS. Notably, the metabolism-inactive and hypoxia-low class demonstrated the most pronounced benefit in terms of OS. The metabolic score predicted immunotherapeutic benefits with high accuracy (AUC: 0.93 at 12 months). SETD3 emerged as a crucial gene, showing strong correlations with improved OS outcomes. This study underscores the importance of metabolic profiling in predicting cancer immunotherapy success. Specifically, patients classified as metabolism-inactive and hypoxia-low appear to derive substantial benefits. SETD3 is established as a promising prognostic marker, linking metabolic activity with patient outcomes, advocating for the integration of metabolic profiling into immunotherapy strategies to enhance treatment precision and efficacy.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.89","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141488825","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}
Puja Jaishwal, Upagya Gyaneshwari, Kisalay Jha, Brijesh Pandey, Thakur P. Yadav, Satarudra P. Singh
{"title":"Lessons from COVID-19: Aspects of prevention, therapeutics, and diagnostics against SARS-CoV-2 with special focus on JN.1 and XBB sublineages","authors":"Puja Jaishwal, Upagya Gyaneshwari, Kisalay Jha, Brijesh Pandey, Thakur P. Yadav, Satarudra P. Singh","doi":"10.1002/mef2.90","DOIUrl":"https://doi.org/10.1002/mef2.90","url":null,"abstract":"<p>The end of second decade in the 21st century witnessed a prominent disease outbreak caused by the novel coronavirus SARS-CoV-2 (including most diverse omicron subvariants), where the death toll crossed the boundary of 6.9 million across the globe by December 19, 2023. All spheres of central dogma of molecular biology and host‒pathogen interaction was explored to find ways in diagnostics, isolation, curtailment, and therapy. Above all, diagnostics and therapeutics against COVID-19 took an enormous jump, which needs to be evaluated for accuracy and feasibility and requires serious compilation for current and future generations. With the same objective, this review encompasses the diverse ways including prevention practiced and proposed during the handling of this pandemic across the globe. It involves the role of mutations in viruses and subsequent epitope mapping with potential immune escape mechanisms of SARS-CoV-2 variants including the conservancy of T-cell epitopes has also been highlighted. The efficacy in antigen/antibody-based diagnostics, RT‒PCR- and NGS-based confirmation of pathogen presence, and imaging (X-ray/CT-scan) for symptoms and damage assessment has been thoroughly filtered. The possibility of errors in diagnostics and their cause and consequences have also been presented for the ease of readers and further improvisers.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.90","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435608","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}
{"title":"Advances in the elucidation of circRNA translocation","authors":"Yang Gu, Xiaoxue Zhou, Long Zhang","doi":"10.1002/mef2.87","DOIUrl":"https://doi.org/10.1002/mef2.87","url":null,"abstract":"<p>Recently a research article titled “Nuclear export of circular RNA” was published online in <i>Nature</i><span><sup>1</sup></span> as a collaboration between Ngo et al. This study revealed a distinct circular RNA (circRNA) transport mechanism compared to that of linear RNA and identified unique molecular pathways involved in circRNA transport, including key proteins such as Ran-GTP, IGF2BP1, and exportin-2.</p><p>CircRNA is a closed-loop structured noncoding RNA formed via pre-messenger RNA (mRNA) back-splicing. It regulates gene expression and participates in translation. CircRNA is associated with varieties of diseases, including those of the autoimmune, heart, liver, Alzheimer's, and cancer. It is important in cellular biology and disease research, and primarily exist in the cytoplasm; however, its translocation mechanism from the nucleus to cytoplasm remains unknown. In view of this, the research team conducted scientific research experiments.</p><p>In this study, the research team confirmed that most circRNAs were primarily located in the cytoplasm. They then depleted candidate proteins known to be involved in the transport of various linear RNA subtypes to examine whether the depletion would lead to circRNAs accumulation in the nucleus. The results showed that depletion of ALY, GANP, NXF1, UAP56, URH49, and exportin-5 did not affect circRNA transport. This indicated that bulk transport of circRNAs did not require a conventional mRNA export pathway. In contrast, they found that depleting the receptor CRM1 for ribosomal RNA and small nuclear RNA transport decreased nuclear circRNA content.<span><sup>2</sup></span> This unusual phenomenon attracted the attention of the research team. To further confirm this phenomenon, the cells were treated with the CRM1 inhibitor Selinexor, which also decreased the nuclear circRNA content and increased the cytoplasmic content.</p><p>The research team speculated that the CRM1 depletion could have been due to Ran-GTP consumption during nuclear transport complex assembly.<span><sup>3</sup></span> Therefore, CRM1 depletion could inhibit the assembly of the nuclear transport complex, thereby enhancing circRNA transport. Thus, they designed two experimental methods: measuring the nuclear and total cellular Ran content after CRM1 depletion using immunofluorescence and treating cells with sorbitol, a Ran-GTP inhibitor. These results confirmed that circRNA export depended on Ran-GTP.</p><p>The research team hypothesized that circRNA was transported via a transport protein under Ran-GTP-dependent conditions. Biotinylated SMARCA5 circRNA and linear RNA were used. The Ran content was controlled to identify protein exportin-2 using SMARCA5. Exportin-2 was then depleted in the cells, which increased nuclear circRNA content, but did not affect linear RNA. To ensure that the effect on circRNA export was not the result of the small interfering RNA (siRNA's) off-target effects, the depletion experiment was repeated with a ","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.87","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141326449","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}
{"title":"Social short video platform assisted care for adverse psychological symptoms in cancer patients: A mixed-methods study","authors":"Shen Li, Xia Liu, Xia Wang, Yilin Wang, Xuelei Ma","doi":"10.1002/mef2.88","DOIUrl":"https://doi.org/10.1002/mef2.88","url":null,"abstract":"<p>The rising psychological issues among cancer patients call for timely treatment. Psychological issues such as anxiety, depression, and distress are particularly common among cancer patients and have a significant impact on their treatment and prognostic outcomes. Distraction has been proven to mitigate mental disorders as a strategy of intervention. Digital tools like social short video platforms offer cost-effective mental healthcare potential, but there is a lack of longitudinal studies demonstrating their intervention effectiveness. This study aimed to assess the impact of social short video platforms on the psychological well-being of cancer patients, focusing on anxiety, depression, and distress. We studied 455 digestive system cancer patients using mixed methods. The effect on psychological symptoms was evaluated via cross-sectional analysis of 392 patients and pre-post intervention analysis of 63 patients, employing the Hospital Anxiety and Depression Scale and Distress Thermometer. The findings showed lower anxiety, depression, and distress scores among regular users of social short video platforms. The intervention led to reduced anxiety and depression scores. As a prevalent app of social short video platforms, these platforms might be a safe and convenient nonpharmacological assisted tool for enhancing mental health care during cancer treatment.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.88","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286804","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}
Panpan Chang, Rui Li, Zhongqing Wang, Wei Chong, Tianbing Wang
{"title":"Bibliometric and visual analysis of severe trauma literature in the past 20 years","authors":"Panpan Chang, Rui Li, Zhongqing Wang, Wei Chong, Tianbing Wang","doi":"10.1002/mef2.81","DOIUrl":"https://doi.org/10.1002/mef2.81","url":null,"abstract":"<p>Severe trauma is a critical aspect of medical practice, profoundly impacting patient care and outcomes. Over the past 20 years, advancements in trauma care concepts and the utilization of advanced technologies have led to substantial growth in severe trauma research, evidenced by a notable increase in research activity and subsequent publications. To understand the publication landscape in severe trauma, identify prevailing research trends, and highlight areas requiring further development for future insights, we conducted a bibliometric analysis. Our analysis indicates that there are 16,939 severe trauma-related publications from the past 20 years, with a continuous increase in publication volume, particularly showing a rapid growth trend from 2018 to 2021. The United States leads in both volume and citation frequency. Moreover, we synthesized data on productive countries/regions and research institutions, showcasing extensive collaboration across diverse geographic locations and institutional affiliations. Substantial progress has been achieved in severe trauma research, particularly in clinical diagnosis, treatment, epidemiology, prevention, and pathogenesis. However, there is still a gap in adopting cutting-edge interdisciplinary methodologies. This study provides a comprehensive overview of the current state of severe trauma research and suggests pathways for future advancement.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.81","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187611","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}
{"title":"Discovering Alu element's role in the tale of tail loss: One giant leap for human evolution","authors":"Xiaoyan Liu, Min Wu, Yongye Huang","doi":"10.1002/mef2.86","DOIUrl":"https://doi.org/10.1002/mef2.86","url":null,"abstract":"<p>In a recent article published in <i>Nature</i>, Xia et al. found that the insertion of a specific AluY element in the sixth intron of the primate TBXT gene may lead to the evolution of tail loss.<span><sup>1</sup></span> The significance of this study emphasizes that uncovering the genetic mechanism in facilitating tail-loss evolution in hominoids can contribute to understanding evolutionary pressure that boosts the formation of human traits and evolutionary diseases.</p><p>From a Darwinian evolutionary perspective, the lack of a tail is one of the key features in the evolution from hominids, signifying the anatomical shift from primitive ancestors to modern humans, especially the disappearance of the external tail.<span><sup>2</sup></span> This unique transformation not only illustrates a remarkable chapter in our biological history, but also underscores the intricate interplay of heredity and evolution. The story of the tail, or more precisely, its absence opens a window into how minor genetic alterations can orchestrate remarkable developmental changes. Alu elements are a type of short interspersed nuclear element (SINE) found abundantly in the human genome. Alu elements, as a class of transposable elements unique to the primate genome, exert a profound influence on genome evolution. These elements increase genomic instability by providing the most common homologous sequences for non-allelic homologous recombination events, which can lead to disease. Through delving deeper into the TBXT gene, Xia et al. revealed a human-specific insertion of an Alu element that is oriented in the opposite direction to the neighboring Alu element, forming a pair that may have led to human-specific gene splicing that affects gene expression. Validated by a mouse model, this splicing was found to alter TBXT gene expression, resulting in missing or shortened tails in mice,<span><sup>1</sup></span> providing strong support for the theory that exon skipping leads to tail deletion (Figure 1).</p><p>To investigate the genetic mechanism of ancient human-specific selective splicing events, Xia et al. used CRISPR-Cas9 to knock out the AluY element and its interaction with the AluSx1 element in human embryonic stem cells. By modeling the developmental expression pattern of the TBXT gene, Xia et al. revealed that the deletion of the AluY element almost completely blocked the <i>TBXT</i><sup><i>Δexon6</i></sup> heterodimeric transcripts production.<span><sup>3</sup></span> These findings highlight the complex role of transposable factor interactions in gene regulation and the importance of TBXT isoform expression in tail development.</p><p>The loss of the tail is a complex and widely debated topic in biological evolution, involving a delicate balance between evolution and degeneration. From an evolutionary perspective, the loss of the tail in humans and other upright walking organisms is considered to be an adaptive evolution to a new environment and way of life, in whic","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.86","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156508","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}