MedComm最新文献

{"title":"Paternal microbiota impacts offspring: health risks and reproductive insights","authors":"Junyu Wang, Anren Zhang, Shugang Qin","doi":"10.1002/mco2.749","DOIUrl":"https://doi.org/10.1002/mco2.749","url":null,"abstract":"<p>In a recent study published in <i>Nature</i>, Argaw-Denboba et al. explored the impact of paternal gut microbiota on the health of offspring.<span><sup>1</sup></span> Perturbations in paternal gut microbiota notably impacted offspring health, causing weight issues, developmental disorders, and raised early mortality. Researchers linked these effects to “gut-germline axis” dysregulation and placental dysfunction, offering new views on preventing adverse pregnancy outcomes (Figure 1).</p><p>The gut microbiota plays a crucial role in regulating human metabolism, hormone secretion, and immune function, helping to maintain overall physiological health. Recent research has established a connection between gut microbiota and male reproductive health. The study revealed that gut microbiota influences vitamin A metabolism, and any disruptions in this process can affect testicular cells through the bloodstream, ultimately impairing sperm function.<span><sup>2</sup></span> The concept of the “Gut-testis axis” suggests that gut microbiota can impact interactions between the gut and testes via metabolites, highlighting the complex communication involved. Traditionally, research has primarily focused on the influence of maternal microbiota on fetal development. It was commonly believed that fetal gut microbiota colonization begins during delivery, influenced by maternal skin bacteria, vaginal secretions, and feces. This early colonization plays a significant role in shaping the physiological state of the offspring.<span><sup>3</sup></span> However, the effects of paternal gut microbiota disorders on offspring and the underlying biological mechanisms remain poorly understood, highlighting the need for further research in this area.</p><p>Argaw-Denboba et al. investigated the impact of paternal gut microbiota disruption on offspring health, specifically focusing on physiological status and viability. The research team initiated their study by establishing a male mouse model with disrupted gut microbiota using non-absorbable antibiotics (nABX). The findings indicated that the offspring of nABX-treated fathers displayed significantly reduced body weight (<i>p </i>= 0.023, nested unpaired t-test; Control (CON) <i>n</i> = 172 (26 L), nABX <i>n</i> = 181) (28 L), severe growth restrictions (SGR; body-weight Z-score < −3), and a marked increase in early postnatal mortality (<i>p </i>= 0.0002, Mantel-Cox test). To confirm these results, the team employed two additional intervention methods: a combination of antibiotics (avaABX) and an osmotic laxative (polyethylene glycol), which similarly disrupted the paternal gut microbiota. These interventions supported the hypothesis that paternal gut microbiota disruption heightens the risk of developmental disorders and early mortality in offspring.</p><p>Further investigations assessed whether reversing the disrupted paternal gut microbiota could mitigate the adverse effects observed in F1 offspring. Upon discontinuing th","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435454","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":"Single-cell transcriptome atlas revealed bronchoalveolar immune features related to disease severity in pediatric Mycoplasma pneumoniae pneumonia","authors":"Xiantao Shen,&nbsp;Zhengjiang Jin,&nbsp;Xiaomin Chen,&nbsp;Zhenhui Wang,&nbsp;Lu Yi,&nbsp;Yangwei Ou,&nbsp;Lin Gong,&nbsp;Chengliang Zhu,&nbsp;Guogang Xu,&nbsp;Yi Wang","doi":"10.1002/mco2.748","DOIUrl":"https://doi.org/10.1002/mco2.748","url":null,"abstract":"<p>The mechanisms underlying protective immunity in mild <i>Mycoplasma pneumoniae</i> pneumonia (MPP) and the pathogenesis of severe MPP, characterized by dysregulated immune responses, remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) to profile bronchoalveolar lavage fluid (BALF) samples from 13 healthy donors and 24 hospitalized pediatric patients with MPP, covering both mild and severe cases. Severe MPP patients exhibited high levels of exhausted T cells and M1-like macrophages, with the exhaustion of T cells attributed to persistent type I interferon signaling and inadequate assistance from CD4⁺ T cells. Significant cell-cell interactions between exhausted T cells and programmed death-ligand 1⁺ (PD-L1⁺) macrophages were detected in severe patients, potentially mediated through inhibitor molecules (e.g., PD1) and their receptors (e.g., PD-L1), as well as human leukocyte antigen class I molecules and their receptors (e.g., KLRC1/D2), resulting in the dysfunction of anti-MP immune responses. Mild MPP patients were featured by an increased abundance of neutrophils, coupled with enhanced activation, contributing to protective immunity. Together, our study provides a detailed characterization of the BALF immune landscape in MPP patients, revealing distinct immune characteristics between mild and severe cases, which offers a valuable resource for understanding MPP immunopathogenesis and formulating effective therapeutic strategies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.748","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435453","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":"Penfluridol inhibits melanoma growth and metastasis through enhancing von Hippel‒Lindau tumor suppressor-mediated cancerous inhibitor of protein phosphatase 2A (CIP2A) degradation","authors":"Fuyan Xu,&nbsp;Jiao Li,&nbsp;Min Ai,&nbsp;Tingting Zhang,&nbsp;Yue Ming,&nbsp;Cong Li,&nbsp;Wenchen Pu,&nbsp;Yang Yang,&nbsp;Zhang Li,&nbsp;Yucheng Qi,&nbsp;Xiaomin Xu,&nbsp;Qingxiang Sun,&nbsp;Zhu Yuan,&nbsp;Yong Xia,&nbsp;Yong Peng","doi":"10.1002/mco2.758","DOIUrl":"https://doi.org/10.1002/mco2.758","url":null,"abstract":"<p>Melanoma's high metastatic potential, especially to the brain, poses significant challenges to patient survival. The blood‒brain barrier (BBB) is a major obstacle to the effective treatment of melanoma brain metastases. We screened antipsychotic drugs capable of crossing the BBB and identified penfluridol (PF) as the most active candidate. PF reduced melanoma cell viability and induced apoptosis. In animal models, PF effectively inhibited melanoma growth and metastasis to the lung and brain. Using immunoprecipitation combined with high-resolution mass spectrometry, and other techniques such as drug affinity responsive target stability, we identified CIP2A as a direct binding protein of PF. CIP2A is highly expressed in melanoma and its metastases, and is linked to poor prognosis. PF can restore Protein Phosphatase 2A activity by promoting CIP2A degradation, thereby inhibiting several key oncogenic pathways, including AKT and c-Myc. Additionally, von Hippel‒Lindau (VHL) is the endogenous E3 ligase for CIP2A, and PF enhances the interaction between VHL and CIP2A, promoting the ubiquitin‒proteasome degradation of CIP2A, thereby inhibiting melanoma growth and metastasis. Overall, this study not only suggests PF's potential in treating melanoma and its brain metastases but also highlights CIP2A degradation as a therapeutic strategy for melanoma.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435457","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 Space Omics and Medical Atlas (SOMA): new resource for medical research in deep space","authors":"Hanwen Zhang,&nbsp;Yingxian Li,&nbsp;Guohui Zhong","doi":"10.1002/mco2.780","DOIUrl":"https://doi.org/10.1002/mco2.780","url":null,"abstract":"&lt;p&gt;Recently, the Space Omics and Medical Atlas (SOMA) was presented by Overbey et al.,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; in &lt;i&gt;Nature&lt;/i&gt;, showcasing the samples and physiological profiles of four crew members from SpaceX's Inspiration4 (I4) mission in 2021. Meanwhile, a series of SOMA-related articles from more than 100 research groups in 25 countries have been published in &lt;i&gt;Nature&lt;/i&gt; and its subjournals. I4 marked the first all-civilians manned space mission globally, featuring a crew composed of a billionaire, a survivor of bone cancer, an air force veteran, and an Earth scientist. The SOMA (https://soma.weill.cornell.edu) is the first biobank of space medicine, expanding the human space omics data 10-fold. It reveals the crew's physiological changes through a range of assays, including intelligent device monitoring, behavioral tests, and multiomics analysis, at various levels from molecules to cells and organs. This provides a reference for health monitoring, prevention, and clinical treatment, applicable to both deep space exploration and survival on Earth.&lt;/p&gt;&lt;p&gt;The field of manned spaceflight saw significant growth in recent years, yet the global space medicine remains nascent. The mental health of astronauts and civilian crew members can be affected by stress, noise, and confined space. The physiological well-being of crew members can be impacted by unique factors such as microgravity and radiation exposure, which can induce the dysfunction of the cardiovascular system, musculoskeletal system, and immune system, even posing the life-threatening risks during spaceflight or long-term space habitation. It is imperative to elucidate the mechanisms of injury and identify biomarkers associated with spaceflight. This will enable us to assess the physiological statuses and develop the precision medicine for space, addressing the challenges of the “Second Space Age.”&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Four civilian astronauts (three men and one woman with the age of 29, 38, 42, and 51 years) completed the I4 orbital mission at 590.6 km elevation for 3 days. To explore the physiological variations profiles of I4 crew, 13 kinds of biospecimen (including whole blood, serum, peripheral blood mononuclear cells [PBMCs], dried blood spots, skin biopsies, stool, etc.) were collected across 10 time points (including three pre-flight, three in-flight, one immediately post-flight, and three recovery time points) and the portable imaging devices, wearables, and multiomics analysis methods were conducted.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The collection and analysis of biological samples are summarized (Figure 1) and some research highlights will be elaborated below.&lt;/p&gt;&lt;p&gt;The novel RNA fingerprints of spaceflight were included in SOMA. Overbey et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; found 95 regions of interest across outer epidermis, inner epidermis, outer dermis, and vasculature on skin biopsies by the spatially resolved transcriptomics. Especially, the melanocyte abundance decreased","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435458","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":"Nanoengineering-armed oncolytic viruses drive antitumor response: progress and challenges","authors":"Yan Zhang,&nbsp;Xinyu Shi,&nbsp;Yifan Shen,&nbsp;Xiulin Dong,&nbsp;Ruiqing He,&nbsp;Guo Chen,&nbsp;Yan Zhang,&nbsp;Honghong Tan,&nbsp;Kun Zhang","doi":"10.1002/mco2.755","DOIUrl":"https://doi.org/10.1002/mco2.755","url":null,"abstract":"<p>Oncolytic viruses (OVs) have emerged as a powerful tool in cancer therapy. Characterized with the unique abilities to selectively target and lyse tumor cells, OVs can expedite the induction of cell death, thereby facilitating effective tumor eradication. Nanoengineering-derived OVs overcome traditional OV therapy limitations by enhancing the stability of viral circulation, and tumor targeting, promising improved clinical safety and efficacy and so on. This review provides a comprehensive analysis of the multifaceted mechanisms through which engineered OVs can suppress tumor progression. It initiates with a concise delineation on the fundamental attributes of existing OVs, followed by the exploration of their mechanisms of the antitumor response. Amid rapid advancements in nanomedicine, this review presents an extensive overview of the latest developments in the synergy between nanomaterials, nanotechnologies, and OVs, highlighting the unique characteristics and properties of the nanomaterials employed and their potential to spur innovation in novel virus design. Additionally, it delves into the current challenges in this emerging field and proposes strategies to overcome these obstacles, aiming to spur innovation in the design and application of next-generation OVs.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429903","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":"MetaPath Chat: multimodal generative artificial intelligence chatbot for clinical pathology","authors":"Haizhu Chen,&nbsp;Ruichong Lin,&nbsp;Yu Yunfang","doi":"10.1002/mco2.769","DOIUrl":"https://doi.org/10.1002/mco2.769","url":null,"abstract":"&lt;p&gt;Recently, two pivotal studies, one published in &lt;i&gt;Nature&lt;/i&gt;&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and another in &lt;i&gt;Cell&lt;/i&gt;,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; present groundbreaking advancements that are set to revolutionize artificial intelligence (AI) in pathology. The first study introduced PathChat, a multimodal generative AI assistant for human pathology.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The second study unveiled TriPath, a weakly supervised AI model designed for analyzing three-dimensional (3D) pathology samples and predicting patient outcomes.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; These findings highlight the potential of AI to revolutionize pathology by enhancing diagnostic and prognostic accuracy and enabling new forms of human–machine collaboration.&lt;/p&gt;&lt;p&gt;Lu et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; introduced PathChat, an AI assistant designed to aid pathologists in diagnostic workflows (Figure 1). PathChat integrated a vision-language model that combined a pretrained vision encoder with a large language model, fine-tuned on over 456,916 visual-language instruction, encompassing 999,202 question–answer turns. The vision encoder, based on the UNI architecture, was pretrained on over 100 million histology image patches from over 100,000 slides and further refined with 1.18 million pathology image-caption pairs.&lt;/p&gt;&lt;p&gt;The performance of PathChat was rigorously evaluated against state-of-the-art multimodal AI assistants, including LLaVA 1.5, LLaVA-Med, and GPT-4 V.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; First, evaluations focused on multiple-choice diagnostic questions using routine H&amp;E whole slide images (WSIs) from both The Cancer Genome Atlas and an in-house pathology archive, covering 54 diagnoses from 11 major pathology practices and organ sites. Evaluations were conducted in two settings: image-only and image with clinical context. PathChat outperformed its counterparts in diagnostic accuracy for multiple-choice questions. Specifically, in the image-only setting, PathChat achieved a 78.1% accuracy (+52.4% vs. LLaVA 1.5 and +63.8% vs. LLaVA-Med, both &lt;i&gt;p&lt;/i&gt; &lt; 0.001). In the image with clinical context setting, PathChat's accuracy improved to 89.5% (+39.0% vs. LLaVA 1.5 and +60.9% vs. LLaVA-Med, both &lt;i&gt;p&lt;/i&gt; &lt; 0.001), demonstrating its ability to leverage multimodal information effectively. Moreover, PathChat outperformed GPT-4 V in both image-only (78.8 vs. 25%) and image with clinical context (90.5% vs. 63.5%) settings, highlighting its superior diagnostic accuracy.&lt;/p&gt;&lt;p&gt;Furthermore, Lu and colleagues&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; assessed the ability of PathChat to generate coherent, clinically relevant responses to open-ended pathology-related questions. Seven expert pathologists ranked the responses of different models based on relevance, correctness, and explanation quality. PathChat produced more preferable responses compared with other multimodal large language models (MLLMs), with a median win rate of 56.5%, 67.7%, and 74.2%, respectively, against GPT-4 V, LLaVA 1.5, and LLaVA-","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429904","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":"Mitochondrial fission factor: a living way for mitochondria sensing food","authors":"Mengmeng Zhi,&nbsp;Rong Cao,&nbsp;Xianghui Fu,&nbsp;Ling Li","doi":"10.1002/mco2.770","DOIUrl":"https://doi.org/10.1002/mco2.770","url":null,"abstract":"&lt;p&gt;Recently, Henschke et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; revealed that protein kinase B/AKT (AKT)-dependent phosphorylation of mitochondrial fission factor (MFF) in the liver triggered by pro-opiomelanocortin (POMC) activation regulates mitochondrial fragmentation and glucose production, illustrating rapid signal transduction over the hypothalamus–liver axis in control of metabolic adaptation to anticipatory nutritional states.&lt;/p&gt;&lt;p&gt;A growing body of research expounds that anticipatory mechanisms in response to incoming nutrient are of essence to balance metabolic homeostasis, despite conventional homeostatic theories rely on internal feedback regulation. Predictive food cues are demonstrated to instantly trigger metabolic pathways in peripheral organs involving the liver and adipose tissue in order to increase nutrient availability. Thus, intensive probes into the principal mechanisms of specific peripheral adaptation to food-sensing may bring profound influences on developing preventative strategies for metabolic diseases.&lt;/p&gt;&lt;p&gt;Notably, this latest study by Henschke et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; focused on the liver mitochondria, which is widely recognized as a nutrient sensor and regulatory hub for energy metabolism, and attempted to determine the roles and underlying mechanisms of liver mitochondrial dynamics in coordinating metabolic adaptation to predictive energy supply (Figure 1). Protein phosphorylation acts as a key sensor of nutrient metabolism to regulate intracellular signal transduction. The investigators first identified significantly up-regulated phosphorylation level of serine 131 of MFF (MFFS131) in hepatic mitochondria exposed to caged food and refeeding via two unbiased phosphoproteomic screens. MFF has been engaged in boosted mitochondrial fission in a proved way of being phosphorylated at S155 and S172 depending on AMP-activated protein kinase or protein kinase D, in response to energy stress and coupling mitochondrial fission to mitotic progression. Intriguingly, this study atypically defined AKT as the upstream trigger for MFF phosphorylation on a differential site (S131), unraveling a new pathway of AKT/MFFS131 that works during the cephalic phase. Attractively, blocking phosphorylation of MFFS131 impaired insulin sensitivity and dissipated insulin-suppressed hepatic glucose production (HGP), suggesting a nonclassical AKT/MFFS131 pathway in control of HGP independent of the recognized glycogen synthase kinase-3 beta. In line with this, recent work has revealed attenuated obesity-associated mitochondrial fission and improved glucose metabolism in MFF-deficient hepatocytes.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; These new findings shed light on potential targets for intervention in metabolic diseases such as diabetes and obesity.&lt;/p&gt;&lt;p&gt;Of note, rapid phosphorylation of MFFS131 and transient mitochondria fragments upon food perception can be also detected by hypothalamic POMC neuronal activation. It has been elaborated that instantaneous","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.770","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429902","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":"Structure-based design of antibodies targeting the EBNA1 DNA-binding domain to block Epstein–Barr virus latent infection and tumor growth","authors":"Yongyue Han,&nbsp;Fang Wu,&nbsp;Ying Zhang,&nbsp;Jun Liu,&nbsp;Yuzhe Wu,&nbsp;Yuecheng Wang,&nbsp;Xiwen Jiang,&nbsp;Xin Chen,&nbsp;Wei Xu","doi":"10.1002/mco2.739","DOIUrl":"https://doi.org/10.1002/mco2.739","url":null,"abstract":"<p>The Epstein–Barr virus (EBV) nuclear antigen 1 (EBNA1) is critically involved in maintaining episomes during latent infection and promoting tumorigenesis. The development of an epitope-specific monoclonal antibody (mAb) for EBNA1 holds great promise due to its high affinity and specificity, offering a new and innovative approach for the treatment of EBV-related diseases. In this proof-of-concept study, we employed a structure-based design strategy to create three unique immunogens specifically targeting the DNA binding state of the EBNA1 DBD. By immunizing mice, we successfully generated a mAb, named 5E2-12, which selectively targets the DNA binding interface of EBNA1. The 5E2-12 mAb effectively disrupts the interaction between EBNA1 and DNA binding, resulting in reduced proliferation of EBV-positive cells and inhibition of xenograft tumor growth in both cellular assays and mouse tumor models. These findings open up new avenues for the development of innovative biological macromolecular drugs that specifically target EBNA1 and provide potential for clinical therapy options for early-stage EBV-positive tumors. The epitope-specific mAb approach demonstrates novelty and innovation in tackling EBV-related diseases and may have broad implications for precision medicine strategies in the field of viral-associated cancers.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.739","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429901","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":"Mapping individual cortico–basal ganglia–thalamo–cortical circuits integrating structural and functional connectome: implications for upper limb motor impairment poststroke","authors":"Xin Xue,&nbsp;Jia-Jia Wu,&nbsp;Xiang-Xin Xing,&nbsp;Jie Ma,&nbsp;Jun-Peng Zhang,&nbsp;Yun-Ting Xiang,&nbsp;Mou-Xiong Zheng,&nbsp;Xu-Yun Hua,&nbsp;Jian-Guang Xu","doi":"10.1002/mco2.764","DOIUrl":"10.1002/mco2.764","url":null,"abstract":"<p>This study investigated alterations in functional connectivity (FC) within cortico–basal ganglia–thalamo–cortical (CBTC) circuits and identified critical connections influencing poststroke motor recovery, offering insights into optimizing brain modulation strategies to address the limitations of traditional single-target stimulation. We delineated individual-specific parallel loops of CBTC through probabilistic tracking and voxel connectivity profiles-based segmentation and calculated FC values in poststroke patients and healthy controls, comparing with conventional atlas-based FC calculation. Support vector machine (SVM) analysis distinguished poststroke patients from controls. Connectome-based predictive modeling (CPM) used FC values within CBTC circuits to predict upper limb motor function. Poststroke patients exhibited decreased ipsilesional connectivity within the individual-specific CBTC circuits. SVM analysis achieved 82.8% accuracy, 76.6% sensitivity, and 89.1% specificity using individual-specific parallel loops. Additionally, CPM featuring positive connections/all connections significantly predicted Fugl-Meyer assessment of upper extremity scores. There were no significant differences in the group comparisons of conventional atlas-based FC values, and the FC values resulted in SVM accuracy of 75.0%, sensitivity of 67.2%, and specificity of 82.8%, with no significant CPM capability. Individual-specific parallel loops show superior predictive power for assessing upper limb motor function in poststroke patients. Precise mapping of the disease-related circuits is essential for understanding poststroke brain reorganization.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396443","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":"Next-generation spatial transcriptomics: unleashing the power to gear up translational oncology","authors":"Nan Wang,&nbsp;Weifeng Hong,&nbsp;Yixing Wu,&nbsp;Zhe-Sheng Chen,&nbsp;Minghua Bai,&nbsp;Weixin Wang,&nbsp;Ji Zhu","doi":"10.1002/mco2.765","DOIUrl":"10.1002/mco2.765","url":null,"abstract":"<p>The growing advances in spatial transcriptomics (ST) stand as the new frontier bringing unprecedented influences in the realm of translational oncology. This has triggered systemic experimental design, analytical scope, and depth alongside with thorough bioinformatics approaches being constantly developed in the last few years. However, harnessing the power of spatial biology and streamlining an array of ST tools to achieve designated research goals are fundamental and require real-world experiences. We present a systemic review by updating the technical scope of ST across different principal basis in a timeline manner hinting on the generally adopted ST techniques used within the community. We also review the current progress of bioinformatic tools and propose in a pipelined workflow with a toolbox available for ST data exploration. With particular interests in tumor microenvironment where ST is being broadly utilized, we summarize the up-to-date progress made via ST-based technologies by narrating studies categorized into either mechanistic elucidation or biomarker profiling (translational oncology) across multiple cancer types and their ways of deploying the research through ST. This updated review offers as a guidance with forward-looking viewpoints endorsed by many high-resolution ST tools being utilized to disentangle biological questions that may lead to clinical significance in the future.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396444","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}