Core Viewpoint - The research published by Harvard University provides a comprehensive understanding of the developmental transitions of Plasmodium falciparum within Anopheles mosquitoes, revealing critical molecular interactions that could lead to new targets for malaria transmission-blocking vaccines and drugs [2][11]. Group 1: Research Findings - The study utilized dual-channel single-cell RNA sequencing to map the complex interactions between the malaria parasite and the mosquito host, highlighting key developmental stages [2][9]. - It identified crucial molecular transformations during the transition from motile ookinetes to spherical oocysts and the subsequent formation of sporozoites [9]. - The research pinpointed two essential genes, PfATP4 and PfLRS, that are vital for oocyst growth, with their inhibition completely blocking the parasite's development within the mosquito [9][11]. Group 2: Molecular Mechanisms - The study confirmed that the transcription factor PfSIP2 is a critical switch for sporozoite infection of human liver cells, presenting a potential target for blocking malaria transmission [9][10]. - It was found that ookinetes preferentially interact with intestinal progenitor cells during their traversal of the midgut epithelium, which serves as a localization signal for their transformation [9]. - In the later developmental stages, oocysts are tightly wrapped by surrounding midgut muscle fibers, which may help maintain gut integrity and support oocyst fixation [9]. Group 3: Implications for Malaria Control - The research constructs the first panoramic molecular map of the Plasmodium-mosquito interaction, providing new targets for the development of precise transmission-blocking vaccines and drugs [11].

Core Viewpoint - The article discusses the global consensus on gene therapy for hereditary hearing loss, marking a significant milestone in the field and providing a standardized framework for clinical applications [3][10][14]. Group 1: Consensus Development - The consensus was led by a team from Fudan University and involved 46 experts from various countries, taking over a year to develop [5][7]. - It was established using a modified Delphi method, resulting in 30 consensus statements covering key areas such as ethical review, patient selection, preoperative diagnosis, gene therapy delivery, postoperative follow-up, and auditory rehabilitation [7][14]. Group 2: Clinical Significance - According to WHO, over 430 million people globally suffer from disabling hearing loss, with genetic factors accounting for 60% of congenital hearing loss cases [10]. - The consensus aims to standardize clinical trials and patient management for gene therapy, particularly for OTOF-related hearing loss, and is expected to provide important references for clinicians, researchers, and regulatory bodies [15]. Group 3: Expert Opinions - Experts emphasized that this consensus represents a crucial step in establishing a unified framework for clinical trials in gene therapy for hearing loss, ensuring safety and scientific rigor [14]. - The consensus is seen as a potential game-changer in the treatment landscape for hereditary hearing loss, filling a significant gap in the guidance for gene therapy in this area [14][15].

Core Viewpoint - The research highlights the role of dietary flavonoid quercetin and its microbial metabolite DOPAC in enhancing CD8⁺ T cell anti-tumor immunity, suggesting DOPAC as a potential candidate for cancer immunotherapy [2][8]. Group 1: Mechanism of Action - Quercetin, when metabolized by gut microbiota, produces DOPAC, which enhances CD8⁺ T cell anti-tumor immunity through NRF2-mediated mitophagy [3][4]. - DOPAC binds directly to KEAP1 protein, disrupting its interaction with NRF2, thereby preventing KEAP1-mediated NRF2 degradation [4]. - Increased NRF2 activity leads to enhanced transcription of BNIP3, promoting mitophagy and improving the adaptability of CD8⁺ T cells in the tumor microenvironment [4][6]. Group 2: Synergistic Effects - DOPAC exhibits a synergistic effect with immune checkpoint blockade (ICB) therapy, further inhibiting tumor growth [5][6]. Group 3: Implications for Cancer Treatment - The findings underscore the importance of dietary nutrients and their microbial metabolites in regulating anti-tumor immune responses, positioning DOPAC as a promising candidate for cancer immunotherapy [8].

Core Viewpoint - CAR-T cell therapy has shown significant efficacy in treating hematological malignancies, prompting research into its application for solid tumors, particularly glioblastoma multiforme (GBM), which presents unique treatment challenges due to its aggressive nature and lack of effective therapies [2][4]. Group 1: T Cell Exhaustion and Mechanisms - T cell exhaustion is a major barrier to the efficacy of CAR-T cell therapy in solid tumors, characterized by reduced proliferation, impaired effector function, and increased expression of inhibitory receptors [2][4]. - Recent advancements in single-cell RNA sequencing (scRNA-seq) have provided insights into the molecular mechanisms of T cell exhaustion, identifying key regulatory factors such as DNMT3A, SOX4, and PRDM1 that limit T cell anti-tumor activity [2][4]. Group 2: Research Findings on NR4A3 and FOS - A study published in Science Advances found that knocking down NR4A3 enhances CAR-T cell efficacy against malignant gliomas, but this effect diminishes due to T cell exhaustion induced by chronic antigen exposure [3][5]. - Enhancing FOS expression in NR4A3-deficient CAR-T cells can reverse T cell functional exhaustion, thereby maintaining tumor clearance capabilities and improving therapeutic efficacy [3][5][6]. Group 3: Implications for CAR-T Cell Therapy - The research highlights the critical role of NR4A3 in regulating T cell cytotoxicity and memory formation during early antigen exposure, suggesting a combined genetic modification strategy of NR4A3 knockdown and FOS overexpression to protect CAR-T cells from exhaustion [6][8]. - This dual modification approach could lead to sustained tumor clearance in solid tumors, offering a promising new strategy for optimizing CAR-T cell therapy in clinical settings [5][6].

Core Insights - The article highlights five significant research papers published in the journal Cell, with four originating from Chinese scholars, focusing on advancements in DNA sensors, anti-aging potential through protein restriction, new antidepressant molecules, and cancer cell immune evasion mechanisms [3]. Group 1: SARM1 and DNA Sensing - The research from Dalian Medical University reveals that SARM1 can sense double-stranded DNA (dsDNA) and induce cell death by degrading NAD+ in a sequence-independent manner [5][6]. - SARM1's interaction with dsDNA is crucial for its activation, and its gene knockout can prevent chemotherapy-induced neuropathy in mice [5][6]. Group 2: Protein Restriction and Aging - The study from West Lake University presents a comprehensive proteomic landscape of aging, showing that protein restriction can reshape the protein expression and epigenomic states associated with aging [9][10]. - The findings suggest that midlife is the optimal period for protein restriction interventions, which are linked to improved cardiovascular health and reduced inflammation risks [9][10]. Group 3: Norepinephrine Transporter and Antidepressants - Research from Lingang Laboratory identifies conformation-selective regulatory mechanisms of the norepinephrine transporter (NET) and proposes a new inhibitor recognition mechanism [14]. - The study led to the discovery of a small molecule with antidepressant activity, providing a structural basis for understanding NET and other monoamine transporters [14]. Group 4: Cancer Cell Immune Evasion - The research from Fudan University reveals that cancer cells can exploit inter-organ neuroimmune circuits to evade immune surveillance by activating pain-sensing neurons [18][20]. - This mechanism involves the secretion of SLIT2, which enhances tumor-associated macrophage polarization towards a pro-tumor state, thereby promoting tumor growth and reducing the efficacy of immune checkpoint blockade therapies [18][20]. Group 5: Coronavirus Replication Mechanisms - A study from Tsinghua University elucidates the molecular mechanisms of RNA template recycling and capping in SARS-CoV-2, resolving long-standing debates in the field [23][24]. - The research captures critical pre-capping and post-capping initiation states, enhancing the understanding of RNA virus transcription and replication processes [23][24].

Core Viewpoint - The article discusses a groundbreaking study on protein restriction (PR) and its potential anti-aging effects, highlighting the importance of dietary interventions in extending lifespan and improving health [1][2][12]. Group 1: Research Findings - The study systematically mapped the proteomic landscape of aging across 41 organs/tissues in male mice, revealing significant protein expression heterogeneity during aging [4]. - Protein restriction was found to significantly alleviate age-related protein expression abnormalities in various tissues [6]. - The research indicated that protein restriction reduces age-related DNA methylation accumulation and reverses abnormal protein phosphorylation patterns in aging tissues [6]. Group 2: Health Implications - The study confirmed that protein restriction has cross-species cardiovascular protective effects, supported by analyses of plasma samples from both mice and humans [7]. - It was noted that lower protein intake is associated with enhanced cardiovascular health and reduced inflammation risk in humans [11]. Group 3: Timing and Gender Differences - The effects of protein restriction vary by gender and timing, with middle age identified as the optimal period for dietary intervention [8][11].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 去甲肾上腺素转运体 （NET） 在突触神经传递中发挥着关键作用，并与 重度抑郁症 和 注意力缺陷/多动障碍 （ADHD） 有关，然而，我们对其别构、构象选择 性调控机制的理解仍然有限，而 这对于开发靶向治疗药物至关重要。 20 25 年 10 月 24 日，临港实验室 蒋轶 研究员团队联合中国科学院上海药物研究所 徐华强 研究员、 杨德华 研究员团队及临港实验室 王震 研究员团队 （ 张 衡 、 章天炜 、 王鼎言 、 代安涛 、 毛建航 伟论文共同第一作者 ） ， 在国际顶尖学术期刊 Cell 上发表了题为： Unveiling conformation-selectivity regulation of the norepinephrine transporter 的研究论文。 该研究鉴定了 去甲肾上腺素转运体 （Norepinephrine Transporter，NET） 内向开放构象特异性变构位点，提出了靶向该构象的抑制剂识别新机制——" 瓣膜模 型 "。 基于该模型，研究团队采用"干–湿"结合的研究策略，发现了具有体内外 抗抑郁活性 的小分子—— F3288 ...

Core Viewpoint - The research published in Science reveals the dynamic evolution of the impacts of biological invasions on terrestrial ecosystems, identifying "residence time" as a core dynamic factor predicting these impacts [1][4]. Group 1: Research Findings - The study analyzed 775 global studies on invasive species, covering 2,223 effect sizes related to the impacts of plants, animals, and microorganisms on 15 key ecosystem properties, creating the most comprehensive "invasion ecological impact database" to date [3]. - Invasive plants consistently reduce local plant diversity and contribute to increased greenhouse gas emissions (CO₂, N₂O), which are identified as the most significant negative impacts [4]. - Contrary to previous studies, local plant diversity is not a strong predictor of the impact of invasive plants; instead, the residence time of invasive species is crucial—longer residence times lead to greater declines in local plant diversity [4][6]. Group 2: Implications for Ecosystem Management - Local plant species diversity is sensitive to species invasions and shows the weakest resistance, thus should be prioritized for protection [6]. - The non-biological properties of soil become more variable with ongoing species invasions and may naturally recover, indicating that immediate intervention may not be necessary [6].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 WDR5 是 SET1/MLL 复合体的一个重要组成部分，该复合体通过组蛋白 H3K4 甲基化来调控基因表达。WDR5 在维持致癌转录程序方面发挥着关键作用，尤其 是在 MLL1 易位白血病中，这使其成为很有前景的治疗靶点。 WDR5 与 MLL1 及其他转录调控因子之间特征明确的相互作用为开发旨在破坏这些蛋白-蛋白相互作用 （PPI） 的癌症治疗药物提供了机会。然而，由于 WDR5 的结合界面复杂，设计有效的抑制剂仍具挑战性。 2025 年 10 月 23 日，华中师范大学生命科学学院闵金荣教授团队在 Cell 子刊 Cell Chemical Biology 上发表了题为： Therapeutic targeting of WDR5-MLL1 by EMBOW-derived peptides suppresses leukemia progression 的研究论文。 该研究开发了 WDR5 内源性微蛋白结合剂 （ EMBOW ） 来源的多肽抑制剂，通过特异性靶向 WDR5-MLL1 抑制 白血病 进展，且具有低毒性 ，该 研究为利 用多肽类药物靶向 WDR5-M ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 髓鞘形成 （ Myelination ） 是 少突胶质细胞 环绕神经元的轴突形成一层绝缘层的过程，能够提高神经传 递的速度和效率。少突胶质细胞由 少突胶质前体细胞 （OPC） 和 成熟少突胶质细胞 （mOL） 组成，后 者由前者分化而来，负责形成髓鞘。 尽管大多数少突胶质前体细胞 （OPC） 在发育过程中分化为成熟少突胶质细胞 （mOL） 以对神经元进行 髓鞘形成，但 OPC 在成年大脑中也普遍存在且分布均匀。 成年人的少突胶质前体细胞 （OPC） 在与病毒感染 （例如脑膜脑炎） 、缺血 （例如中风） 、精神压力 （例如抑郁和焦虑） 或衰老相关的受损髓鞘 （脱髓鞘神经元） 的髓鞘再生 （ Remyelination ） 过程中发 挥着尤为重要的作用。针对脱髓鞘现象，少突胶质前体细胞 （OPC） 会迁移到损伤部位，增殖并分化为成 熟少突胶质细胞，重新包裹暴露的神经元轴突。因此，髓鞘再生对于维持成年大脑的正常神经功能至关重 要。 众所周知， 髓鞘再生是中枢神经系统中为数不多的再生过程之一 ，它取决于少突胶质前体细胞 （OPC） 增殖并分化为成熟少突胶质细胞 （mOL） 的能 ...