Expanding the utility of variant effect predictions with phenotype-specific models
V2P模型通过多任务学习方法，针对单核苷酸变异和插入/缺失变异进行致病性预测，结合人类表型本体论的疾病表型，显著提高了变异致病性预测的准确性。该模型在真实和模拟患者的基因组数据中表现优异，展示了其在临床应用中的潜力。研究团队来自多家知名机构，具备强大的技术背景和科研实力。
Towards antibody-based immunotherapy development for platinum-resistant high-grade serous ovarian cancer
本研究探讨了针对铂耐药高分化浆液性卵巢癌的抗体基础免疫疗法的发展。研究显示，抗体S2和Yth53.1在铂耐药细胞系中表现出显著的细胞溶解效应，且与铂基治疗相比，抗体疗法在铂耐药性方面的影响较小。这一发现为铂耐药高分化浆液性卵巢癌的治疗提供了新的思路，具有较高的早期投资潜力。
MRI signature of brain age underlying post-traumatic stress disorder in World Trade Center responders
研究表明，创伤后应激障碍（PTSD）可能导致脑龄加速，使用新型MRI技术BrainAgeNeX进行分析，发现911事件的应急响应者中，PTSD患者的脑龄显著高于非PTSD患者。这一发现为理解PTSD与脑部结构损伤之间的关系提供了重要线索，具有潜在的临床应用价值。
Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission
本研究揭示了AKAP11作为自噬受体在调控PKA信号通路和突触传递中的关键作用，特别是在双相情感障碍和精神分裂症等精神疾病中的潜在机制。通过多组学分析，研究表明AKAP11缺失会导致突触传递的显著减弱，影响神经元功能，提供了新的生物医学研究方向和治疗靶点。
Multi-omics framework integrating genetics microbiome and immunity for understanding motor neuron degeneration pathogenesis
该研究通过多组学方法探讨了肌萎缩侧索硬化症（ALS）的发病机制，发现心血管因素、肠道微生物群和免疫细胞在ALS易感性中起重要作用。研究结果表明，特定的微生物种类与ALS风险呈负相关，且开发的五基因生物标志物面板在预测ALS风险方面表现出高准确性。这些发现为ALS的风险分层和预防提供了新的治疗靶点，具有重要的临床应用潜力。
Divergent evolution of fungal P450 monooxygenase unlocks simultaneous access to C12β and C15α oxyfunctionalization of steroids
本研究展示了一种新颖的方法，通过工程化的真菌P450酶增强类固醇的羟基化，表明在生物催化领域具有显著的工业潜力。研究中成功实现了对孕酮的C12β和C15α羟基化的高选择性，且高密度发酵法产生了大量羟基化类固醇，显示出其工业可行性。结合的SSM和FRISM策略有效提高了P450酶的选择性和活性，为未来的类固醇药物合成提供了新的可能性。
Dual blockades of TIM-3 and PD-1 effectively prevent hyper-progression and enhance the efficacy of anti-PD-1 therapy in high-grade serous ovarian cancer
本研究探讨了TIM-3和PD-1联合阻断在高等级浆液性卵巢癌（HGSOC）中的应用，发现其能够有效防止超进展现象并增强抗PD-1治疗的效果。研究显示，TIM-3的上调与肿瘤微环境中的免疫抑制状态相关，联合治疗能够显著改善CD8+肿瘤浸润淋巴细胞（TILs）和树突状细胞（TIDCs）的功能。这一发现为HGSOC患者提供了新的治疗策略，具有重要的临床前应用价值。
SLC7A5-ERBB2 axis drives olaparib resistance via de novo lipid synthesis in ovarian cancer
研究发现SLC7A5在卵巢癌中通过ERBB2轴驱动Olaparib耐药性，主要通过调控脂质代谢实现。这一发现为卵巢癌的治疗提供了新的靶点，可能改善患者的临床结果。SLC7A5的抑制能够显著增强卵巢癌细胞对Olaparib的敏感性，提示其在临床应用中的潜力。
Discovery of a bifunctional PKMYT1-targeting PROTAC empowered by AI-generation
D16-M1P2, a novel bifunctional PROTAC targeting PKMYT1, was developed using an AI-driven generative platform. It exhibits dual mechanisms of action, effectively degrading and inhibiting PKMYT1, leading to significant antitumor responses in xenograft models. The compound shows high selectivity and favorable pharmacokinetic properties, indicating its potential as a therapeutic agent for cancers with specific genetic alterations. This research underscores the promise of AI in drug discovery and the development of targeted cancer therapies.
Methanol biotransformation for the production of biodegradable plastic monomer L-lactate in yeast
研究表明，通过工程化酵母菌Ogataea polymorpha，可以从甲醇中高效生产可生物降解的塑料单体L-乳酸。该技术结合了液态阳光技术和甲醇生物转化，展示了碳负生产的潜力。技术经济分析和生命周期评估表明，该生产过程在商业上具有可行性，并能显著降低温室气体排放，推动可持续塑料生产。
The expression, regulation, and function of human endogenous retroviruses in genitourinary cancers
The review discusses the expression, regulation, and function of human endogenous retroviruses (HERVs) in genitourinary cancers, highlighting their role in oncogenesis and potential as biomarkers and therapeutic targets. It emphasizes the need for further research to validate HERVs in clinical applications, including immunotherapy and early detection strategies.
Inhibition of TBK1/IKKε mediated RIPK1 phosphorylation sensitizes tumors to immune cell killing
本研究探讨了TBK1和IKKε在肿瘤细胞对免疫细胞攻击中的作用，发现抑制这两种激酶可以增强肿瘤对CD8 T细胞和自然杀伤细胞的敏感性。研究表明，RIPK1的磷酸化状态是调节肿瘤细胞生存与死亡的重要因素，揭示了新的治疗靶点，可能为癌症免疫治疗提供新的策略。
Disruption of the PIKfyve complex unveils an adaptive mechanism to promote lysosomal repair and mitochondrial homeostasis
该研究探讨了PIKfyve复合体在细胞应激下的适应机制，揭示其在溶酶体修复和线粒体功能中的关键作用。研究表明，PIKfyve抑制剂在神经退行性疾病模型中具有潜在的治疗应用，可能通过增强溶酶体膜的完整性和线粒体的代谢能力来发挥作用。这一发现为针对神经退行性疾病的治疗策略提供了新的思路。
Isoallolithocholic acid ameliorates intestinal inflammation via metabolically reprogrammed macrophages
IsoalloLCA, a bile acid metabolite, has been shown to alleviate intestinal inflammation in pediatric patients with inflammatory bowel disease (IBD). The study demonstrates that isoalloLCA reduces TNF production and enhances the expression of anti-inflammatory regulatory T cells in both human and murine models. By metabolically reprogramming macrophages, isoalloLCA enhances oxidative phosphorylation, thereby amplifying its anti-inflammatory effects. This research highlights the potential of isoalloLCA as a promising therapeutic avenue for treating IBD, addressing a significant global health concern.
Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho)lipid peroxidation as a potential therapeutic strategy
Sibiriline is a newly identified dual inhibitor of necroptosis and ferroptosis, showing significant potential in treating complex diseases like Parkinson's and cystic fibrosis. The study reveals its mechanisms of action, including inhibition of RIPK1 kinase activity and lipid peroxidation, positioning it as a promising candidate for innovative therapies. Its favorable safety profile and efficacy in preclinical models suggest strong investment potential in the biotechnology sector.