以下文章来源于肥胖世界ObesityWorld ，作者欢迎订阅 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 从低碳水饮食、间歇性禁食，到减重手术和司美格鲁肽，越来越多的人不断尝试各种饮食方式、医疗手段和药物来实现减肥目标。 近年大量研究表明，减少食物摄入不仅能帮助动物模型，甚至对人类健康老化也有积极作用。而权威期刊《Science》上的一项新研究则带 来了全新视角：仅仅是"饥饿感"本身，就足以延缓衰老，为抗衰领域打开了新的大门。 2023年5月，密歇根大学团队在《Science》杂志发表题为"Effects of hunger on neuronal histone modifications slow aging in Drosophila"的 论文。研究发现，无论是通过限制饮食还是用大脑刺激手段，只要让果蝇产生饥饿感，它们的寿命都会延长。科学家们指出，饥饿会引发大 脑表观遗传变化，调控基因表达，从而影响进食行为和衰老进程。 研究人员进一步表示，这项成果在一定程 ...

Core Viewpoint - The study reveals that hypoxia inhibits ferroptosis through a HIF-independent mechanism by suppressing KDM6A, a key player in lipid metabolism and ferroptosis resistance [2][5]. Group 1: Mechanism of Ferroptosis Regulation - Long-term hypoxia can inhibit ferroptosis in a HIF-independent manner [5]. - Hypoxia suppresses KDM6A, reshaping the lipid profile to confer resistance to ferroptosis [3][5]. - KDM6A acts as a non-classical oxygen sensor in the ferroptosis process, indicating a novel regulatory pathway [2][5]. Group 2: Implications for Cancer - The loss of KDM6A, a tumor suppressor, is commonly observed in bladder cancer, leading to resistance to ferroptosis [5]. - Pharmacological inhibition of EZH2, which opposes KDM6A activity, restores sensitivity to ferroptosis in bladder tumors carrying KDM6A mutations [4][5].

Core Insights - The research reveals a convergent mechanism of echolocation in different mammalian species, providing new perspectives on the evolutionary origins of this complex behavior [1][2] - The study highlights the significance of non-coding regulatory regions in the convergent evolution of behaviors, challenging the traditional focus on protein-coding genes [2] Group 1: Research Findings - The study identifies 222 shared open chromatin regions in the hippocampal area of echolocating species, significantly higher than random expectations, indicating a complex gene regulatory network [1] - Traditional auditory-related genes are found to be abnormally active in the hippocampal regulatory networks of echolocating mammals, suggesting their role in spatial localization functions [2] Group 2: Methodology and Implications - The research employs innovative techniques such as chromatin accessibility sequencing, transcriptome sequencing, and transmission electron microscopy to compare the hippocampal gene regulatory features of various species [1] - The establishment of the Daluoshan pig-tailed mouse as a new model organism offers a valuable platform for further exploration of the neural mechanisms underlying echolocation [2]

Core Viewpoint - The latest research published in Nature reveals that maternal iron deficiency during pregnancy can lead to significant impacts on fetal sex development, specifically causing XY mouse embryos to develop ovaries instead of testes [2][14]. Group 1: Research Findings - The study conducted by a team from Osaka University demonstrates that iron, particularly ferrous ions (Fe²⁺), plays a crucial role in activating male sex determination genes [2][11]. - The Sry gene, located on the Y chromosome, is essential for male development and is activated during a specific time window in embryonic development [3][11]. - Iron metabolism is linked to the expression of the Sry gene, where iron deficiency leads to increased suppression of Sry expression due to epigenetic modifications [5][11]. Group 2: Mechanisms of Action - The research indicates that iron accumulates in key cells responsible for sex determination, with iron-related gene expression significantly higher in these cells compared to others [6][11]. - Experiments showed that blocking iron supply resulted in decreased Sry expression and a shift in XY embryos towards female characteristics [7][11]. - Maternal iron deficiency, induced through dietary means or iron chelation, resulted in a notable percentage of XY offspring exhibiting sex reversal [8][9][11]. Group 3: Implications for Human Health - The findings suggest that severe maternal iron deficiency could be an underrecognized environmental risk factor for certain cases of 46-XY disorders of sex development in humans [14]. - The study emphasizes the importance of adequate iron intake during pregnancy to prevent anemia and ensure proper fetal sex development [14]. - This research challenges traditional views on iron's role, highlighting its influence on gene expression and fetal development, thus calling for nutritional interventions during pregnancy [14].

Core Viewpoint - The research conducted by the team led by Academician Cao Xiaofeng from the Chinese Academy of Sciences provides direct molecular evidence supporting the theory of "acquired inheritance" by demonstrating that environmentally induced epigenetic variations can mediate adaptive traits across generations in rice [2][10]. Group 1: Research Findings - The study established a multi-generational cold stress screening system, successfully obtaining rice strains with significantly enhanced cold resistance that exhibit stable inheritance over at least five generations after the removal of cold stress [4][7]. - The research identified a key variation site in the promoter region of the Arabidopsis galactin gene ACT1, where the loss of methylation allows for the expression of ACT1 to no longer be suppressed by low temperatures [5][8]. - The findings revealed a complete regulatory pathway for cold adaptation, where low-temperature stress downregulates the expression of DNA methyltransferase MET1b, leading to the loss of DNA methylation at the ACT1 promoter, which activates ACT1 expression and confers cold resistance to rice [7][10]. Group 2: Implications for Agriculture - The research introduces a new breeding strategy termed "adversity domestication-epigenetic variation identification-precise editing," which offers innovative solutions for agricultural production challenges posed by global climate change [2]. - The study's analysis of DNA methylation in 131 local rice varieties from three major rice-growing regions in China indicates a "south high, north low" gradient in DNA methylation status of ACT1, suggesting that epigenetic variation is a key domestication site for cold adaptation in rice as it migrates northward [8].

Core Viewpoint - The research highlights the critical role of the epigenetic regulator BAZ2B in hepatic senescence and metabolic dysfunction-associated steatohepatitis (MASH) fibrosis, providing a theoretical foundation for developing new therapeutic strategies [2][4][7]. Group 1: Research Findings - The study reveals an epigenetic mechanism linking liver aging to MASH fibrosis, with the upregulation of chromatin remodeler BAZ2B associated with MASH pathology in certain liver cells [4]. - In mouse models, gene knockout or liver cell-specific knockdown of Baz2b alleviates hepatic senescence and MASH fibrosis by maintaining PPARα-mediated lipid metabolism, which is impaired in naturally aged and MASH mice [4][5]. - BAZ2B directly binds to the promoter regions of genes related to the PPARα signaling pathway, reducing chromatin accessibility and downregulating gene expression [5]. Group 2: Implications - The BAZ2B-PPARα-lipid metabolism signaling axis is identified as a crucial link in the progression from liver aging to MASH fibrosis, suggesting that BAZ2B may serve as a potential therapeutic target for liver aging and fibrosis [7].

Company Overview - Microchip Biotech is a pioneer in original innovative drugs in China, focusing on providing clinically needed revolutionary mechanism drugs for patients [7][38] - The company has established a complete industrial chain layout from early exploratory discovery to commercialization, offering original innovative drugs globally [38] Financial Performance - For the fiscal year 2024, the company reported a net profit attributable to shareholders of -114.57 million yuan, with the parent company achieving a net profit of -88.42 million yuan [5] - The board decided not to distribute cash dividends or issue bonus shares for the fiscal year 2024, despite having positive undistributed profits [5] Product Pipeline - The company has developed two innovative drugs, with multiple indications approved for sale globally, including in the fields of malignant tumors, metabolic diseases, autoimmune diseases, central nervous system diseases, and antiviral treatments [7][39] - Key products include: - **Sida Benamide (西达本胺)**: A first-in-class HDAC inhibitor with multiple indications approved in China and Japan, including for peripheral T-cell lymphoma and breast cancer [8][9][39] - **Siglitazone (西格列他钠)**: A first-in-class PPAR agonist approved for type 2 diabetes and recently for combination therapy with metformin [12][13][40] Research and Development - The company employs a team of experienced scientists to drive drug development, focusing on understanding disease mechanisms and optimizing drug design [22] - The R&D pipeline includes several promising candidates targeting various cancers and metabolic diseases, with ongoing clinical trials demonstrating significant efficacy [17][21][40] Industry Context - The biopharmaceutical industry in China is rapidly evolving, with increasing participation in global biotech innovation and a focus on meeting domestic healthcare needs [26][30] - Despite a low-risk appetite in global financing, Chinese companies are becoming significant players in licensing transactions, with a notable increase in outbound licensing activities [29][41] - The market for innovative drugs in China is projected to grow significantly, with a forecasted market size of approximately $197 billion by 2025 [30]

Financial Data and Key Metrics Changes - Sangamo Therapeutics reduced non-GAAP operating expenses by nearly half year-over-year since 2023 [9] - The company raised over $100 million in funding through non-dilutive license fees, milestone payments, and equity financing in 2024 [9] Business Line Data and Key Metrics Changes - The company advanced its neurology therapies, securing its first-ever neurology IND for idiopathic small fiber neuropathy [7] - The Fabry gene therapy study continues to generate best-in-class data, with pivotal data readout expected in mid-2025 [9][22] Market Data and Key Metrics Changes - Interest in the Fabry program has been strong, with ongoing business development negotiations for a commercial partner [11] - The company is actively engaged in advanced contract negotiations for a third STAC-BBB license agreement [12] Company Strategy and Development Direction - Sangamo's number one priority is addressing its financing needs to fulfill its potential [11] - The company aims to secure a partnership for Fabry that provides capital for executing other programs [12] - The regulatory pathway for accelerated approval in Fabry disease could reduce the time to potential approval by approximately three years [8][29] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the progress made towards becoming a clinical-stage neurology company [28] - The company is focused on raising additional capital to support its operations and development [30] Other Important Information - The company plans to begin patient enrollment and dosing for ST-503 in mid-2025, with preliminary proof of efficacy data expected in the fourth quarter of 2026 [19] - The FDA has provided a clear regulatory pathway to accelerate approval for ST-920, with a potential BLA submission in the second half of 2025 [25][26] Q&A Session Summary Question: Is the company still waiting on any data for the Fabry program? - Management confirmed they are in late-phase discussions with several partners and look forward to seeing the one-year data for the last patient soon [34][36] Question: Have potential partners seen any data beyond the WORLDSymposium data? - Management indicated that partners have not seen efficacy data beyond what was presented at the WORLDSymposium [45] Question: What is the status of the STAC-BBB deal? - Management hopes to finalize the deal by the end of the quarter and indicated that the partner is a logical blue-chip choice [55] Question: How is the company managing operating expenses going forward? - Management has reduced operating expenses by nearly half year-over-year and plans to maintain the same level of expenses as last year while advancing the neurology pipeline [58] Question: What are the patient enrollment criteria for the Nav1.7% study? - Management stated that the criteria will be published on clinical trial registries and emphasized the importance of a clear result for the one-time treatment [73][76]