Core Viewpoint - The article discusses the ecological risks associated with biodegradable plastics, despite their perceived environmental benefits, and emphasizes the need for strategies to mitigate these risks [1][3]. Group 1: Ecological Risks of Biodegradable Plastics - Biodegradable plastics, while seen as eco-friendly alternatives to traditional plastics, can release microplastics and nanoplastics that pose potential health risks [1][3]. - The degradation of biodegradable plastics can lead to the release of diverse oligomers, which are persistent organic pollutants, raising concerns about their adverse effects on ecosystems [4]. - Chemicals released from biodegradable plastics, such as phthalates and bisphenol A, have been shown to disrupt cellular metabolism and can have genetic, reproductive, and immunotoxic effects on organisms [5]. Group 2: Production and Demand Trends - The global demand for biodegradable plastics is increasing, with production expected to reach 2.47 million tons in 2024 and 5.73 million tons by 2029 [2]. Group 3: Mitigation Strategies - To reduce the potential risks associated with biodegradable plastics, collaboration among research institutions, companies, and policymakers is essential [5]. - Key strategies include identifying the sources and degradation pathways of toxic oligomers, developing biodegradable plastics with controllable and complete degradation capabilities, and redesigning the structure of biodegradable plastics for safer alternatives [5][6].

Core Viewpoint - The article highlights the appointment of Zhang Qiao as the youngest president of Suzhou University since its renaming in 1982, emphasizing his academic and administrative background in materials science and technology [1]. Background of Zhang Qiao - Zhang Qiao, born in June 1982, graduated with a bachelor's degree from the University of Science and Technology of China in 2004, followed by a master's degree in 2007 and a Ph.D. from the University of California, Riverside in 2012 [2]. - He has held various positions at Suzhou University, including professor and vice dean, and has served in local government roles such as deputy mayor of Kunshan and Suzhou, and deputy director of the Jiangsu Provincial Department of Science and Technology [2]. Research Contributions - Zhang Qiao's research focuses on physical chemistry, materials science, catalysis, and nanomaterials, with over 200 published papers and a total citation count of 29,242, achieving an H-index of 87 [3][4]. - His notable works include a review on oriented attachment growth and functional materials synthesis, which has been cited 693 times [6]. - A significant paper during his doctoral studies demonstrated that H₂O₂ is a key reagent in the synthesis of silver nanoplates, challenging previous beliefs and garnering 933 citations [9]. Independent Research Phase - After establishing an independent lab at Suzhou University in 2014, Zhang published a paper on the one-pot synthesis of highly stable CsPbBr₃@SiO₂ core-shell nanoparticles, contributing to the field of nanomaterials [12][14]. - His most cited work, published in 2016, reviews the synthesis, properties, and applications of hollow micro/nanostructures, with 1,426 citations, discussing various synthesis strategies and applications across multiple fields [14].

Core Viewpoint - The article emphasizes the importance of the Cre-loxP system in gene editing research and announces a series of courses aimed at addressing practical issues related to the application of Cre tools in research settings [1][2]. Group 1: Course Announcement - A new session of the "Cre-loxP system combined with AAV applications" course will be held on June 12, featuring experts from the company [2][7]. - The course will focus on questions raised by participants, exploring the core principles of the Cre-loxP system and AAV technology, as well as optimization strategies and case studies [2][4]. Group 2: Technical Insights - The article discusses the advantages of using AAV for delivering Cre recombinase compared to traditional methods involving Cre transgenic mice [4]. - It highlights specific applications where AAV-Cre demonstrates unique benefits, such as in brain neuroscience and organ-specific editing [4]. Group 3: Course Content Overview - The course will cover foundational knowledge of the Cre-loxP system and AAV, technical discussions on their combination, and typical application case studies [12][9]. - Participants will have the opportunity to submit questions for live answers during the course [6][2]. Group 4: Instructor Background - The course will be led by Liu Fanrui, a senior product manager with extensive experience in genetic modification of model organisms, and Xiong Zehao, a project manager specializing in AAV gene therapy [15][17]. Group 5: Additional Resources - A comprehensive manual titled "Cre-loxP Recombinase System User Manual" is available for free, providing detailed insights into the Cre-loxP system [19].

Core Viewpoint - The article discusses the development of a deep learning system called DeepRETStroke, which utilizes retinal images to detect silent brain infarction (SBI) and predict stroke risk, providing a cost-effective and non-invasive method for identifying high-risk populations [2][3][12]. Summary by Sections Traditional Stroke Risk Assessment - Traditional stroke risk assessments rely on clinical risk factors primarily from self-reported data, which have shown limited accuracy in identifying high-risk individuals, with consistency indices ranging from 0.58 to 0.73 [2]. Development of DeepRETStroke - The research team developed DeepRETStroke, a deep learning system that detects SBI and predicts stroke risk using only retinal images, eliminating the need for brain imaging [3][12]. Importance of Detecting SBI - SBI affects nearly 20% of the general population, indicating potential ischemic cerebrovascular disease and an increased risk of future strokes. Identifying SBI can help in better risk stratification and management of patients [6][12]. Limitations of Current Imaging Techniques - Current imaging techniques like MRI and CT for detecting SBI are impractical and costly for general screening, highlighting the need for simpler and more economical detection methods [7][8]. Advancements in Retinal Imaging - Recent advancements in medical imaging and deep learning emphasize the retina as a unique window to observe the brain, with retinal vessels sharing similarities with cerebral vessels, allowing for non-invasive early detection of cerebrovascular changes [8]. Research Methodology - The study involved three phases: pre-training DeepRETStroke with 895,640 retinal images, validating the system with 213,762 images from multiple countries, and conducting a real-world proof-of-concept study [9]. Performance Metrics - DeepRETStroke demonstrated strong performance in predicting new strokes with an area under the curve (AUC) of 0.901 and for recurrent strokes with an AUC of 0.769, showing consistent results across various datasets [9]. Real-World Validation - A prospective study involving 218 stroke patients showed that DeepRETStroke could stratify stroke risk effectively, leading to an 82.44% reduction in recurrent stroke events through appropriate interventions [10][12].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 结直肠癌 是全世界范围内发病人数第三的癌症 （每年新增近 200 万人，仅次于 肺癌 和 乳腺癌 ） ，死亡 人数第二的癌症 （每年死亡近 100 万人，仅次于 肺癌 ） 。对于 III 期或高危 II 期结肠癌患者的标准治疗 方案包括手术后进行 3-6 个月的 FOLFOX （ 亚叶酸钙+5-氟尿嘧啶+奥沙利铂 ） 或 CAPOX （卡培他滨 +奥沙利铂） 或氟嘧啶 单药 治疗。尽管采取了这些治疗方法，仍有 20%-40% 的患者会出现复发。此 外，结肠癌的手术和辅助化疗会带来副作用，损害生活质量，降低身体机能。对于这一患者群体，需要采 取既能提高生存率又能改善生活质量的干预措施。 临床前研究显示， 运动 能够减缓癌症发展 （包括结肠癌） 。此外，观察性研究显示，结直肠癌患者 （ 包括 III 期结肠癌 ） 在接受治疗后增加休闲体育活动量，其癌症复发和死亡的风险会降低。这些关联的可 能机制包括运动对代谢生长因子、炎症和免疫功能的影响。尽管这些发现表明运动可能有益于延长癌症患 者的寿命，但由于观察性研究设计存在方法学上的局限性，缺乏 1 级证据 （最高证据等级） ，所以 ...

Core Viewpoint - The article discusses the challenges and advancements in delivering therapeutic molecules across the blood-brain barrier (BBB), particularly focusing on the potential of using CRISPR-modified human induced pluripotent stem cell-derived microglia (iMG) for treating central nervous system (CNS) diseases [1][4][18]. Group 1: Blood-Brain Barrier and Its Implications - The blood-brain barrier is crucial for preventing harmful substances from entering the brain but also limits the delivery of most small and large molecule drugs, hindering the treatment of CNS diseases [1][2]. - There is an urgent need for technologies that can effectively deliver biotherapeutics across the BBB to improve treatment options for CNS disorders [2]. Group 2: Research Developments - A study published by researchers at the University of California, Irvine, demonstrated the use of CRISPR-modified iMG for CNS-wide delivery of disease-modifying proteins, showing potential in treating Alzheimer's disease, breast cancer brain metastasis, and demyelination [3][4][18]. - The research indicates that iMG can respond to pathological changes and deliver therapeutic proteins effectively, reducing various pathological biochemical markers associated with Alzheimer's disease [16][18]. Group 3: Delivery Mechanisms and Challenges - Previous attempts to deliver therapeutic antibodies using non-invasive techniques have shown limited success, with concentrations in the brain remaining below 2% of plasma levels [7]. - Direct injection methods for proteins or viral vectors have also faced challenges, including the need for multiple treatments for long-term efficacy and potential immune reactions [8][9]. Group 4: Future Prospects - iMG derived from human induced pluripotent stem cells present a promising new platform for cell therapy, capable of delivering therapeutic molecules across the CNS [10][12][16]. - The study's findings suggest that iMG can alleviate Aβ pathology and reduce inflammation and neurodegeneration, indicating a significant advancement in the treatment of CNS diseases [16][18].

Core Viewpoint - The study highlights the unintended adverse effects of CRISPR-Cas9/AAV6-mediated gene editing in hematopoietic stem cells (HSPC), specifically focusing on senescence and inflammation, which can negatively impact the efficacy and safety of gene therapy [4][5][15]. Group 1: Gene Editing Techniques and Challenges - Gene editing in HSPC represents a transformative approach for treating immune, blood, and metabolic genetic diseases, utilizing platforms like CRISPR-Cas9 and AAV6 for targeted gene modifications [8]. - A major limitation of efficient homologous recombination (HDR) gene editing is that primitive HSCs are in a quiescent state, which hinders long-term proliferation of HDR-edited human HSPC [9][10]. - The activation of DNA damage response (DDR) due to double-strand breaks (DSB) can adversely affect the adaptability of HSPC, leading to increased sensitivity and reduced clonal diversity in xenotransplantation [10]. Group 2: Adverse Effects and Mitigation Strategies - The study found that CRISPR-Cas9/AAV6-mediated gene editing induces senescence-like phenotypes and inflammatory responses in HSPC, which impair the functionality of HDR-edited cells [12][15]. - Short-term suppression of p53 can alleviate the negative impacts of gene editing-induced DDR, but complete inactivation of p53 raises concerns about genetic toxicity [11]. - The use of Anakinra, an IL-1 signaling antagonist, has been identified as a promising strategy to enhance the clonal output of HDR-edited cells while minimizing genetic toxicity risks associated with the editing process [5][14][15]. Group 3: Research Findings and Implications - The core findings of the research indicate that CRISPR-Cas9/AAV6 gene editing leads to significant accumulation of senescence markers in HDR-edited HSPC, which can be mitigated to enhance long-term hematopoietic reconstitution [15]. - The study proposes strategies to overcome key obstacles in HDR-based gene therapy for HSPC, aiming to improve clinical efficacy and safety [6][17].

Core Viewpoint - A long-term study from Harvard University suggests that moderate caffeine consumption, particularly from coffee, may be linked to healthier and longer lives for middle-aged women [2][4]. Group 1: Research Overview - The study, led by Professor Hu Pingchang from Harvard's Chan School of Public Health, tracked 47,513 women over 30 years, starting in 1984, collecting detailed dietary and lifestyle information [4][5]. - The core question of the research was how caffeine intake habits in middle age (ages 45-60) affect health in later years [5]. Group 2: Definition of Healthy Aging - The research team defined "healthy aging" strictly, requiring participants aged 70 and above to meet several criteria, including the absence of major chronic diseases and the ability to perform daily activities independently [6][7][8]. Group 3: Key Findings - Among the 3,706 women who achieved "healthy aging" by 2016, the average daily caffeine intake was about 315 mg, primarily from caffeinated coffee [10]. - Drinking an additional small cup (approximately 120ml) of caffeinated coffee daily was associated with a 2%-5% increased probability of achieving "healthy aging" [12]. - The study found no significant association between tea or decaffeinated coffee and improved "healthy aging" probabilities, while consuming caffeinated cola was linked to a 20%-26% decrease in the likelihood of achieving "healthy aging" [12]. Group 4: Research Significance - This study is notable for being the first to evaluate the comprehensive impact of coffee on multiple aging-related health aspects over a 30-year period, highlighting the unique role of caffeinated coffee [13][14]. Group 5: Recommendations - It is advised to choose caffeinated coffee for potential health benefits, with a recommended limit of no more than 2 cups (approximately 480ml) per day [17][18]. - The benefits of coffee are considered moderate and should be part of an overall healthy lifestyle, including balanced diet and regular exercise [19]. - Individuals sensitive to caffeine or with specific health conditions should consult with healthcare providers regarding coffee consumption [20].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 尽管嵌合抗原受体 （CAR） -T 细胞疗法在血液系统恶性肿瘤中取得了显著成功，但由于治疗效果不佳或剂量限制性毒性，其在 实体瘤 中的临床应用效果有 限。 开发能够引发强大但可控的免疫反应、从而消除高度异质性和免疫抑制性的实体肿瘤细胞群的 CAR-T 细胞疗法，仍然是一个关键挑战。 2025 年 6 月 5 日，宾夕法尼亚大学佩雷尔曼医学院的研究人员在 Cell 子刊 Cancer Cell 上发表了题为： Mutant KRAS peptide targeted CAR-T cells engineered for cancer therapy 的研究论文。 在这项最新研究中，研究团队利用多种遗传学方法开发了一种新型 CAR-T 细胞疗法。 首先，研究团队筛选了针对由肽-MHC复合物呈递的致癌性 KRAS G12V 突变 （即癌症新抗原） 的结合剂。随后， 将这些新抗原结合剂整合到 CAR-T 细胞中， 构建了 mKRAS-NeoCAR-T 细胞 ，并在转移性肺癌、胰腺癌和肾细胞癌的异种移植模型中证明了其有效性。最后，研究团队通过诱导分泌 IL-12 和基因敲除 T ...

Core Viewpoint - Alzheimer's disease (AD) is a destructive neurodegenerative disorder characterized by gradual cognitive decline, necessitating therapies that can slow or halt its progression [2][6]. Group 1: Current Treatments and Limitations - Currently, only a few FDA-approved monoclonal antibodies targeting amyloid-beta (Aβ) are available for early-stage Alzheimer's treatment, such as Lecanemab and Donanemab, which show efficacy in reducing amyloid burden but have limited impact on disease progression [2]. - The focus on Aβ alone is insufficient to address the progressive nature of Alzheimer's disease [2]. Group 2: Gene Therapy as a Promising Strategy - Gene therapy that enhances intrinsic neuroprotective pathways presents a promising new strategy to slow neurodegenerative changes and prevent further cognitive decline [3][6]. - Caveolin-1 (Cav-1), a membrane scaffolding protein, regulates various growth-promoting and survival signaling pathways, indicating its potential in Alzheimer's treatment [6]. Group 3: Research Findings - A recent study from the University of California, San Diego, demonstrated that delivering Cav-1 via AAV9 to symptomatic Alzheimer's mouse models can mitigate cognitive loss and pathological transcriptome changes [4][5]. - The study involved administering SynCav1 to symptomatic Alzheimer's mouse models (PSAPP and APPKI) and showed that it maintained hippocampal-dependent memory abilities [7][8]. - Transcriptomic analysis indicated that the profiles of PSAPP-SynCav1 mice were similar to those of age-matched wild-type mice, with downregulation of neurodegenerative pathways and upregulation of synaptic and cognitive-related pathways [8][10]. Group 4: Mechanisms of Action - The delivery of SynCav1 to the hippocampus during the symptomatic stage protected learning and memory abilities, with increased expression levels of p-CaMKII and p-CREB in primary cortical neurons, suggesting enhanced neuronal and synaptic activity [10]. - Activity-dependent neuroprotective protein (ADNP) was identified as a potential mediator of SynCav1's neuroprotective effects, retaining PAC1R, a known regulator of ADNP expression [11][12].