Core Viewpoint - CRISPR-Cas9 technology, known as "molecular scissors," is a revolutionary tool in biomedical research, offering new strategies for treating genetic diseases and tumors through precise gene editing [1][5]. Group 1: CRISPR-Cas9 Mechanism - The CRISPR-Cas9 system is derived from bacterial immune mechanisms and has been adapted into a powerful gene editing tool for various applications, including gene knockout, insertion, and regulation [5][8]. - Key components include the Cas9 protein, which cuts DNA, and sgRNA, which guides Cas9 to specific gene sequences [7][8]. Group 2: Challenges in Delivery - Despite its powerful editing capabilities, the application of CRISPR-Cas9 in primary immune cells and stem cells faces significant challenges due to the cells' sensitivity and limited in vitro expansion [2][3]. - Current delivery methods, such as chemical transfection and electroporation, have limitations in efficiency and can cause cell damage, while viral vectors pose risks of insertion mutations and immune responses [2][3]. Group 3: ProteanFect Delivery System - The ProteanFect CRISPRMax Ultra transfection kit, developed by West Lake Aggregates and West Lake University, addresses the delivery bottleneck for difficult-to-transfect primary cells by utilizing innovative biomolecular aggregation technology [9][13]. - This system allows for high transfection efficiency and cell compatibility without relying on harsh physical or chemical methods, thus maintaining cell viability and functionality [9][13]. Group 4: Successful Applications - The ProteanFect CRISPRMax Ultra kit has demonstrated high editing efficiency in various primary cells, including mouse and human T cells, achieving mutation rates of 84.3% and 80.1% respectively [14][16]. - Additionally, it has been successfully used to deliver gene editing systems to induced pluripotent stem cells (iPSCs), achieving a base substitution efficiency of 55% [17]. Group 5: Future of Gene Editing - The demand for efficient gene editing in various functional cells is growing, driven by advancements in precision medicine and cell therapy [19][20]. - Innovations like ProteanFect represent a paradigm shift in research, enabling more gentle and efficient interactions with cells while preserving their functionality [19][20].

Group 1 - The core viewpoint of the article is the recruitment of postdoctoral researchers in the field of nanomaterials, pharmaceuticals, chemistry, and biotechnology at Peking University, emphasizing the research group's strong funding and interdisciplinary focus [2][3]. Group 2 - The job requirements include a PhD degree or obtaining one within three years, age under 35, research experience in relevant fields, publication in influential journals, proficiency in English literature, and strong communication skills [2]. Group 3 - The benefits for the position include national and Peking University postdoctoral welfare, housing subsidies, support for applying to prestigious postdoctoral programs, and opportunities to apply for national research funds [3]. Group 4 - The application process requires candidates to send a detailed resume to the specified email, with a response expected within 3-5 working days [4]. Group 5 - The article also mentions the establishment of professional WeChat groups for promoting research communication, with specific instructions for joining [8].

Core Viewpoint - The development of mRNA and lipid nanoparticles (LNP) has shown significant clinical success in delivering gene drugs to the liver, but the tendency of LNP to accumulate in the liver poses a major bottleneck for broader applications in gene therapy [2][4]. Group 1: Research Development - A collaborative research paper titled "Tissue-specific mRNA delivery and prime editing with peptide–ionizable lipid nanoparticles" was published in Nature Materials, showcasing a new platform for organ-targeted mRNA delivery [3]. - The research combines peptides and ionizable lipids to create a novel material called peptide-ionizable lipid (PIL), establishing a platform (PILOT) for organ-specific and tunable mRNA delivery [4][5]. Group 2: Engineering and Design - Researchers have invested significant effort into engineering mRNA-LNP to reach organs beyond the liver, utilizing ligand coupling, component optimization, and the development of new ionizable lipids [7]. - The study highlights the importance of ionizable lipids in determining the efficacy and organ selectivity of LNP, with a focus on customizing lipid structures through combinatorial chemistry [7][8]. Group 3: Synthesis and Modifications - The research team developed over 120 structurally diverse PILs using solid-phase supported synthesis (SPSS), which offers advantages over traditional liquid-phase synthesis [9]. - Specific modifications to amino acids, such as lysine and arginine, enhance mRNA delivery to the lungs, while cysteine and histidine modifications target the liver [11]. Group 4: Efficacy and Safety - The PILOT platform demonstrated effective delivery of Cre mRNA, achieving specific gene editing in targeted tissues, with editing efficiencies of 13.1% in the liver and 7.4% in the lungs [13]. - The study provides a universal design strategy for developing organ-targeted ionizable lipids, indicating the potential of the PILOT LNP platform in advancing organ-specific gene editing therapies [15].

Core Viewpoint - The article discusses the rising prevalence of autism and explores the underlying reasons for this increase, emphasizing that the rise is largely attributed to improved diagnostic practices rather than an actual increase in cases [3][6][16]. Summary by Sections Increase in Autism Diagnosis - The prevalence of autism has risen significantly, with the rate in the U.S. increasing from 1 in 150 children in 2000 to 1 in 31 children by 2022 [5][18]. - This trend is not limited to the U.S.; other high-income countries like the UK, Denmark, South Korea, and Japan have also reported similar increases [8]. Factors Contributing to Increased Diagnosis - Changes in diagnostic criteria over the years have led to more individuals being classified as autistic. For instance, the DSM and ICD have broadened their definitions, allowing for a wider range of symptoms and age groups to be included [12][14]. - A study indicated that approximately 60% of the increase in autism prevalence in Denmark from 1980 to 1991 could be attributed to changes in diagnostic standards [13]. - Increased awareness and reduced stigma around autism have led to more parents seeking diagnoses for their children, especially as educational support becomes more accessible [14][15]. Current Autism Prevalence Estimates - The U.S. Autism and Developmental Disabilities Monitoring Network reported that 1 in 31 children are diagnosed with autism, but some researchers question the accuracy of this data [18]. - A global estimate from 2021 suggested that the prevalence of autism spectrum disorder is approximately 1 in 127 individuals, totaling around 62 million people [18]. Genetic and Environmental Factors - Genetic factors are believed to play a significant role in autism, with a study estimating the heritability of autism at around 80% [22]. - Environmental factors are thought to have a smaller impact, with some studies linking advanced parental age and prenatal exposures to increased autism risk [23][24]. - Research indicates that there is no single environmental factor that significantly influences autism, and the interaction between genetic and environmental factors remains complex [25]. Research Initiatives and Funding - The NIH's Autism Data Science Initiative aims to explore the causes of autism and the effectiveness of existing interventions, focusing on the interaction between genetic and environmental factors [27]. - However, there are concerns about funding cuts to autism research, which have decreased from $274 million in early 2024 to $212 million in early 2025 [27].

Core Viewpoint - Air pollution is a global environmental issue with significant impacts on air quality, climate, ecosystems, and human health. China's severe smog pollution, characterized by high PM2.5 concentrations, has shown improvement since 2013 due to regulatory measures [2][3]. Group 1 - The unique formation mechanism of smog in China involves both high-intensity primary pollutant emissions and efficient secondary transformation processes [2][3]. - The current stage in China is marked by a mix of agricultural and industrial societies, leading to high emissions of secondary aerosol precursors from various sources, including ammonia from agricultural activities and nitrogen oxides from industrial activities [3][4]. - A recent review published in the journal Science highlights the complex interactions of multiple atmospheric factors contributing to the unique formation mechanism of secondary organic aerosols (SOA) in urban China [4][10]. Group 2 - Despite significant progress in environmental pollution control over the past decade, uncertainties remain regarding the precursors, formation processes, and impacts of SOA on radiation budgets and human health in Chinese cities [6][9]. - The substantial decrease in PM2.5 concentrations in urban China has led to a significant increase in ground-level ozone concentrations, which facilitates SOA formation [6][9]. - Understanding the sensitivity of ozone-nitrogen oxides-volatile organic compounds in urban areas is crucial for developing economically effective strategies to control precursors that lead to high concentrations of both SOA and ozone [6][9]. Group 3 - The study identifies that high atmospheric oxidation capacity in winter results from various factors, including high concentrations of gas-phase nitrous acid photolysis and nitrogen oxides participating in olefin ozonolysis [7][9]. - The increase in nitrate proportions has also enhanced the liquid water content of aerosols, further promoting the generation of liquid-phase SOA [7][9]. - Future research should focus on exploring unknown oxidation pathways, characterizing precursors and multi-generation oxidation products at the molecular level, and understanding the corresponding generation and aging mechanisms [7][9]. Group 4 - The paper summarizes the scientific status of SOA formation in urban China, emphasizing the dominant role of anthropogenic precursors, the main mechanisms of SOA formation, and the importance of multi-pollutant and multiphase processes in SOA evolution [9][10]. - This research deepens the understanding of the formation mechanisms of haze pollution in China and provides a reference for global atmospheric pollution studies, offering important scientific basis for future air pollution control and policy-making [10].

Core Viewpoint - The article emphasizes the significant advancement of Foundation Models (FM) in the potential applications of artificial intelligence (AI) in clinical care, highlighting the need for rigorous prospective validation and randomized controlled trials to bridge the gap between AI capabilities and real-world clinical environments [2][3][6]. Group 1: Foundation Model Development - A multi-modal visual-language ophthalmic foundation model named EyeFM was developed, which was validated through a prospective deployment across various global regions, including Asia, North America, Europe, and Africa [3][6]. - EyeFM was pre-trained using a diverse dataset of 14.5 million eye images, enabling it to perform various core clinical tasks effectively [6][11]. Group 2: Clinical Evaluation and Effectiveness - The effectiveness of EyeFM as a clinical assistance tool was evaluated through a randomized controlled trial involving 668 participants, showing a higher correct diagnosis rate of 92.2% compared to 75.4% in the control group [11][13]. - The study also indicated improved referral rates (92.2% vs 80.5%) and better self-management adherence (70.1% vs 49.1%) among the intervention group using EyeFM [11][13]. Group 3: Application and Future Implications - EyeFM serves as a comprehensive assistance system for ophthalmology, with potential applications across various clinical scenarios, enhancing the diagnostic capabilities of ophthalmologists and improving patient outcomes [12][13].

Core Viewpoint - The article discusses a groundbreaking study published in the journal Cell Death & Disease, which reveals the efficacy of iPSC-derived spinal neural progenitors (spNPG) in treating spinal cord injuries, highlighting a novel therapeutic mechanism that addresses both cell replacement and microenvironment regulation [2][5][20]. Group 1: Spinal Cord Injury Overview - Spinal cord injury (SCI) affects approximately 15 million people globally, with over 3 million cases in China and 100,000 new cases annually [7]. - The injury often leads to paralysis and loss of motor and sensory functions, severely impacting the quality of life, as current treatments primarily focus on rehabilitation and supportive care [6][8]. Group 2: iPSC and spNPG Development - The research utilizes iPSC-derived spNPG cells, developed by Shizai Biomedicine, which have received dual regulatory approval from both Chinese and U.S. drug authorities for clinical trials [5][23]. - iPSCs are reprogrammed from human somatic cells, avoiding ethical issues associated with embryonic stem cells, and can differentiate into various cell types with low immunogenicity [10][11]. Group 3: Animal Study and Efficacy - In animal models of spinal cord injury, spNPG transplantation significantly improved motor function compared to control groups receiving saline [12][14]. - The study employed various behavioral tests, showing that the treatment group had a Basso animal score of 4.5, indicating the ability to walk independently but with instability, compared to 1.2 in the control group [21]. Group 4: Mechanism of Action - The therapeutic effects of spNPG are attributed to a dual mechanism: replenishing lost neural cells and improving the damaged microenvironment [15][16]. - The spNPG cells differentiate into key neural cell types, including motor neurons and interneurons, which integrate into the host's neural circuitry, facilitating signal transmission [17][18]. Group 5: Future Implications - This research represents a significant milestone in the field of spinal cord injury treatment, offering hope for patients previously deemed incurable [20][23]. - The successful transition of this technology into clinical practice could transform the treatment landscape for spinal cord injuries, making recovery a tangible reality [20].

Core Viewpoint - The research reveals the critical role of endocytosis in cysteine-deprivation-induced ferroptosis, challenging previous understandings of lysosomal inhibitor mechanisms and suggesting different execution pathways for ferroptosis [3][7]. Group 1: Key Findings - Lysosomal inhibitors can independently suppress cysteine-deprivation-induced (CDI) ferroptosis, regardless of autophagy [5]. - Endocytosis is essential for CDI ferroptosis but is not required for ferroptosis induced by GPX4 depletion [5]. - Endocytic defects reduce intracellular iron levels and prevent CDI ferroptosis [5]. Group 2: Mechanisms and Implications - Transferrin's clathrin-mediated endocytosis (CME) is crucial for driving CDI ferroptosis [4][5]. - Inhibition of lysosomal proteolytic activity does not prevent ferroptosis, while disrupting endosomal acidification and removing endocytic protein AP2M1 can block ferroptosis [4]. - Supplementing iron through ammonium iron citrate, independent of endocytosis, can restore CDI ferroptosis in cells with endocytic defects [4].

编辑丨王多鱼 排版丨水成文 绝大多数合金及其微结构设计在过去数十年间主要针对室温及高温环境下的力学性能优化。 随着我国在极 地、深海、深空及能源等极端环境领域的持续探索，低温严苛工况对金属结构材料的综合力学性能提出了 前所未有的挑战。在此类环境下，结构材料不仅需要具备 高强度 ，还必须兼顾优异的 延展性 与 断裂韧性 。然而，低温强韧性协同提升始终是工程应用中的世界性难题。 | 2025 年 月 27 | 8 | 日，华东理工大学 | 张显程 | | 教授作为共同通讯作者 | （ 陆体文 | | 博士和 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | 孙彬涵 | | 教授作为 | | | | 共同第一作者） | | | | ，在国际顶尖学术期刊 | | | | Nature | | 上发表了题为： | | Dual-scale | | chemical ordering | | for cryogenic | properties | in | CoNiV-based | alloys | 的研究论文。 | | 该研究通过对材料熵和焓的同 ...

Core Viewpoint - The article discusses the potential of engineered long-lived CAR-T cells as a delivery platform for biologics, particularly for chronic diseases requiring long-term treatment, highlighting the advantages of a single-dose, long-lasting therapeutic approach [2][3][15]. Group 1: Challenges of Current Biologics - Recombinant proteins, while effective in treating various diseases, have a short half-life in the body, necessitating repeated injections for chronic conditions [2]. - GLP-1 drugs, such as semaglutide and tirzepatide, require weekly injections to maintain their effects, leading to potential weight regain upon discontinuation [2]. - Repeated infusions of peptide/protein biologics can lead to the formation of immune responses, reducing efficacy and potentially causing immunopathological issues [2]. Group 2: Innovations in Delivery Platforms - The research team from Tsinghua University developed long-lived CAR-T cells as a novel delivery platform for biologics, achieving stable delivery of GLP-1 in animal models with a single infusion [3][14]. - Previous methods using AAV vectors for delivering therapeutic proteins have limitations due to their short duration of effect, typically less than two years [5]. - CAR-T cells have shown promise in treating rare diseases, functioning as "living" drugs that can replicate and survive in the body, potentially achieving long-term efficacy [5]. Group 3: Recent Research Developments - The team created immortal-like functional T cells (T IF cells) through gene editing, which can exist safely in the body for extended periods and provide long-term tumor relief [6]. - Further modifications to T IF cells allowed for the targeting and elimination of eosinophils, providing a potential long-term treatment for allergic asthma with a single injection [9]. - The GD2T IF cells were engineered to deliver GLP-1, effectively controlling weight and blood sugar levels in obese mice with a single infusion, achieving "cure" indicators [14][15]. Group 4: Practical Considerations for CAR-T Cell Therapy - For CAR-T cells to be a practical delivery platform for chronic disease biologics, three conditions must be met: elimination of chemotherapy preconditioning, long-term maintenance of sufficient CAR-T cell numbers, and careful selection of targets to avoid damage to normal cells [11][12][13]. - The GD2 target was chosen due to its overexpression in certain tumors and minimal expression in normal tissues, showing good efficacy in clinical trials without significant off-target effects [13]. Group 5: Future Implications - The research indicates that the engineered GD2T IF cells could serve as a reliable platform for stable production of biologics, offering a one-time treatment solution for chronic diseases [15]. - Although current CAR-T cell therapies are costly, the expectation is that as prices decrease, this method will become more cost-effective compared to repeated injections of biologics [15].