Core Insights - The article discusses two research projects by the same principal investigator (PI) focusing on the effects of a natural product on neuroblastoma cells and the potential for promoting endogenous neural regeneration through improving the microenvironment of neural stem cells [1][2]. Group 1: Research Projects - Project A aims to validate the inhibitory effect of a natural product on the proliferation and differentiation of neuroblastoma cells, utilizing the human SH-SY5Y cell line for high-throughput screening and target gene validation [1]. - Project B investigates whether the same natural product enhances endogenous neural regeneration by improving the microenvironment of neural stem cells, using conditioned media from SH-SY5Y cells treated with the product on primary mouse neural stem cells [2]. Group 2: Cell Model Selection - The article introduces a "Cell Model Selection Matching" initiative by Cyagen, which helps researchers choose the most suitable cell models based on their experimental needs, including purpose, modification methods, and expected timelines [3]. - The initiative includes a promotional event where 80 participants can win prizes, emphasizing the importance of accurate information submission from eligible biological and medical institutions [5][6]. Group 3: Cell Model Types - The article outlines seven mainstream cell models and their respective characteristics and research scenarios, including: - Conventional cell lines for initial screening and target validation [8]. - Stem cells for developmental mechanisms and regenerative medicine [8]. - Primary cells for clinical relevance and microenvironment studies [8]. - Fluorescent labeled cells for live imaging and tracking [8]. - Reporter gene cell lines for immune regulation and drug screening [8]. - Genetically modified cell lines for precise gene editing [8]. - Humanized cell lines for evaluating antibody functions [8]. Group 4: Company Overview - Cyagen, established in 2006, is a national high-tech enterprise focused on life sciences, providing a wide range of cell models and services to support global life science research [15]. - The company boasts extensive experience in gene editing projects and offers a comprehensive one-stop service platform for cell culture, gene expression regulation, and functional validation [8].

Core Viewpoint - Systemic treatment is the best option for patients with unresectable or advanced hepatocellular carcinoma (HCC), but its efficacy is limited by drug resistance [2][3]. Group 1: Research Findings - Ferroptosis is a unique form of regulated cell death that plays a crucial role in the systemic treatment of HCC [3]. - A study published in Nature Cancer reveals that SCRN1 confers resistance to ferroptosis in HCC by stabilizing GPX4 through STK38-mediated phosphorylation, providing potential therapeutic targets and strategies for HCC treatment [4][8]. - The research team found that high expression of SCRN1 is closely related to ferroptosis resistance and poor prognosis in HCC [7]. Group 2: Mechanism of Action - SCRN1 enhances the interaction between STK38 and GPX4, promoting the phosphorylation of GPX4 at the S45 site, which impairs HSC70's recognition of GPX4 and reduces its degradation via chaperone-mediated autophagy, thereby alleviating lipid peroxidation and ferroptosis [7][8].

Core Insights - The article discusses the critical role of the immune system during the mid-pregnancy period (13-28 weeks), highlighting the expansion and maturation of immune cell lineages that provide protection after birth [2] - Recent research challenges the traditional view of the fetal immune system as being in a state of relative inactivity, revealing that fetal immune cells, particularly T cells, possess functional pre-activation and immune response capabilities [3][4] - The study published in the journal Cell integrates single-cell RNA sequencing data from 321 samples of 15 mid-pregnancy fetuses and 4 adult donors, creating a multi-organ single-cell atlas that compares the immune systems of fetuses and adults [5][11] Research Findings - The research identifies a CD4 T cell subset outside the thymus that mediates the transition of TOX2 precursor cells to mature naive CD4 T cells, indicating widespread memory/activated T cells in mid-pregnancy fetuses [12][15] - The study reveals two tolerance mechanisms that inhibit fetal T cell activation, involving ARG1+ neutrophils and the PTGES3/PTGER4 signaling pathway [12][15] - The immune cell atlas redefines the immune architecture of mid-pregnancy fetuses and adults, showing dynamic cross-organ exchange of tissue-resident memory T cells and extensive hematopoiesis to support immune development [15][18] Implications - The findings provide new insights into the balance between immune activation and tolerance during mid-pregnancy, a critical phase of human development, and highlight the unique developmental pathways of fetal and adult immunity [18]

Core Viewpoint - The article discusses a groundbreaking research published in Nature, which introduces a new method for direct deaminative functionalization using N-nitroamines, providing a safer and more efficient alternative to traditional aromatic amine transformations that rely on hazardous diazonium salts [1][2]. Group 1: Research Breakthrough - The research presents a novel approach that allows for the direct conversion of inert aromatic carbon-nitrogen (C-N) bonds into various important chemical bonds, including carbon-halogen, carbon-oxygen, carbon-nitrogen, and carbon-carbon bonds [1][2]. - This method utilizes common laboratory reagents and enables kilogram-scale synthesis, challenging the traditional processes that have been in use for 140 years [2][3]. Group 2: Industrial Implications - The new strategy is expected to have broad applications in critical fields such as pharmaceuticals and materials manufacturing, offering a safe and economical alternative to the widely used but hazardous aryl diazonium chemistry [2][3]. - The direct deaminative functionalization method simplifies the synthesis process and subsequent functionalization by combining deaminative functionalization with transition metal-catalyzed arylation [2][3]. Group 3: Mechanism and Advantages - Mechanistic studies indicate that the reactivity of the aromatic carbon cation equivalent during the deamination process is typically dominant, highlighting the potential of this method in synthetic chemistry [3]. - The direct deamination approach provides a significant advantage over other deaminative functionalization methods, as it is applicable to a wide range of drug-relevant heteroaryl amines with varying electronic and structural properties [2][3].

Core Insights - The article discusses the groundbreaking research on regulatory T cells (Treg cells) and their role in controlling autoimmune responses, leading to potential new therapies for autoimmune diseases and cancer [2][3]. Group 1: Discovery and Significance - In 1995, Shimon Sakaguchi discovered a previously unknown T cell type that protects against autoimmune diseases, which was later linked to the Foxp3 gene mutations causing such diseases [3]. - The findings by Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi opened new avenues for treating autoimmune diseases and cancer by targeting specific Treg cells to suppress pathogenic autoimmune responses [3]. Group 2: Recent Research Developments - On October 22, 2025, Shimon Sakaguchi's team published two papers demonstrating the successful conversion of conventional effector T cells into stable regulatory T cells (S/F-iTreg cells) for treating inflammatory and autoimmune diseases [4]. - The first paper focuses on generating functionally stable and antigen-specific Treg cells from effector T cells for cell therapy in inflammatory diseases [4]. Group 3: Mechanism of Action - The research team utilized CDK8/19 kinase inhibitors to enhance Foxp3 expression in Tconv cells under specific stimulation conditions, establishing epigenetic changes that promote Treg characteristics [6]. - By reprogramming effector/memory CD4+ Tconv cells, including TH1, TH2, and TH17 subsets, into Foxp3+ Treg cells, the study achieved a stable and functional Treg cell population [7]. Group 4: Clinical Implications - The induced Treg cells effectively suppressed inflammatory bowel disease (IBD) and graft-versus-host disease (GvHD) in mouse models, suggesting a new strategy for antigen-specific immunotherapy [8]. - The second paper demonstrated the conversion of pathogenic T cells into stable Treg cells for treating pemphigus vulgaris, a skin autoimmune disease, providing proof of concept for clinical applications [9].

Core Viewpoint - The study identifies ribosome dysregulation as a potential causal mechanism driving female reproductive aging, particularly highlighting the upregulation of ribosomal gene transcription in oocytes and cumulus cells around the age of 34, which correlates with a decline in fertility. It suggests that short-term intervention with rapamycin may serve as an effective treatment for age-related infertility [2][11]. Group 1: Mechanisms of Female Reproductive Aging - Female fertility declines with age, especially after 35, primarily due to decreased oocyte quality, which affects embryo development and leads to repeated failures in assisted reproduction [2][4]. - Chromosomal segregation errors increase with age, particularly after 35, contributing to aneuploidy in embryos, which often results in developmental arrest or miscarriage [4]. - Other factors contributing to ovarian aging include DNA damage response, oxidative stress, mitochondrial dysfunction, telomere shortening, autophagy, inflammation, and fibrosis [5]. Group 2: Molecular Changes in Oocytes and Cumulus Cells - The study utilized multi-omics analysis to discover molecular changes in aging oocytes and cumulus cells, revealing significant transcriptional alterations at age 34, including upregulation of ribosomal gene transcription [8][9]. - The research indicates that specific genomic loci exhibit DNA hypomethylation and abnormal heterochromatin deposition, closely associated with the activation of ribosomal gene transcription [8][9]. - The abundance of histone H3K9me3 decreases with age, which is linked to the upregulation of ribosomal genes [9]. Group 3: Implications for Treatment - Short-term treatment with the clinically approved immunosuppressant rapamycin can effectively inhibit protein translation in cumulus cells and restore protein homeostasis, leading to improved embryo quality and higher rates of pregnancy and live births [9][11].

Core Viewpoint - The research highlights the critical role of the maternal transcription factor OTX2 in initiating human embryonic genome activation (EGA) and its implications for early human development [2][6]. Group 1: Research Findings - OTX2 is identified as an essential maternal PRD-like homeobox protein transcription factor necessary for EGA and early development in humans [5]. - At the 4-cell stage, OTX2 activates key EGA genes, including TPRX1 and TPRX2, as well as EGA-related repetitive sequences HERVL-int and MLT2A1 [5]. - OTX2 directly binds to promoters and presumed enhancers at EGA target sites, many of which overlap with OTX2 motif-containing Alu and MaLR repetitive elements, enhancing chromatin accessibility [5]. Group 2: Implications and Significance - The findings establish OTX2 as a key maternal transcription factor that awakens the genome at the beginning of human life, providing insights into molecular regulatory mechanisms in developmental biology and reproductive medicine [6]. - A related article in Nature Genetics emphasizes the largely unknown transcription factors responsible for initiating EGA in humans, underscoring the significance of the new research on OTX2 [6].

Core Viewpoint - The article discusses the development of ProteanFect®, a novel protein condensate gene delivery platform that enables efficient and low-toxicity gene delivery in primary immune cells, significantly advancing functional immune research and key signaling pathway analysis [2][3]. Group 1: ProteanFect® Overview - ProteanFect® is based on engineered mammalian proteins that mimic the natural formation mechanisms of cellular condensates, creating stable "nucleic acid-protein" complexes under mild conditions without the need for viruses, electroporation, or liposomes [3]. - The platform demonstrates excellent biocompatibility and broad cell adaptability, representing a new direction in gene delivery technology [3]. Group 2: Case Studies - **Case Study 1**: Research from Harbin Medical University published in *Nature Cell Biology* reveals the role of CD160⁺ CD8⁺ T cells in maintaining anti-exhaustion characteristics and reversing colorectal cancer anti-PD-1 resistance [5][10]. - **Case Study 2**: A study from Tongji University in *Nature Microbiology* uncovers how Mycobacterium tuberculosis manipulates Treg cell function through the metabolite linoleic acid, revealing a molecular mechanism for immune evasion [12][15]. - **Case Study 3**: Research from Sichuan University in *Signal Transduction and Targeted Therapy* shows that high fructose intake regulates T cell metabolism, promoting Th1 and Th17 cell differentiation, thereby exacerbating inflammatory bowel disease (IBD) [16][20]. - **Case Study 4**: A study from the Chinese Academy of Sciences published in *Nature Communications* reveals how histone variant H2A.Z regulates memory CD8⁺ T cell responses through epigenetic modulation [22][26]. Group 3: Key Findings and Challenges - The key findings from the studies highlight the effectiveness of ProteanFect® in achieving significant gene knockdown and elucidating complex immune mechanisms, such as the interaction between CD160 and PI3K signaling pathways [10][20][26]. - The core challenges addressed include precise gene expression regulation in primary immune cells to understand underlying mechanisms of immune responses and disease resistance [8][19][24]. Group 4: Advantages of ProteanFect® - ProteanFect® offers three core advantages: 1. High adaptability for various carriers including siRNA, mRNA, and CRISPR/Cas9 mRNA, suitable for multiple primary immune cell types [30]. 2. Low cytotoxicity, maintaining over 85% cell viability post-transfection, ensuring core functions of T cells are unaffected [30]. 3. High transfection efficiency, achieving over 70% in primary T cells, meeting the needs for precise gene regulation [30].

具有优异光电特性的金属卤化物钙钛矿材料，已成为推动光伏效率突破的有力候选。研究中的 钙钛矿太阳 能电池 （PSC） 的功率转换效率 （PCE， 即太阳能转换为电能的效率 ） 的最新记录可比肩商用硅电 池，其产业化进程已现曙光。 然而，基于 自组装分子 （SAM） 体系的高效倒置结构钙钛矿太阳能电池，普遍面临分子聚集和疏水特性 带来的技术障碍。 编辑丨王多鱼 排版丨水成文 2025 年 10 月 27 日， 上海交通大学环境科学与工程学院 赵一新 教授、 陈悦天 副教授、 缪炎峰 博士， 及宁德时代 郭永胜 等人，在国际顶尖学术期刊 Nature 上发表了题为： A matrix-confined molecular layer for perovskite photovoltaic modules 的研究论文。 该研究提出了 " SAM-in-matrix " 策略，在此基础上成功 制备了 1 米 × 2 米级的大面积钙钛矿太阳能组 件，且 PCE 认证效率达到了创纪录的 20.05%。 基于" SAM-in-matrix "结构的空穴传输层 （HTL） 器件展现出普适性优势：在多种 SAM 体系中均实现 更 ...

Core Viewpoint - The research presents a breakthrough in all-perovskite tandem solar cells with a record power conversion efficiency (PCE) of 30.6% through the implementation of a dipolar passivation strategy [3][6]. Group 1: Research Findings - The study developed all-perovskite tandem solar cells utilizing dipolar passivation, achieving a record PCE of 30.6% [3]. - The dipolar passivation strategy effectively reduced the trap density at the buried interface of mixed Pb-Sn perovskite, allowing for precise energy level alignment at the HTL/perovskite interface [5]. - This strategy enhanced Ohmic contact, facilitating efficient hole injection into the HTL while repelling electrons at the HTL/Pb-Sn perovskite interface [5]. Group 2: Performance Metrics - The carrier diffusion length was increased to 6.2 μm, resulting in a significant PCE improvement of the Pb-Sn perovskite solar cell to 24.9%, with an open-circuit voltage (Voc) of 0.911 V, a short-circuit current density (Jsc) of 33.1 mA cm⁻², and a fill factor (FF) of 82.6% [5]. - The dipolar passivation also alleviated contact losses caused by the interconnection layer of the tandem device, pushing the PCE of the all-perovskite tandem solar cell to 30.6%, with a certified steady-state efficiency of 30.1% [6].