Core Viewpoint - The article discusses the challenges of treating castration-resistant prostate cancer (CRPC), particularly the neuroendocrine subtype (CRPC-NE), and highlights a new dual-targeting therapeutic strategy involving NSD2 and androgen receptor (AR) to address drug resistance and tumor plasticity [1][2][6]. Group 1: CRPC and Its Subtypes - CRPC often retains adenocarcinoma histological features and AR expression but can progress to neuroendocrine subtypes that are highly resistant to AR inhibitors [1][4]. - CRPC-NE occurs in approximately 5%-25% of metastatic CRPC cases and is characterized by aggressive behavior, treatment resistance, and poor clinical prognosis [1][4]. Group 2: NSD2 Targeting Research - A study published in Nature indicates that targeting NSD2 can reverse plasticity and drug resistance in prostate cancer, providing a potential new treatment avenue for lethal CRPC subtypes [2][6]. - NSD2, a histone lysine methyltransferase, plays a crucial role in regulating chromatin structure and gene expression, and its inhibition can successfully reverse treatment resistance in CRPC [4][5]. Group 3: Mechanism of Action - In engineered mouse models and human CRPC-NE organoids, knocking out NSD2 can revert the CRPC-NE phenotype back to adenocarcinoma, restoring sensitivity to AR inhibitors like enzalutamide [5]. - The use of first-in-class NSD2 small molecule inhibitors has shown promise in reversing tumor plasticity and enhancing the efficacy of AR inhibitors in various CRPC subtypes [5][6]. Group 4: Broader Implications - The findings suggest that targeting the NSD2-H3K36me2 signaling axis could serve as an effective treatment strategy for difficult-to-treat cancers, including lung and pancreatic cancers, as indicated by related research [7][9].

Core Viewpoint - The research highlights the role of dendritic cells (DC) in regulating the balance between innate and adaptive immunity in lymph nodes, which is crucial for optimal host defense [2][4]. Group 1: Research Findings - Dendritic cells drive the rapid and polarized recruitment of innate effector cells to lymph nodes [4]. - This innate cell infiltration aids in controlling pathogens but limits the adaptive immune response [4]. - Dendritic cells and monocytes clear neutrophils to restore tissue structure and adaptive immune function [4]. - Dendritic cells act as a regulator, balancing the innate and adaptive immune functions in lymph nodes [4]. Group 2: Mechanisms and Processes - Following infection or vaccination, lymph node structures undergo rapid remodeling, with neutrophils and monocytes being recruited from inflammatory blood vessels [3]. - Dendritic cells facilitate this process by expressing inflammatory chemokines and integrin ligands [3]. - After the threat of infection is resolved, dendritic cells and recruited monocytes phagocytize neutrophils, thereby restoring the tissue architecture and creating conditions for the activation of downstream adaptive immune cells [3].

Core Viewpoint - The research conducted by Westlake University identifies a significant number of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in the human brain, revealing their genetic control and implications for complex traits, thus providing new insights into the genetic regulatory mechanisms of non-coding RNAs in relation to brain-related complex traits [2][3][12]. Summary by Sections Research Findings - The study analyzed RNA sequencing data from 2,865 human brain cortex samples, identifying 38,441 lncRNAs and 23,548 circRNAs, with 27,453 lncRNAs and all circRNAs not included in the GENCODE database [3][6]. - It determined 15,362 lncRNAs and 1,312 circRNAs with cis-expression quantitative trait loci (eQTL), highlighting the independent nature of eQTLs for lncRNAs and circRNAs compared to their adjacent protein-coding genes [3][7]. - The research found that lncRNA-eQTL and circRNA-eQTL account for an average of 11.14% and 3.20% of the SNP heritability for 14 brain-related complex traits, respectively, compared to 17.19% for protein-coding gene eQTLs [7]. Implications for Complex Traits - The study suggests that certain lncRNAs (e.g., those near VPS45, MAPT, and RGS6) and circRNAs (e.g., those related to GRIN2A) may influence complex traits through non-coding RNA genetic regulation [3][12]. - It integrates lncRNA-eQTL and circRNA-eQTL data with genome-wide association study (GWAS) summary statistics, identifying 795 lncRNAs and 8 circRNAs associated with brain-related traits, indicating shared genetic regulatory mechanisms [7][12]. Research Context - The research addresses the challenge of understanding the molecular mechanisms behind GWAS signals, particularly focusing on non-coding regions where many trait-related variants reside [4][5]. - Previous studies have primarily focused on protein-coding genes, leaving a gap in understanding the genetic control mechanisms of non-coding RNAs, especially in the context of brain-related traits and diseases [6][12].

Core Insights - The article discusses the emergence of the field of Science of Science (SciSci), which aims to explore how science is conducted, funded, and applied through interdisciplinary approaches [1] - A new AI system called SciSciGPT has been developed to enhance human-AI collaboration in the field of SciSci, capable of processing vast amounts of literature and data efficiently [2] Group 1: SciSciGPT Architecture and Functionality - SciSciGPT features a multi-agent collaboration framework with five specialized AI agents, each responsible for different aspects of research [5][6][7] - The system is designed to mimic the division of labor in research teams, allowing it to handle complex tasks and ensure transparency and reproducibility in research processes [11] Group 2: Practical Applications and Case Studies - In a case study, SciSciGPT successfully generated a collaboration network for Ivy League schools from 2000 to 2020, completing tasks in minutes that would traditionally take hours [15] - Another case study demonstrated SciSciGPT's ability to replicate classic research findings regarding team size and research impact, showcasing its potential for validating and expanding existing research [19] Group 3: AI Maturity Model and Future Directions - The research team proposed a four-tier capability maturity model for AI research collaboration systems, outlining a roadmap for future development [21][22][23][24] - SciSciGPT currently implements core components of this model, balancing technical complexity with research utility [25] Group 4: Performance Evaluation and Expert Feedback - Exploratory experiments showed that SciSciGPT completed tasks in about 10% of the time taken by experienced researchers, with outputs rated superior in various dimensions by expert reviewers [27] - Experts noted the system's significant value in early data exploration but highlighted areas for improvement, particularly in information presentation and cognitive load reduction [27] Group 5: Broader Implications and Challenges - SciSciGPT's framework has potential applications beyond the Science of Science, particularly in data-intensive and interdisciplinary fields [29] - The technology raises challenges related to authorship, skill development, and research direction preferences, which could shift as AI tools become more prevalent [29] Group 6: Paradigm Shift in Scientific Research - SciSciGPT represents a significant milestone in the transformation of scientific research processes, allowing human researchers to focus on critical aspects of creativity and inquiry [32] - The future of research may favor those who excel in collaborating with AI rather than those with traditional technical skills [33]

Core Viewpoint - Westlake Laboratory, established in July 2020, focuses on breakthroughs in life sciences and biomedicine, particularly in aging-related diseases and cancer research [3]. Group 1: Recruitment Information - Westlake Laboratory is publicly recruiting for multiple tenure-track positions across all academic levels, encouraging scholars with expertise in aging and neurodegenerative fields to apply [5]. - Applicants must hold a PhD or equivalent degree, have an outstanding research record, innovative future research plans, and a commitment to teaching excellence and diversity [5]. Group 2: Benefits and Resources - Successful applicants will receive competitive salaries and benefits, substantial startup funding, modern laboratory space, and access to advanced core facilities, including cryo-electron microscopy and mass spectrometry [6]. - The laboratory has developed a supportive and vibrant research community aimed at exploring fundamental biological and disease-related questions, developing advanced technologies for human health, and nurturing the next generation of research leaders [6]. Group 3: Application Requirements - Applicants are required to submit a cover letter outlining their research goals, significant achievements, and relevant experience [8]. - A complete academic CV and a research summary statement (maximum 1 page) along with a research proposal (maximum 3 pages) must also be included [9][10]. - Candidates for the assistant professor position must arrange for three referees to send recommendation letters directly [11].

Core Viewpoint - The research conducted by the Wellcome Sanger Institute provides a comprehensive cellular map of the developing human reproductive tract, revealing key mechanisms of sexual dimorphism and potential insights into developmental reproductive disorders [1][12]. Group 1: Research Methodology - The study utilized advanced technologies such as single-cell RNA sequencing (scRNA-seq) to analyze over 500,000 cells, identifying cell types and gene expression [3]. - The combination of these technologies allowed researchers to track cell differentiation and movement, identifying 52 specific cell types related to the reproductive tract [5]. Group 2: Key Findings - The origin of sexual dimorphism was explored, showing that both male and female embryos initially possess Müllerian and Wolffian ducts, which later differentiate under the influence of sex chromosomes and hormones [7]. - HOX genes were identified as crucial for organ positioning, with specific HOX genes expressed in different regions of the reproductive tract, correcting previous mouse model assumptions [8]. - The study found that functional regions of the adult reproductive organs, such as the non-ciliated epithelium of the fallopian tubes and epididymis, are established as early as the fetal stage, with transcriptional gradients reflecting this regionalization [9]. - The potential impact of environmental disruptors, such as BPA and phthalates, on development was assessed, indicating that exposure during critical developmental windows could lead to long-term health risks [10]. Group 3: Applications and Future Prospects - The open-source cellular atlas created from this research can be utilized for various applications, including disease research, drug development, and regenerative medicine, providing valuable insights into the causes of developmental reproductive disorders and potential therapeutic approaches [12][14].

Core Viewpoint - Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, with a median survival of only 12-18 months post-diagnosis, and current treatments have limited efficacy in extending patient lifespan [2] Group 1: Research Development - A research team led by Professor Lin Lisen from Fuzhou University and Professor Chen Xiaoyuan from the National University of Singapore published a study in Nature Nanotechnology, introducing a biohybrid chiral hydrogel that enhances postoperative GBM therapy by multi-pronged inhibition of tumor stemness [3][5] - The biohybrid chiral hydrogel is designed for intracavitary implantation after GBM tumor resection, aiming to comprehensively regulate glioblastoma stem cells (GSC) and improve postoperative treatment outcomes [5] Group 2: Mechanism and Efficacy - The hydrogel encapsulates GSC membrane-coated nanoparticles that serve as effective decoys to neutralize chemokines targeting GSC, achieving functional blockade of GSC and hydrogel infiltration [5] - The D-type chiral biohybrid hydrogel, through geometric regulation of mechanical transduction pathways, further diminishes the stemness phenotype of GSC compared to L-type and DL-type counterparts [5] - In three orthotopic GBM models, this multi-faceted GSC stemness inhibition enhances the efficacy of a gold nanoparticle-based hydrogel scaffold sensitized radiotherapy, thereby suppressing postoperative GBM recurrence [5][6]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 我们的大脑在年轻时 （发育期） 具有很强的可塑性，便于学习和适应环境。但在成年后，大脑的基本神经回路需要保持相对稳定，以确保日常功能和个人记忆的 连续性。这种从" 可塑性 "到" 稳定性 "的转变机制，一直是未解之谜。 过去，大脑中的非神经元细胞—— 星形胶质细胞 （ Astrocyte ） ，被认为只是神经元的被动支撑细胞。但近年研究显示，星形胶质细胞 在塑造大脑回路方面发 挥着重要作用。星形胶质细胞如何随着年龄的增长维持这些不同的可塑性水平，以及它们是否在成年后稳定感觉回路特性，一直都不清楚。 近日，索尔克研究所的研究人员在国际顶尖学术期刊 Nature 上发表了题为： Astrocyte CCN1 stabilizes neural circuits in the adult brain 的研究论文。 这项研究表明， 星形胶 质细胞 分泌的 CCN1 蛋白对于 成年期大脑神经回路的稳定 至关重要 ，这一发现为 阿尔茨海默病 、 抑郁症 、 脑中风 及 创伤后应激障 碍 （PTSD） 等神经系统疾病的治疗提供了全新靶点。 发现 CCN1：星形胶质细胞的"稳定因子" ...

Core Insights - The article discusses the increasing global health issue of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), highlighting its progression to Metabolic Dysfunction-Associated Steatohepatitis (MASH) and the associated risks of morbidity and mortality [1][4]. Group 1: Research Findings - A recent study published in Cell Reports Medicine identified blood metabolic panels that can detect significant fibrosis and inflammation in MASLD patients, revealing key metabolites such as Guanidinoacetic Acid (GAA) and Decanoic Acid (SA) that show therapeutic potential in mouse models [2][5]. - The research involved 293 participants across three independent cohorts, utilizing machine learning techniques to develop a non-invasive diagnostic model for detecting significant fibrosis (≥F2) and moderate to severe inflammation (≥I2) [4]. - The area under the receiver operating characteristic curve (AUROC) for fibrosis detection reached 0.928, 0.829, and 0.806 in the discovery, validation cohort 1, and validation cohort 2, respectively, outperforming existing indices like FIB-4 and APRI [4]. Group 2: Implications for Diagnosis and Treatment - The study's findings provide a systematic exploration of the key metabolic features of MASLD, paving the way for new non-invasive diagnostic and treatment strategies [7]. - The identified metabolites GAA and SA can improve liver fat deposition, inflammation, and fibrosis through dual mechanisms of "regulating lipid metabolism" and "promoting inflammation resolution," indicating their potential in advancing MASLD management [5].

Core Viewpoint - The study identifies two opposing subsets of regulatory T cells (Treg cells) in colorectal cancer: IL-10⁺ Treg cells, which are anti-tumor, and IL-10⁻ Treg cells, which are pro-tumor, suggesting a potential for targeted cancer immunotherapy by preserving anti-tumor Treg cells while selectively depleting pro-tumor Treg cells [3][7][11]. Group 1 - The research highlights the heterogeneity of tumor-associated Treg cells in colorectal cancer, identifying IL-10⁺ Treg cells and IL-10⁻ Treg cells as distinct subsets with opposing functions [5][10]. - Selective depletion of IL-10⁺ Treg cells promotes tumor growth by removing their inhibitory effect on effector CD4⁺ T cells, while depleting IL-10⁻ Treg cells leads to significant tumor regression [5][10]. - The abundance of IL-10⁺ Treg cells correlates with good prognosis, whereas IL-10⁻ Treg cells are associated with poor prognosis in human colorectal cancer [6][11]. Group 2 - The study suggests that the functional dichotomy of Treg cell subsets may be a universal phenomenon observed in other barrier tissues such as skin, lungs, and gastrointestinal tract tumors [3][7]. - This research proposes a new paradigm for cancer immunotherapy, shifting from a broad approach of enhancing or suppressing the entire immune system to a more precise strategy of targeting immunosuppressive Treg cell subsets while preserving protective ones [11].