撰文丨王聪 编辑丨王多鱼 排版丨水成文 雌性生殖干细胞 （FGSC） 是最近发现的存在于哺乳动物出生后卵巢中的生殖系干细胞，其能够分化为卵母细胞，并在移植入卵巢后产生可育后代。长期以来， 人们一直认为，在雌性哺乳动物出生前，雌性生殖细胞在减数分裂前期 I 的双线期停滞不前。FGSC 的发现使得生成新的卵母细胞以恢复受损的女性生殖功能成为 可能，这在生殖医学和再生医学领域引起了极大的关注。 该领域的一个关键挑战在于体外调控 FGSC 在静息和激活状态之间的转换，以确保其固有的干细胞特性得以保持。然而，由于干细胞命运在很大程度上取决于天 然细胞外基质 （ECM） 的生物物理特性，尤其是其粘弹性机械特性，传统的 2D 刚性培养环境 （例如玻璃或塑料培养皿） ，难以提供调节细胞命运所必需的粘 弹性机械信号。这种缺陷会导致干细胞的复制能力下降以及应激相关基因的上调，从而抑制其发育潜能。 上海交通大学 樊春海 院士、 吴际 教授，上海大学 李江 研究员等 Cell 子刊 Cell Biomaterials 上发表了题为： Dictating the fate of female germline stem cells u ...

Core Viewpoint - Triple-negative breast cancer (TNBC) is characterized by high metastasis rates, poor prognosis, and low survival rates, making it the most aggressive and deadly subtype of breast cancer. The lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) makes identifying specific therapeutic targets a pressing challenge in TNBC research [2]. Group 1 - Increasing evidence suggests that non-coding RNAs, such as circular RNA (circRNA) and long non-coding RNA (lncRNA), can encode functional peptides/proteins that play significant regulatory roles in physiological and pathological processes. In TNBC, some peptides encoded by non-coding RNAs have been confirmed to participate in key oncogenic processes, including tumor growth, metastasis, and the development of treatment resistance [2]. - A novel peptide, 66CTG, encoded by lncRNA, has been identified to stabilize the c-Myc proto-oncogene protein, promoting cancer growth in TNBC. This discovery provides a new potential biomarker and therapeutic target for TNBC diagnosis and treatment [3]. - The research team identified an upregulated lncRNA, CDKN2B-AS1, in TNBC, which encodes a 66-amino acid peptide through CUG initiation translation. The peptide 66CTG was confirmed to be endogenously expressed in TNBC cells through CRISPR-Cas9 gene editing and mass spectrometry analysis [6]. Group 2 - Mechanistically, during the late G1 phase of cell division, 66CTG stabilizes c-Myc through competitive interaction with FBW7α, an E3 ligase that mediates the ubiquitination and degradation of c-Myc [7]. - Overall, the findings suggest that 66CTG could be developed as a target for TNBC diagnosis and treatment. The study reveals a regulatory axis where 66CTG interacts with FBW7α to stabilize c-Myc, providing a new mechanistic explanation for the overexpression of c-Myc in TNBC. Patients with overexpression of 66CTG, c-Myc, and Cyclin D1 may benefit from targeted therapy along this signaling axis [9].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 众所周知，人类的性别由性染色体 X 和 Y 决定，XY 为男性，XX 为女性。然而，X染色体上的基因数量远超 Y 染色体，为了保证两性基因表达数量的大致相当， 女性的两条 X 染色体中会有一条随机失活，这种剂量补偿机制是由 X 染色体上的长链非编码基因 X-IST 所介导的。 而对于鸟类 （包括鸡） ，它们的性别由性染色体 Z 和 W 决定，ZW 为雌性，ZZ 为雄性，而 Z 染色体上的基因数量远超 W 染色体，这导致雄性鸟类的基因数量 显著多于雌性，然而，鸟类的剂量补偿程度以及机制，至今仍不清楚。 2025 年 7 月 16 日，德国海德堡大学、英国爱丁堡大学、 瑞典乌普萨拉大学的研究人员在国际顶尖学术期刊 Nature 上发表了题为： A male-essential miRNA is key for avian sex chromosome dosage compensation 的研究论文。 该研究揭示了 鸟类独特的性染色体剂量补偿机制 ，其通过一种 miRNA—— miR-2954 来抑制特定的基因表达，防止雄性鸟类中这些基因过表达，从而确保雄性 鸟类的存活， ...

Core Insights - The study reveals that phosphorylated Toll-like receptor 3 (TLR3) translocation to the nucleus in cancer cells promotes metastasis and chemoresistance, indicating a non-classical function of innate immune sensors in cancer [3][8] - The JAK1/TLR3/PRMT5/c-Myc signaling axis may serve as a potential prognostic marker and therapeutic target to overcome chemoresistance [3][8] Group 1 - The research team utilized immunohistochemical analysis on pancreatic ductal adenocarcinoma (PDAC) and various other cancer samples to observe TLR3's nuclear translocation under chemotherapy stress [6] - In vitro experiments demonstrated that nuclear TLR3 enhances cancer cell invasiveness and proliferation while inhibiting chemotherapy-induced apoptosis [6] - Mice models with nuclear TLR3-expressing cancer cells exhibited increased liver metastasis and shortened survival, indicating a malignant phenotype [6] Group 2 - Mechanistically, JAK1 phosphorylates serine 155 (S155) of TLR3, facilitating its nuclear translocation through cooperation with importin α5 [6] - The abnormal accumulation of double-stranded RNA in the nucleus under chemotherapy stress may activate nuclear TLR3 [6] - Nuclear TLR3 recruits protein arginine methyltransferase 5 (PRMT5) and interacts with c-Myc, promoting c-Myc's symmetric dimethylation and activation of downstream tumor-promoting signaling pathways [6] Group 3 - High levels of nuclear TLR3 in clinical samples predict poor patient prognosis, characterized by shorter disease-free survival and overall survival, along with a poor response to neoadjuvant chemotherapy [8] - The findings underscore the potential of the JAK1/TLR3/PRMT5/c-Myc signaling axis as a novel target for therapeutic intervention in chemoresistant cancers [8]

Core Viewpoint - Ferroptosis is a newly discovered iron-dependent form of programmed cell death that plays a significant role in the development of various diseases, including cancer [2][4]. Group 1: Mechanism of Ferroptosis - Reactive oxygen species (ROS) are crucial in initiating lipid peroxidation and ferroptosis, significantly affecting chemotherapy resistance in cancer [3][10]. - The study published in Nature Cell Biology reveals that O-GlcNAc transferase (OGT) acts as a ROS sensor in hepatocellular carcinoma (HCC) [4][10]. - ROS-induced oxidation activates OGT, which then modifies the transcription factor FOXK2, promoting its nuclear translocation and upregulating the expression of the key gene SLC7A11, thereby inhibiting ferroptosis and enhancing chemotherapy resistance in liver cancer cells [4][8]. Group 2: Implications for Cancer Treatment - The research elucidates a ROS-mediated oxidation-O-GlcNAcylation cascade that integrates ROS signaling, O-GlcNAc modification, and FOXK2-mediated transcriptional regulation of SLC7A11, contributing to resistance against ferroptosis and chemotherapy [10]. - Targeting this mechanism may provide a novel approach to reactivate ferroptosis, offering new strategies to overcome cancer resistance [10].

Core Viewpoint - The research identifies a novel ionizable lipid, C-a16, which reduces immunogenicity and enhances mRNA delivery efficiency, providing a promising avenue for mRNA therapies and vaccines [3][5][8]. Group 1: Research Findings - The study published in Nature Biomedical Engineering highlights the development of C-a16, an antioxidant ionizable lipid that shows significantly reduced immunogenicity [3][5]. - C-a16, when incorporated into lipid nanoparticles (LNP) for mRNA delivery, decreases the generation of reactive oxygen species (ROS), thereby prolonging protein expression duration [7][8]. - In vivo experiments demonstrated that C-a16-LNP significantly improved gene editing efficiency by 2.8 times and increased protein expression levels by 3.6 times compared to commercial LNPs [7]. Group 2: Implications for mRNA Therapy - The findings suggest that C-a16 could enhance the therapeutic applications of mRNA by inducing stronger antigen-specific immune responses when delivering mRNA encoding tumor neoantigens or SARS-CoV-2 spike protein [7][8]. - The research indicates a potential shift in mRNA delivery systems, focusing on reducing immunogenicity while improving efficacy, which is crucial for the success of mRNA-based therapies and vaccines [3][8].

Core Findings - The study reveals a "same-sex clustering" phenomenon in families with multiple children, challenging the traditional view that each child's gender is an independent event with a 50% probability for boys and girls [3][4][5][7] - For families with three or more children, the likelihood of having all boys or all girls is higher than having both genders [7] - The probability of a woman having another boy after already having one boy is 57%, and this probability increases to 61% after having three boys. Similarly, the probability of having another girl after having one girl is 53%, increasing to 58% after three girls [4][5] Maternal Age Influence - The research indicates that a mother's age at the time of her first childbirth significantly affects the gender of her children. Women who give birth after the age of 29 have a 13% higher probability of having only boys or only girls compared to those who give birth before age 23 [9][10] - This suggests that the maternal environment, which changes with age, may influence the success of sperm carrying X or Y chromosomes [10] Genetic Factors - The study identifies specific genes associated with a tendency to give birth to boys or girls. A particular SNP (rs58090855) on chromosome 10 is linked to a higher likelihood of having girls, while another SNP (rs1506275) near the TSHZ1 gene on chromosome 18 is associated with a higher likelihood of having boys [12][13] - This indicates that some women may have a genetic predisposition that affects the gender ratio of their offspring, providing a new perspective on family gender patterns [13] Conclusion - Overall, the research demonstrates that the gender of newborns is not entirely random, with maternal age and specific genetic mutations playing significant roles in determining offspring gender [14][15] - The findings open new avenues for exploring the complex biological mechanisms influencing gender determination, while emphasizing that the study's purpose is to reveal natural patterns rather than to facilitate gender selection [15][16]

Core Viewpoint - The research presents a breakthrough in the growth of two-dimensional indium selenide (InSe) wafers, which are expected to surpass silicon-based electronic devices, addressing the challenges of achieving high-quality thin films for scalable applications [2][5]. Group 1: Research Methodology - The research team developed a solid-liquid-solid growth strategy that constructs an indium-rich liquid interface and strictly controls the 1:1 stoichiometry of indium selenide, successfully converting amorphous InSe films into high-crystallinity wafers [4]. - The resulting InSe wafers exhibit excellent uniformity, phase purity, and crystallinity over a diameter of approximately 5 centimeters [4]. Group 2: Performance Metrics - The transistors fabricated from the InSe wafers demonstrate superior electrical performance compared to existing two-dimensional thin-film devices, achieving an average mobility of 287 cm²/Vs at room temperature and a subthreshold swing as low as 67.3 mV/dec, nearing the Boltzmann limit [4]. Group 3: Implications for Industry - This research addresses the core challenges in the preparation of 2D InSe wafers, providing a high-performance material platform for integrated circuits in the post-silicon era, potentially advancing the development of next-generation low-power, high-performance computing and communication chips [5].

在这项最新研究中，研究团队展示了非双曲晶体 钒酸钇 （ YVO₄ ） 中双曲表面声子极化激元的涌现。通 过结合实空间纳米成像与理论分析，研究团队观察到， YVO₄ 晶体表面在其非双曲频率范围内 （此时材料 的介电张量分量均为负值） 存在声子极化激元的双曲波前。 编辑丨王多鱼 排版丨水成文 在双曲晶体 （即介电张量分量符号相反的各向异性材料） 中，物质-光子杂化激发因其通过双曲极化激元 形式展现的强烈光-物质相互作用而备受关注。然而，此类现象此前仅限于双曲晶体，其光学响应被束缚于 固定光谱范围且缺乏可调性，因而广泛适用性受限。 2025 年 7 月 16 日， 中国地质大学（武汉） 戴志高 教授、 李国岗 教授及 南洋理工大学 胡光维 教授、 王岐捷 教授作为共同通讯作者，在国际顶尖学术期刊 Nature 上发表了题为： Long-range hyperbolic polaritons on a non-hyperbolic crystal surface 的研究论文。 该研究首次在 非双曲晶体 钒酸钇 （YVO₄） 表面 实现了长程双曲声子极化激元，这一突破不仅摆脱了对 双曲晶体的依赖，还 拓展了双曲纳米光学 ...

Core Insights - The article highlights significant research published in the journal Cell, with a focus on studies led by Chinese scholars, covering various biological mechanisms and their implications for health and disease [2]. Group 1: Adeno-Associated Virus Research - A study identified an alternative receptor for adeno-associated viruses (AAV), named AAVR2, which can restore transduction in the absence of AAVR and provide a unique entry pathway for unclassified AAVs [4][6]. - The research suggests that overexpressing a minimal functional AAVR2 can enhance AAV transduction in vivo, allowing low doses of AAV to achieve similar therapeutic effects [6][8]. Group 2: Glucose Restriction and Tumor Metastasis - Research revealed that glucose restriction influences the pre-metastatic immune landscape in the lungs through exosomal TRAIL, suggesting a new mechanism of immune regulation [10][11]. - The study warns that extreme low-carbohydrate diets may inhibit tumor growth but could also promote lung metastasis, highlighting the need for careful evaluation of metabolic intervention strategies [11][13]. Group 3: Neurovascular Coupling - A study demonstrated that endothelial gap junction coupling enables rapid propagation of vasodilation during neurovascular coupling, crucial for meeting the brain's instantaneous energy demands [15][16]. - The findings indicate that the molecular composition of gap junctions varies along the arterial-venous axis, with the strongest connections found in the arterial segments [16][18]. Group 4: pH-Dependent Inflammatory Responses - Research uncovered how acidic environments during inflammation regulate immune responses through pH-dependent transcriptional condensates, identifying BRD4 condensates as pH sensors [20][21]. - The study suggests that pH acts not only as a byproduct of inflammation but also as an active regulator of the inflammatory response, providing new insights into chronic inflammation and autoimmune diseases [23]. Group 5: Thyroid Hormone Transport Mechanism - A study elucidated the structural mechanisms of thyroid hormone transport via MCT8 and OATP1C1, revealing their binding interactions with active thyroid hormones [25][26]. - The research highlights the importance of these transport mechanisms in development and disease, providing insights into the pathogenic mechanisms of related mutations [28].