Group 1 - The article highlights seven research papers published in the prestigious journal Cell during the week of September 1 to September 7, 2025, with four of them authored by Chinese scholars [3] - The first study discusses a newly discovered gene SCREP that drives the diversification of rose scent, revealing a multi-step process of its origin and its role in inhibiting the synthesis of the key aromatic compound eugenol [5][8] - The second study presents a breakthrough in the reprogramming of microspore fate, establishing a new technique for efficient in vivo haploid induction without stress treatment, highlighting the roles of the transcription factors BBM and BAR1 [10][12][13] Group 2 - The third study uncovers how cancer cells hijack iron-rich macrophages to promote bone metastasis and anemia, providing insights into potential therapies to mitigate these conditions [15][18] - The fourth study introduces a high-throughput, high-precision single-cell DNA and RNA multi-omics technology called wellDR-seq, which decodes the mechanisms of breast cancer progression by integrating single-cell genomes and transcriptomes [20][23]

Core Viewpoint - The article discusses a research paper published by a team from Rutgers University, BioViva, and Harvard University, which proposed a gene therapy using cytomegalovirus (CMV) to extend healthy lifespan in mice. The paper was later retracted due to data discrepancies identified during an internal review [5][8][12]. Research Findings - The study demonstrated that gene therapies targeting TERT and FST genes could extend the lifespan of mice by approximately 40% without increasing cancer risk [5][12]. - Mice treated with TERT gene therapy had a median lifespan of 37.5 months, while those treated with FST gene therapy had a median lifespan of 35.1 months, compared to 26.7 months for the control group [12][13]. - The therapies also improved metabolic functions, glucose tolerance, and prevented weight loss and hair loss, indicating a broader impact on health beyond lifespan extension [13]. Gene Therapy Mechanism - TERT gene therapy activates telomerase, which can extend telomeres and potentially reverse aging processes, while FST gene therapy enhances muscle mass and function [10][11]. - CMV was chosen as a delivery vector due to its ability to carry larger genetic payloads and its safety profile, as most humans are already infected with it without symptoms [11]. Retraction Reasons - The paper was retracted following the discovery of issues in the data presented in figures, including over-saturation and image duplication [15][16]. - The retraction was supported by George Church, one of the authors, who acknowledged the lack of sufficient data backup but maintained that the core findings were not fundamentally flawed [20]. Author Responses - Elizabeth Parrish expressed shock at the retraction, arguing that the image issues were non-substantial and had been previously corrected [21]. - Zhuo Hua, another co-author, indicated a lack of necessity to respond due to retirement [21]. - The first author, Dabbu Kumar Jaijyan, stated there was nothing to address regarding the retraction [22].

Core Viewpoint - The research highlights the potential of targeting necrotic lipid release in tumors to enhance immunosurveillance and improve cancer immunotherapy for glioblastoma, providing new therapeutic targets for this deadly brain tumor [2][5]. Group 1: Research Findings - The study utilized non-cancerous mouse embryonic stem cells to construct a genetically identical mouse teratoma model and identified genes affecting early cancer immune editing through whole-genome CRISPR screening [5]. - The deletion of pro-apoptotic tumor suppressor genes, including Trp53, exacerbated cell necrosis within teratomas, leading to the release of APOE lipid particles into the extracellular environment [5]. - Infiltrating T cells attracted to necrotic tumor regions accumulated lipids and became dysfunctional, but blocking T cell lipid uptake or inactivating mitochondrial permeability transition pore (mPTP) could reduce cell necrosis and restore immune surveillance [5]. Group 2: Implications for Human Cancer - The research further investigated the interaction between tumors and immunity in human glioblastoma (GBM), revealing that infiltrating T cells in TP53 mutant human GBM also exhibited APOE accumulation and dysfunction [5]. - The combination of anti-APOE antibodies with anti-PD-1 antibodies was found to synergistically enhance anti-tumor immune responses and prolong survival in mouse models [5]. Group 3: Mechanistic Insights - The study elucidated the association between mPTP-mediated tumor necrosis and immune evasion, indicating that inhibiting the uptake of lipids released from necrotic tumor cells by infiltrating immune cells can enhance the efficacy of cancer immunotherapy [5].

Core Viewpoint - The rapid development of antibiotic resistance outpaces the discovery of new antibiotics, highlighting the potential of antimicrobial peptides (AMPs) as promising alternatives due to their broad-spectrum antimicrobial activity and unique mechanisms of action [2][6]. Group 1: Antimicrobial Peptides (AMPs) - AMPs are small molecules (10-50 amino acids) that play a crucial role in the host immune defense system, targeting bacteria, fungi, viruses, and parasites [2]. - The mechanisms of AMPs differ from traditional antibiotics, primarily disrupting pathogen cell membranes or interfering with metabolic processes [2][6]. - Despite their potential, the discovery of AMPs remains challenging, necessitating advanced tools like machine learning and deep learning to accelerate research [6][8]. Group 2: Generative Artificial Intelligence in AMP Design - Generative artificial intelligence, particularly through models like AMP-Diffusion, offers a powerful approach for designing AMPs by exploring sequence space systematically [3][7]. - AMP-Diffusion utilizes a pre-trained latent diffusion model to generate potent AMP sequences, ensuring integration with established protein language models like ESM-2 [7][9]. - The model has successfully generated 50,000 candidate AMP sequences, with 76% demonstrating low toxicity and effective bacterial killing capabilities [8][9]. Group 3: Research Findings and Implications - The research team synthesized and validated 46 top-ranking AMP candidates, which exhibited broad-spectrum antimicrobial activity, including against multidrug-resistant strains, with low cytotoxicity [8][9]. - In preclinical mouse models, lead AMPs significantly reduced bacterial load, showing efficacy comparable to polymyxin B and levofloxacin without adverse effects [8][9]. - AMP-Diffusion represents a robust platform for antibiotic design, addressing the urgent need for new antimicrobial agents in the face of rising antibiotic resistance [8][9].

Core Viewpoint - The study highlights the significant role of the oral virome in human health, particularly its connection to obesity and type 2 diabetes, and introduces the Human Oral Virome Database (HOVD) as a valuable resource for understanding these relationships [3][5][7]. Group 1: Research Findings - The research team constructed the Human Oral Virome Database (HOVD), which includes 24,440 viral operational taxonomic units (vOTUs) and 83 eukaryotic viruses, providing a comprehensive resource for studying oral viromes [3][5][7]. - The study found that the oral virome diversity is reduced in obese patients with type 2 diabetes, indicating a weak correlation with clinical features and enhanced oral-gut virus transmission [6][7]. - The research identified phages that infect Porphyromonas gingivalis, a key pathogen in periodontal disease, and screened for six potential endolysins that can inhibit its growth, suggesting a new therapeutic avenue for managing periodontal disease associated with type 2 diabetes [6][7]. Group 2: Implications for Disease Understanding - The findings suggest that oral viruses may influence the progression of diseases such as oral cancer, periodontal disease, and rheumatoid arthritis, indicating potential prognostic and diagnostic applications based on microbiome composition [5][6]. - The study enhances understanding of host-virus interactions within the oral microbiome and provides new insights for the diagnosis and treatment of human diseases [9].

Core Viewpoint - The research highlights the development of a method to efficiently differentiate human pluripotent stem cells (hPSCs) into A10-like midbrain dopaminergic neurons (A10 mDA), which can integrate into mouse brain circuits and alleviate depression-like behaviors [3][6][8]. Group 1: Research Methodology - The study established a protocol for differentiating hPSCs into A10 mDA neurons, demonstrating that these neurons can selectively integrate into host neural circuits and alleviate depression-like phenotypes [6][7]. - The differentiation process involved the use of Notch inhibitors, glial cell-derived neurotrophic factor (GDNF), and ascorbic acid (AA) to induce A10 subtype specification [7]. Group 2: Findings and Implications - The A10-like mDA neurons exhibited characteristics of the A10 subtype, including specific gene expression profiles and electrophysiological properties [7]. - Transplanted A10-like mDA neurons specifically projected to their endogenous target brain regions, inducing anxiolytic effects in normal mice and antidepressant-like effects in depression model mice [7][8]. - The findings suggest that therapies based on A10 mDA neurons hold potential for treating major depressive disorder and provide a theoretical basis for using hPSC-derived neuronal subtypes in treating a wide range of neuropsychiatric disorders [8].

Core Viewpoint - The article discusses the birth of the world's first CRISPR gene-edited horses, highlighting the implications of this technology in animal breeding and the controversies surrounding it [3][5][7]. Group 1: CRISPR Gene-Edited Horses - The first CRISPR gene-edited horses were born in Argentina, created by Kheiron Biotech, using CRISPR-Cas9 technology to enhance muscle growth by knocking out the myostatin gene [7]. - These horses are clones of the award-winning racehorse Polo Pureza and exhibit stronger muscles and faster speeds compared to ordinary horses [5][7]. - The introduction of these gene-edited horses has sparked controversy, particularly in the equestrian community, with concerns about the impact on traditional breeding practices and livelihoods [8]. Group 2: Broader Applications of CRISPR Technology - Prior to the CRISPR horses, gene editing had been widely applied in agriculture and disease treatment, such as the development of PRLR-SLICK cattle, which are more heat-resistant due to a gene edit [9]. - The FDA approved PRLR-SLICK for meat production in 2022, showcasing the regulatory acceptance of gene-edited animals [9]. - Other examples include CRISPR sheep for increased meat yield and CRISPR pigs that are resistant to diseases like PRRS, with FDA approval for market sale expected by 2026 [10]. Group 3: Ethical and Health Concerns - The rise of CRISPR gene-edited animals raises ethical questions, particularly regarding animal health and the potential unforeseen consequences of genetic modifications [11]. - Concerns include the long-term health effects on the animals and the possibility of genetic changes being passed to future generations or affecting wild populations [12]. - There is a call for further research to monitor any adverse health impacts resulting from gene editing in animals [12].

Core Viewpoint - Tumor immunotherapy, particularly immune checkpoint blockade (ICB) targeting the PD-1/PD-L1 pathway, shows significant promise in treating various advanced cancers, but low immune response rates hinder its efficacy and widespread application [2] Group 1: Research Findings - The study developed a self-luminous nanosystem that enhances the activation of pyroptosis in tumor cells, leading to a strong antitumor immune response when combined with anti-PD-L1 monoclonal antibodies [3][6] - Pyroptosis, a newly discovered form of immunogenic cell death (ICD), releases pro-inflammatory cytokines and damage-associated molecular patterns, triggering a robust antigen-specific immune response [5] - The self-luminous nanoparticles can emit light within the tumor without the need for an external light source, enhancing the generation of reactive oxygen species (ROS) and achieving significant tumor-killing effects [7] Group 2: Mechanism and Components - The nanosystem consists of amphiphilic porphyrin lipids, camptothecin derivatives, and a targeting moiety, which together facilitate the release of oxygen and hydrogen peroxide in the acidic tumor microenvironment [6] - The combination of chemotherapy and self-enhanced photodynamic therapy synergistically activates pyroptosis, driving immune activation that enhances the antitumor response to PD-L1 therapy [7]

Core Viewpoint - The research led by Sana Biotechnology offers a potential breakthrough in treating Type 1 Diabetes (T1D) by enabling the survival of transplanted allogeneic beta cells without the need for immunosuppression, which could significantly improve patient outcomes and reduce the risks associated with long-term immunosuppressive therapy [2][4][7]. Group 1: Research Findings - A study published in NEJM demonstrated that CRISPR-Cas12b gene editing was used to modify donor beta cells to avoid immune rejection, allowing these cells to be transplanted into a Type 1 Diabetes patient without immunosuppressive drugs [2][4]. - The patient showed no immune response to the transplanted cells within 12 weeks, and the cells continued to produce insulin, effectively regulating blood sugar levels [2][9]. - This approach represents a significant advancement towards achieving a long-term cure for T1D, with the potential for a one-time treatment that eliminates the need for insulin injections and immunosuppressive medications [9][10]. Group 2: Comparison with Other Companies - Other companies, such as Vertex and Reprogenix, are also exploring stem cell-derived therapies for T1D, but these methods still require immunosuppressive drugs to prevent immune attacks on either donor or patient-derived cells [6][7]. - Vertex's research involved transplanting stem cell-derived islets into 12 patients, with 10 no longer needing insulin after one year, while Reprogenix successfully reprogrammed patients' own fat cells into insulin-producing cells [6][7]. - Unlike these approaches, Sana's method aims to eliminate the need for immunosuppression entirely, which could revolutionize treatment for T1D [7][9]. Group 3: Future Directions and Challenges - The ultimate goal of Sana's research is to apply the "immune stealth" gene editing technique to stem cells, guiding their development into insulin-secreting beta cells, with clinical trials expected to begin next year [9][10]. - However, there are concerns regarding the reproducibility of the protective effects of CD47 and the limited scope of the initial study, which involved only one patient and a small number of transplanted cells [10].

Core Viewpoint - The global prevalence of type 2 diabetes is rapidly increasing, with an estimated 700 million people affected by 2045, posing a significant public health threat. Aging mechanisms are closely related to the progression of diabetes, and delaying aging may be crucial for improving diabetes and other age-related diseases [3][4]. Group 1: SGLT2 Inhibitors and Aging - Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are important anti-diabetic drugs that lower blood sugar by inhibiting glucose reabsorption in the kidneys. They also enhance lipid metabolism and ketone production, potentially mimicking caloric restriction (CR) and exerting anti-aging effects [3][4]. - SGLT2i can simulate the effects of caloric restriction without the need for strict dietary control, providing a more feasible alternative for anti-aging interventions in diabetic patients [4][5]. Group 2: Clinical Study Findings - A multicenter, randomized, double-blind, placebo-controlled study published in Cell Reports Medicine revealed that the SGLT2i drug Henagliflozin can extend telomere length and may exert anti-aging effects through various pathways, including the IGF-1 system, glucose metabolism, and immune function [5][6][9]. - In the clinical trial involving 150 type 2 diabetes patients, those treated with Henagliflozin showed significant increases in telomere length, insulin-like growth factor binding protein-3 (IGFBP-3) levels, and β-hydroxybutyrate levels, along with improved glucose metabolism [8][9]. - The study also indicated that Henagliflozin significantly increased granzyme B expression in cytotoxic T lymphocytes and showed trends of increased perforin expression, suggesting enhanced immune function [8][9]. Group 3: Implications and Future Research - The findings highlight the potential of SGLT2i in the anti-aging domain, with Henagliflozin receiving the highest score among nine FDA-approved drugs evaluated for anti-aging potential [6][9]. - However, there is still a lack of direct clinical data regarding the anti-aging effects of SGLT2i, indicating a need for further research in this area [6].