Core Viewpoint - The recent research published in PNAS by a team from Westlake University reveals the structural basis of auxin binding and transport by the AUX1 protein in Arabidopsis thaliana, which is crucial for understanding plant growth and development [2][5]. Group 1: Research Findings - The study elucidates the cryo-electron microscopy structures of AUX1 in both IAA-unbound and IAA-bound states, highlighting the significant conformational changes that occur upon IAA binding [3][5]. - AUX1 exists as a monomer and comprises 11 transmembrane helices, with TM1 to TM5 and TM6 to TM10 forming two halves of the classic LeuT fold, while TM11 interacts at the junction of these halves [5]. - The central pocket formed by TM1, TM3, TM6, and TM8 specifically recognizes IAA, and the conformational changes in TM1 and TM6 are critical for the transport of IAA [5]. Group 2: Implications and Future Research - The findings provide a molecular basis for AUX1-mediated IAA binding and transport, laying the groundwork for future structural-based functional studies of the AUX1/LAX family and the application of auxin analogs in agriculture [5]. - Following the PNAS publication, a related study from institutions in France, Denmark, and Germany was published in Nature Plants, which also analyzed the structures and mechanisms of AUX/LAX transporters involved in auxin import [6].

Core Viewpoint - Plastic poses a severe and escalating threat to human and planetary health, with annual health-related economic losses exceeding $1.5 trillion. The impact is particularly severe for low-income and high-risk populations [2][3]. Group 1: Plastic Production and Pollution - Global plastic production has surged from 2 million tons in 1950 to 475 million tons in 2022, and is projected to reach 1.2 billion tons by 2060. In North America, per capita plastic consumption is as high as 195 kg/year, while in Europe it is 187 kg/year [7]. - Currently, there are 8 billion tons of plastic waste globally, with a recycling rate of less than 10%. This equates to each person carrying over 10,000 plastic bags worth of waste [8]. Group 2: Health Impacts of Plastic - Plastics are linked to various health issues across different life stages, including liver cancer in workers at PVC factories, asthma in children near incineration plants, and significant correlations with cardiovascular diseases and diabetes in older adults [6]. - Over 16,000 types of plastic chemicals exist, with 75% not undergoing safety assessments. 4,200 of these are classified as high-risk, potentially leading to decreased IQ in children and infertility in adults. Microplastics have been detected in human blood, organs, and even the brain, correlating with serious health conditions [12][13]. Group 3: Global Response and Policy Initiatives - The ongoing deterioration of plastic hazards is not inevitable. Effective mitigation is possible through evidence-based policies, transparent tracking, and adequate funding. In 2022, UN member states agreed to develop a comprehensive, legally binding treaty on plastic pollution, known as the Global Plastic Treaty, which addresses the entire lifecycle of plastics [14]. - The core strategies of the Global Plastic Treaty include limiting the production of virgin plastics, banning the use of 4,200 high-risk additives, and regulating medical plastics, which account for 10% of global usage [15]. Additionally, The Lancet is launching a global monitoring system to track progress in reducing plastic exposure and its health impacts [15][16].

Core Viewpoint - The study identifies AKR1B1 as a key regulatory enzyme in metabolic reprogramming and a potential biomarker and therapeutic target for hepatocellular carcinoma (HCC), suggesting that targeting AKR1B1 can reverse systemic therapy resistance in HCC [3][7]. Group 1: Research Findings - HCC is a major subtype of liver cancer and a leading cause of cancer-related deaths globally, with high incidence and mortality rates [2]. - The research team established HCC cell lines with multidrug resistance characteristics, observing enhanced metabolic activity in these cells [5]. - Multi-omics analysis revealed that glucose-lipid and glutathione metabolic pathways are overactive, playing critical roles in supporting tumor cell proliferation and survival [5]. Group 2: Mechanism of Resistance - The study constructed a metabolic reprogramming map for resistant HCC cells, identifying AKR1B1 as a key regulatory factor that maintains resistance by modulating energy metabolism and enhancing stress tolerance [5]. - The expression level of AKR1B1 is closely related to drug resistance and poor prognosis in HCC patients, highlighting its predictive value [5]. Group 3: Therapeutic Implications - The combination of Epalrestat, a clinically approved AKR1B1 inhibitor, with standard therapy (Lenvatinib) significantly alleviated resistance in HCC [7]. - The findings provide new insights into the mechanisms of resistance in HCC and lay the theoretical foundation for developing new predictive biomarkers and therapeutic strategies to overcome resistance [7].

Core Insights - The article discusses a significant advancement in chronic kidney disease (CKD) diagnosis through a non-invasive model utilizing retinal images, developed by a research team from Sun Yat-sen University [2][3][6]. Group 1: Research Development - The Kidney Intelligent Diagnosis System (KIDS) was created to predict kidney biopsy outcomes non-invasively, achieving an area under the curve (AUC) of 0.839-0.993 in CKD screening [3][11]. - KIDS can accurately identify five common pathological types of CKD with an AUC of 0.790-0.932, outperforming nephrologists by 26.98% in accuracy [3][12]. Group 2: Clinical Implications - The non-invasive model has the potential to improve clinical management of CKD, especially for patients who are unsuitable for traditional kidney biopsies [3][16]. - KIDS provides objective pathological and prognostic predictions, which could enhance kidney care quality and reduce the incidence of end-stage renal disease, particularly in underdeveloped regions [16]. Group 3: Background and Challenges - CKD affects approximately 850 million people globally and poses significant health risks, with kidney biopsy being the gold standard for diagnosis but often limited by various factors [6][7]. - Complications from kidney biopsies, such as bleeding, occur in 11% of cases, highlighting the need for safer diagnostic alternatives [6].

Core Viewpoint - The article discusses the importance of metabolism in maintaining homeostasis and its role in various diseases, while announcing the upcoming C2-MERIT conference focused on metabolic research, innovation, and translation [2][4]. Conference Overview - The C2-MERIT conference will be held from August 22 to August 25, 2025, at Wenzhou Junting Hotel, Zhejiang Province, China [5][6]. - The conference aims to share cutting-edge scientific insights and foster innovative ideas within the scientific community [3]. Conference Schedule - Key events include a face-to-face meeting with Cell Press editors on August 21, 2025, and various academic sessions from August 22 to August 25, 2025 [4][6]. - The schedule features a Young Scholar Forum, plenary lectures, and multiple sessions focusing on different aspects of metabolism [16][21]. Registration Details - Registration fees vary: 1700 RMB for regular representatives before July 1, 2025, and 1900 RMB thereafter; student representatives pay 1100 RMB [20]. - Payment methods include online payment, bank transfer, and on-site payment options [22]. Organizing Bodies - The conference is organized by the Chinese Biophysical Society Metabolism Biology Branch and Cell Press, with support from various academic institutions [8][9].

Core Viewpoint - The research presents a breakthrough in T cell therapy by designing the world's first soluble Notch agonist, enabling efficient T cell differentiation in suspension culture and enhancing T cell function and anti-tumor immunity [3][7][8]. Group 1: Research Background - Notch signaling pathway is one of the most evolutionarily conserved pathways, crucial for the development and function of immune cells, particularly T cells [2][10]. - Traditional methods for T cell production rely on complex environments, making large-scale production challenging and costly [7][11]. Group 2: Research Breakthrough - The research team utilized AI protein design tools to create a soluble Notch agonist that activates the Notch signaling pathway in suspension culture, overcoming the mechanical activation challenge [3][8][12]. - The designed C3-DLL4 structure effectively bridges cells, facilitating the formation of immune synapses and activating Notch signaling [13][14]. Group 3: Applications and Advantages - The new method allows for the mass production of T cells in suspension bioreactors, significantly reducing production time and costs compared to traditional methods [16][19]. - In vivo experiments showed that C3-DLL4 enhances T cell function, indicating potential for developing Notch enhancers to improve cancer vaccines and infection prevention [18][19]. Group 4: Future Prospects - The research team is developing an upgraded version, C515H-DLL4, which further improves T cell differentiation efficiency, marking a step towards practical applications [22]. - The AI-designed proteins offer advantages in manufacturing, storage, and clinical administration, potentially transforming CAR-T cell production and vaccine development [23].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肿瘤相关微生物群在 结直肠癌 （CRC） 的肿瘤发生和进展中发挥着关键作用，尤其是 具核梭杆菌 （ Fusobacterium nucleatum ） ，是推动结直肠癌的 进展、转移和耐药性的关键病原体，然而，目前的策 略 （例如使用抗生素） 缺乏特异性，会破坏有益的肠道微生物群，且无法直接消灭肿瘤细胞。 近日， 复旦大学附属肿瘤医院马延磊团队在 Cell 子刊 Cell Biomaterials 上发表了题为 ： Biomimetic "Trojan Horse" nanoparticles with biotactic behavior toward tumor-associated bacteria for targeted therapy of colorectal cancer 的研究论文，该论文还被选为当期的封面论文。 该研究开发了一种 仿生"特洛伊木马"纳米颗粒 —— Mel- SiO 2 @CCM ， 这种纳米颗粒可同时靶向具核 梭杆菌和结直肠癌细胞，通过双重细菌-肿瘤裂解诱导细胞凋亡，并激活肿瘤特异性免疫。 该设计利用了两种天然相互作用：1）CCM 上 ...

Core Viewpoint - The article discusses new evidence regarding nicotine's potential anti-aging effects, suggesting that nicotine can reprogram aging-related metabolism and protect against motor decline in mice [3]. Group 1: Research Findings - A study published by researchers from the Shenzhen Institute of Advanced Technology indicates that chronic low-dose nicotine acts as an activator of NAD⁺ biosynthesis, improving glucose metabolism and cognitive function in mice [8]. - The research highlights that the beneficial effects of nicotine occur at significantly lower concentrations than those typically associated with smoking, emphasizing the need for further studies on nicotine dosage and duration [10]. - The study also found that long-term oral nicotine treatment can mitigate age-related declines in motor function in mice, with no pathological changes observed in peripheral organs related to metabolism [11][13]. Group 2: Aging and Metabolism - Aging is characterized by systemic physiological deterioration, including metabolic dysregulation and reduced physical activity, which are critical factors for healthy aging [5]. - Recent advancements in aging research utilize multi-dimensional omics and machine learning to depict biological aging trajectories, revealing the interconnectedness of energy metabolism, mitochondrial efficiency, and nutrient signaling networks [6]. - The decline in NAD⁺ levels during aging negatively impacts cellular energy homeostasis and genomic integrity, while restoring NAD⁺ can alleviate age-related decline [6]. Group 3: Nicotine's Biological Activity - Epidemiological data show a paradoxical relationship between smoking and certain diseases, where nicotine may have protective associations against conditions like ulcerative colitis and Parkinson's disease [7]. - The study indicates that nicotine influences the gut microbiome, which plays a crucial role in overall physiology, and its effects vary depending on conditions, necessitating context-specific analyses [10]. - Nicotine's impact on sphingolipid metabolism is linked to improved energy metabolism and reduced accumulation of neurotoxic ceramides, which are associated with age-related muscle dysfunction [13][15].

Core Viewpoint - The study indicates that the human brain can anticipate potential infections and trigger an immune response even before actual contact with pathogens occurs, showcasing a predictive capability of the brain in response to environmental threats [3][10][11]. Group 1: Research Findings - Researchers equipped healthy volunteers with VR devices to simulate encounters with virtual individuals showing signs of infection, which activated immune responses similar to actual infections [6][9]. - The study found that the presence of virtual infected individuals increased the frequency and activation of innate lymphoid cells (ILCs), crucial for the body's first line of defense against pathogens [9][10]. - Functional MRI results identified key brain regions involved in this anticipatory immune response, including the insula, pre-motor cortex, anterior cingulate cortex, and medial prefrontal cortex, indicating a neural network's role in predicting infection threats [9][10]. Group 2: Implications for Vaccine Development - The findings suggest potential improvements in vaccine strategies by utilizing VR to enhance the activation of immune cells targeted by vaccines, potentially increasing their effectiveness against pathogens [12].

Core Viewpoint - The inhibition of ACLY promotes tumor immunity and suppresses liver cancer, particularly in the context of metabolic dysfunction-related fatty liver disease driving hepatocellular carcinoma (MASH-HCC) [3][8]. Group 1: Research Findings - The study published in Nature indicates that inhibiting ACLY can significantly reduce tumor burden in MASH-HCC mouse models by over 70% [6]. - A novel ACLY small molecule inhibitor, EVT0185, was developed, which enhances the efficacy of standard treatment regimens including tyrosine kinase inhibitors and immunotherapy [7]. - The research demonstrated that reduced levels of ACLY in tumors correlate with increased levels of chemokine CXCL13, increased tumor-infiltrating B cells, and the formation of tertiary lymphoid structures [7]. Group 2: Mechanisms of Action - Cancer cells reprogram their metabolic processes to support uncontrolled growth and evade immune surveillance, often through enhanced glycolysis and de novo lipogenesis [5]. - The unique immune-suppressive microenvironment of MASH-HCC poses challenges for immunotherapy, as it is characterized by features such as reduced B cell infiltration and downregulated expression of chemokines [5][6]. - The study suggests that targeting tumor metabolism can reshape immune function and inhibit the carcinogenic process in MASH-HCC [8].