The Innovation最新文献

Natural components, evolved to help organisms adapt and defend against threats, are also vital sources for drug discovery due to their diverse and potent bioactivities. In the present work, we proposed the Gene-encoded Natural Diverse Components Repository (GNDC, https://cbcb.cdutcm.edu.cn/gndc/), a primary and most extensive database dedicated to cataloging diverse natural components. GNDC currently catalogs over 234 million natural components that are organized into four specialized sub-databases: HerbalMDB for 2.32 million secondary metabolites, HerbalPDB for 229 million small peptides, HerbalRDB for 2.38 million small RNAs, and HerbalCDB for 0.26 million carbohydrates. By leveraging customized pipelines for high-throughput multi-omics data and AI technologies, the GNDC enables large-scale discovery and annotation of natural products from nuclear and organellar genomes of species listed in eight global pharmacopoeias and multi-resource data. Compared to existing resources, GNDC achieves a 10-fold increase in component yield and introduces over 200 million previously unreported components. To support this unprecedented data volume and complexity, state-of-the-art AI tools are seamlessly integrated to decipher and annotate vast data collections, such as classification and gene expression signature generation of millions of secondary metabolites. We envision that the GNDC will drive the transformation of drug discovery from an "experience-driven" approach to a "big data-driven" paradigm.

Somatic mutations accumulate with age in human tissues. Clonal amplification of some mutations causes cancers and other diseases. However, it is unclear if random mutation accumulation affects cellular function without clonal amplification. We tested this in cell culture, avoiding the limitation that mutation accumulation in vivo leads to cancer. We performed single-cell whole-genome sequencing of fibroblasts from DNA-mismatch-repair-deficient Msh2 ^-/- mice and controls after long-term passaging. While maintaining the same growth rates, in the Msh2 ^-/- fibroblasts, single-nucleotide variants increased up until >50,000 per cell, with small insertions and deletions plateauing at ∼16,000 per cell. We provide evidence for genome-wide negative selection and large-scale mutation-driven population changes, including significant clonal expansion of preexisting mutations and widespread cell-strain-specific hotspots, likely caused by positive selection of mutations in specific genes. Since negative selection to prevent mutations with adverse effects in vivo during aging is difficult to envision, these results suggest a causal role of somatic mutations in age-related cell functional decline.

Global agrifood systems face three interconnected challenges: ensuring food security, promoting environmental sustainability, and restoring soil health in the face of climate change. Conventional practices have prioritized productivity over ecological resilience, leading to soil degradation, increased greenhouse gas (GHG) emissions, and inefficient resource utilization. Here, we introduce a "triple-goal" agrifood framework that enhances food production, soil health, and GHG mitigation simultaneously through integrated innovations. Using a second-order meta-analysis of 104 meta-analyses that cover 39,162 studies and 300,139 global field comparisons, we identified key interventions, including optimized fertigation, diversified cropping systems, organic amendments, and precision N management, that increased productivity by 14%-28% while reducing environmental impacts. Diversified systems boosted yields by 19.6% and reduced land use by 19%. Integrating legumes and cover crops lowered N₂O emissions by 18%-65%, while organic amendments increased soil organic carbon stocks by 7%-13%. Structural equation modeling identified nitrogen use efficiency and microbial activity as central to the food-soil-emissions nexus. However, tradeoffs remain; yield-focused strategies can elevate emissions if not tailored to local conditions. By integrating agronomic, biological, and technological interventions such as conservation tillage, biofertilization, and digital agriculture, this triple-goal framework supports a 15%-30% reduction in anthropogenic CO₂-equivalent emissions. These findings underscore the need for policy reform and multi-stakeholder collaboration to scale up the adaptation of integrated strategies in alignment with the UN's Sustainable Development Goals and the "One Health" initiative. The triple-goal framework provides a transformative pathway to climate-smart, equitable, and resilient agrifood systems that strike a balance between productivity and planetary health.

Immunotherapy has transformed cancer treatment, but its effectiveness in breast cancer remains suboptimal. Tumor-associated macrophages (TAMs), a key component of the tumor microenvironment (TME), contribute significantly to immune evasion. In this study, we identified gamma-interferon-inducible lysosomal thiol reductase (IFI30) as a critical regulator of TAM function in breast cancer. IFI30 expression is upregulated in breast cancer via enhanced Histone 3 lysine 27 acetylation (H3K27ac) modification and promotes tumor progression and metastasis in an immune-dependent manner. Mechanistically, IFI30 in breast cancer cells recruits TAMs by activating the ATF3-CCL5 axis. Within macrophages, it promotes M2-like polarization and PD-L1 upregulation, fostering an immunosuppressive TME. Our findings established IFI30 as a promising therapeutic target for disrupting TAM-mediated immune suppression and enhancing breast cancer immunotherapy.

Global ocean acidification driven by atmospheric CO₂ uptake is well recognized; however, coastal zones are subject to additional, localized acidification pressures. Among these, the chronic discharge of low-pH-treated wastewater (often pH 6.0), permitted under many current regulations, represents a significant but often overlooked stressor. This practice introduces highly acidic loads into sensitive nearshore ecosystems that are chemically incompatible with ambient seawater (pH ∼8.1). This perspective argues for reframing effluent pH not only as a pollutant parameter to be bounded but also as a modifiable policy lever. Revising discharge standards to require a minimum effluent pH > 8.0 for marine outfalls offers a novel pathway to mitigate localized coastal acidification. Furthermore, this approach aligns with emerging ocean alkalinity enhancement strategies, potentially enhancing coastal carbon sequestration and offering cobenefits such as reduced metal toxicity. Such a policy shift necessitates technological adaptation but promises significant benefits for coastal resilience and broader ocean sustainability goals.

Advancements in single-molecule electrical detection techniques have provided a novel microscopic perspective for investigating the properties of single DNA molecules. These state-of-the-art technologies, with their ultra-high resolution at the single-event/single-base level, significantly enhance our understanding of the dynamic properties of single DNA molecules, thus providing valuable guidance for deciphering biological mechanisms, including DNA replication, repair, and transcription. In this review, we highlight the progress achieved through single-molecule electrical detection methodologies, including single-molecule junctions, single-molecule field-effect transistors, and single-molecule nanopores, in studying DNAs at the single-molecule level. Emphasis will be placed on notable discoveries concerning charge-transport properties, conformational dynamics, and sequence-specific analyses within single DNA molecules utilizing single-molecule electrical detection techniques. The application of single-molecule electrical detection techniques in clarifying the structure-function relationship of single DNA molecules is expected to catalyze revolutionary advancements in the fields of bioelectronics, molecular electronics, and nanotechnology.

Radiative cooling utilizes the ultracold (∼3 K) deep space to cool terrestrial objects at no cost to active energy consumption. It finds widespread applications across various fields and paves a promising strategy for tackling global energy and environmental issues, such as scorching and freshwater shortages. However, a comprehensive review of the applications, efficacy, and future of radiative cooling technologies has not been reported. This review takes a retrospective view and summarizes the emerging radiative cooling applications for enhanced energy efficiency in various fields, encompassing building cooling, personal thermal management, solar cell cooling, thermoelectric power generation, freshwater collection, food production and storage, and other miscellaneous fields. The design novelties, achievements, and energy-saving capabilities are analyzed and discussed for each application field. By analyzing the cutting-edge research processes, we also extract the advantages and limitations of the present radiative cooling applications. Additionally, we summarize the up-to-date designs and performance achieved via radiative cooling implementations in various fields. Finally, we highlight the challenges and opportunities of extending radiative cooling technologies to multitudinous scenarios. The comparative and conclusive results in this work clarify the application progress and development direction of radiative cooling, promoting prototype designs and real-world implementations of radiative cooling-driven technologies.