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Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology research 2025年第1期33卷 67-81页

作者： XIANG LI WENKE JIN LIFENG WU HUAN WANG XIN XIE WEI HUANG BO LIU State Key Laboratory of Southwestern chinese medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

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Prospects on mangrove knowledge services in the smart era: From plant atlas to knowledge graphs

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Science China Earth Sciences 2025年第1期68卷 111-127页

作者： Zhi-Wei HOU Wenlong JING Cheng-Zhi QIN Ji YANG Qing XIA Xiaoling YIN Key Laboratory of Guangdong for Utilization of Remote Sensing and Geographical Information System Guangdong Open Laboratory of Geospatial Information Technology and Application Guangzhou Institute of Geography Guangdong Academy of Sciences Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) State Key Laboratory of Resources and Environmental Information System Institute of Geographic Sciences and Natural Resources ResearchChinese Academy of Sciences College of Resources and Environment University of Chinese Academy of Sciences School of Traffic & Transportation Engineering Changsha University of Science and Technology

Mangroves are crucial to the ecological security of the Earth and human well-being. Their management, conservation, and restoration are of great importance and necessitate the support of spatio-temporal information and multidisciplinary knowledge such as biology and ecology. Traditional knowledge services such as plant atlas provide illustrated textual knowledge of mangroves. However, this kind of service is oriented to information retrieval and is incapable of effectively mining and utilizing fragmented knowledge from multi-source heterogeneous data, facing the problem of “massive data, rare knowledge”. Knowledge graphs are capable of extracting, organizing, and fusing the knowledge contained in massive data into semantic networks that can be understood and computed by computers. They provide a solution for the realization of intelligent knowledge services. Focusing on the urgent need for mangrove knowledge acquisition, formal representation, and intelligent services, this paper proposes a research prospect on mangrove knowledge graphs and knowledge services. We first analyze the similarities and differences between various domain-specific concepts of Tupu. On this basis, we define the mangrove knowledge graph as a large-scale knowledge base that integrates multi-disciplinary knowledge and spatio-temporal information with mangrove ecosystems as the core. Then, we propose a research framework for mangrove knowledge services that can realize the transformation from multi-modal data to intelligent knowledge services, including multiple research levels such as ubiquitous data sensing and aggregation, knowledge organization and graph construction, and intelligent mangrove knowledge services. Subsequently, the methods and workflow for constructing mangrove knowledge graphs are introduced. Finally, we discuss the challenges and possible future directions of mangrove knowledge services in the smart era, including the construction of a mangrove knowledge system that integra

关键词： Mangrove Tupu Knowledge graph Multi-modal Knowledge service

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of medicine Shanghai UniversityShanghaiChina institute of Basic Medical Sciences chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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Emerging trends in the selective production of value-added aromatics

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Science China Chemistry 2025年第1期68卷 15-20页

作者： Yuchao Wu Houliang Dai Weisheng Yang Yaxing Li Lichen Liu Petrochemical research institute Company Limited China National Petroleum Corporation Engineering research Center of Advanced Rare Earth Materials Department of Chemistry Tsinghua University

1 Introduction Aromatics (mainly benzene, toluene, and xylenes, BTX) are essential intermediates in the chemical industry. They are employed in the synthesis of a broad spectrum of chemicals and materials, e.g., various polymers, plastics, resins, solvents, dyes, pharmaceuticals [1]. The manufacturing pathway of BTX mainly includes petroleum reforming of naphtha, coal-to-aromatics, methanol-to-aromatics [2].

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Marine dispersion of Fukushima-derived radiocesium in the North Pacific and its implications

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Science China Earth Sciences 2025年

作者： Tong ZHANG Xiaolin HOU Yukun FAN State Key Laboratory of Loess and Quaternary Geology Shaanxi Key Laboratory of Accelerator Mass Spectrometry Technology and Application Xi'an AMS Center Institute of Earth Environment Chinese Academy of Sciences University of chinese Academy of Sciences Xi'an institute for Innovative Earth Environment research

A key scientific approach to addressing the environmental radiation risks from Fukushima nuclear contaminated water （FNCW） discharge into the ocean is understanding and predicting the marine dispersion of *** dispersion of radiocesium (CsF:134Cs,137Cs) from the Fukushima nuclear accident in the North Pacific and its marginal seas post-2011 was systematically summarized,focusing on pathways,vertical distribution changes,and transit *** research examined CsFdispersion through the Kuroshio Extension and denser central mode water （D-CMW） to the eastern North Pacific,as well as through subtropical mode water （STMW）,lighter central mode water （L-CMW）,and D-CMW to the subtropical western North Pacific,China Seas,and Sea of *** considered broader implications of CsFdispersion in light of ongoing FNCW *** this prolonged liquid discharge and Kuroshio Extension’s barrier effect,it is crucial to emphasize the role of CMW besides STMW in transporting FNCW to the subtropical western North Pacific and its marginal *** research should focus on the key mechanism and longitude range of CMW crossing the Kuroshio *** short-lived134Cs decays rapidly during the storage and dispersion of FNCW,long-lived135Cs and135Cs/137Cs ratios can serve as valuable tracers for detecting and quantifying ***,there is an urgent need for high-precision analysis of these key radionuclides and their characteristic *** promptly detect,assess,and respond to FNCW intrusion,continuous monitoring and identification of nuclear pollution sources in key ocean currents and straits are ***,interdisciplinary research integrating monitoring with marginal sea circulation dynamics and high-resolution numerical simulations should be a priority

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Analysis of the anti-T2DM components in dichloromethane fraction of Schisandra sphenanthera and its mechanism

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Traditional medicine research 2025年第1期10卷 27-43页

作者： Shi-Bo Feng Hai-Hui Jiang Hui-Li Kang Yi Jiang Hua-Wei Zhang Xiao-Mei Song Yu-Ze Li Wen-Li Huang Dong-Dong Zhang Chong Deng School of Pharmacy Shaanxi University of Chinese MedicineXianyang 712046China School of Pharmacy and Shaanxi Qinling Application Development and Engineering Center of chinese Herbal medicine Shaanxi University of Chinese MedicineXianyang 712046China Key Laboratory for research and Development of“Qin medicine”of Shaanxi Administration of Traditional chinese medicine Xianyang 712046China Shaanxi Key Laboratory of research and Application of“Taibai Qi Yao” Xianyang 712046China

Background:The type 2 diabetes mellitus(T2DM)pharmacodynamic study of various parts of Schisandra sphenanthera was conducted in the previous stage,and it was found that dichloromethane extracted part(SDP)had a significant hypoglycemic ***,the components of SDP were analyzed,and the specific mechanism of its anti-T2DM was ***:We used a high-fat,high-sugar diet in combination with streptozotocin to induce a T2DM rat model,and the model rats were divided into two groups according to body weight and blood ***,oral glucose tolerance test,fasting blood glucose,low density lipoprotein cholesterol,superoxide dismutase,insulin,glycated hemoglobin,total cholesterol,nonesterified free fatty acids,alanine aminotransferase,high-density lipoprotein cholesterol,aspartate aminotransferase,malondialdehyde,and glutathione peroxidase were measured,organ indices were calculated,and pathological sections of pancreas and liver were *** 16S rRNA V3–V4 region of intestinal flora was sequenced to explore the effect of SDP on biochemical indicators and intestinal *** on the above indicators,the anti-T2DM mechanism of SDP in Schisandra sphenanthera was ***:After six weeks of administration,the biochemical indices of diabetic rats were diminished compared to the control *** SDP could significantly increase the gut microbialα-diversity index,resulting in significant changes in the flora of T2DM rats,with increased richness and diversity,reduced harmful flora,and significantly back-regulated the levels of acetic acid,propionic acid,and butyric ***:SDP can improve the symptoms associated with elevated blood glucose,dyslipidemia,elevated fasting insulin levels,and damaged glucose tolerance in *** against T2DM may be through the control of intestinal flora to normalize and exert anti-diabetic effect;its main active components may be lignans and terpenoids.

关键词： Schisandra sphenanthera T2DM intestinal flora HPLC

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Pharmacological intervention for chronic phase of spinal cord injury

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Neural Regeneration research 2025年第5期20卷 1377-1389页

作者： Chihiro Tohda Section of Neuromedical Science Institute of Natural MedicineUniversity of ToyamaToyamaJapan

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidat

关键词： axonal growth chronic phase clinical study pharmacotherapy spinal cord injury

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Specific staining and precise killing of cancer cells through fusion of pharmaceutical chemistry and π-bridge effect design philosophy

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Science China Chemistry 2025年

作者： Qiong Liu Qiyun Deng Changxu Zhu Kongqi Chen Lidan Chen Zhaohui Sun Ben Zhong Tang Zhiming Wang AIE institute Center for Aggregation-Induced Emission State Key Laboratory of Luminescent Materials and Devices Key Laboratory of Luminescence from Molecular Aggregates of Guangdong Province South China University of Technology Department of Laboratory medicine General Hospital of Southern Theater Command School of Life Sciences The Chinese University of Hong Kong Shenzhen institute of Aggregate Science and Technology School of Science and Engineering The Chinese University of Hong Kong HKUST-Shenzhen research institute

The development of an advanced phototheranostic platform that combines imaging and therapy in a single agent is an appealing yet challenging *** this study,we successfully constructed three novel fluorescent probes by leveraging pharmaceutical chemistry and the design philosophy of theπ-bridge *** a systematic comparative analysis of their fluorescence properties,water solubility,molecular conformation,and electrostatic potential,we revealed the fundamental principles governing the optical behavior and biological selectivity of these ***,the probe TPhIQ-CNTh demonstrated extended fluorescence in the near-infrared region,a significant aggregation-induced emission (AIE) effect,and the ability to distinguish tumor cells from normal ***,it efficiently generated reactive oxygen species (ROS) and specifically labeled lipid droplets,enabling the precise staining and killing of cancer *** study presents a practical strategy for designing precise tumor treatments that integrate efficient imaging-guided photodynamic therapy (PDT) by harnessing the unique properties of AIE materials.

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Spatiotemporal evolution of wildfire activity during the PaleoceneEocene Thermal Maximum in China

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Science China Earth Sciences 2025年

作者： Xueting WANG Zuoling CHEN Linlin CUI Xu WANG State Key Laboratory of Lithospheric and Environmental Coevolution Institute of Geology and Geophysics Chinese Academy of Sciences University of chinese Academy of Sciences College of Earth and Planetary Sciences institute of Geology and Geophysics Chinese Academy of Sciences

The Paleocene-Eocene Thermal Maximum（PETM） was the most prominent warming event in the Cenozoic and serves as a geological analog for the current global warming driven by anthropogenic CO2emissions from burning fossil *** a primary disruptor of Earth's ecosystems, wildfire activity affects the balance of ecosystems, the global carbon cycle, and climate change. Therefore, studying the evolution and driving mechanisms of wildfires during the PETM is essential for predicting wildfire activity under global warming scenarios and for understanding the carbon cycle in the context of wildfire disturbances. Current research on wildfires during the PETM has mainly focused on the Northern Hemisphere, particularly Europe and North America, whereas studies on chinese mainland remain limited. In this study, we analyzed black carbon（BC）concentration and carbon isotope(δ13C) in the Beigou section of the Nanyang Basin and the Xilutian section of the Fushun Basin to reconstruct the spatiotemporal evolution of wildfires in arid/semi-arid and humid zones. We integrated these findings with those of previous studies on the paleoclimate of the research area to elucidate the driving mechanisms behind wildfire occurrences. Our results indicate that wildfire activity weakened at the onset of the PETM, with the negative carbon isotope period characterized by low wildfire activity, except for a brief resurgence in the Nanyang Basin. During the recovery phase of the PETM, wildfire activity gradually increased, returning to the pre-PETM levels. The prolonged low wildfire state was likely caused by extremely high temperatures and precipitation as well as the resulting vegetation succession. During the PETM recovery phase, increased wildfire activity transformed “short-term carbon sinks” of the biological-atmospheric carbon cycle into “long-term carbon sinks” through the burial of BC. This process of carbon sink conversion may have acted as a negative feedback mechanism, contributing to carbo

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A robust statistical prediction model for late-summer heavy precipitation days in North China

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Science China Earth Sciences 2025年第1期68卷 158-171页

作者： Shunli JIANG Tingting HAN Xin ZHOU Huijun WANG Zhicong YIN Xiaolei SONG Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters/Key Laboratory of Meteorological Disaster Ministry of Education Nanjing University for Information Science and Technology Nansen-Zhu International research Centre Institute of Atmospheric Physics Chinese Academy of Sciences Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)

Recently, heavy precipitation(HP) events have occurred frequently in North China(NC), causing devastating economic losses and human fatalities. However, the short-term climate prediction of HP is quite limited. Combining year-to-year increment(DY) method and sliding correlations, we developed a robust seasonal prediction model for late-summer HP days(HPDs) in NC during 1982–2022, utilizing three independent predictors—February sea surface temperature(SST) in the Indian Ocean(SST＿IO), February snow depth over North Asia(SDE＿NA), and May melted snow depth in NC(MSDE＿NC). The SST＿IO anomalies affect NC's precipitation through the Pacific-Japan pattern. The SDE＿NA anomalies are associated with East Asian anomalous anticyclone by southeastern propagation of Rossby wave at Eurasia. The MSDE＿NC anomalies are followed by vertical motion and moisture anomalies in situ and thereby cause precipitation anomalies. This prediction model can well simulate the variations of the HPDs, with a correlation coefficient(CC) of 0.81(0.65) between the observed and predicted HPDs＿DY(HPDs＿anomaly). The percentage with the same sign for 15 extreme HPDs＿anomaly years(PSSE) is 100%.Moreover, in the cross-validation test during 1982–2022, the PSSE for HPDs＿anomaly is as high as 100%, along with a low rootmean-square error of 1.14. For independent hindcasts during 2013–2022, the CC between the observed and predicted HPDs＿DY(HPDs＿anomaly) is 0.93(0.83), together with high Nash-Sutcliffe efficiency(0.82) and agreement index(0.89). Specifically, the predictions are broadly consistent with the observations for 2015, 2016, 2017, 2021, and 2022, reflecting excellent performance of this prediction model of HPDs in NC.

关键词： Heavy precipitation at North China Year-to-year increment approach Robust seasonal prediction Sea surface temperature Snow depth

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