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Management of locally advanced non-small cell lung cancer: State of the art and future directions

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Cancer Communications 2024年第1期44卷 23-46页

作者： Da Miao Jing Zhao Ying Han jiaqi Zhou Xiuzhen Li Ting Zhang wen Li Yang Xia Key Laboratory of Respiratory Disease of Zhejiang Province Department of Respiratory and Critical Care MedicineSecond Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiangP.R.China Department of Oncology Shaoxing Second HospitalShaoxingZhejiangP.R.China Department of Medical Oncology Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiangP.R.China Department of Chemoradiotherapy The Affiliated People’s Hospital of Ningbo UniversityNingboZhejiangP.R.China Key Discipline of Jiaxing Respiratory Medicine Construction Project Jiaxing Key Laboratory of Precision Treatment for Lung CancerAffiliated Hospital of Jiaxing UniversityJiaxingZhejiangP.R.China Department of Pathology Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiangP.R.China Department of Radiation Oncology Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiangP.R.China Cancer Center Zhejiang UniversityHangzhouZhejiangP.R.China

Lung cancer is the second most common and the deadliest type of cancer worldwide.Clinically,non-small cell lung cancer(NSCLC)is the most com-mon pathological type of lung cancer;approximately one-third of affected patients have locally advanced NSCLC(LA-NSCLC,stage III NSCLC)at diag-nosis.Because of its heterogeneity,LA-NSCLC often requires multidisciplinary assessment.Moreover,the prognosis of affected patients is much below satisfac-tion,and the efficacy of traditional therapeutic strategies has reached a plateau.With the emergence of targeted therapies and immunotherapies,as well as the continuous development of novel radiotherapies,we have entered an era of novel treatment paradigm for LA-NSCLC.Here,we reviewed the landscape of relevant therapeutic modalities,including adjuvant,neoadjuvant,and periop-erative targeted and immune strategies in patients with resectable LA-NSCLC with/without oncogenic alterations;as well as novel combinations of chemora-diation and immunotherapy/targeted therapy in unresectable LA-NSCLC.We addressed the unresolved challenges that remain in the field,and examined future directions to optimize clinical management and increase the cure rate of LA-NSCLC.

关键词： locally advanced non-small cell lung cancer neoadjuvant therapy adjuvant therapy immunotherapy targeted therapy

Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1711-1725页

作者： Yingting Wu jiaqi Xin Xinyu Li Ting Yang Yi Liu Yongsheng Zhao wen Xie Mengxi Jiang Department of Pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Department of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100069China

Drug repurposing offers an efficient approach to therapeutic development.In this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal ulcers.We went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in mice.Treatment with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy metabolism.Mechanistically,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent manner.Our results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor signaling.In summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.

关键词： Lansoprazole Proton pump inhibitors Adipose thermogenesis Energy expenditure Metabolic syndrome PHOSPHO1 inhibitor Cannabinoid receptor signaling Drug repurposing

Efficacy and safety of clarithromycin for patients with sepsis or septic shock:a systematic review and meta-analysis

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Emergency and Critical Care Medicine 2024年第2期4卷 90-96页

作者： Pengyue Zhao Renqi Yao jiaqi Yang Wei wen Yongming Yao Xiaohui Du Department of General Surgery First Medical Center of the Chinese PLA General HospitalBeijingChina Translational Medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General HospitalBeijingChina Department of Burn Surgery the First Affiliated Hospital of Naval Medical UniversityShanghaiChina Department of General Surgery Hainan Hospital of Chinese PLA General HospitalSanyaHainanChina.

Background:Clarithromycin exerts an immunomodulatory role in several human diseases.However,whether this effect improves the prognosis in patients with sepsis remains controversial,and higher levels of clinical evidence are urgently needed.To the best of our knowledge,no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in sepsis.Methods:A comprehensive literature search of PubMed,EMBASE,and the Cochrane Library was conducted up to December 31,2022.Only randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were included.Data were pooled by applying a fixed-effects model and a relative risk(RR)estimate with 95%confidence intervals(CIs)using Review Manager(version 5.3;Cochrane Collaboration,Copenhagen,Denmark).Results:Three randomized controlled trials involving a total of 910 patients were included.The pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome(RR:1.51;95%CI:1.02-2.25;P=0.04;I^(2)=0%),28-day mortality(RR:1.09;95%CI:0.87-1.36;P=0.46;I^(2)=0%),and 90-day mortality(RR:0.86;95%CI:0.71-1.03;P=0.10;I^(2)=81%)in patients with sepsis or septic shock.Moreover,there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group(RR:1.02;95%CI:0.87-1.19;P=0.83;I^(2)=18%).Conclusion:Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with clarithromycin.However,administration of clarithromycin did not increase the risk of adverse events.

关键词： Clarithromycin Meta-analysis Outcomes Sepsis Septic shock

Thermodynamic theory of flotation for a complex multiphase solid -liquid system and high-entropy flotation

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1177-1197页

作者： Shuming wen State Key Laboratory of Complex Nonferrous Metal Resources Clean Utilization Faculty of Land Resource EngineeringKunming University of Science and TechnologyKunming 650093China

The flotation of complex solid–liquid multiphase systems involve interactions among multiple components,the core problem facing flotation theory.Meanwhile,the combined use of multicomponent flotation reagents to improve mineral flotation has become an important issue in studies on the efficient use of refractory mineral resources.However,studying the flotation of complex solid–liquid systems is extremely difficult,and no systematic theory has been developed to date.In addition,the physical mechanism associated with combining reagents to improve the flotation effect has not been unified,which limits the development of flotation theory and the progress of flotation technology.In this study,we applied theoretical thermodynamics to a solid–liquid flotation system and used changes in the entropy and Gibbs free energy of the reagents adsorbed on the mineral surface to establish thermodynamic equilibrium equations that de-scribe interactions among various material components while also introducing adsorption equilibrium constants for the flotation reagents adsorbed on the mineral surface.The homogenization effect on the mineral surface in pulp solution was determined using the chemical potentials of the material components of the various mineral surfaces required to maintain balance.The flotation effect can be improved through synergy among multicomponent flotation reagents;its physical essence is the thermodynamic law that as the number of compon-ents of flotation reagents on the mineral surface increases,the surface adsorption entropy change increases,and the Gibbs free energy change of adsorption decreases.According to the results obtained using flotation thermodynamics theory,we established high-entropy flotation theory and a technical method in which increasing the types of flotation reagents adsorbed on the mineral surface,increasing the adsorption entropy change of the flotation reagents,decreasing the Gibbs free energy change,and improving the adsorption efficiency and stability of the flotation reagents improve

关键词： multicomponent flotation reagent adsorption entropy change equations of thermodynamic equilibrium adsorption equilibri-um constant high-entropy flotation

RSPSSL:A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization

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Light(Science & Applications) 2024年第2期13卷 366-386页

作者： jiaqi Hu Gina Jinna Chen Chenlong Xue Pei Liang Yanqun Xiang Chuanlun Zhang Xiaokeng Chi Guoying Liu Yanfang Ye Dongyu Cui De Zhang Xiaojun yu Hong Dang wen Zhang Junfan Chen Quan Tang Penglai Guo Ho-Pui Ho Yuchao Li Longqing Cong Perry Ping Shum State Key Laboratory of Optical Fiber and Cable Manufacture Technology Guangdong Key Laboratory of Integrated Optoelectronics IntellisenseDepartment of EEESouthern University of Science and TechnologyShenzhen 518055China College of Optical and Electronic Technology China Jiliang UniversityHangzhou 310018China Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhou 510060China Department of Ocean Science and Engineering Southern University of Science and TechnologyShenzhen 518055China Department of Nephrology Chaozhou People’s HospitalChaozhou 521011China Clinical Research Design Division Sun Yatsen Memorial HospitalGuangzhouGuangdong 510120China School of Automation Northwestern Polytechnical UniversityXi’anShaanxi 710072China Department of Biomedical Engineering The Chinese University of Hong KongHong KongChina Guangdong Provincial Key Laboratory of Nanophotonic Manipulation Institute of NanophotonicsJinan UniversityGuangzhou 511443China

Raman spectroscopy has tremendous potential for material analysis with its molecular fingerprinting capability in many branches of science and technology.It is also an emerging omics technique for metabolic profiling to shape precision medicine.However,precisely attributing vibration peaks coupled with specific environmental,instrumental,and specimen noise is problematic.Intelligent Raman spectral preprocessing to remove statistical bias noise and sample-related errors should provide a powerful tool for valuable information extraction.Here,we propose a novel Raman spectral preprocessing scheme based on self-supervised learning(RSPSSL)with high capacity and spectral fidelity.It can preprocess arbitrary Raman spectra without further training at a speed of~1900 spectra per second without human interference.The experimental data preprocessing trial demonstrated its excellent capacity and signal fidelity with an 88%reduction in root mean square error and a 60%reduction in infinite norm(L__(∞))compared to established techniques.With this advantage,it remarkably enhanced various biomedical applications with a 400%accuracy elevation(ΔAUC)in cancer diagnosis,an average 38%(few-shot)and 242%accuracy improvement in paraquat concentration prediction,and unsealed the chemical resolution of biomedical hyperspectral images,especially in the spectral fingerprint region.It precisely preprocessed various Raman spectra from different spectroscopy devices,laboratories,and diverse applications.This scheme will enable biomedical mechanism screening with the label-free volumetric molecular imaging tool on organism and disease metabolomics profiling with a scenario of high throughput,cross-device,various analyte complexity,and diverse applications.

关键词： spectral scheme resolution

Goal-Oriented Control Systems(GOCS):From HOW to WHAT

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 816-819页

作者： wen-Hua Chen the Department of Aeronautical and Automotive Engineering Loughborough UniversityLeicestershireLE113TUU.K.

Brief:New control theory is required to underpin safe design and deployment of future highly automated systems to deal with uncertain environments and complicated tasks,enabled by AI and other advanced technologies.Goal-Oriented Control Systems offer potential to transform the control system design from currently instructing a control system how to perform a task to specifying what is to be achieved.

关键词： automated instru system

Observation of gapless corner modes of photonic crystal slabs in synthetic translation dimensions

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Photonics Research 2024年第3期12卷 444-455页

作者： wen-JIN ZHANG HAO-CHANG MO wen-JIE CHEN XIAO-DONG CHEN JIAN-wen DONG School of Physics&State Key Laboratory of Optoelectronic Materials and Technologies Sun Yat-sen UniversityGuangzhou 510275China

Second-order topological photonic crystals support localized corner modes that deviate from the conventional bulk-edge correspondence.However,the frequency shift of corner modes spanning the photonic band gap has not been experimentally reported.Here,we observe the gapless corner modes of photonic crystal slabs within a parameter space by considering translation as an additional synthetic dimension.These corner modes,protected by topological pumping in synthetic translation dimensions,are found to exist independently of the specific corner configuration.The gapless corner modes are experimentally imaged via the near-field scanning measurement and validated numerically by full-wave simulations.We propose a topological rainbow with gradient translation,demonstrating the ability to extract and separate specific frequency components of light into different spatial locations.Our work contributes to the advancement of topological photonics and provides valuable insights into the exploration of gapless corner modes in synthetic dimensions.

关键词： translation dimensions corner

Modeling tuberous sclerosis complex with human induced pluripotent stem cells

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World Journal of Pediatrics 2024年第3期20卷 208-218页

作者： Weibo Niu Benjamin Siciliano Zhexing wen Department of Psychiatry and Behavioral Sciences Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA 30322USA The Graduate Program in Molecular and Systems Pharmacology Laney Graduate SchoolEmory UniversityAtlanta.GA 30322.USA Department of Cell Biology Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA30322USA Department of Neurology Emory University School of MedicineWhitehead Research Building 447.615 Michael StreetAtlantaGA 30322USA

Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of I:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and skin.Importantly,TSCis also associated with signicant neurological manifestations including epilepsy TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum disorder.Mutations in the TSCI or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling pathway.Animal models have been widely used to study the effect of TSCl/2 genes on the development and function of the brain.Despite considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSCl/2 mutations that are unique to human neurodevelopment.Data sources Literature reviews and research articles were published in PubMed-indexed journals.Results Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human brain.Conclusions In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.

关键词： Induced pluripotent stem cells Three-dimensional cultures Tuberous sclerosis complex Two-dimensional cultures

Isotopic insights on quantitative assessments of interaction of eco-hydrological processes in multi-scale karst watersheds

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International Soil and Water Conservation Research 2024年第1期12卷 156-170页

作者： Zhuo Hao Yang Gao Qingwen Zhang wen wen Agricultural Clean Watershed Research Group Institute of Environment and Sustainable Development in AgricultureCAASBeijing100081China Key Laboratory of Ecosystem Network Observation and Modeling Institute of Geographic Sciences and Natural Resources ResearchCASBeijing100101China School of Humanities and Social Sciences Beijing Institute of TechnologyBeijing100081China

The dynamics of hydrological processes and the storage mechanisms of karst water resources are the most important issues in karst hydrology.The impact of environmental changes on water quantity,and the evaluation and quantification of eco-hydrological processes remain poorly addressed.In this study,high-frequency continuous monitoring in multi-scale karst watersheds in Southwest China combined the approaches of water isotopes and the hybrid single-particle lagrangian integrated trajectory(HYSPLIT)model to identify the recharge mechanisms between atmospheric vapor,rainfall,surface water,and groundwater,and to reveal the interaction of eco-hydrological processes.The dominant moisture sources in Puding(PD)County were the Indian Ocean(43-69%)and local moisture(24-33%).Theδ^(18)O and deuterium excess(d-excess)values showed a positive correlation indicating that secondary or sub-cloud evaporation was prominent in the wet seasons.Karst water line-conditioned excess(lc-excess)indicated that karst water interacted with recent precipitation,groundwater,and evaporation across seasons.Owing to its specific hydrogeological structure,surface water and rainwater have a higher contribution rate to groundwater replenishment.The Chenqi stream replenished the Houzhai River mainly in the form of groundwater,with percentages ranging from 38.1 to 93.5%in the wet season,and 47.8-80.1%in the dry season.In the Houzhai outlet,surface water and groundwater interconverted frequently with a percentage of 45.6-49.1%.We believe this is the first systematic study to quantify the supply relationship between water vapor transport,rainfall,surface water and groundwater in the Chinese karst zone,making a significant move forward in the field of karst hydrological processes and improving the efficiency of water resource evaluation and management.

关键词： Stable isotope Moisture sources Water cycle Karst watersheds