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Harnessing innate immune pathways for therapeutic advancement in cancer

Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao lin Yuheng Liao Hui yang ying Mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer therapy.This pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal cells.Agonists targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical studies.However,to date,the clinical success of drugs targeting the innate immune pathway remains limited.Interestingly,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor progression.The uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate investigation.In this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell types.We propose that within the TME,the innate immune pathway exhibits multidimensional diversity.This diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling networks.The pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative pathways.Refining our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

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Revealing the stability origins of 596 days-humidity-stable semitransparentperovskite solar cells

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Journal of Energy Chemistry 2024年第7期94卷 208-216页

作者： Tian Chen ying yang Congtan Zhu Weihuang lin Qilin Dai Xueyi Guo School of Metallurgy and Environment Central South UniversityChangsha 410083HunanChina Department of Chemistry Physics and Atmospheric SciencesJackson State UniversityJacksonMS 39217USA

Hybrid organic-inorganic perovskites(HOIPs)hold promise in the field of optoelectronics due to their excellent photoelectric conversion efficiency.However,the ion migration and hygroscopicity of these perovskite solar cells need to be addressed.Here,we presented semitransparent perovskite solar cells(ST-PSCs)using hole transport layer(HTL)combined with polyaniline(PANI)to stabilize HTL/perovskite interface,achieving a humidity durability(RH,50%-90%)for 596 days(14304 h)without encapsulation.Moreover,the decrease in hydrolysis products(LiF)showed the interaction between PANI with the addi-tives in HTL dramatically inhibited the water uptake and corrosion on MAPbI_(3),layer.The PANI modified samples had a higher I/Pb ratio and lower trap state density,which indicated the passivation effect of PANI on the uncoordinated Pb^(2+)and iodine vacancies.Subsequently,PANI successfully stabilized the interface and perovskite by inhibiting the formation of Pb^(0) and Au migration as long period storage.This work presented an interfacial design to develop HOiP in air with high humidity stability.

关键词： HTL/perovskite interface Polyaniline-passivation Humidity-degradation mechanism lon migration

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Understanding Urban Vitality from the Economic and Human Activities Perspective:A Case Study of Chongqing,China

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Chinese Geographical Science 2024年第1期34卷 52-66页

作者： yang Fiona Fan lin Geng LEI Yubing WANG ying YI Zheng School of Geography and Planning Sun Yat-sen UniversityGuangzhou510006China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai519100China Chongqing Planning and Design Institute Chongqing401147China

The literature on urban vitality tends to focus on the built environment.This paper argues that some important processes in shaping vitality may be overlooked without examining the intensity and diversity of economic and human activities.Using newly developed spatial big data and adopting the methods of multi-indicator measurement and spatial analysis methods,we analyzed the pattern of urban vitality in Chongqing,a provincial city in western China and,on this basis,evaluated the creation and maintenance of urban vitality from the economic and human activities perspective.Our findings indicate that the impacts of economic and human activities are positive and significant.Among the three intensity and diversity indicators,economic intensity and population density show an effect on urban vitality stronger than that of economic diversity.However,economic diversity has the strongest superposition or interactive effect,and is thus an important foundation dynamic.The positive effect of population density on urban vitality is largely a result of Chongqing’s jobs-housing balance.The case of Chongqing highlights the importance of topographic features,historical inheritance,large-scale migration,and cultural activities in shaping the distinctive vitality pattern of a city.This study contends that the creation and maintenance of urban vitality can not be fully explained without incorporating the impacts of economic and human activities.It contributes to a comprehensive measurement of urban vitality and enriches its connotations.

关键词： urban vitality economic diversity economic intensity population density Chongqing,China

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Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors

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Biomedical and Environmental Sciences 2024年第2期37卷 133-145页

作者： LIU Xiao CAO ying lin Xiao Wan GAO Dan yang MIAO Hui Hui LI Tian Zuo Department of Anesthesiology Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers.Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples.Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively.“Pyruvate”“alpha-linolenic acid”and“2-oleoyl-1-palmitoy-snglycero-3-phosphocholine”are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine.Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

关键词： Metabolomic Postoperative delirium(POD) Mechanism Biological marker

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Normal sperm head morphometric reference valuesin fertile Asian males

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Asian Journal of Andrology 2024年第3期26卷 315-320页

作者： Ye-lin Jia ying-Bi Wu lin Yu Yan Zheng Ting-Ting yang Yan-Yun Wang Bin Zhou lin Zhang Fu-Ping Li Laboratory of Andrology West China Second University Hospital Human Sperm BankChengdu 610000China Laboratory of Molecular Translational Medicine Center for Translational MedicineChengdu 610061China Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University) Ministry of EducationChengdu 610061China NHC Key Laboratory of Chronobiology West China Second University HospitalSichuan UniversityChengdu 610000China

Sperm head morphology is crucial for male factor infertility diagnosis and assessment of male reproductive potential.Severalcriteria are available to analyze sperm head morphology,but they are limited by poor methodology comparability and populationapplicability.This study aimed to explore comprehensive and new normal morphometric reference values for spermatozoa heads infertile Asian males.An automated sperm morphology analysis system captured 23152 stained spermatozoa from confirmed fertilemales.Of these samples,1856 sperm head images were annotated by three experienced laboratory technicians as“normal”.Weemployed 14 novel morphometric features to describe sperm head size(head length,head width,length/width ratio,and girth),shape(ellipse intersection over union,girth intersection over union,short-axis symmetry,and long-axis symmetry),area(head,acrosome,postacrosomal areas,and acrosome area ratio),and degrees of acrosome and nuclear uniformity.This straight-forwardmethod for the morphometric analysis of sperm by accurate visual measurements is clinically applicable.The measured parameterspresent valuable information to establish morphometric reference intervals for normal sperm heads in fertile Asian males.Thepresented detailed measurement data will be valuable for interlaboratory comparisons and technician training.In vitro fertilizationand andrology laboratory technicians can use these parameters to perform objective morphology evaluation when assessing malefertilization potential.

关键词： fertile Asian males head morphometric reference value normal spermatozoa

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Identification and functional characterization of female antennae-biased odorant receptor 23 involved in acetophenone detection of the Indian meal moth Plodia interpunctella

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Insect Science 2024年第1期31卷 59-78页

作者： Qi Chen Xiaoyan Zhu Guoqing Kang Qiling Yu Qingxin Liu lin Du Yi yang Xinyu He ying Zhao Junjie Zhang ying Hu Bingzhong Ren Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization School of Life SciencesNortheast Normal UniversityChangchunChina Key Laboratory of Vegetation Ecology Ministry of EducationNortheast Normal UniversityChangchunChina Jilin Provincial Engineering Laboratory of Avian Ecology and Conservation Genetics Northeast Normal UniversityChangchunChina Engineering Research Center of Natural Enemies Institute of Biological ControlJilin Agricultural UniversityChangchunChina

The Indian meal moth,Plodia interpunctella(Lepidoptera:Pyralidae),a globally distributed storage pest,relies on odors that are emitted from stored foods to select a suitable substrate for oviposition.However,the molecular mechanism underlying the chemical communication between P.interpunctella and its host remains elusive.In this study,130 chemosensory genes were identified from the transcriptomes of 7 P.interpunctella tissues,and the quantitative expression levels of all 56 P.interpunctella odorant receptor genes(PintORs)were validated using real-time quantitative polymerase chain reaction.The functional characteristics of 5 PintORs with female antennae-biased expression were investigated using 2-electrode voltage clamp recordings in Xenopus laevis oocytes.PintOR23 was found to be specifically tuned to acetophenone.Acetophenone could elicit a significant electrophysiological response and only attracted mated females when compared with males and virgin females.In addition,molecular docking predicted that the hydrogen bonding sites,TRP-335 and ALA-167,might play key roles in the binding of PintOR23 to acetophenone.Our study provides valuable insights into the olfactory mechanism of oviposition substrate detection and localization in P.interpunctella and points toward the possibility of developing eco-friendly odorant agents to control pests of stored products.

关键词： acetophenone docking EAG odorant receptor Plodia interpunctella TEVC

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Construction of algal-bacterial consortia using green microalgae Chlorella vulgaris and As(Ⅲ)-oxidizing bacteria:As tolerance and metabolomic profiling

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Journal of Environmental Sciences 2024年第5期139卷 258-266页

作者： Xiaoman He Guobing lin Jiayuan Zeng Zhaoguang yang lin Wang College of Chemistry and Chemical Engineering Central South UniversityChangsha 410083China Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety Central South UniversityChangsha 410083China

Bioremediation became a promising technology to resolve arsenic(As)contamination in aquatic environment.Since monoculture such as microalgae or bacteria was sensitive to environmental disturbance and vulnerable to contamination,green microalgae Chlorella vulgaris and arsenite(As(Ⅲ))-oxidizing bacteria Pseudomonas sp.SMS11 were co-cultured to construct algal-bacterial consortia in the current study.The effects of algae-bacteria(A:B)ratio and exposure As(Ⅲ)concentration on algal growth,As speciation and metabolomic profile were investigated.Algal growth arrested when treated with 100 mg/L As(Ⅲ)without the co-cultured bacteria.By contrast,co-cultured with strain SMS11 significantly enhanced As tolerance in C.vulgaris especially with A:B ratio of 1:10.All the As(Ⅲ)in culture media of the consortia were oxidized into As(Ⅴ)on day 7.Methylation of As was observed on day 14.Over 1% and 0.5% of total As were converted into dimethylarsinic acid(DMA)after 21days cultivation when the initial concentrations of As(Ⅲ)were 1 and 10 mg/L,respectively.Metabolomic analysis was further performed to reveal the response of consortia metabolites to external As(Ⅲ).The enriched metabolomic pathways were associated with carbohydrate,amino acid and energy metabolisms.Tricarboxylic acid cycle and glyoxylate and dicarboxylate metabolism were upregulated under As stress due to their biological functions on alleviating oxidative stress and protecting cells.Both carbohydrate and amino acid metabolisms provided precursors and potential substrates for energy production and cell protection under abiotic stress.Alterations of the pathways relevant to carbohydrate or amino acid metabolism were triggered by energy requirement.

关键词： Microalgae Algal-bacterial consortia As(Ⅲ)-oxidizing bacteria Metabolomics Energy metabolism

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Associations between the use of red yeast rice preparations and adverse health outcomes:An umbrella review of meta-analyses of randomized controlled trials

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Journal of Integrative Medicine 2024年第2期22卷 126-136页

作者： Zhen-yu Ma Shu-ping yang ying Li Tian-tian Xu Ya-lin yang Hui-yong yang Heng-bing Li Le-jin Zhou Yong Diao Su-yun Li School of Medicine Huaqiao UniversityQuanzhou 362021Fujian ProvinceChina College of Traditional Chinese Medicine Shandong University of Traditional Chinese MedicineJinan 250355Shandong ProvinceChina Second Clinical Medical College Nanjing Medical UniversityNanjing 211166Jiangsu ProvinceChina

Background:Red yeast rice(RYR),a natural lipid-lowering agent,is widely used in clinical practice.However,the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results,and the credibility of the evidence has not been quantified.Objective:This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes.Search strategy:Seven literature databases were searched from inception to May 5,2023,using medical subject headings and free-text terms(e.g.,“red yeast rice,”“Xuezhikang,”and“Zhibitai”).Inclusion criteria:Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study.Data extraction and analysis:Two researchers independently extracted data using a standardized data collection table;any disagreements were resolved by consulting a third researcher.Based on the participant,intervention,comparator and outcome(PICO)framework in each eligible meta-analysis,a series of unique associations between the use of RYR preparations and adverse health outcomes were determined.The associations’effect estimates were re-evaluated using random-effect models.Results:Fifteen meta-analyses,comprising 186(164 unique)randomized controlled trials,were identified.Based on A Mea Surement Tool to Assess Systematic Reviews version 2,3(20%)and 12(80%)of these meta-analyses had low and critically low confidence,respectively.A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible metaanalyses.Based on the random-effect models,10(16.4%)associations indicated a significant protective effect of RYR preparations against adverse health outcomes,while 5(8.2%)indicated an increased risk of adverse health outcomes related to uric acid,alanine transaminase and aspartate transaminase levels.The other 46(75.4%)associations s

关键词： Red yeast rice Safety Adverse health outcomes Umbrella review Meta-analysis Systematic review

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Compatibility evaluation between waterborne epoxy resin and SBR latex modified asphalt emulsion

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第1期11卷 160-171页

作者： Jianhua yang Zhengqi Zhang ying Fang Key Laboratory for Special Area Highway Engineering of Ministry of Education Chang'an UniversityXi'an 710064China

Good compatibility between waterborne epoxy resin(WER)modifier and styrene-butadiene rubber(SBR)latex modified asphalt emulsion(SBRE)is an essential premise for good pavement performance of WER and SBR latex compositely modified asphalt emulsion(WSAE).This study aims to explore the compatibility between WER modifier and SBRE.To achieve the goal,several WER modifiers produced by two methods were first selected to modify SBRE,thus the WSAEs were prepared.Next,storage stability and workability of the WSAEs themselves,and high-temperature performance,rheological behavior and temperature sensitivity of their evaporated residues were compared and evaluated via performing a series of experiments,respectively,thus the WER modifier possessing an optimal modification effect was recommended.Results show that the storage stability of WSAEs is sensitive to the amount of WERs.The incorporation of 1%WERs by the mass of SBRE improves the storage stability of SBRE,while WERs that exceed 1%weaken its storage stability.When the WERs reach 3%and 4%,the 5 d storage stability of prepared WSAEs will be beyond the limitation of specification.Incorporating WERs into SBRE negatively affects the workability of SBRE,and the workability of WSAEs is adversely influenced by the WERs content and the storage time.To ensure the construction,the WSAEs with 3%and 4%WERs should not be stored for more than 36 h and 48 h,respectively.The WERs effectively improve the high-temperature performance of SBRE residue,especially the 3%WERs.Besides,the WERs notably enhance the rheological property and thermal stability of SBRE residue.In contrast,the WER modifier produced by chemically modified method has a smaller adverse impact on the storage stability and workability of WSAE,and a larger enhancement on the high-temperature performance,rheological property and thermal stability of SBRE residue,which is thus recommended to modify SBRE.

关键词： Waterborne epoxy resin SBR modified asphalt emulsion Workability Rheological property Temperature sensitivity Compatibility evaluation

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Application and mechanisms of Sanhua Decoction in the treatment of cerebral ischemia-reperfusion injury

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World Journal of Clinical Cases 2024年第4期12卷 688-699页

作者： Ya-Kuan Wang Huang lin Shu-Rui Wang Ru-Tao Bian yang Tong Wen-Tao Zhang ying-lin Cui Department of Encephalopathy The Second Clinical College of Henan University of Chinese MedicineZhengzhou 450000Henan ProvinceChina Department of Encephalopathy Henan Provincial Hospital of Integrated Chinese and Western MedicineZhengzhou 450000Henan ProvinceChina Department of Traditional Chinese Medicine Classics Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina Department of Central Laboratory Zhengzhou Traditional Chinese Medicine HospitalZhengzhou 450000Henan ProvinceChina Department of Encephalopathy Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina Famous Doctor Hall Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina

Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.

关键词： Sanhua Decoction Cerebral ischemia-reperfusion Mechanism of action Application progress Traditional Chinese medical science Review

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