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Mitochondria-targeted nano-AIEgens as a powerful inducer for evoking immunogenic cell death

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Chinese Chemical Letters 2024年第5期35卷 338-343页

作者： kun-Heng Li Hong-Yang Zhao Dan-Dan Wang Ming-hui Qi Zi-Jian Xu Jia-Mi Li Zhi-Li zhang Shi-Wen Huang Key Laboratory of Biomedical Polymers of Ministry of Education Department of ChemistryWuhan UniversityWuhan 430072China

AIEgens can serve as an effective platform for the construction of photosensitizer-based immunogenic cell death(ICD)*** date,several mitochondria or endoplasmic reticulum(ER)-targeted aggregationinduced emission(AIE)molecules have been developed and have evoked massive ICD in ***,due to the complex physicochemical environment in cells,these small AIE molecules cannot maintain a stable aggregate state,which not only affects the fluorescence intensity of the photosensitizer but also decreases the generation of reactive oxygen species(ROS),and thus reducing the effect of the photosensitizer to elicit ***-based nanomicelles,which maintain a stable micellar structure,can prevent defects of AIE molecules in photodynamic therapy(PDT)***,in this study,a mitochondria-targeted AIE nanophotosensitizer was synthesized and used as a highly potent ICD inducer for vaccine preparation and tumor prevention.

关键词： Aggregation induced emission Photodynamic therapy Immunogenic cell death Reactive oxygen species Nanophotosensitizer Mitochondria

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

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Oncology Research 2024年第6期32卷 1063-1078页

作者： kun FENG HAO PENG QINGPENG LV YEWEI zhang Hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Medical School Southeast UniversityNanjing210000China

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable *** dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment *** elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also ***,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of ***,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT *** findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer *** methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver ***,noteworthy associations were observed between PHLDA2 expression and immune infiltration in *** addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in *** vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy ***,we found that TGF-βinduced the expression of PHLDA2 in *** GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling *** study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

关键词： HCC Immune infiltration Drug resistance TME PHLDA2

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1564-1577页

作者： Sai-Nan Li Shan Yang Hao-Qi Wang Tian-Li hui Meng Cheng Xi zhang Bao-kun Li Gui-Ying Wang The First Department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina The Second Department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina Department of General Surgery The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality *** to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient *** noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain *** To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this *** Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin *** bioinformatics tools were employed to elucidate molecular *** expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain *** assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA *** between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream ***,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy *** LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)*** was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 *** expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing *** RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of *** PRNT/ZNF184

关键词： Colorectal cancer Oxaliplatin resistance Prion protein testis specific Zinc finger protein 184 Homeodomain interacting protein kinase 2

Semaphorin 3C (Sema3C) reshapes stromal microenvironment to promote hepatocellular carcinoma progression

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3429-3448页

作者： Hao Peng Meng Yang kun Feng Qingpeng Lv Yewei zhang Medical School Southeast UniversityNanjing 210009China Department of Ultrasound State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of MedicalSciencesPeking Union Medical CollegeBeijing 100730China Hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210009China

More than 90% of hepatocellular carcinoma(HCC)cases develop in the presence of fibrosis or cirrhosis,making the tumor microenvironment(TME)of HCC distinctive due to the intricate interplay between cancer-associated fibroblasts(CAFs)and cancer stem cells(CSCs),which collectively regulate HCC ***,the mechanisms through which CSCs orchestrate the dynamics of the tumor stroma during HCC development remain *** study unveils a significant upregulation of Sema3C in fibrotic liver,HCC tissues,peripheral blood of HCC patients,as well as sorafenib-resistant tissues and cells,with its overexpression correlating with the acquisition of stemness properties in *** further identify NRP1 and ITGB1 as pivotal functional receptors of Sema3C,activating downstream AKT/Gli1/c-Myc signaling pathways to bolster HCC self-renewal and tumor ***,HCCcells-derived Sema3Cfacilitated extracellular matrix(ECM)contraction and collagen deposition in vivo,while also promoting the proliferation and activation of hepatic stellate cells(HSCs).Mechanistically,Sema3C interacted with NRP1 and ITGB1 in HSCs,activating downstream NF-kB signaling,thereby stimulating the release of IL-6 and upregulating HMGCR expression,consequently enhancing cholesterol synthesis in ***,CAF-secreted TGF-β1 activates AP1 signaling to augment Sema3C expression in HCC cells,establishing a positive feedback loop that accelerates HCC ***,blockade of Sema3C effectively inhibits tumor growth and sensitizes HCC cells to sorafenib in *** sum,our findings spotlight Sema3C as a novel biomarker facilitating the crosstalk between CsCs and stroma during hepatocarcinogenesis,thereby offering a promising avenue for enhancing treatment efficacy and overcoming drug resistance in HCC.

关键词： Sema hepatocellular thereby

A comparison of the effect of alendronate and You-Gui-Wan on osteoporosis in female rats with kidney-yang deficiency

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Traditional Medicine Research 2024年第6期9卷 31-41页

作者： Mei-Mei wu Xing-Peng He Wan-Ting wu Wen-Jie Lu Yan-Yang Mai kun-Cai Xu Yao-Feng Zhi Hai-Xin Mo Jia-di He Xin zhang Peng-Fei Li Clinical Experimental Center Jiangmen Engineering Technology Research Center of Clinical Biobank and Translational ResearchJiangmen Central HospitalJiangmen 529030China Traumatic Orthopedics Baiyun Hospital of The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510470China Department of Intelligent Engineering Guiyang Institute of Information Science and TechnologyGuiyang 550025China

Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang ***,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with *** further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang ***:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN *** for the control group,osteoporosis was induced by the removal of bilateral *** 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 *** were treated with YGW or ALN for 12 *** weights of rats were ***-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of *** of the growth plate cartilage of rats in different groups was observed by safranine-O *** expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical *** expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection *** expression levels of the main indices of liver function(ALT and AST)were detected in different ***:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantl

关键词： osteoporosis kidney-yang deficiency You-Gui-Wan alendronate

Programmable repulsive potential for tight-binding from ChenM?bius inversion theorem

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Science China(Physics,Mechanics & Astronomy) 2024年第1期 75-87页

作者： Jian-Gao Li Jin-kun tang Hong-Quan Song Gotthard Seifert Dong-Bo zhang College of Nuclear Science and Technology Beijing Normal University Department of Physics Beijing Normal University College of Physics and Telecommunication Engineering Zhoukou Normal University Theoretische Chemie Technische Universit?t Dresden

An accurate total energy calculation is essential in materials computation. To date, many tight-binding(TB) approaches based on parameterized hopping can produce electronic structures comparable to those obtained using first-principles ***, TB approaches still have limited applicability for determining material properties derived from the total energy. That is, the predictive power of the TB total energy is impaired by an inaccurate evaluation of the repulsive energy. The complexity associated with the parametrization of TB repulsive potentials is the weak link in this evaluation. In this study, we propose a new method for obtaining the pairwise TB repulsive potential for crystalline materials by employing the Chen-M?bius inversion theorem. We show that the TB-based phonon dispersions, calculated using the resulting repulsive potential, compare well with those obtained by first-principles calculations for various systems, including covalent and ionic bulk materials and twodimensional materials. The present approach only requires the first-principles total energy and TB electronic band energy as input and does not involve any parameters. This striking feature enables us to generate repulsive potentials programmatically.

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Exploration of the Existence Forms and Patterns of dissolved Oxygen Molecules in Water

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Nano-Micro Letters 2024年第10期16卷 337-349页

作者： Hewei Yuan Yaozhong zhang Xiaolu Huang Xiwu zhang Jinjin Li Yufeng Huang kun Li Haotian Weng Yang Xu Yafei zhang Key Laboratory of Thin Film and Microfabrication(Ministry of Education) Department of Micro/Nano ElectronicsSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240People's Republic of China School of Materials Science and Engineering Shanghai Jiao Tong UniversityShanghai 200240People's Republic of China Jinduo Yuchen Water Environment Engineering Co. LtdShanghai 201702People's Republic of China

The structure of liquid water is primarily composed of three-dimensional networks of water clusters formed by hydrogen bonds,and dis-solved oxygen is one of the most important indicators for assessing water *** this work,distilled water with different concentration of dissolved oxygen were prepared,and a clear negative correlation between the size of water clus-ters and dissolved oxygen concentration was ***,a phenomenon of rapid absorption and release of oxygen at the water interfaces was unveiled,suggesting that oxygen molecules predominantly exist at the interfaces of water *** molecules can move rapidly through the interfaces among water clusters,allowing dissolved oxygen to quickly reach a saturation level at certain partial pressure of oxygen and *** exploration into the mechanism by molecular dynamics simulations of oxygen and water clusters found that oxygen molecules can only exist stably at the interfaces among water clusters.A semi-empirical formula relating the average number of water molecules in a cluster(n)to ^(17)O NMR half-peak width(W)was summarized:n=0.1 W+*** findings provide a foundation for exploring the structure and properties of water.

关键词： Water clusters dissolved oxygen ^(17)O NMR Molecular dynamics simulation

A continuous and long-term in-situ stress measuring method based on fiber optic. Part I: Theory of inverse differential strain analysis

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Petroleum Science 2024年第2期21卷 1171-1189页

作者： kun-Peng zhang Mian Chen Chang-Jun Zhao Su Wang Yong-Dong Fan State Key Laboratory of Petroleum Resources and Prospecting China University of PetroleumBeijing102249China MOE Key Laboratory of Petroleum Engineering in China University of Petroleum Beijing102249China Beijing International Center for Gas Hydrate School of Earth and Space SciencesPeking UniversityBeijing100871China

A method for in-situ stress measurement via fiber optics was proposed. The method utilizes the relationship between rock mass elastic parameters and in-situ stress. The approach offers the advantage of long-term stress measurements with high spatial resolution and frequency, significantly enhancing the ability to measure in-situ stress. The sensing casing, spirally wrapped with fiber optic, is cemented into the formation to establish a formation sensing nerve. Injecting fluid into the casing generates strain disturbance, establishing the relationship between rock mass properties and treatment ***, an optimization algorithm is established to invert the elastic parameters of formation via fiber optic strains. In the first part of this paper series, we established the theoretical basis for the inverse differential strain analysis method for in-situ stress measurement, which was subsequently verified using an analytical model. This paper is the fundamental basis for the inverse differential strain analysis method.

关键词： In-situ stress Fiber optic Orthotropic elastic differential evolution ABAQUS

High Temperature Deformation Behavior of Fe-9Ni-C Alloy

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Journal of Iron and Steel Research International 2012年第5期19卷 58-62页

作者： zhang kun wu hui-bin tang di Engineering Research Institute University of Science and Technology BeijingBeijing 100083China

The high temperature deformation behavior of the 9Ni steel has been studied by the Gleeble-3500 tester. The relationship between deformation resistance and deformation degree, deformation temperature and deformation rate was revealed. The results show that when the deformation degree is less than 0.2, the deformation resistance increases by about 70 to 200 MPa, while the deformation degree varied between 0.2 and 0.4, the deformation resist- ance increases by about 30--40 MPa, when the deformation degree is larger than 0.4, the deformation resistance in- creases slowly, some become stable gradually. The influence of deformation temperature on deformation resistance is larger, and deformation resistance at higher temperature is about 160 MPa smaller than at lower temperature. Higher deformation rate leads to larger deformation resistance. The deformation resistance increases about 70 to 110 MPa with the increase of the deformation rate. A new and highly accurate mathematical model of the steel was established to describe the deformation behavior during rolling.

关键词： 9Ni steel high temperature deformation resistance mathematical model