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CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Oncology Research 2024年第2期32卷 261-272页

作者： SHUANGSHUANG ZENG xi chen QIAOLI YI ABHIMANYU THAKUR HUI YANG YUANLIANG YAN SHAO LIU Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha410008China Pritzker School of Molecular Engineering Ben May Department for Cancer ResearchUniversity of ChicagoChicagoILUSA Department of Pathology The Second Affiliated Hospital of Shandong First Medical UniversityTaian271000China

Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.

关键词： CRABP2 Melanoma PD-1 Cancer-associated fibroblasts Immune infiltration

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Recent advances in electrocatalytic generation of indole-derived radical cations and their applications in organic synthesis

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Chinese Chemical Letters 2024年第4期35卷 106-123页

作者： Wei Zhou xi chen Lin Lu xian-Rong Song Mu-Jia Luo Qiang xiao Key Laboratory of Organic Chemistry of Jiangxi Province Jiangxi Science&Technology Normal UniversityNanchang 330013China

Indole-derived radical cations, open-shell reactive species, display distinctive dual reactivity due to the carbon-centered radical and more electrophilic carbocation, which frequently appear in a variety of single electron oxidation reactions for synthesizing structurally diverse functionalized indoles and indolines. Electrocatalysis is considered as a synthetically attractive and environmentally friendly alternative for driving the single electron oxidation of indoles. Remarkable achievements in electrocatalytic indolederived radical cation-mediated indole functionalization have been realized so far. This review comprehensively summarizes the recent progresses in the applications of electrocatalytic indole radical cations,including C(sp~2)–H functionalization, dearomative 2,3-difunctionalization, and ring-opening reaction, emphasizing the vital single electron oxidation steps of indoles, the substrates scope and limitations, and the reaction mechanisms.

关键词： Electrocatalysis Indole radical cation C-H functionalizatin Dearomative 2 3-difunctionalization

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A Single-Event-Transient Hardened Phase Locked Loop for Clock and Data Recovery

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Chinese Journal of Electronics 2024年第2期33卷 353-361页

作者： Hengzhou YUAN Bin LIANG Hao SANG Weixia XU Yang GUO xi chen National University of Defense Technology

A radiation-hardened phase-locked loop is proposed for phase interpolator clock and data recovery purposes. A sensitive node-compressed charge pump and multi-node cross coupling voltage-controlled oscillators are proposed in this phase-locked loop with the goal of achieving good jitter performance and improving anti-SET（SET,single-event transient） capability. The root mean square（RMS） jitter of the phase-locked loop is reduced from 3.7 ps to 2.58 ps at 2 GHz, while the laser threshold is improved from 120 p J to 370 p J compared to the unhardened phaselocked loop. The hardened phase-locked loop also does not lose its lock state from linear energy transfers（LETs） of 3.3 to 37.3 Me V·cm2/mg.

关键词： Phase-locked loop Clock data recovery Voltage-controlled oscillator Radiation-hardened Charge pump

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Ceria nanoparticles: biomedical applications and toxicity

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第5期25卷 361-388页

作者： xiaoxuan FU Peng LI xi chen Yuanyuan MA Rong WANG Wenxuan JI Jiakuo GU Bowen SHENG Yizhou WANG Zhuhong ZHANG School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University)Ministry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityYantai 264005China Department of Nephrology Yantai Yuhuangding HospitalQingdao UniversityYantai 264005China Institute of Crop Science College of Agriculture and BiotechnologyZhejiang UniversityHangzhou 310058China

Ceria nanoparticles(CeO_(2) NPs)have become popular materials in biomedical and industrial fields due to their potential applications in anti-oxidation,cancer therapy,photocatalytic degradation of pollutants,sensors,etc.Many methods,including gas phase,solid phase,liquid phase,and the newly proposed green synthesis method,have been reported for the synthesis of CeO_(2) NPs.Due to the wide application of CeO_(2) NPs,concerns about their adverse impacts on human health have been raised.This review covers recent studies on the biomedical applications of CeO_(2) NPs,including their use in the treatment of various diseases(e.g.,Alzheimer's disease,ischemic stroke,retinal damage,chronic inflammation,and cancer).CeO_(2) NP toxicity is discussed in terms of the different systems of the human body(e.g.,cytotoxicity,genotoxicity,respiratory toxicity,neurotoxicity,and hepatotoxicity).This comprehensive review covers both fundamental discoveries and exploratory progress in CeO_(2) NP research that may lead to practical developments in the future.

关键词： Ceria nanoparticle Synthetic method Biomedical application Oxidative stress Toxicity

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Bone tissue engineering scaffold materials: Fundamentals, advances, and challenges

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Chinese Chemical Letters 2024年第2期35卷 176-186页

作者： Chang Xu Zhize Liu xi chen Yang Gao Wenjun Wang xijing Zhuang Hao Zhang Xufeng Dong Department of Cardiovascular Surgery Central Hospital of Dalian University of TechnologyDalian 116089China School of Materials Science and Engineering Dalian University of TechnologyDalian 116024China Department of Orthopaedics Central Hospital of Dalian University of TechnologyDalian 116089China Department of Dermatology Allergologyand VenereologyUniversity of LübeckLübeck 23562Germany

Bone damage caused by trauma and tumors is a serious problem for human health, therefore, three-dimensional (3D) scaffolding materials that stimulate and promote the regeneration of broken bone tissues have become the focus of current research in the field of bone damage repair.To this regard, a preferential combination of materials and preparation techniques is considered crucial for the preparation of advanced bone tissue engineering scaffolds to better facilitate the regeneration of broken bone.In this review, current research advances and challenges in bone tissue engineering scaffolds are discussed and analyzed in detail.First, we elucidated the structure and self-healing mechanism of bone tissue.Subsequently, the main applications of different materials, including inorganic and organic materials, in bone tissue engineering scaffolds are summarized.Moreover, we overview the latest research progress of the mainstream preparation strategies of bone tissue engineering scaffolds, and provide an in-depth analysis of the different advantages of each method.Finally, promising future directions and challenges of bone tissue engineering scaffolds are systematically discussed.

关键词： Biomaterials Bone defects Tissue engineering Scaffolds Osteogenesis

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Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1637-1650页

作者： Yuanliang Yan Shangjun Zhou xi chen Qiaoli Yi Songshan Feng Zijin Zhao Yuanhong Liu Qiuju Liang Zhijie Xu Zhi Li Lunquan Sun Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangsha 410008China Department of Pathology Xiangya HospitalCentral South UniversityChangsha 410008China xiangya Cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Molecular Radiation Oncology Hunan Province Changsha 410008China institute of Cancer Research National Clinical Research Center for Geriatric Disorders(Xiangya)Xiangya HospitalCentral South UniversityChangsha 410008China

Temozolomide(TMZ)represents a standard-of-care chemotherapeutic agent in glioblastoma(GBM).However,the development of drug resistance constitutes a significant hurdle in the treatment of malignant glioma.Although specific innovative approaches,such as immunotherapy,have shown favorable clinical outcomes,the inherent invasiveness of most gliomas continues to make them challenging to treat.Consequently,there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug development.This investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors.A total of 648 proteins exhibiting significant differential expression were identified.Gene Set Enrichment Analysis(GSEA)unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OxiDATIONS between the primary and recurrent groups.Validation through glioma tissue arrays and the xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate(IP3)kinase B(ITPKB)in the recurrence group,correlating with poor survival in glioma patients.In TMZ-resistant cells,the depletion of ITPKB led to an increase in reactive oxygen species(ROS)related to NADPH oxidase(NOX)activity and restored cell sensitivity to TMz.Mechanistically,the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ubiquitination.This,in turn,elevated ITPKB stability and impaired ROS production.Furthermore,ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse model.These findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target forTMZ-resistant GBM.

关键词： TMZ homeostasis impaired

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A four-band index for both liquid and solid water and its applications in the Aral Sea Basin

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Science China Earth Sciences 2024年第3期67卷 769-788页

作者： Bing YUE xi chen Saibo LI Zhengping DU John WILSON Junhui YANG Yimen JIAO Shuangyan HUANG chenghu ZHOU xinjiang Institute of Ecology and Geography Chinese Academy of SciencesUrumqi 830011China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China Institute of Geographical Sciences and Natural Resources Research Chinese Academy of SciencesBeijing 100101China Spatial Sciences Institute University of Southern CaliforniaLos AngelesCA 90089-0374USA

Various investigations have been conducted to analyze the water-coverage area of the Aral Sea and the Aral Sea Basin(ASB). However, the investigations incorporated considerable uncertainty and the used water indices had misclassification problem, which made different research groups present different results. Thus we first ascertain the boundaries of the ASB, the Syr and Amu river basins as well as their upper, middle and lower reaches. Then a four-band index for both liquid and solid water(ILSW) is proposed to address the misclassification problems of the classic water indices. ILSW is calculated by using the reflectance values of the green, red, near infrared, and thermal infrared bands, which combines the normalized difference water index(NDWI) and land surface temperature(LST) together. Validation results show that the ILSW water index has the highest accuracy by far in the Aral Sea Basin. Our results indicate that annual average decline of the water-coverage area was 963 km^(2) in the southern Aral Sea, whereas the northern Aral Sea has experienced little change. In the meanwhile, permanent ice and snow in upper reach of ASB has retreated considerably. Annual retreating rates of the permanent ice and snow were respectively 6233and 3841 km^(2) in upper reaches of Amu river basin(UARB) and Syr river basin(USRB). One of major reasons is that climate has become warmer in ASB. The climate change has caused serious water deficit problem. The water deficit had an increasing trend since the 1990s and its increasing rates was 3.778 billion m^(3) yearly on average. The total water deficit was 76.967 billion m^(3) on average in the whole area of ASB in the 2010s. However, up reaches of Syr river basin(USRB), a component area of ASB, had water surplus of 25.461 billion m^(3). These conclusions are useful for setting out a sustainable development strategy in ASB.

关键词： Aral Sea Basin Syr river basin Amu river basin Water indices Water-coverage area Water deficit Climate change

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Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

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Zoological Research 2024年第1期45卷 108-124页

作者： Huanpeng Lu Jinwei Chai Zijian Xu Jiena Wu Songzhe He Hang Liao Peng Huang xiaowen Huang xi chen Haishan Jiang Shaogang Qu Xueqing Xu Department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence GuangzhouGuangdong 510515China Key Laboratory of Mental Health of the Ministry of Education Southern Medical UniversityGuangzhouGuangdong 510515China Department of Dermatology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Neurology Ganzhou Hospital-Nanfang HospitalSouthern Medical UniversityGanzhouJiangxi 341001China

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for Cath-KP.In vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant properties.Using the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway activation.Both focal adhesion kinase(FAK)and p38 were also identified as regulatory elements.In the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated dyskinesia.To the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress.These findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

关键词： Cath-KP Peptide Parkinson’s disease Oxidative stress Neuroprotection

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A potential giant gallium deposit hosted in the tailing dam of the Fankou Zn-Pb deposit in northern Guangdong Province, South China

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China Geology 2024年第1期7卷 157-160页

作者： Peng-peng Yu Zhao-bin Hu Yi Zheng Lan-xuan Guo Shi-yuan Ouyang Gui-qiang Yuan Shang-zhou chen cheng-ming Wang xi chen School of Earth Sciences and Geological Engineering Sun Yat-sen UniversityGuangzhou 510275China Guangdong Provincial Key Lab of Geological Process and Mineral Resources Survey Sun Yat-sen UniversityGuangzhou 510275China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519000China Zhongjin Lingnan Nonfemet Co. LtdShenzhen 518000China

1.Objective The Fankou giant zinc(Zn)-lead(Pb)deposit in Guangdong Province is well-known for its huge reserves of over 10 Mt(million ton)Zn+Pb metals and high ore-grade with Zn+Pb exceeding 15%(Guangdong Fankou Deposit Investigation Group,1980;Zhu XY et al.,2017).After 60 years of exploration and exploitation,the deposit has accumulated millions of tons of tailings.One interesting question is that what components are hosted in these tailings,and whether some key and critical metals such as gallium and germanium are extremely enriched and worth further comprehensive utilization.This motivated us to conduct an integrated set of field investigation,sampling,major-trace element analyses and reserve assessments about the Fankou tailings.In this contribution,we discover that the tailings contain a variety of metal elements such as zinc,lead and gallium with comprehensive utilization potential.These data can act as a scientific guidance for further exploration and utilization of the Fankou tailings,and aid to enhance the utilization efficiency of the key mineral resource in China.Our study also provide demonstration for future green mine construction in China.

关键词： deposit comprehensive Guangdong

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Clinical application of reserved gastric tube in neuroendoscopic endonasal surgery for pituitary tumor

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World Journal of Clinical Oncology 2024年第3期15卷 411-418页

作者： xi chen Long-Yao Zhang Zhi-Feng Wang Yi Zhang Yu-Hua Yin Xue-Jian Wang Department of Nursing Affiliated Hospital 2 of Nantong UniversityNantong 226000Jiangsu ProvinceChina Department of Neurosurgery Affiliated Hospital 2 of Nantong UniversityNantong 226000Jiangsu ProvinceChina Department of Neurosurgery Renji HospitalShanghai Jiao Tong UniversityShanghai 226000China

BACKGROUND The neuroendoscopic approach has the advantages of a clear operative field,convenient tumor removal,and less damage,and is the development direction of modern neurosurgery.At present,transnasal surgery for sphenoidal pituitary tumor is widely used.But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts.AIM To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors.METHODS A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups,with 30 in each group.Experimental group:After anesthesia,a gastric tube was placed through the mouth under direct vision using a visual laryngoscope,and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection,during the operation,and when the patient recovered from anesthesia.Control group:Given the routine intraoperative care,no gastric tube was left.The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups;the scores of pharyngalgia after waking up,6 h post-operation,and 24 h postoperation.The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared.The hospitalization days of the two groups were statistically compared.RESULTS The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group,and the difference in the incidence of nausea was statistically significant(P<0.05).After the patient woke up,the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group,and the difference was statistically significant(P<0.05).The number of cases of postoperative cerebrospinal fluid leakage and intracran

关键词： Neuroendoscopy Endonasal approach Pituitary tumor Reserved gastric tube Nausea Vomiting Aspiration Complications

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