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Chinese Journal of Chemistry 2024年第12期42卷 1399-1406页

作者： Yu Bao Zhi-Jie Song Jin-Long Dai Shenghu Yan Yue Zhang Jia-Yin Wang Guigen Li school of pharmacy Changzhou UniversityChangzhouJiangsu 213164China Department of Chemistry and Biochemistry Texas Tech University79409USA

Comprehensive Summary A general and convenient photoredox-catalyzed acylation and alkylcyanation of MBH acetates has been established,enabling the assembly of the C(sp2)–C(sp3)bond by a nitrogen-centered radical strategy for the synthesis of trisubstituted alkenes in moderate to excellent chemical yields(48 examples in total).The reaction of MBH acetates with acyl(indanone)oxime esters afforded trisubstituted alkenes containing 1,4-dicarbonyl ***,the use of Eosin Y as a photocatalyst in the catalytic system resulted in the formation of distal cyano group-anchored trisubstituted alkenes via deconstructive functionalization of cycloketone oxime ***,these resulting 1,4-dicarbonyl compounds could be applied to late-stage transformations,providing important methods for the synthesis of dihydropyridazin-3(2H)-one.

关键词： Photocatalysis Radical reactions MBH acetates Oxime esters Stereoselectivity Acylation Alkylation Green chemistry

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

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Neuroscience Bulletin 2024年第5期40卷 621-634页

作者： Xiuxiu Liu Ying Zhang Yanming Zhao Qian Zhang Feng Han Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases Ministry of EducationNanjing211166China International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjing211166China Institute of Brain Science The Affiliated Brain Hospital of Nanjing Medical UniversityNanjing211166China Gusu school Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou210019China

Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous *** pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous *** current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting *** this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic *** early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic *** this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

关键词： Epileptogenesis Neurovascular unit Molecular mechanisms Drug targets

Traditional Chinese Medicine in the treatment of recurrent respiratory tract infections in children: An overview of systematic reviews and Meta-analyses

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Journal of Traditional Chinese Medicine 2024年

作者： DENG Yasheng HAN Siyin XI Lanhua HUANG Hui LIANG Tianwei ZHENG Yiqing FAN Yanping LIN Jiang school of Basic Medical Sciences Guangxi University of Chinese Medicine school of Basic Medical Sciences Guangxi University of Chinese Medicine Guangxi Key Laboratory of Marine Drugs Department of pharmacy Hainan Traditional Chinese Medicine hospital

OBJECTIVE: To evaluate and summarise the evidence from published Meta-analyses/systematic reviews (MAs/SRs) of Traditional Chinese Medicine (TCM) in the treatment of recurrent respiratory tract infections (RRTIs) and to provide a scientific basis for the clinical treatment of RRTIs with ***: Studies were retrieved from Chinese and English databases including the China National Knowledge Infrastructure， Wanfang database， China Science and Technology Journal Database， SinoMed， PubMed， Web of Science， the Cochrane Library and EMbase from their establishment date to March 2023. Involved studies were screened， extracted， and evaluated for quality by two researchers independently. The a measurement tool to assess systematic reviews (AMSTAR) 2 scale was used for methodological quality evaluation， as well as the preferred reporting items for systematic reviews and Meta-analyses (PRISMA) 2020 statement for report quality evaluation， the risk of bias in systematic reviews (ROBIS) tool for risk of bias， and the grading of recommendations， assessment， development and evaluation (GRADE) quality assessment tool for evidence ***: Twenty MAs/SRs studies were included， including analyses of 274 original studies involving 38 335 patients with RRTIs. The AMSTAR 2 scale evaluation results showed that 19 studies were of very low quality and one of moderate quality. The ROBIS evaluation results showed that 11 MAs/SRs were at high risk and nine at low risk of bias. The PRISMA 2020 report quality showed the included studies had scores between 23.5 and 35.5， among them one with high quality， 17 with moderate quality and two with low quality. The GRADE system results showed that among 126 outcome indicators， only 17 had moderate quality of evidence， 27 had low quality， 82 had very low quality， and none had high ***: The MAs/SRs methodological quality of using TCM for treatment RRTIs is generally poor， the quality of reports as well as of evidence is genera

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Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

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Journal of Pharmaceutical Analysis 2024年第4期14卷 439-459页

作者： Lan Chen Yuan Zhang Yi-Xin Zhang Wei-Lai Wang De-Mei Sun Peng-Yun Li Xue-Song Feng Yue Tan school of pharmacy China Medical UniversityShenyang110122China Institute of Pharmacology and Toxicology Institution National Engineering Research Center for Strategic DrugsBeijing100850China Department of Gastroenterology Shengjing Hospital of China Medical UniversityShenyang110022China

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling ***,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse ***,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different *** paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since *** also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing *** addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

关键词： TKIs Microextraction technique HRMS methods Pharmacokinetic studies Therapeutic drug monitoring

Engineering nanomedicines for immunogenic eradication of cancer cells:Recent trends and synergistic approaches

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2475-2504页

作者： Ahmed O.Elzoghby Omar Samir Hagar E.Emam Ahmed Soliman Riham M.Abdelgalil Yomna M.Elmorshedy Kadria A.Elkhodairy Mahmoud L.Nasr Division of Engineering in Medicine and Division of Renal Medicine Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston 02115MAUSA Cancer Nanotechnology Research Laboratory(CNRL) Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune *** therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune ***,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic ***,we outline the current state of using nanomedicines for boosting ICD of cancer ***,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were *** further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune *** reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative *** challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

关键词： Immunogenic cell death Immunogenic eradication Nanomedicines Drug delivery Cancer immunotherapy Antitumor immunity T cells Tumor associated antigens Synergistic immune response

Inonotus obliquus(Chaga)against HFD/STZ-induced glucolipid metabolism disorders and abnormal renal functions by regulating NOS-cGMP-PDE5 signaling pathway

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Chinese Journal of Natural Medicines 2024年第7期22卷 619-631页

作者： FENG Yating LIU Jing GONG Le HAN Zhaodi ZHANG Yan LI Rongshan LIAO Hui school of pharmacy Shanxi Medical UniversityTaiyuan 030001China Drug Clinical Trial Institution The Fifth Hospital of Shanxi Medical University(Shanxi Provincial People’s Hospital)Taiyuan 030012China Department of Nephrology The Fifth Hospital of Shanxi Medical University(Shanxi Provincial People’s Hospital)Taiyuan 030012China

Our prior investigations have established that Inonotus obliquus(Chaga)possesses hypoglycemic *** hyperglycemia is known to precipitate renal function *** functionality of the kidneys is intricately linked to the levels of cyclic guanosine-3',5'-monophosphate(cGMP),which are influenced by the activities of nitric oxide synthase(NOS)and phosphodiesterase(PDE).Enhanced cGMP levels can be achieved either through the upregulation of NOS activity or the downregulation of PDE *** objective of the current study is to elucidate the effects of Chaga on disorders of glucolipid metabolism and renal abnormalities in rats with type 2 diabetes mellitus(T2DM),while concurrently examining the NOS-cGMP-PDE5 signaling pathway.A model of T2DM was developed in rats using a high-fat diet(HFD)combined with streptozotocin(STZ)administration,followed by treatment with Chaga extracts at doses of 50 and 100 mg·kg^(−1)for eight *** findings revealed that Chaga not only mitigated metabolic dysfunctions,evidenced by improvements in fasting blood glucose,total cholesterol,triglycerides,and insulin resistance,but also ameliorated renal function markers,including serum creatinine,urine creatinine(UCr),blood urea nitrogen,24-h urinary protein,and estimated creatinine ***,enhancements in glomerular volume,GBM thickness,podocyte foot process width(FPW),and the mRNA and protein expressions of podocyte markers,such as nephrin and wilms tumor-1,were *** was found to elevate cGMP levels in both serum and kidney tissues by increasing mRNA and protein expressions of renal endothelial NOS and neural NOS,while simultaneously reducing the expressions of renal inducible NOS and *** summary,Chaga counteracts HFD/STZ-induced glucolipid metabolism and renal function disturbances by modulating the NOS-cGMP-PDE5 signaling *** research supports the potential application of Chaga in the clinical prevention and treatment of T2DM and

关键词： Inonotus obliquus Diabetic nephropathy Glucolipid metabolism disorders Renal functions NOS-cGMP-PDE5 signaling

2-APQC,a small-molecule activator of Sirtuin-3(SIRT3),alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2748-2764页

作者： Fu Peng Minru Liao Wenke Jin Wei Liu Zixiang Li Zhichao Fan Ling Zou Siwei Chen Lingjuan Zhu Qian Zhao Gu Zhan Liang Ouyang Cheng Peng Bo Han Jin Zhang Leilei Fu West China school of pharmacy and Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese MedicineSchool of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China school of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China school of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Sirtuin 3(SIRT3)is well known as a conserved nicotinamide adenine dinucleotide^(+)(NAD^(+))-dependent deacetylase located in the mitochondria that may regulate oxidative stress,catabolism and ATP *** evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis,myocardial fibrosis and even heart failure(HF),through its deacetylation ***,discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently ***,we identified a new small-molecule activator of SIRT3(named 2-APQC)by the structure-based drug designing strategy.2-APQC was shown to alleviate isoproterenol(ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat ***,in SIRT3 knockout mice,2-APQC could not relieve HF,suggesting that 2-APQC is dependent on SIRT3 for its protective ***,2-APQC was found to inhibit the mammalian target of rapamycin(mTOR)-p70 ribosomal protein S6 kinase(p70S6K),c-jun N-terminal kinase(JNK)and transforming growth factor-β(TGF-β)/small mother against decapentaplegic 3(Smad3)pathways to improve ISO-induced cardiac hypertrophy and myocardial *** upon RNA-seq analyses,we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1(PYCR1)axis was closely assoiated with *** activating PYCR1,2-APQC was shown to enhance mitochondrial proline metabolism,inhibited reactive oxygen species(ROS)-p38 mitogen activated protein kinase(p38MAPK)pathway and thereby protecting against ISO-induced mitochondrialoxidative ***,activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase(AMPK)-Parkin axis to inhibit ISO-induced ***,our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis,which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

关键词： SIRT3 homeostasis metabolism

Bimolecular reduction of carbon dioxide: double synthons for alkynes trifunctionalization

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Science China Chemistry 2024年第3期67卷 841-847页

作者： Wenfang Xiong Xiaobin Tan Hongjian Liu Baiyao Zhu Jinwu Zhao Jianxiao Li Chaorong Qi Huanfeng Jiang school of pharmacy Guangdong Medical UniversityDongguan 523808China Key Lab of Functional Molecular Engineering of Guangdong Province School of Chemistry and Chemical EngineeringSouth China University of TechnologyGuangzhou 510640China

Carbon dioxide reduction, as a sustainable and versatile strategy for the access of chemical fuels, has attracted increasing attention and enormous efforts have been devoted to it in recent years. However, employing carbon dioxide as double synthons via bimolecular reduction remains challenging. Here, by leveraging the bimolecular reduction of carbon dioxide to carbonyl and methyl respectively, we describe a Pd-catalyzed trifunctionalization of alkynes with aryl iodide for the first time and showcase its advantages on the formation of various β-diketones and their application in the constructing of heterocyclic compounds with important biological activity, including pyrimidine, oxazole, pyrazole.

关键词： carbon dioxide bimolecular reduction trifunctionalization double synthons

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

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International Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 599-610页

作者： Yi Tian Zhiguang Fu Xiaosheng Zhu Chunjing Zhan Jinwei Hu Li Fan Chaojun Song Qian Yang Yu Wang Mei Shi Department of Radiation Oncology Xijing HospitalThe Fourth Military Medical UniversityXi’an 710032China Department of Oncology Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Tumor Radiotherapy Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Gastroenterology Air Force Hospital of Southern Theater CommandGuangzhou 510062China Department of Pharmaceutical Chemistry and Analysis School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China school of Life Sciences Northwestern Polytechnical UniversityXi’an 710072China Institue of Materia Medica School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration ***,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT *** address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet *** system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after *** immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were *** the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor ***-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,*** by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,***,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

关键词： X-ray excited photodynamic therapy singlet oxygen low dose X-Ray irradiation efficient antitumor therapy anti-tumor immunity

Identification prognostic features related to sphingolipid metabolism and experimental validation of TRIM47 in hepatocellular carcinoma

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BIOCELL 2024年第4期48卷 639-651页

作者： JIAN TANG CHENQIANG ZHU YUN CHEN YUNLONG WU MING HE YI ZHOU MINGHUA XIE Department of Intensive Care Unit The First People’s Hospital of Linping DistrictHangzhouChina Department of pharmacy The First People’s Hospital of Linping DistrictHangzhouChina

Background:The speciﬁc impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains *** study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug ***:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GSE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)*** classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were ***,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso *** expression of 8 risk genes was veriﬁed in ***:8 risk genes were used to construct the Sphingolipid score ***-Sphingolipid score predicted poor prognosis of HCC *** score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK *** the High-Sphingolipid score group,a signiﬁcantly higher proportion of patients with TP53(p53)mutations was signiﬁcantly higher(56%).Furthermore,patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy *** vitro validation showed that compared with normal liver cells LX-2,TRIM47,and S100A9 signiﬁcantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while SLC1A7,LPCAT1,and CFHR4 signiﬁcantly *** TRIM47 reduced the proliferation and promoted *** levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis ***:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk ***47 may affect the development of liver cancer by regulating the relevant indicators of

关键词： Hepatocellular carcinoma Sphingolipid metabolism TRIM47 Prognosis