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Light-triggered nitric oxide release and structure transformation of peptide for enhanced intratumoral retention and sensitized photodynamic therapy

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Bioactive Materials 2022年第6期7卷 303-313页

作者： Lingdong Jiang Danyang Chen Zhaokui Jin Chao Xia Qingqing Xu Mingjian Fan Yunlu Dai Jia Liu Yuanpei Li Qianjun He Marshall Laboratory of Biomedical Engineering School of Biomedical EngineeringHealth Science CenterShenzhen UniversityNo.1066 Xueyuan AvenueShenzhen518060GuangdongChina Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Optoelectronic EngineeringShenzhen UniversityShenzhen518060GuangdongChina Central Laboratory Longgang District People’s Hospital of Shenzhen&The Third Affiliated Hospital(Provisional)of The Chinese University of Hong KongShenzhen518172GuangdongChina Department of Biochemistry and Molecular Medicine UC Davis Comprehensive Cancer CenterUniversity of California DavisSacramentoCA95817USA Cancer Centre and Institute of Translational Medicine Faculty of Health SciencesUniversity of MacaoMacao SAR999078China

Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects.Unfortunately,nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical requirements.In this work,we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide(NO)release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy(PDT).The designed nanoparticle is self-assembled from a chimeric peptide monomer,TPP-RRRKLVFFK-Ce6,which contains a photosensitive moiety(chlorin e6,Ce6),aβ-sheet-forming peptide domain(Lys-Leu-Val-Phe-Phe,KLVFF),an oligoarginine domain(RRR)as NO donor and a triphenylphosphonium(TPP)moiety for targeting mitochondria.When irradiated by light,the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod,enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light irradiation.More importantly,the conversion of generated NO and reactive oxygen species(ROS)in a light-responsive way to peroxynitrite anions(ONOO􀀀)with higher cytotoxicity enables NO to sensitize PDT in cancer treatment.Both in vitro and in vivo studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors efficiently.The light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome.

关键词： Nitric oxide Photodynamic therapy Structural transformation Peptide Enhanced intratumoral retention Nanomedicine

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续写中国化马克思主义文艺理论评论新篇章

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中国文艺评论 2022年第6期 13-16页

作者：夏潮中国文艺评论家协会

从毛泽东同志《在延安文艺座谈会上的讲话》到习近平总书记关于文艺工作重要论述,是跨世纪的理论接力,是马克思主义文艺理论中国化道路上的里程碑。推进新时代文艺繁荣发展,必须坚持马克思主义文艺理论指导地位,坚持人民至上,坚持把文... 详细信息

从毛泽东同志《在延安文艺座谈会上的讲话》到习近平总书记关于文艺工作重要论述,是跨世纪的理论接力,是马克思主义文艺理论中国化道路上的里程碑。推进新时代文艺繁荣发展,必须坚持马克思主义文艺理论指导地位,坚持人民至上,坚持把文艺评论作为党领导文艺工作的重要手段,续写中国化马克思主义文艺理论新篇章。

关键词：毛泽东《讲话》中国化马克思主义文艺理论文艺评论

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Polyphenols Extracted from Enteromorpha clathrata Induce Apoptosis in Hepa1-6 Cell by Activating the Mitochondrial Apoptosis Signaling Pathways

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中国海洋大学学报:英文版 2023年第5期22卷 1393-1402页

作者： ZHANG Panxue SUN Bolun TONG Jingjing xia Geran ZHANG Jinjie LI chao YANG Wenge College of Food and Pharmaceutical Sciences Ningbo UniversityNingbo 315211China Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province Ningbo UniversityNingbo 315211China

Green alga Enteromorpha clathrata(E.clathrata)contains a variety of bioactive compounds,including polysaccharides,polyphenols and fat-soluble pigments etc.,among which polyphenols exhibit a wide range of medicinal properties.E.clathrata polyphenols(ECPs)have shown various biological activities such as antioxidant,anti-inflammatory and antidiabetic effects;however,the potential of ECPs as an anti-cancer reagent remains unclear.The aim of this study was to investigate the anti-tumor activity and underlying mechanisms of ECPs on hepatocellular carcinoma.The cytotoxicity of Hepa1-6 cells was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and lactate dehydrogenase(LDH)assay.Flow cytometry and fluorescence microscope analysis of cell apoptosis after annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining.2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)assay was used for intracellular reactive oxygen species(ROS)detection.caspase-9 activity was determined using cspase-9 colorimetric assay.Mitochondrial transmembrane potential(Δψm)was measured using JC-1.Western blot and quantitative real-time PCR(qPCR)were used to assess the expressions of the apoptosis regulators Bax,Bcl-2,cytochrome c and caspase-3.It was found that ECPs showed a dose-dependent cytotoxicity against Hepa1-6 cells by inducing apoptosis.The apoptosis in ECPs-treated Hepa1-6 cells was accompanied by the loss of mitochondrial membrane potential,elevated ROS generation,increased release of mitochondrial cytochrome c,and up-regulation of caspase-9 and caspase-3.The expressions of Bax(pro-apoptotic molecule)and Bcl-2(apoptosis suppressor)were up-regulated and down-regulated,respectively,at both mRNA and protein levels.These molecular alterations revealed that ECPs caused apoptosis of cells through the mitochondrial pathway,suggesting that ECPs are potential candidates to be developed for liver cancer treatment.

关键词： Enteromorpha clathrate polyphenol anti-cancer activity apoptosis mitochondrial-dependent pathway

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One-pot calcination synthesis of Cd_(0.5)Zn_(0.5)S/g-C_(3)N_(4) photocatalyst with a step-scheme heterojunction structure

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Journal of Materials Science & Technology 2020年第21期56卷 206-215页

作者： Dongran Qin Yang xia Qin Li chao Yang Yanmin Qin Kangle Lv Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education&Hubei Key Laboratory of Catalysis and Materials Science South-Central University for NationalitiesWuhan 430074China

Cd_(0.5)Zn_(0.5)S/g-C_(3)N_(4)(CZS/CN)step-like heterojunction composites were facilely synthesized by annealing a sandwich of cadmium-zinc-thiourea precursors in one pot.The types of the used raw materials and the preparation procedure were simplified as much as possible in this work.The obtained hybrid exhibited enlarged specific surface area and higher separation/transfer efficiency of charge carriers compared to pure Cd_(0.5)Zn_(0.5)S and g–C_(3)N_(4),thus exhibited much enhanced photocatalytic efficiency for dye degradation under visible-light irradiation.The interfacial charge-transfer mechanism of the formed step-scheme(Sscheme)heterojunction between Cd_(0.5)Zn_(0.5)S and g–C_(3)N_(4) were carefully investigated and discussed.This work could widen the application prospect of the Cd_(x)Zn_(1-x)S/g-C_(3)N_(4) composite and provide new ideas to the design and fabrication of novel heterojunctions with robust photocatalytic performance.

关键词： Cd_(0.5)Zn_(0.5)S g-C_(3)N_(4) S-scheme heterojunction Photocatalysis Visible light

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开辟马克思主义文艺理论新境界

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中国文艺评论 2022年第1期 35-37页

作者：夏潮中国文艺评论家协会

习近平总书记在中国文联十一大、中国作协十大开幕式上的重要讲话,与党的十八大以来习近平总书记关于文艺工作的一系列重要讲话精神一脉相承,进一步回答了新时代新阶段事关社会主义文艺繁荣发展的根本性、基础性、战略性问题,为铸就中... 详细信息

习近平总书记在中国文联十一大、中国作协十大开幕式上的重要讲话,与党的十八大以来习近平总书记关于文艺工作的一系列重要讲话精神一脉相承,进一步回答了新时代新阶段事关社会主义文艺繁荣发展的根本性、基础性、战略性问题,为铸就中华民族伟大复兴时代文艺新高峰提供了根本遵循。

关键词：中国作协中国文联战略性问题十一大时代文艺文艺繁荣根本遵循习近平总书记

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Electrochemical synthesis of functionalized gem-difluoroalkenes with diverse alkyl sources via a defluorinative alkylation process

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Organic Chemistry Frontiers 2022年第1期9卷 95-101页

作者： Haoxiang Zhang Mengze Liang xiao Zhang Meng-Ke He chao Yang Lin Guo Wujiong xia State Key Lab of Urban Water Resource and Environment School of ScienceHarbin Institute of Technology(Shenzhen)Shenzhen518055China Wenzhou University WenzhouZhejiang 325000China School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiangHenan 453007China

An electrochemical defluorinative alkylation protocol ofα-trifluoromethyl alkenes is described.This reaction enables the preparation of functionalized gem-difluoroalkenes with the use of diverse alkyl sources including organohalides,N-hydroxyphthalimide(NHP)esters and Katritzky salts.This method exhibits lots of synthetic advantages including mild conditions,simple operation,and convenience of amplification,and provides a new route for the synthesis of gem-difluoroalkenes。

关键词： synthesis alkyl alkylation

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Apolipoprotein E2 inhibits mitochondrial apoptosis in pancreatic cancer cells through ERK1/2/CREB/BCL-2 signaling

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Hepatobiliary & Pancreatic Diseases International 2023年第2期22卷 179-189页

作者： Hui Wang Hui-chao Zhou Run-Ling Ren Shao-xia Du Zhong-Kui Guo xiao-Hong Shen Tianjin Institute of Medical&Pharmaceutical Sciences Tianjin 300020China School of Medicine Nankai UniversityTianjin 300071China

Background: Apolipoprotein E2(ApoE2) is a pleiotropic protein that influences several aspects of cancer metabolism and development. Evading apoptosis is a vital factor for facilitating cancer cell growth. However, the role and mechanism of ApoE2 in regulating cell apoptosis of pancreatic cancer remain unclear. Methods: In this study, we firstly detected the m RNA and protein expressions of ApoE2 in PANC-1 and Capan-2 cells by real-time polymerase chain reaction and Western blotting. We then performed TUNEL and flow cytometric analyses to explore the role of recombinant human ApoE2, p CMV6-ApoE2 and si ApoE2 in the apoptosis of PANC-1 and Capan-2 cells. Furthermore, we investigated the molecular mechanism through which ApoE2 affected apoptosis in PANC-1 cells using immunofluorescence, immunoprecipitation, Western blotting and co-immunoprecipitation analysis. Results: ApoE2 phosphorylated ERK1/2 and inhibited pancreatic cancer cell apoptosis. In addition, our data showed that ApoE2/ERK1/2 altered the expression and mitochondrial localization of BCL-2 via activating CREB. ApoE2/ERK1/2/CREB also increased the total BCL-2/BAX ratio, inhibited the opening of the mitochondrial permeability transition pore and the depolarization of mitochondrial transmembrane potential, blocked the leakage of cytochrome-c and the formation of the apoptosome, and consequently, suppressed mitochondrial apoptosis. Conclusions: ApoE2 regulates the mitochondrial localization and expression of BCL-2 through the activation of the ERK1/2/CREB signaling cascade to evade the mitochondrial apoptosis of pancreatic cancer cells. ApoE2 may be a distinct prognostic marker and a potential therapeutic target for pancreatic cancer.

关键词： Apolipoprotein E2 ERK1/2 Mitochondrial apoptosis Pancreatic cancer

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Huangqin Decoction Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via Inhibiting TNF-α-Induced NF-κB Activation

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Chinese Journal of Integrative Medicine 2022年第2期28卷 124-129页

作者： GU Li-mei LI Hui xia Jun-quan PAN Cheng-yu GU chao TIAN Yao-zhou Gastroenterology Department Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing(210028)China Gastroenterology Department Jiangsu Province Hospital on Integration of Chinese and Western MedicineNanjing(210028)China Jiangsu Province Academy of Traditional Chinese Medicine Nanjing(210028)China

Objective:To investigate the protective effect of Chinese herbal formula Huangqin Decoction(HQD)on ulcerative colitis mouse model induced by dextran sulphate sodium(DSS)and human intestinal epithelial cell injury induced by tumour necrosis factor-α(TNF-α).Methods:In vivo,30 male C57BL/6 mice were divided into 5 groups using a random number table(n=6 per group),including control,DSS,5-aminosalicylic acid(5-ASA),HQD low-(HQD-L)and high-dose(HQD-H)groups.The colitis mouse model was established by 3%(w/v)DSS water for 5 days.Meanwhile,mice in the HQD-L,HQD-H and 5-ASA groups were administrated with 100,200 mg/kg HQD or 100 mg/kg 5-ASA,respectively,once daily by gavage.After 9 days of administration,the body weight,disease activity index(DAI)score and colon length of mice were measured,the pathological changes of colons were analyzed by hematoxylin-eosin staining(HE)staining,and the levels of serum interleukin(IL)-6,IL-1βand TNF-αwere measured by enzyme linked immunosorbent assay.In vitro,the human colon epithelial normal cells(FHC cells)were exposed to HQD(0.6 mg/mL)for 12 h and then treated with TNF-α(10 ng/mL)for 24 h.The tight junction(TJ)protein expression levels of Claudin-4 and Occludin,and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB(NF-κB)-α(IκBα)were measured by Western blot.Results:In vivo,compared with the DSS group,HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day(P<0.05).Moreover,HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice(P<0.05).HE staining showed HQD attenuated the pathological changes of colitis mice,and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group(P<0.05).Meanwhile,HQD-H and 5-ASA significantly decreased the serum IL-1β,IL-6 and TNF-αlevels of mice(P<0.05).In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBαlevels in FHC cells compared with the TNF-αgroup(P<0.

关键词： Huangqin Decoction ulcerative colitis tumour necrosis factor-α nuclear factor kappaB pathway tight conjunction protein Chinese medicine

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Dynamical nonlinear excitations induced by interaction quench in a two-dimensional box-trapped Bose-Einstein condensate

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Chinese Physics B 2024年第2期33卷 209-215页

作者：牛真霞高超 Department of Physics Zhejiang Normal UniversityJinhua 321004China Key Laboratory of Optical Information Detection and Display Technology of Zhejiang Zhejiang Normal UniversityJinhua 321004China

Manipulating nonlinear excitations,including solitons and vortices,is an essential topic in quantum many-body physics.A new progress in this direction is a protocol proposed in[Phys.Rev.Res.2043256(2020)]to produce dark solitons in a one-dimensional atomic Bose–Einstein condensate(BEC)by quenching inter-atomic interaction.Motivated by this work,we generalize the protocol to a two-dimensional BEC and investigate the generic scenario of its post-quench dynamics.For an isotropic disk trap with a hard-wall boundary,we find that successive inward-moving ring dark solitons(RDSs)can be induced from the edge,and the number of RDSs can be controlled by tuning the ratio of the after-and before-quench interaction strength across different critical values.The role of the quench played on the profiles of the density,phase,and sound velocity is also investigated.Due to the snake instability,the RDSs then become vortex–antivortex pairs with peculiar dynamics managed by the initial density and the after-quench interaction.By tuning the geometry of the box traps,demonstrated as polygonal ones,more subtle dynamics of solitons and vortices are enabled.Our proposed protocol and the discovered rich dynamical effects on nonlinear excitations can be realized in near future cold-atom experiments.

关键词： Bose-Einstein condensate quench interaction soliton vortex

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Dual emission of singlet and triplet states boost the sensitivity of pressure-sensing

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Chinese Chemical Letters 2021年第9期32卷 2869-2872页

作者： Xingyu Cui xia Xing Xinrui Wang Wenying Shi chao Lua State Key Laboratory of Chemical Resource Engineering Beijing University of Chemical TechnologyBeijing 100029China Key Laboratory of Cosmetic China National Light IndustryBeijing Technology and Business UniversityBeijing 100048China

Pressure-related sensing materials in mechanochromic luminescent materials have received wide attention.However,at present,most piezochromic luminescence(PCL)materials have problems such as aggregation-caused quenching(ACQ)effect due to the presence of powder form,complicated preparation methods and fluorescence quenching effect under high pressure.To solve these problems,we employ three components containing carbon dots(CDs),layered double hydroxides(LDHs)and polyvinyl alcohol(PVA)to construct the CDs-LDHs/PVA film.The LDHs can provide a rigid environment for CDs and improve the luminescent efficiency of CDs.The film shows high sensitivity,stability and reversibility.Moreover,the compressed film can recover to its original state by heating.Therefore,the PCL film with dual emission(fluorescence and phosphorescence)characteristic is constructed,which boosts the sensitivity of pressure-sensing.

关键词： Layered double hydroxides Carbon dots Composite film Dual emission Pressure-sensing

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