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Harnessing bacteria for tumor therapy:Current advances and challenges

Chinese Chemical Letters 2024年第2期35卷 97-106页

作者： Lina guo Jinsong ding Wenhu Zhou Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Changsha Medical University Academician WorkstationChangsha 410219China Key Laboratory of Biological Nanotechnology of National Health Commission Changsha 410008China

After a century of standstill,bacteria-based tumor therapy has resurged recently benefiting from the revolution of tumor immunotherapy,which provides unique solutions to tackle the obstacles of traditional tumor treatments.Obligate and facultative anaerobes with active tropism can selectively colonize at tumor sites and suppress tumor growth via different mechanisms,serving as attractive tools for tumor treatment either as a monotherapy or combining with other therapies for synergistic anti-tumor effects.In this critical review,we introduce the recent advances of bacteria-based tumor therapy from the following aspects.First,the general properties of bacteria are reviewed emphasizing on their structural components related to tumor immunotherapy,and the main bacteria that have been used in tumor therapy are listed.Then,the benefits of bacteria for tumor therapy are illustrated,such as tumor targetability,deep penetration,and facile genetic engineering for attenuation,enhanced efficacy,as well as bioimaging.Next,anti-tumor mechanisms of bacteria are summarized,which refer to intrinsic tumoricidal activities,immune activation,bacteria metabolism,and their capability to regulate gut microbiota homeostasis.Moreover,bacteria could act as carriers to deliver various types of therapeutics to achieve combination therapy with improved efficacy.In addition,several challenges for anti-tumor applications of bacteria are discussed regarding the delivery,efficacy and safety issues,and potential solutions are also provided.Finally,the possible improvements and perspectives are discussed in the end,which provide a guideline for the design of advanced bacteria-based tumor therapeutics in the future.

关键词： Bacteria Tumor targeting Immunotherapy Combination therapy Genetic engineering Surface decoration

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Self-assembly multifunctional DNA tetrahedron for efficient elimination of antibiotic-resistant bacteria

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Aggregate 2024年第1期5卷 204-215页

作者： Tiantian Wu Yu fu Shuang guo Yanqiang Shi Yuxin Zhang Zhijin Fan Bin Yang Baoquan ding Yuhui Liao Molecular Diagnosis and Treatment Center for Infectious Diseases Dermatology HospitalSouthern Medical UniversityGuangzhouChina CAS Key Laboratory of Nanosystem and Hierarchical Fabrication CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina Longgang District Central Hospital of Shenzhen ShenzhenChina

Antibiotic resistance is a major challenge in the clinical treatment of bacterial infectious diseases.Herein,we constructed a multifunctional DNA nanoplatform as a versatile carrier for bacteria-specific delivery of clinical antibiotic ciprofloxacin(CIP)and classic nanoantibiotic silver nanoparticles(AgNP).In our rational design,CIP was efficiently loaded in the self-assembly double-bundle DNA tetrahedron through intercalation with DNA duplex,and single-strand DNA-modified AgNP was embedded in the cavity of the DNA tetrahedron through hybridization.With the site-specific assembly of targeting aptamer in the well-defined DNA tetrahedron,the bacteria-specific dual-antibiotic delivery system exhibited excellent combined bactericidal properties.With enhanced antibiotic accumulation through breaking the out membrane of bacteria,the antibiotic delivery system effectively inhibited biofilm formation and promoted the healing of infected wounds in vivo.This DNAbased antibiotic delivery system provides a promising strategy for the treatment of antibiotic-resistant infections.

关键词： antibiotic resistance anti-infection therapy biofilm DNA nanotechnology targeted delivery

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Evolution of copper species during heat treatment and its effect on CO oxidation reaction on CuCeZrO_(y) catalyst synthesized by a facile solvent-free route

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Journal of Rare Earths 2024年第4期42卷 660-667页

作者： Guangying fu Dongsen Mao Jun Yu Qiangsheng guo School of Chemical and Environmental Engineering Shanghai Institute of TechnologyShanghai21418 China The ZeoMat Group Qingdao Institute of Bioenergy and Bioprocess TechnologyCASQingdao26611China

Several ternary oxides CuCeZrO_(y)(CCZ)were synthesized by a facile grinding method followed by calcination at high temperatures,and used as catalysts for CO oxidation at low temperatures.The influences of calcination temperature(400-600℃)on the physicochemical properties of the assynthesized ternary oxides were investigated by thermogravimetric analysis/differential scanning calorimetry(TGA/DSC),X-ray diffraction(XRD),transmission electron microscopy(TEM),Raman,inductively coupled plasma-optical emission spectrometry(ICP-OES),N_(2) adsorption,H_(2)-temperature programmed reduction(H_(2)-TPR),and X-ray photoelectron spectroscopy(XPS)characterizations.The results show that the increase in calcination temperature from 400 to 500℃is conducive to the high dispersion of CuOx on catalyst surface and the incorporation of Cu species into the support to form the Cu-Ce-Zr-O solid solution.further raising of calcination temperature from 500 to 600℃,however,leads to the segregation of Cu species from the solid solution to aggregate on support surface and growth of highly dispersed CuOx nanoparticles.The highest catalytic activity is acquired over the CCZ calcined at 500℃,which can be ascribed to the largest contents of Cu+species and oxygen vacancies owing to the formation of the maximum amount of Cu-Ce-Zr-O solid solution.

关键词： CuCeZrO_(y)catalyst co oxidation Calcination temperature Grinding method Oxalate precursor Rare earths

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Bioactive Hydrogels with Pro-coagulation Effect for Hemostasis

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Chinese Journal of Chemistry 2024年第1期42卷 87-103,I0004页

作者： Quanshi guo Yihang ding Lisha Yu Zongrui Tong Zhengwei Mao MOE Key Laboratory of Macromolecular Synthesis and functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhouZhejiang 310058China Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310009China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province HangzhouZhejiang 310009China

Hemostatic hydrogels are widely applied for wound management of damaged tissues,traumatic wounds,and surgical incisions.Some hydrogels composed of bioactive components,including fibrin and thrombin,showed great promise in the clinic due to their good pro-coagulation effect.With the expanding knowledge of cascade reaction of blood coagulation and emerging bioactive substances,massive bioactive hydrogels consisting of peptides,hemocoagulase,polyphosphate(polyP),etc.,have been developed as effective hemostatic materials.Based on the coagulation process and mechanism,we summarize the role of reported bioactive hydrogels in hemostasis in this review.We conclude the key points in the coagulation process,including activation of coagulation factors,fibrinogen polymerization,etc.,then discuss how to design bioactive hydrogels to accelerate coagulation targeted to these points.Finally,we conclude the progress and propose a perspective of bioactive hydrogels with a pro-coagulation effect for hemostasis.

关键词： Hemostasis Biological activity Biomaterials Enzyme catalysis Composites

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Chemical Composition, Pharmacological Effects and Clinical Applications of Cinobufacini

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Chinese Journal of Integrative Medicine 2024年第4期30卷 366-378页

作者： ZUO Qian XU ding-qiao YUE Shi-jun fu Rui-jia TANG Yu-ping Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility Shaanxi University of Chinese MedicineXi'an(712046)China

Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor,with active ingredients of bufadienolides and indole alkaloids.With further research and clinical applications,it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells,promoting apoptosis,inhibiting formation of tumor neovascularization,reversing multidrug resistance,and regulating immune response;it also has the functions of relieving cancer pain and regulating immune function.In this paper,the chemical composition,pharmacological effects,clinical applications,and adverse reactions of cinobufacini are summarized.However,the extraction of monomer components of cinobufacini,the relationship between different mechanisms,and the causes of adverse reactions need to be further studied.Also,high-quality clinical studies should be conducted.

关键词： cinobufacini chemical composition Chinese medicine pharmacological effect clinical application adverse effect

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Improving mathematical model of burden distribution and correcting chute angle to cope with fluctuation of stock line

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Journal of Iron and Steel Research(International) 2024年第2期31卷 342-356页

作者： Jian-sheng Chen Wen-guo Liu Hao guo Wang ding Qing-guo Xue Jing-song Wang Hai-bin Zuo State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing100083China MCC Capital Engineering&Research Incorporation Limited Beijing100176China Hunan Valin Xiangtan Iron and Steel Co. Ltd.Xiangtan411101HunanChina

Accurate evaluations of the burden distribution are of critical importance to stabilize the operation of blast furnace.The mathematical model and discrete element method(DEM)are two attractive methods for predicting burden distribution.Based on DEM,the initial velocities of the pellet,sinter,and coke were calculated,and the velocity attenuations of the above three particles between the burden and the chute were analyzed.The initial velocity and velocity attenuation were applied to a mathematical model for improving the accuracy.Additionally,based on the improved model,a scheme for rectifying the chute angles was proposed to address the fluctuation of the stock line and maintain a stable burden distribution.The validity of the scheme was confirmed via a stable burden distribution under different stock lines.The mathematical model has been successfully applied to evaluate the online burden distribution and cope with the fluctuation of the stock line.

关键词： Burden distribution Mathematical model Discrete element method Velocity attenuation Stock line fluctuation

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mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion

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Acta Pharmaceutica Sinica B 2024年第2期14卷 808-820页

作者： Huan Wang Zhuxuan Jiang Zhiwei guo Gan Luo Tianhao ding Changyou Zhan Department of Pharmacology School of Basic Medical Sciences&Department of PharmacyShanghai Pudong HospitalFudan UniversityShanghai 200032China Department of Pharmaceutical Sciences School of PharmacyNaval Medical UniversityShanghai 200433China Shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghai 200032China

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities.Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B(MZB)cells.Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M(IgM),targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor(BCR)complex and block immune responses.The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens.Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies,which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions.Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies,and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

关键词： Membrane-bound IgM Anti-drugantibodies Bcell anergy Folic acid Marginal zoneBcells Bcell receptor Biologics Targeting

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Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis

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Chinese Medical Journal 2024年第2期137卷 162-171页

作者： Kaixiong Liu Qifu guo Ying ding Li Luo Jianchai Huang Qijie Zhang Department of Respiratory and Critical Care Medicine The First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350005China Department of Respiratory and Critical Care MedicineNational Regional Medical CenterBinhai Campus of The First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China Department of Neurology Fujian Institute of NeurologyThe First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350005China Department of NeurologyNational Regional Medical CenterBinhai Campus of The First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China

Background:Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis(ALS)have previously been reported.This study aimed to examine the microbiota in the nasal cavity of ALS.Methods:Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled.High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid(rDNA)gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa,predict function,and conduct correlation analysis between specific taxa and clinical features.Results:The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members.Genera Gaiella,Sphingomonas,Polaribacter_1,Lachnospiraceae_NK4A136_group,Klebsiella,and Alistipes were differentially enriched in ALS patients compared to controls.Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects(unweighted UniFrac P=0.001),while Linear discriminant analysis Effect Size(LEfSe)analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level,whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients.Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised(ALSFRS-R;r_(s)=0.349,P=0.020 and r_(s)=0.393,P=0.008),while Prevotella-9 and Bacteroides operational taxonomic units(OTUs)were positively associated with lung function(FVC)in ALS patients(r_(s)=0.304,P=0.045,and r_(s)=0.300,P=0.048,respectively).Prevotella-1 was positively correlated with white blood cell counts(WBC,r_(s)=0.347,P=0.021),neutrophil percentage(Neu%,r_(s)=0.428,P=0.004),and neutrophil-to-lymphocyte ratio(NLR,r_(s)=0.411,P=0.006),but negatively correlated with lymphocyte percentage(Lym%,r_(s)=-0.408,P=0.006).In contrast,Streptococcus was negatively associated with Neu%(r_(s)=-0.445,P=0.003)and NLR(r_(s)

关键词： Amyotrophic lateral sclerosis Nasal microbiota Dysbiosis Inflammation

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Probiotic cocktails accelerate baicalin metabolism in the ileum to modulate intestinal health in broiler chickens

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Journal of Animal Science and Biotechnology 2024年第2期15卷 779-794页

作者： Mingkun Gao Chaoyong Liao Jianyang fu Zhonghua Ning Zengpeng Lv Yuming guo State Key Laboratory of Animal Nutrition and Feeding College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China National Engineering Laboratory for Animal Breeding College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China

Background Baicalin and probiotic cocktails are promising feed additives with broad application prospects.While probiotic cocktails are known to enhance intestinal health,the potential synergistic impact of combining baicalin with probiotic cocktails on the gut health of broiler chickens remains largely unexplored.Therefore,this study aims to investigate the influence of the combined administration of baicalin and probiotic cocktails on the composition of ileal and cecal microbiota in broiler chickens to elucidate the underlying mechanisms responsible for the healthpromoting effects.Results A total of 3201-day-old male Arbor Acres broilers were divided into 4 groups,each with 8 replicates of 10 chicks per replicate.Over a period of 42 d,the birds were fed a basal diet or the same diet supplemented with 37.5 g/t baicalin(BC),1,000 g/t probiotic cocktails(PC),or a combination of both BC(37.5 g/t)and PC(1,000 g/t).The results demonstrated that BC+PC exhibited positive synergistic effects,enhancing intestinal morphology,immune function,and barrier function.This was evidenced by increased VH/CD ratio,sIgA levels,and upregulated expression of occludin and claudin-1(Pfurthermore,Flavonifractor positively correlated with chicken ileum crypt depth(P<0.05).While BC+PC had a limited effect on cecal microbiota structure,the PC group had a very similar microbial composition to BC+PC,suggesting that the effect of PC at the distal end of the gut overshadowed those of BC.Conclusions We demonstrated the synergistic enhancement of gut health regulation in broiler chickens by combining baicalin and probiotic cocktails.Probiotic cocktails enhanced the effects of baicalin and accelerated its metabolism in the ileum,thereby influencing the ileal

关键词： Baicalin Gut health Ileal microbiota Probiotic cocktails Synergistic effects

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Water–soluble and polarity–sensitive near–infrared fluorescent probe for long–time specific cancer cell membranes imaging and C. Elegans label

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Chinese Chemical Letters 2024年第4期35卷 321-323页

作者： Lixian fu Yiyun Tan Yue ding Weixia Qing Yong Wang Henan International Joint Laboratory of Medicinal Plants Utilization College of Chemistry and Molecular SciencesHenan UniversityKaifeng 475004China School of Basic Medical Science Henan UniversityKaifeng 475004China

A novel D–π –A structure and near–infrared fluorescent probe(DCITT) with high polarity sensitivity and membrane targeting was reported. The fluorescent spectra of DCITT were polarity dependent and Stokes shift was greater than 300 nm. Due to its high fluorescence quantum yield, low cytotoxicity and photostability, DCITT could be used as a labeling probe in multicellular organisms. In particular, DCITT effectively distinguished tumor cells from normal cells because it could specifically light up the cancer cells membrane based on strong red fluorescence for a long time. On this basis, a polar–sensitive cell membrane probe is developed to differentiate tumor cells from normal cells, which provides an idea and method for the early diagnosis of tumor at cellular level.

关键词： NIR–fluorescent probe Polarity–sensitive Bioimaging Targeting cell membrane Differentiate tumor and normal cells

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