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Recombinant adeno-associated virus 8 vector in gene therapy:Opportunities and challenges

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Genes & Diseases 2024年第1期11卷 283-293页

作者： Liyuan Zhao Zixuan Yang Minhui Zheng Lei Shi Mengyun Gu Gang Liu Feng Miao Yan Chang Fanghua Huang Naping Tang Anhui University of Traditional Chinese medicine HefeiAnhui 230000China Yangtze Delta Drug Advanced Research Institute Yangtze Delta Pharmaceutical CollegeNantongJiangsu226133China Shanghai Innostar bio-Technology Co. LtdChina State Institute of Pharmaceutical IndustryShanghai 201203China Innostar bio-tech Nantong Co. Ltd.NantongJiangsu 226133China Center for Drug Evaluation National Medical Products AdministrationBeijing 100022China

In recent years,significant breakthroughs have been made in the field of gene ***-associated virus(AAV)is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of *** the AAV vectors,AAV serotype 8(AAv8)has attracted much attention for its efficient and stable gene transfection into specific ***,recombinant AAv8 has been widely used in gene therapy research on a va-riety of diseases,including genetic diseases,cancers,autoimmune diseases,and viral diseases.

关键词： AAV8 Adeno-associated virus Gene therapy Primates

Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

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Journal of Pharmaceutical Analysis 2024年第2期14卷 177-195页

作者： Haochen Hui Zhuoya Wang Xuerong Zhao Lina Xu Lianhong Yin Feifei Wang Liping Qu Jinyong Peng Department of Pharmaceutical Analysis College of PharmacyDalian Medical UniversityDalianLiaoning116044China Innovation Materials Research and Development Center Botanee Research InstituteYunnan Botanee Bio-technology Group Co.Ltd.Kunming650106China Department of Traditional Chinese medicine Pharmacology School of PharmacyAnhui University of Chinese MedicineHefei230012China

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is *** acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and *** results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism *** transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model *** conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against *** is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

关键词： Gut microbiota Inflammatory bowel disease Polysaccharide Selaginella uncinata(Desv.)Spring Thiamine metabolism

Molecular mechanism of exopolysaccharide biosynthesis regulated by wze and wzd genes on the immunomodulatory effects of probiotic Lacticaseibacillus paracasei S-NB

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Food Science and Human Wellness 2024年

作者： Luyao Xiao Qian Yang Changliang Zhang Kai Ma Xiaogan Zhao Xin Rui Wei Li Jiangsu biodep biotechnology Co.， ltd. Jiangsu New-bio biotechnology Co.， ltd. Sanya Institute of Nanjing Agricultural University， College of Food Science and Technology， Nanjing Agricultural University

The surface macromolecules of probiotic bacteria play crucial roles in modulating immune responses in the host. Exopolysaccharide (EPS) from lactic acid bacteria (LAB) have been widely reported to exhibit immunomodulatory activity. In this study， the EPS biosynthesis gene cluster of Lacticaseibacillus paracasei S-NB was analyzed and a deletion mutant S-NB△7576 (two genes S-NB＿2175/wze and S-NB＿2176/wzd were responsible for the chain length determination and export of EPS) was successfully constructed， resulting a 40.02% decrease in the production of EPS. The deletion of wze and wzd had little effect on the monosaccharide composition and major groups of the two EPS fractions (BEPS1 and BEPS2). Both BEPS1 and BEPS2 could inhibit the transcriptional level of tumor necrosis factor-α (TNF-α)， interleukin-1β (IL-1β)， inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA in RAW 264.7 cells induced by lipopolysaccharide (LPS)， and enhance host immune tolerance via suppressing NF-κB and MAPK signaling. Notably， the S-NB△7576 mutant supplied with the BEPS1/BEPS2 exhibited more significant inhibition of cytokines production and the phosphorylation of p65 and c-Jun N-terminal kinase (JNK) in LPS-stimulated cells compared with the S-NB△7576 mutant alone. Our study provided the immunomodulatory effect of BEPS1 and BEPS2 from L. paracasei S-NB， in which the wze and wzd genes associated with EPS biosynthesis may play an important role.

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Evaluation of Anti-Wrinkle, Relieving Effect and Safety of A Group of Hexapeptide Compounds

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China Detergent & Cosmetics 2024年第3期9卷 56-61页

作者： Huang Jia He Xingxing Zhao Yue Ma Xiaoyu Lu Chaogang Li Xiang Shaanxi HuiKang bio-Tech Co. Ltd.China

The anti-wrinkle,relieving effect and safety of a group of hexapeptide compounds(HCs)were evaluated by in vitro antioxidant test,hyaluronidase inhibition test and human clinical *** results showed that HCs possess+high overall antioxidant activity,and the scavenging activity of ABTS•radical and DPPH radical by 4 mg/mL HCs solution were(92.23±1.15)%and(90.24±1.25)%.The scavenging activity of PTIO radical by 80 mg/mL HCs solution was(80.29±2.41)%.The inhibition rate of 80 mg/mL HCs on hyaluronidase was(75.00±6.13)%.The test of clinical results showed that the HCs have good anti-wrinkle and relieving effect,and no case of grade 1 or above skin adverse reactions occurred,indicating that HCs have good safety.

关键词： hexapeptide compounds anti-wrinkle relieving effect antioxidant activity safety

A novel insight of enhancing the hydrogen peroxide tolerance of unspecific peroxygenase from Daldinia caldariorum based on structure

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Chinese Chemical Letters 2024年第4期35卷 426-430页

作者： Tiantian Li Ruochen Jin Bin Wu Dongming Lan Yunjian Ma Yonghua Wang School of Food Science and Engineering South China University of TechnologyGuangzhou 510640China School of bioscience and bioengineering South China University of TechnologyGuangzhou 510006China Guangdong Youmei Institute of Intelligent bio-manufacturing Co. Ltd.Foshan 528200China

Unspecific peroxygenases(UPOs, EC 1.***.2.1) is a kind of thioheme enzyme capable of catalyzing various oxidations of inert C–H bonds using H_(2)O_(2) as an oxygen donor without cofactors. However, the enhancement of the H_(2)O_(2) tolerance of UPOs is always challenging. In this study, the A161C mutant of r Dca UPO,which originates from Daldinia caldariorum, was found to be highly H_(2)O_(2)-resistant. Compared with the wild type, the mutant r Dca UPO-A161C showed a 10-h prolonged half-life and a 64% improved enzyme activity when incubated in 10 mmol/L H_(2)O_(2). The crystal structure analysis at 1.47 A showed that r Dca UPOA161C exhibited 10 α-helixes(cyan) and a series of ordered rings, forming a single asymmetric spherical structure. The two conserved domains near heme formed an active site with the catalytic PCP and EHD regions(Glu86, His87, Asp88 residues). The H_(2)O_(2) tolerance of r Dca UPO-A161C was preliminarily explored by comparing its structure with the wild type. Notably, r Dca UPO-A161C showed significantly higher catalytic efficiency than the wild type for the production of hydroxyl fatty acids. This study is anticipated to provide an insight into the structure-function relationship and expand potential applications of UPOs.

关键词： Unspecific peroxygenase Molecular modification Hydrogen peroxide stability Crystal structure Hydroxyl fatty acids

Unique double-layer solid electrolyte interphase formed with fluorinated ether-based electrolytes for high-voltage lithium metal batteries

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Journal of Energy Chemistry 2024年第1期88卷 532-542,I0012页

作者： Ruo Wang Jiawei Li Bing Han Qingrong Wang Ruohong Ke Tong Zhang Xiaohu Ao Guangzhao Zhang Zhongbo Liu Yunxian Qian Fangfang Pan Iseult Lynch Jun Wang Yonghong Deng Department of Materials Science&Engineering School of Innovation and EntrepreneurshipSouthern University of Science and TechnologyShenzhen 518055GuangdongChina School of Geography Earth and Environmental SciencesUniversity of BirminghamEdgbastonBirmingham B152TTUK Key Laboratory of Marine Environmental Corrosion and bio-Fouling Institute of OceanologyChinese Academy of SciencesQingdao 266071ShandongChina Shenzhen CAPCHEM Technology Co. Ltd.Shenzhen 518118GuangdongChina CALB Group Co. Ltd.Changzhou 213200JiangsuChina

Li metal batteries using high-voltage layered oxides cathodes are of particular interest due to their high energy ***,they suffer from short lifespan and extreme safety concerns,which are attributed to the degradation of layered oxides and the decomposition of electrolyte at high voltage,as well as the high reactivity of metallic *** key is the development of stable electrolytes against both highvoltage cathodes and Li with the formation of robust interphase films on the ***,we report a highly fluorinated ether,1,1,1-trifluoro-2-[(2,2,2-trifluoroethoxy)methoxy]ethane(TTME),as a cosolvent,which not only functions as a diluent forming a localized high concentration electrolyte(LHCE),but also participates in the construction of the inner solvation *** TTME-based electrolyte is stable itself at high voltage and induces the formation of a unique double-layer solid electrolyte interphase(SEI)film,which is embodied as one layer rich in crystalline structural components for enhanced mechanical strength and another amorphous layer with a higher concentration of organic components for enhanced *** Li||Cu cells display a noticeably high Coulombic efficiency of 99.28%after 300 cycles and Li symmetric cells maintain stable cycling more than 3200 h at 0.5 mA/cm^(2) and 1.0m Ah/cm^(2).In addition,lithium metal cells using LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2) and Li CoO_(2) cathodes(both loadings~3.0 m Ah/cm^(2))realize capacity retentions of>85%over 240 cycles with a charge cut-off voltage of 4.4 V and 90%for 170 cycles with a charge cut-off voltage of 4.5 V,*** study offers a bifunctional ether-based electrolyte solvent beneficial for high-voltage Li metal batteries.

关键词： Lithium metal batteries High-voltage layered oxides Fluorinated ether-based electrolytes Solid electrolyte interphase Cathode electrolyte interphase

Sensory Evaluation of Freeze-Dried Facial Mask and Analysis of User Profile

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China Detergent & Cosmetics 2024年第3期9卷 41-49页

作者： Qi Rong Chu LiLing Wang Feifei Yunnan Botanee bio-technology Group Co. Ltd.China Yunnan Yunke Characteristic Plant Extraction Laboratory Co. Ltd.China

To thoroughly understand market opportunity of freeze-dried facial mask and deeply get insight of consumers’usage behavior and needs,evaluate sensory feelings of 10 screened commercial freeze-dried facial mask products,group test products according to the differences of sensory attributions via Principal Component Analysis(PCA)and Agglomerative Hierarchical Clustering(AHC),pick up the representative ***-dried facial mask users evaluate satisfaction degree of picked up products and participate survey of usage behavior/*** consumer data by AHC to get consumer segmentations and their *** test results show that,sensory data and consumer data,which is from consumers test of screened representative products by performing PCA and AHC on sensory data,can be verified *** is helpful to understand the needs of consumer segmentations and reason to buy by combining sensory data and consumer test.

关键词： freeze-dried facial mask sensory evaluation consumer satisfaction evaluation PCA AHC user profile

Synthesizing active and durable cubic ceria catalysts(<6 nm)for fast dehydrogenation of bio-polyols to carboxylic acids coproducing green H_(2)

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Green Energy & Environment 2024年第3期9卷 529-543页

作者： Mengyuan Liu Puhua Sun Guangyu Zhang Xin Jin Chaohe Yang Honghong Shan State Key Laboratory of Heavy Oil Processing College of Chemical EngineeringChina University of PetroleumNo.66 Changjiang West RoadQingdaoShandong266580China SINOPEC Research Institute of Safety Engineering Co. Ltd.No.339 Songling RoadQingdaoShandong266000China

Dehydrogenation is considered as one of the most important industrial applications for renewable *** ceria-based catalysts are known to display promising dehydrogenation performances in this *** particle size(>20 nm)and less surface defects,however,hinder further application of ceria ***,an alternative strategy involving lactic acid(LA)assisted hydrothermal method was developed to synthesize active,selective and durable cubic ceria ofbio-derived polyols at 200℃.We also found that quenching Vo defects at air atmosphere causes activity loss of PtCo/CeO_(2) *** regenerate Vo defects,a simple strategy was developed by irradiating deactivated catalysts using hernia *** outcome of this work will provide new insights into manufacturing durable catalyst materials for aqueous phase dehydrogenation applications.

关键词： Cubic ceria Oxygen vacancy Dehydrogenation C-H bond activation

Study on Skin Care Efficacy of the Active Ingredients in Camellia Japonica Flowers at High and Low Altitudes

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China Detergent & Cosmetics 2024年第1期9卷 76-80页

作者： Cao Yimiao Gao Hongqi Gao Cong Deng Quanzhi R&D Center Shanghai Forest Cabin Bio-tech Co.Ltd.China

The active ingredients of Camellia japonica flowers(CJF)at high and low altitudes,as well as their skin care efficacy were *** dried red CJF at high and low altitudes were ultrasonically extracted with 70%ethanol,and these extracts were concentrated and then diluted to a constant *** content of total flavonoids,total polyphenols and total proteins was tested and *** addition,DPPH free radical scavenging,inhibition of the formation of advanced glycation end products,and inhibitory activity against elastase was measured to compare their skin care efficacy in anti-oxidation,anti-glycation,anti-wrinkling and *** results showed that,based on the dry weight of CJF,the content of total flavonoids and total proteins of the CJF at high altitude was approximately 1.5 times of the CJF at low altitude,while the content of total polyphenols was approximately 2.4 times that of the CJF at low *** skin care efficacy of CJF at high altitude was significantly better than that of the CJF at low *** work could provide theoretical basis for the selection and application of Camellia japonica flowers in the field of cosmetics.

关键词： camellia japonica flowers at high and low altitudes active ingredients skin care efficacy