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| 1 | UHPLC-MS/MS analysis of cAMP and cGMP in rat plasma as potential biomarkers of Yin-Yang disharmony in traditional Chinese medicine显示文摘Cyclic 3’,5’-adenosine monophosphate(cAMP)and cyclic 3’,5’-guanosine monophosphate(cGMP)are considered as potential biomarkers for Yin-Yang disharmony in traditional Chinese medicine.However,phosphodiesterase-mediated ex vivo degradation of these molecules in biological samples may result in their underestimation.In the present study,a ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)method was developed for determination of cAMP and cGMP in rat plasma,with special consideration of their stability ex vivo.Following precipitation of proteins from plasma samples with 0.4 M perchloric acid,the analytes were chromatographed on a Shimadzu Shimpack-XR-ODS II column with 2.5 mM ammonium acetate and methanol in gradient mode.The MS/MS detection was performed using multiple reaction monitoring in the positive electrospray ionization mode.The lower limit of quantification was 0.27 ng/mL for cAMP and 0.37 ng/mL for cGMP.The method was used to determine the plasma cAMP and cGMP levels in normal and Yin deficiency diabetic rats treated with or without Rehmannia glutinosa.The developed method may be useful for evaluating the regulatory effects of Chinese herbal medicine on the levels of cAMP and cGMP in the body. | Xin Wang Yue Du Cuiting Wu Ming Xu Youping Liu Xin Di | 2021 | Journal of Pharmaceutical Analysis2021，11，4： | 3 |
| 2 | Spatiotemporal variations and determinants of stream nitrogen and phosphorus concentrations from a watershed in the Three Gorges Reservoir Area,China显示文摘Socioeconomic development induced nonpoint source(NPS)pollution has aroused an increasing concern,however,most of the previous studies were concentrated on the impacts of environmental determinants.Here,total nitrogen(TN)and total phosphorus(TP)concentrations from 13 sampling sites were collected biweekly from January 2018 to October 2021,and 26 potential factors including environmental and socioeconomic were considered in the Wangjiaqiao watershed of the Three Gorges Reservoir Area,China.Impacts of these factors on TN and TP were evaluated by partial least squares regression(PLSR)model.It showed that average TN and TP concentrations in wet seasons(TN,14.68 mg L^(-1):TP,0.113 mg L^(-1))were higher than that in dry seasons(TN,11.73 mg L^(-1);TP,0.087 mg L^(-1)).Additionally,the TN concentrations were greater in downstream than upstream,however,the highest TP concentrations were found in the middle of the watershed.The optimal PLSR model explained 69.6%,73.1%and 66.1%of the variance in TN concentration,as well as 65.7%,79.5%and 67.4%of the variance in TP concentration during the annual,dry and wet seasons,respectively.Moreover,TN was primarily influenced by topographic wetness index,planting structure,interspersion and juxtaposition index,orchard proportion,nitrogen fertilization,per capita income,and catchment area,whereas TP was mainly controlled by slope gradient,topographic wetness index,hypsometric integral,interspersion and juxtaposition index,and population density.Collectively,environmental factors had greater impacts on the TN and TP concentrations than socioeconomic factors.Raising farmers'awareness of the hazards of NPS pollution is beneficial to watershed NPS pollution control. | Jun Deng Yiwen Zhou Lin Chu Yujie Wei Zhaoxia Li Tianwei Wang Cuiting Dai | 2023 | International Soil and Water Conservation Research2023，11，3： | 0 |
| 3 | Expanding the Coverage of Metabolic Landscape in Cultivated Rice with Integrated Computational Approaches显示文摘Genome-scale metabolomics analysis is increasingly used for pathway and function discovery in the post-genomics era.The great potential offered by developed mass spectrometry(MS)-based technologies has been hindered,since only a small portion of detected metabolites were identifiable so far.To address the critical issue of low identification coverage in metabolomics,we adopted a deep metabolomics analysis strategy by integrating advanced algorithms and expanded reference databases.The experimental reference spectra and in silico reference spectra were adopted to facilitate the structural annotation.To further characterize the structure of metabolites,two approaches were incorporated into our strategy,i.e.,structural motif search combined with neutral loss scanning and metabolite association network.Untargeted metabolomics analysis was performed on 150 rice cultivars using ultra-performance liquid chromatography coupled with quadrupoleOrbitrap MS.Consequently,a total of 1939 out of 4491 metabolite features in the MS/MS spectral tag(MS2T)library were annotated,representing an extension of annotation coverage by an order of magnitude in rice.The differential accumulation patterns of flavonoids between indica and japonica cultivars were revealed,especially O-sulfated flavonoids.A series of closely-related flavonolignans were characterized,adding further evidence for the crucial role of tricin-oligolignols in lignification.Our study provides an important protocol for exploring phytochemical diversity in other plant species. | Xuetong Li Hongxia Zhou Ning Xiao Xueting Wu Yuanhong Shan Longxian Chen Cuiting Wang Zixuan Wang Jirong Huang Aihong Li Xuan Li | 2022 | Genomics, Proteomics & Bioinformatics2022，20，4： | 0 |
| 4 | Ultra-short-course and intermittent TB47-containing oral regimens produce stable cure against Buruli ulcer in a murine model and prevent the emergence of resistance for Mycobacterium ulcerans显示文摘Buruli ulcer(BU),caused by Mycobacterium ulcerans,is currently treated with rifampin estreptomycin or rifampineclarithromycin daily for 8 weeks recommended by World Health Organization(WHO).These options are lengthy with severe side effects.A new anti-tuberculosis drug,TB47,targeting QcrB in cytochrome bc1:aa3 complex is being developed in China.TB47-containing regimens were evaluated in a well-established murine model using an autoluminescent M.ulcerans strain.Highlevel TB47-resistant spontaneous M.ulcerans mutants were selected and their qcrB genes were sequenced.The in vivo activities of TB47 against both low-level and high-level TB47-resistant mutants were tested in BU murine model.Here,we show that TB47-containing oral 3-drug regimens can completely cure BU in 2 weeks for daily use or in 3 weeks given twice per week(6 doses in total).All high-level TB47-resistant mutants could only be selected using the low-level mutants which were still sensitive to TB47 in mice.This is the first report of double mutations in QcrB in mycobacteria.In summary,TB47-containing regimens have promise to cure BU highly effectively and prevent the emergence of drug resistance.Novel QcrB mutations found here may guide the potential clinical molecular diagnosis of resistance and the discovery of new drugs against the high-level resistant mutants. | Yamin Gao HMAdnan Hameed Yang Liu Lingmin Guo Cuiting Fang Xirong Tian Zhiyong Liu Shuai Wang Zhili Lu Md Mahmudul Islam Tianyu Zhang | 2021 | Acta Pharmaceutica Sinica B2021，11，3： | 0 |
| 5 | Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals显示文摘Live attenuated vaccines might elicit mucosal and sterilizing immunity against SARS-CoV-2 that the existing mRNA,adenoviral vector and inactivated vaccines fail to induce.Here,we describe a candidate live attenuated vaccine strain of SARS-CoV-2 in which the NSP16 gene,which encodes 2′-O-methyltransferase,is catalytically disrupted by a point mutation.This virus,designated d16,was severely attenuated in hamsters and transgenic mice,causing only asymptomatic and nonpathogenic infection.A single dose of d16 administered intranasally resulted in sterilizing immunity in both the upper and lower respiratory tracts of hamsters,thus preventing viral spread in a contact-based transmission model.It also robustly stimulated humoral and cell-mediated immune responses,thus conferring full protection against lethal challenge with SARS-CoV-2 in a transgenic mouse model.The neutralizing antibodies elicited by d16 effectively cross-reacted with several SARS-CoV-2 variants.Secretory immunoglobulin A was detected in the blood and nasal wash of vaccinated mice.Our work provides proof-of-principle evidence for harnessing NSP16-deficient SARS-CoV-2 for the development of live attenuated vaccines and paves the way for further preclinical studies of d16 as a prototypic vaccine strain,to which new features might be introduced to improve safety,transmissibility,immunogenicity and efficacy. | Zi-Wei Ye Chon Phin Ong Kaiming Tang Yilan Fan Cuiting Luo Runhong Zhou Peng Luo Yun Cheng Victor Sebastien Gray Pui Wang Hin Chu Jasper Fuk-Woo Chan Kelvin Kai-Wang To Honglin Chen Zhiwei Chen Kwok-Yung Yuen Guang Sheng Ling Shuofeng Yuan Dong-Yan Jin | 2022 | Cellular & Molecular Immunology2022，19，5： | 0 |
| 6 | Modification of compact TiO_(2) layer by TiCl_(4)-TiCl_(3) mixture treatment and construction of high-efficiency carbon-based CsPbI_(2)Br perovskite solar cells显示文摘In the construction of high performance planar perovskite solar cells(PSCs),the modification of compact TiO_(2) layer and engineering of perovskite/TiO_(2) interfaces are essential for efficient electron transfer and retarded charge recombination loss.In this work,a facile and effective strategy is developed to modify the surface of compact TiO_(2) layer by TiCl_(4)-TiCl_(3) mixture treatment.Compared with conventional sole TiCl_(4),the TiCl_(4)-TiCl_(3) treatment takes the advantage of accelerated and controlled hydrolysis of TiCl_(3),therefore TiO_(2) with dominating anatase phase and moderate roughness is obtained to facilitate the growth of CsPbI_(2) Br perovskite layer with high quality.Furthermore,the oxidation-driven hydrolysis of TiCl_(3) component results in surface Cl doping that facilitates interfacial electron transfer with retarded recombination loss.The average power conversion efficiency(PCE) of carbon-based CsPbI_(2) Br planar PSCs based on TiCl_(4)-TiCl_(3) treatment increases to 14.18% from the intial 13.04% based on conventional sole TiCl_(4) treatment.The champion PSC exhibits a PCE of 14.46%(V_(oc)=1.28 V,J_(sc)=14.21 mA/cm^(2),and FF=0.794),which is one of the highest PCEs for carbon-based CsPbI_(2) Br PSCs. | Wenran Wang Yu Lina Guizhi Zhang Cuiting Kang Zhenxiao Pan Xinhua Zhong Huashang Rao | 2021 | Journal of Energy Chemistry2021，30，12： | 0 |
| 7 | Nonalcoholic steatohepatitis critically rewires the ischemia/ reperfusion-induced dysregulation of cardiolipins and sphingolipids in mice显示文摘Background:Lipid dysregulation plays a fundamental role in nonalcoholic steatohepatitis(NASH),which is an emerging critical risk factor that aggravates hepatic ischemia/reperfusion(I/R)injury.However,the specific lipids that mediate the aggressive I/R injury in NASH livers have not yet been identified.Methods:The mouse model of hepatic I/R injury on NASH was established on C56B/6J mice by first feeding the mice with a Western-style diet to induce NASH,then the NASH mice were subjected to surgical procedures to induce hepatic I/R injury.Untargeted lipidomics were performed to determine hepatic lipids in NASH livers with I/R injury through ultra-high performance liquid chromatography coupled with mass spectrometry.The pathology associated with the dysregulated lipids was examined.Results:Lipidomics analyses identified cardiolipins(CL)and sphingolipids(SL),including ceramides(CER),glycosphingolipids,sphingosines,and sphingomyelins,as the most relevant lipid classes that characterized the lipid dysregulation in NASH livers with I/R injury.CER were increased in normal livers with I/R injury,and the I/R-induced increase of CER was further augmented in NASH livers.Metabolic pathway analysis revealed that the enzymes involved in the synthesis and degradation of CER were highly upregulated in NASH livers with I/R injury,including serine palmitoyltransferase 3(Sptlc3),ceramide synthase 2(Cers2),neutral sphingomyelinase 2(Smpd3),and glucosylceramidase beta 2(Gba2)that produced CER,and alkaline ceramidase 2(Acer2),alkaline ceramidase 3(Acer3),sphingosine kinase 1(Sphk1),sphingosine-1-phosphate lyase(Sgpl1),and sphingosine-1-phosphate phosphatase 1(Sgpp1)that catalyzed the degradation of CER.CL were not affected by I/R challenge in normal livers,but CL was dramatically reduced in NASH livers with I/R injury.Consistently,metabolic pathway analyses revealed that the enzymes catalyzing the generation of CL were downregulated in NASH-I/R injury,including cardiolipin synthase(Crls1)and tafazzin(Taz).Notably,the I/R-induced oxidative stress and cell death were found to be aggravated in NASH livers,which were possibly mediated by the reduction of CL and accumulation of CER.Conclusions:The I/R-induced dysregulation of CL and SL were critically rewired by NASH,which might potentially mediate the aggressive I/R injury in NASH livers. | Sheng Yu Kai Wang Qingping Li Yiran Wei Yiyi Li Qifan Zhang Pengxiang Huang Hanbiao Liang Hang Sun Hongxian Peng Xixin Huang Cuiting Liu Jie Zhou Jianping Qian Chuanjiang Li | 2023 | Hepatobiliary Surgery and Nutrition2023，12，1： | 0 |
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