Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,f...Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.展开更多
Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation inv...Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation involve either C6-C10 cyclization(path a) or C2-C10 cyclization(path b) after the C10carbocation formation,but neither has been experimentally validated.Here,we have identified a second mangicdiene synthase Man D,which is derived from Fusarium sp.JNU-XJ070152-01 and shares high amino acid sequence identity with Fg MS.Through heterologous expression of man D in Aspergillus oryzae NSAR1,we observed production not only of mangicdiene(1) and variecoltetraene(2),previously identified by expression of Fg MS in Escherichia coli,but also two novel sesterterpene skeletons fusadiene(3)and fusatriene(4).The identification of fusadiene and fusatriene supports the occurrence of two key carbocation intermediates in path b,thus experimentally confirming that mangicdiene is built via path b for the first time,consistent with previous density functional theory(DFT) calculation results.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affec...Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.展开更多
Traditionally,the construction of stable interphases relies on solvent structures dominated by aggregated anionic structures(AGG/AGG+).Nonetheless,we find that the construction of stable interphases in hightemperature...Traditionally,the construction of stable interphases relies on solvent structures dominated by aggregated anionic structures(AGG/AGG+).Nonetheless,we find that the construction of stable interphases in hightemperature environments is based on contact ion pairs(CIPs)dominated solvation structure here.In detail,in the long-chain phosphate ester-based electrolyte,the spatial site-blocking effect enables the strong solvation co-solvent ether(diethylene glycol dimethyl ether,G2)to exhibit strong ion-dipole interactions,further multicomponent competitive coordination maintaining the CIP,balancing electrode kinetics,and optimizing the high-temperature interphases.High-temperature in-situ Raman spectroscopy monitors the changes in the stable solvent structure during charge/discharge processes for the first time,and time of flight secondary ion mass spectrometry(TOF-SIMS)reveals the stable solid electrolyte interphase(SEI)with full-depth enrichment of the inorganic component.Benefiting from the high-temperature interfacial chemistry-dependent solvent structure,the advanced electrolyte enables stable cycling of 1.6 Ah 18650 batterie at 100-125℃and discharging with high current pulses(~1.83 A)at 150℃,which has rarely been reported so far.In addition,pin-pricking of 18650 batteries at100%state of charge(SoC)without fire or smoke and the moderate thermal runaway temperature(187℃)tested via the accelerating rate calorimetry(ARC)demonstrate the excellent safety of the optimized electrolyte.展开更多
Background: As the population age structure gradually ages, more and more elderly people were found to have pulmonary nodules during physical examinations. Most elderly people had underlying diseases such as heart, lu...Background: As the population age structure gradually ages, more and more elderly people were found to have pulmonary nodules during physical examinations. Most elderly people had underlying diseases such as heart, lung, brain and blood vessels and cannot tolerate surgery. Computed tomography (CT)-guided percutaneous core needle biopsy (CNB) was the first choice for pathological diagnosis and subsequent targeted drugs, immune drugs or ablation treatment. CT-guided percutaneous CNB requires clinicians with rich CNB experience to ensure high CNB accuracy, but it was easy to cause complications such as pneumothorax and hemorrhage. Three-dimensional (3D) printing coplanar template (PCT) combined with CT-guided percutaneous pulmonary CNB biopsy has been used in clinical practice, but there was no prospective, randomized controlled study. Methods: Elderly patients with lung nodules admitted to the Department of Oncology of our hospital from January 2019 to January 2023 were selected. A total of 225 elderly patients were screened, and 30 patients were included after screening. They were randomly divided into experimental group (Group A: 30 cases) and control group (Group B: 30 cases). Group A was given 3D-PCT combined with CT-guided percutaneous pulmonary CNB biopsy, Group B underwent CT-guided percutaneous pulmonary CNB. The primary outcome measure of this study was the accuracy of diagnostic CNB, and the secondary outcome measures were CNB time, number of CNB needles, number of pathological tissues and complications. Results: The diagnostic accuracy of group A and group B was 96.67% and 76.67%, respectively (P = 0.026). There were statistical differences between group A and group B in average CNB time (P = 0.001), number of CNB (1 vs more than 1, P = 0.029), and pathological tissue obtained by CNB (3 vs 1, P = 0.040). There was no statistical difference in the incidence of pneumothorax and hemorrhage between the two groups (P > 0.05). Conclusions: 3D-PCT combined with CT-guided percutaneous CNB can improve the puncture accuracy of elderly patients, shorten the puncture time, reduce the number of punctures, and increase the amount of puncture pathological tissue, without increasing pneumothorax and hemorrhage complications. We look forward to verifying this in a phase III randomized controlled clinical study. .展开更多
AIM: To explore the mechanism of protection against acetaminophen-induced acute liver injury by Liuweiwuling tablets.METHODS: Intraperitoneal injections of acetaminophen(250 mg/kg) were used to induce acute liver inju...AIM: To explore the mechanism of protection against acetaminophen-induced acute liver injury by Liuweiwuling tablets.METHODS: Intraperitoneal injections of acetaminophen(250 mg/kg) were used to induce acute liver injury in male C57BL/6 mice.A total of 24 healthy mice were randomly assigned to two groups: an acute liver injury group(control group) and a Liuweiwuling tablet group.Mice were given Liuweiwuling tablets or a vehicle(PBS) orally prior to the administration of acetaminophen.Serum alanine aminotransferase(ALT) and aspartate aminotransaminase(AST) levels were measured at different time points within one week,and pathological examinations of liver tissues were performed 36 h after induction of acute liver injury.Serum inflammatory cytokines,such as high mobility group box protein B1(HMGB1),tumor necrosis factor(TNF)-α and interleukin IL-1b,were detected using an ELISA method according to the manufacturer's instructions.Hepatic morphological changes at 36 h were assessed by hematoxylin and eosin staining.Expression of proliferating cell nuclear antigen(PCNA) in liver tissue was determined by Western blot analysis.The m RNA levels of hepatocyte proliferation markers(PCNA,Cyclin D1 and p21) were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS: The levels of ALT/AST in the Liuweiwuling tablet group were decreased significantly at 6,12 and 24 h compared to that of the control group(654.38 ± 120.87 vs 1566.17 ± 421.64,1154.18 ± 477.72 vs 4654.84 ± 913.71 and 935.13 ± 252.34 vs 4553.75 ± 727.37,P < 0.01).Serum HMGB1 levels at 6 and 12 h for the Liuweiwuling tablet group were significantly lower than those of the control group(23.49 ± 3.89 vs58.6 ± 3.65,61.62 ± 13.07 vs 27.32 ± 5.97,P < 0.01).Furthermore,serum TNF-α and IL-1b levels at 12 h in the Liuweiwuling tablet group were also significantly lower than those of the control group(299.35 ± 50.61 vs 439.03 ± 63.59,57.42 ± 12.98 vs 160.07 ± 49.87,P < 0.01).Centrilobular necrosis was evident in liver tissue of mice with acetaminophen-induced acute liver injury,but was almost abolished in the Liuweiwuling tablet group.The expression levels of PCNA and Cyclin D1 were up-regulated in liver tissue in the Liuweiwuling tablet group(321.08 ± 32.87 vs 157.91 ± 21.52,196.37 ± 25.39 vs 68.72 ± 11.27,P < 0.01); however,expression of p21 in liver tissue was downregulated compared to that of the control group(40.26 ± 9.97 vs 138.24 ± 13.66,P < 0.01).CONCLUSION: Liuweiwuling tablets can attenuate acute liver injury by decreasing inflammatory cytokine(HMGB1,TNF-α and IL-1b) levels and promoting liver regeneration.展开更多
AIM: To determine the therapeutic potential of sphingosine kinase 1(Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced acute ...AIM: To determine the therapeutic potential of sphingosine kinase 1(Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced acute liver failure(ALF).METHODS: Balb/c mice were randomly assigned to different groups,with ALF induced by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1(HMGB1),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,IL-10,and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western blot.RESULTS: The expression of Sphk1 in liver tissue and PBMCs was upregulated in Gal N/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells,the resident macrophages of the liver. The survival rates of mice in the N,Ndimethylsphingosine(DMS,a specific inhibitor of Sph K1) treatment group were significantly higher than that of the control group(P < 0.001). DMS treatment significantly decreased the levels of serum ALT and AST at 6,12,and 24 h compared with that of the control group(P < 0.01 for all). Serum HMGB1 levels at 6,12,and 24 h,as well as serum TNF-α,IL-6,and IL-1β levels at 12 h,were significantly lower in the DMS treatment group than in the control group(P < 0.01 for all). Furthermore,hepatic inflammation,necrosis,and HMGB1 cytoplasm translocation in liver cells were significantly decreased in the DMS treatment group compared to the control group(43.72% ± 5.51% vs 3.57% ± 0.83%,χ2 = 12.81,P < 0.01).CONCLUSION: Inhibition of Sph K1 ameliorates ALF by reducing HMGB1 cytoplasmic translocation in liver cells,and so might be a potential therapeutic strategy for this disease.展开更多
AIM: To investigate the role of protein kinase C(PKC)-δ activation in the pathogenesis of acute liver failure(ALF) in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced ALF.M...AIM: To investigate the role of protein kinase C(PKC)-δ activation in the pathogenesis of acute liver failure(ALF) in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced ALF.METHODS: BALB/c mice were randomly assigned to five groups, and ALF was induced in mice by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multiparameteric analyzer. Serum levels of high-mobility group box 1(HMGB1), tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6, and IL-10 as well as nuclear factor(NF)-κB activity were determined by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of PKC-δ in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western blot.RESULTS: The expression and activation of PKC-δ were up-regulated in liver tissue and PBMCs of mice with D-Gal N/LPS-induced ALF. Inhibition of PKC-δ activation with rottlerin significantly increased the survival rates and decreased serum ALT/AST levels at 6, 12 and 24 h compared with the control group(P < 0.001). Rottlerin treatment also significantly decreased serum levels of HMGB1 at 6, 12, and 24 h, TNF-α, IL-6 and IL-1 β at 12 h compared with the control group(P < 0.01). The inflammatory cell infiltration and necrosis in liver tissue were also decreased in the rottlerin treatment group. Furthermore, sphingosine kinase 1(Sph K1) dependent PKC-δ activation played an important role in promoting NF-κB activation and inflammatory cytokine production in ALF.CONCLUSION: Sph K1 dependent PKC-δ activation plays an important role in promoting NF-κB activation and inflammatory response in ALF, and inhibition of PKC-δ activation might be a potential therapeutic strategy for this disease.展开更多
Capillary electrophoresis-mass spectrometry（CE-MS） is a powerful separation and analytical technique in the field of analytical chemistry. This review provides an update of instrumentation developments in the method...Capillary electrophoresis-mass spectrometry（CE-MS） is a powerful separation and analytical technique in the field of analytical chemistry. This review provides an update of instrumentation developments in the methodology of CE-MS systems. A selection of relevant articles covers the literatures published from Jan. 2013 to Feb. 2017. Special attentions were paid to the sample injection and ionization processes.Applications of these CE-MS systems were also introduced through representative examples. General conclusions and perspectives were given at the last.展开更多
A new concentrated ternary salt ether-based electrolyte enables stable cycling of lithium metal battery(LMB)cells with high-mass-loading(13.8 mg cm^(−2),2.5 mAh cm^(−2))NMC622(LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2))cathodes ...A new concentrated ternary salt ether-based electrolyte enables stable cycling of lithium metal battery(LMB)cells with high-mass-loading(13.8 mg cm^(−2),2.5 mAh cm^(−2))NMC622(LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2))cathodes and 50μm Li anodes.Termed“CETHER-3,”this electrolyte is based on LiTFSI,LiDFOB,and LiBF4 with 5 vol%fluorinated ethylene carbonate in 1,2-dimethoxyethane.Commer-cial carbonate and state-of-the-art binary salt ether electrolytes were also tested as baselines.With CETHER-3,the electrochemical performance of the full-cell battery is among the most favorably reported in terms of high-voltage cycling stability.For example,LiNi_(x)Mn_(y)Co_(1-x-y)O_(2)(NMC)-Li metal cells retain 80%capacity at 430 cycles with a 4.4 V cut-off and 83%capacity at 100 cycles with a 4.5 V cut-off(charge at C/5,discharge at C/2).According to simulation by density functional theory and molecular dynamics,this favorable performance is an outcome of enhanced coordination between Li^(+)and the solvent/salt molecules.Combining advanced microscopy(high-resolution transmission electron microscopy,scanning electron microscopy)and surface science(X-ray photoelectron spectroscopy,time-of-fight secondary ion mass spectroscopy,Fourier-transform infrared spectroscopy,Raman spectroscopy),it is demonstrated that a thinner and more stable cathode electrolyte interphase(CEI)and solid electrolyte interphase(SEI)are formed.The CEI is rich in lithium sulfide(Li_(2)SO_(3)),while the SEI is rich in Li_(3)N and LiF.During cycling,the CEI/SEI suppresses both the deleterious transformation of the cathode R-3m layered near-surface structure into disordered rock salt and the growth of lithium metal dendrites.展开更多
Mixed-cation perovskite solar cells have attracted tremendous attention in space applications due to their excellent power conversion efficiency (PCE) and stability to light and heat.Although the evolution of photovol...Mixed-cation perovskite solar cells have attracted tremendous attention in space applications due to their excellent power conversion efficiency (PCE) and stability to light and heat.Although the evolution of photovoltaic performance in different space environments has been investigated,the role of inorganic cesium ions (Cs^(+)) in the enhancement of irradiation resistance needs to be further clarified.Herein,the structure and performance evolution of Cs-doped CH_(3)NH_(3)PbI_(3)(MAPbI_(3)) films and planar heterojunction devices under proton irradiation up to 1×10^(16)p cm^(-2) were studied.5%of Cs^(+) doping can increase the cohesive energy of MAPbI_(3)and effectively alleviate the lattice strain induced by proton irradiation,thereby enhancing the crystallinity and stability of films.The bandgap changes of irradiated Cs_(0.05)MA_(0.95)PbI_(3) films under the identical fluence were only one third of that of MAPbI_(3) films.Upon irradiation under the fluence of 1×10^(14)p cm^(-2),the density of trap states in the undoped and 5%Cs-doped films increased by 71%and 9%,respectively,and the average PCE of 20 corresponding devices decreased only by 12%and 9%,respectively.This proves that the replacement of organic methylamine ion with inorganic cesium ion contributes to the improvement of MAPbI_(3) resistance to proton irradiation,thus confirming the application prospects of mixed-cation or all-inorganic perovskite solar cells in spacecraft.展开更多
基金National Natural Science Foundation of China(No.22264013)Hainan Province Clinical Medical Center(No.2021)Hainan Province Science and Technology Special Fund(No.ZDYF2024SHFZ104).
文摘Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.
基金financially supported by grants from the National Key Research and Development Program of China (No.2024YFE0102000)the National Natural Science Foundation of China (Nos.81925037,82321004,U22A20371,U24A20782,32170060,22177037,22207039,22307045)+6 种基金the Guangdong Major Project of Basic and Applied Basic Research (No.2023B0303000026)the Guangdong Natural Science Funds for Distinguished Young Scholars (No.2022B1515020028,China)the Guangdong International Science and Technology Cooperation Base (No.2021A0505020015,China)the Guangdong Basic and Applied Basic Research Foundation (Nos.2023B1515040016,2023A1515110388)the Innovative and Research Teams Project of Guangdong Higher Education Institution (No.2021KCXTD001,China)the Guangzhou Science and Technology Project (Nos.202206010020,2024A04J6241,2023A04J0080,China)the Fundamental Research Funds for the Central Universities (Nos.21623105,21624210)。
文摘Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation involve either C6-C10 cyclization(path a) or C2-C10 cyclization(path b) after the C10carbocation formation,but neither has been experimentally validated.Here,we have identified a second mangicdiene synthase Man D,which is derived from Fusarium sp.JNU-XJ070152-01 and shares high amino acid sequence identity with Fg MS.Through heterologous expression of man D in Aspergillus oryzae NSAR1,we observed production not only of mangicdiene(1) and variecoltetraene(2),previously identified by expression of Fg MS in Escherichia coli,but also two novel sesterterpene skeletons fusadiene(3)and fusatriene(4).The identification of fusadiene and fusatriene supports the occurrence of two key carbocation intermediates in path b,thus experimentally confirming that mangicdiene is built via path b for the first time,consistent with previous density functional theory(DFT) calculation results.
基金supported by the National Natural Science Foundation of China(82072432)the China-Japan Friendship Hospital Horizontal Project/Spontaneous Research Funding(2022-HX-JC-7)+1 种基金the National High Level Hospital Clinical Research Funding(2022-NHLHCRF-PY-20)the Elite Medical Professionals project of China-Japan Friendship Hospital(ZRJY2021-GG12).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.
基金supported by the National Natural Science Foundation of China(grant no.52072322,52202235)the Department of Science and Technology of Sichuan Province(CN)(grant no.23GJHZ0147)the Research and Innovation Fund for Graduate Students of Southwest Petroleum University(No.:2022KYCX111)。
文摘Traditionally,the construction of stable interphases relies on solvent structures dominated by aggregated anionic structures(AGG/AGG+).Nonetheless,we find that the construction of stable interphases in hightemperature environments is based on contact ion pairs(CIPs)dominated solvation structure here.In detail,in the long-chain phosphate ester-based electrolyte,the spatial site-blocking effect enables the strong solvation co-solvent ether(diethylene glycol dimethyl ether,G2)to exhibit strong ion-dipole interactions,further multicomponent competitive coordination maintaining the CIP,balancing electrode kinetics,and optimizing the high-temperature interphases.High-temperature in-situ Raman spectroscopy monitors the changes in the stable solvent structure during charge/discharge processes for the first time,and time of flight secondary ion mass spectrometry(TOF-SIMS)reveals the stable solid electrolyte interphase(SEI)with full-depth enrichment of the inorganic component.Benefiting from the high-temperature interfacial chemistry-dependent solvent structure,the advanced electrolyte enables stable cycling of 1.6 Ah 18650 batterie at 100-125℃and discharging with high current pulses(~1.83 A)at 150℃,which has rarely been reported so far.In addition,pin-pricking of 18650 batteries at100%state of charge(SoC)without fire or smoke and the moderate thermal runaway temperature(187℃)tested via the accelerating rate calorimetry(ARC)demonstrate the excellent safety of the optimized electrolyte.
文摘Background: As the population age structure gradually ages, more and more elderly people were found to have pulmonary nodules during physical examinations. Most elderly people had underlying diseases such as heart, lung, brain and blood vessels and cannot tolerate surgery. Computed tomography (CT)-guided percutaneous core needle biopsy (CNB) was the first choice for pathological diagnosis and subsequent targeted drugs, immune drugs or ablation treatment. CT-guided percutaneous CNB requires clinicians with rich CNB experience to ensure high CNB accuracy, but it was easy to cause complications such as pneumothorax and hemorrhage. Three-dimensional (3D) printing coplanar template (PCT) combined with CT-guided percutaneous pulmonary CNB biopsy has been used in clinical practice, but there was no prospective, randomized controlled study. Methods: Elderly patients with lung nodules admitted to the Department of Oncology of our hospital from January 2019 to January 2023 were selected. A total of 225 elderly patients were screened, and 30 patients were included after screening. They were randomly divided into experimental group (Group A: 30 cases) and control group (Group B: 30 cases). Group A was given 3D-PCT combined with CT-guided percutaneous pulmonary CNB biopsy, Group B underwent CT-guided percutaneous pulmonary CNB. The primary outcome measure of this study was the accuracy of diagnostic CNB, and the secondary outcome measures were CNB time, number of CNB needles, number of pathological tissues and complications. Results: The diagnostic accuracy of group A and group B was 96.67% and 76.67%, respectively (P = 0.026). There were statistical differences between group A and group B in average CNB time (P = 0.001), number of CNB (1 vs more than 1, P = 0.029), and pathological tissue obtained by CNB (3 vs 1, P = 0.040). There was no statistical difference in the incidence of pneumothorax and hemorrhage between the two groups (P > 0.05). Conclusions: 3D-PCT combined with CT-guided percutaneous CNB can improve the puncture accuracy of elderly patients, shorten the puncture time, reduce the number of punctures, and increase the amount of puncture pathological tissue, without increasing pneumothorax and hemorrhage complications. We look forward to verifying this in a phase III randomized controlled clinical study. .
文摘AIM: To explore the mechanism of protection against acetaminophen-induced acute liver injury by Liuweiwuling tablets.METHODS: Intraperitoneal injections of acetaminophen(250 mg/kg) were used to induce acute liver injury in male C57BL/6 mice.A total of 24 healthy mice were randomly assigned to two groups: an acute liver injury group(control group) and a Liuweiwuling tablet group.Mice were given Liuweiwuling tablets or a vehicle(PBS) orally prior to the administration of acetaminophen.Serum alanine aminotransferase(ALT) and aspartate aminotransaminase(AST) levels were measured at different time points within one week,and pathological examinations of liver tissues were performed 36 h after induction of acute liver injury.Serum inflammatory cytokines,such as high mobility group box protein B1(HMGB1),tumor necrosis factor(TNF)-α and interleukin IL-1b,were detected using an ELISA method according to the manufacturer's instructions.Hepatic morphological changes at 36 h were assessed by hematoxylin and eosin staining.Expression of proliferating cell nuclear antigen(PCNA) in liver tissue was determined by Western blot analysis.The m RNA levels of hepatocyte proliferation markers(PCNA,Cyclin D1 and p21) were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS: The levels of ALT/AST in the Liuweiwuling tablet group were decreased significantly at 6,12 and 24 h compared to that of the control group(654.38 ± 120.87 vs 1566.17 ± 421.64,1154.18 ± 477.72 vs 4654.84 ± 913.71 and 935.13 ± 252.34 vs 4553.75 ± 727.37,P < 0.01).Serum HMGB1 levels at 6 and 12 h for the Liuweiwuling tablet group were significantly lower than those of the control group(23.49 ± 3.89 vs58.6 ± 3.65,61.62 ± 13.07 vs 27.32 ± 5.97,P < 0.01).Furthermore,serum TNF-α and IL-1b levels at 12 h in the Liuweiwuling tablet group were also significantly lower than those of the control group(299.35 ± 50.61 vs 439.03 ± 63.59,57.42 ± 12.98 vs 160.07 ± 49.87,P < 0.01).Centrilobular necrosis was evident in liver tissue of mice with acetaminophen-induced acute liver injury,but was almost abolished in the Liuweiwuling tablet group.The expression levels of PCNA and Cyclin D1 were up-regulated in liver tissue in the Liuweiwuling tablet group(321.08 ± 32.87 vs 157.91 ± 21.52,196.37 ± 25.39 vs 68.72 ± 11.27,P < 0.01); however,expression of p21 in liver tissue was downregulated compared to that of the control group(40.26 ± 9.97 vs 138.24 ± 13.66,P < 0.01).CONCLUSION: Liuweiwuling tablets can attenuate acute liver injury by decreasing inflammatory cytokine(HMGB1,TNF-α and IL-1b) levels and promoting liver regeneration.
基金Supported by the National Natural Science Foundation of ChinaNo.81160065
文摘AIM: To determine the therapeutic potential of sphingosine kinase 1(Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced acute liver failure(ALF).METHODS: Balb/c mice were randomly assigned to different groups,with ALF induced by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1(HMGB1),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,IL-10,and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western blot.RESULTS: The expression of Sphk1 in liver tissue and PBMCs was upregulated in Gal N/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells,the resident macrophages of the liver. The survival rates of mice in the N,Ndimethylsphingosine(DMS,a specific inhibitor of Sph K1) treatment group were significantly higher than that of the control group(P < 0.001). DMS treatment significantly decreased the levels of serum ALT and AST at 6,12,and 24 h compared with that of the control group(P < 0.01 for all). Serum HMGB1 levels at 6,12,and 24 h,as well as serum TNF-α,IL-6,and IL-1β levels at 12 h,were significantly lower in the DMS treatment group than in the control group(P < 0.01 for all). Furthermore,hepatic inflammation,necrosis,and HMGB1 cytoplasm translocation in liver cells were significantly decreased in the DMS treatment group compared to the control group(43.72% ± 5.51% vs 3.57% ± 0.83%,χ2 = 12.81,P < 0.01).CONCLUSION: Inhibition of Sph K1 ameliorates ALF by reducing HMGB1 cytoplasmic translocation in liver cells,and so might be a potential therapeutic strategy for this disease.
基金Supported by The National Natural Science Foundation of ChinaNo.81160065
文摘AIM: To investigate the role of protein kinase C(PKC)-δ activation in the pathogenesis of acute liver failure(ALF) in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced ALF.METHODS: BALB/c mice were randomly assigned to five groups, and ALF was induced in mice by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multiparameteric analyzer. Serum levels of high-mobility group box 1(HMGB1), tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6, and IL-10 as well as nuclear factor(NF)-κB activity were determined by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of PKC-δ in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western blot.RESULTS: The expression and activation of PKC-δ were up-regulated in liver tissue and PBMCs of mice with D-Gal N/LPS-induced ALF. Inhibition of PKC-δ activation with rottlerin significantly increased the survival rates and decreased serum ALT/AST levels at 6, 12 and 24 h compared with the control group(P < 0.001). Rottlerin treatment also significantly decreased serum levels of HMGB1 at 6, 12, and 24 h, TNF-α, IL-6 and IL-1 β at 12 h compared with the control group(P < 0.01). The inflammatory cell infiltration and necrosis in liver tissue were also decreased in the rottlerin treatment group. Furthermore, sphingosine kinase 1(Sph K1) dependent PKC-δ activation played an important role in promoting NF-κB activation and inflammatory cytokine production in ALF.CONCLUSION: Sph K1 dependent PKC-δ activation plays an important role in promoting NF-κB activation and inflammatory response in ALF, and inhibition of PKC-δ activation might be a potential therapeutic strategy for this disease.
基金supported by Ministry of Science and Technology(MOST)instrumentation program of China(No.2012YQ04014007)National Natural Science Foundation of China(NSF)(No.21475010)+1 种基金Beijing Natural Science Foundation(BNSF)(No.16L00065)State Key Laboratory Explosion Science and Technology(No.YBKT16-17)
文摘Capillary electrophoresis-mass spectrometry（CE-MS） is a powerful separation and analytical technique in the field of analytical chemistry. This review provides an update of instrumentation developments in the methodology of CE-MS systems. A selection of relevant articles covers the literatures published from Jan. 2013 to Feb. 2017. Special attentions were paid to the sample injection and ionization processes.Applications of these CE-MS systems were also introduced through representative examples. General conclusions and perspectives were given at the last.
基金National Natural Science Foundation of China,Grant/Award Numbers:21905265,52072322,U1930402,61974042National Science Foundation,Civil,Mechanical and Manufacturing Innovation,Grant/Award Number:1911905+3 种基金Fundamental Research Funds for the Central Universities,Grant/Award Number:WK2060140026Department of Science and Technology of Sichuan Province,Grant/Award Numbers:2019‐GH02‐00052‐HZ,2019YFG0220Scientific and Technological Innovation Foundation of Shunde Graduate School,Grant/Award Number:BK19BE024National Key Research and Development Program of China,Grant/Award Number:2017YFA0303403。
文摘A new concentrated ternary salt ether-based electrolyte enables stable cycling of lithium metal battery(LMB)cells with high-mass-loading(13.8 mg cm^(−2),2.5 mAh cm^(−2))NMC622(LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2))cathodes and 50μm Li anodes.Termed“CETHER-3,”this electrolyte is based on LiTFSI,LiDFOB,and LiBF4 with 5 vol%fluorinated ethylene carbonate in 1,2-dimethoxyethane.Commer-cial carbonate and state-of-the-art binary salt ether electrolytes were also tested as baselines.With CETHER-3,the electrochemical performance of the full-cell battery is among the most favorably reported in terms of high-voltage cycling stability.For example,LiNi_(x)Mn_(y)Co_(1-x-y)O_(2)(NMC)-Li metal cells retain 80%capacity at 430 cycles with a 4.4 V cut-off and 83%capacity at 100 cycles with a 4.5 V cut-off(charge at C/5,discharge at C/2).According to simulation by density functional theory and molecular dynamics,this favorable performance is an outcome of enhanced coordination between Li^(+)and the solvent/salt molecules.Combining advanced microscopy(high-resolution transmission electron microscopy,scanning electron microscopy)and surface science(X-ray photoelectron spectroscopy,time-of-fight secondary ion mass spectroscopy,Fourier-transform infrared spectroscopy,Raman spectroscopy),it is demonstrated that a thinner and more stable cathode electrolyte interphase(CEI)and solid electrolyte interphase(SEI)are formed.The CEI is rich in lithium sulfide(Li_(2)SO_(3)),while the SEI is rich in Li_(3)N and LiF.During cycling,the CEI/SEI suppresses both the deleterious transformation of the cathode R-3m layered near-surface structure into disordered rock salt and the growth of lithium metal dendrites.
基金financially supported by the National Key R&D Program of China (2018YFB2003900)。
文摘Mixed-cation perovskite solar cells have attracted tremendous attention in space applications due to their excellent power conversion efficiency (PCE) and stability to light and heat.Although the evolution of photovoltaic performance in different space environments has been investigated,the role of inorganic cesium ions (Cs^(+)) in the enhancement of irradiation resistance needs to be further clarified.Herein,the structure and performance evolution of Cs-doped CH_(3)NH_(3)PbI_(3)(MAPbI_(3)) films and planar heterojunction devices under proton irradiation up to 1×10^(16)p cm^(-2) were studied.5%of Cs^(+) doping can increase the cohesive energy of MAPbI_(3)and effectively alleviate the lattice strain induced by proton irradiation,thereby enhancing the crystallinity and stability of films.The bandgap changes of irradiated Cs_(0.05)MA_(0.95)PbI_(3) films under the identical fluence were only one third of that of MAPbI_(3) films.Upon irradiation under the fluence of 1×10^(14)p cm^(-2),the density of trap states in the undoped and 5%Cs-doped films increased by 71%and 9%,respectively,and the average PCE of 20 corresponding devices decreased only by 12%and 9%,respectively.This proves that the replacement of organic methylamine ion with inorganic cesium ion contributes to the improvement of MAPbI_(3) resistance to proton irradiation,thus confirming the application prospects of mixed-cation or all-inorganic perovskite solar cells in spacecraft.
