Background The benefits of combining benzoic acid and essential oils(BAO)to mitigate intestinal impairment during the weaning process have been well established,while the detailed underlying mechanism has not been ful...Background The benefits of combining benzoic acid and essential oils(BAO)to mitigate intestinal impairment during the weaning process have been well established,while the detailed underlying mechanism has not been fully elucidated.Previous research has primarily focused on the reparative effects of BAO on intestinal injury,while neglecting its potential in enhancing intestinal stress resistance.Methods In this study,we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure.Piglets were pre-supplemented with BAO for 14 d,followed by a challenge with LPS or saline to collect blood and intestinal samples.Results Our findings demonstrated that BAO supplementation led to significant improvements in piglets’final weight,average daily gain,and feed intake/body gain ratio.Additionally,BAO supplementation positively influenced the composition of intestinal microbiota,increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota,Prevotella and Oscillospira.Furthermore,BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge.This was evidenced by elevated levels of T-AOC,SOD,and GSH,as well as decreased levels of MDA,TNF-α,and IL-6 in the plasma.Moreover,piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity,as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts.Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway.Additionally,the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO.Conclusions In summary,our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition,reinforcing the intestinal barrier,and enhancing antioxidative and anti-inflammatory capabilities.These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.展开更多
Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical...Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical events.Early diagnosis of arrhythmias,particularly AF and ventricular arrhythmias,is very important for the treatment and prognosis of patients.Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia.However,it has some shortcomings such as fixed detection timings,delayed report and inability of remote real-time detection.To deal with such problems,we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram(ECG)device with a remote cloud-based ECG platform and an expertsupporting system.In this study,31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded.In the H3-ECG group,ECG signals were transmitted using remote real-time modes,and confirmed reports were made by doctors in the remote expert-supporting system,while the traditional modes and detection systems were used in the Holter group.The results showed no significant differences between the two groups in 24-hour total heart rate(HR),averaged HR,maximum HR,minimum HR,premature atrial complexes(PACs)and premature ventricular complexes(PVCs)(P>0.05).The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs,PVCs,and AF by H3-ECG were 93%and 99%,98%and 99%,94%and 98%,respectively.Therefore,the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.展开更多
Background:Intrauterine growth restriction(IUGR)is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth(CUG)before weanling could significantly restore this negative influence.But ...Background:Intrauterine growth restriction(IUGR)is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth(CUG)before weanling could significantly restore this negative influence.But there was limited knowledge about the underlying mechanism of CUG occurrence.Methods:Eighty litters of newborn piglets were divided into normal birth weight(NBW)and IUGR groups according to birth weight.At 26 d,those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG,and the piglets with IUGR still below average body weight were considered as NCUG.This study was conducted to systemically compare the intestinal difference among NBW,CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth.Results:The results indicated that the m RNA expression of nutrients(amino acids,glucose,and fatty acids)transporters,and mitochondrial electron transport chain(ETC)I were upregulated in CUG piglets'gut with improved morphology compared with those NCUG,as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism.Meanwhile,CUG piglet's gut showed higher antioxidative capacity with increased SOD and GSHPx activity,decreased MDA levels,as well as higher m RNA expressions of Nrf2,Keap1,SOD,and GSH-Px.Furthermore,inflammatory parameters including TNF-α,IL-1β,IL-6,and IL-12 factors,and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine,while the protein expression of ZO-1,Occludin and Claudin-1 was reduced.The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets,and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets.Conclusions:CUG piglet's intestine showed comprehensive restoration including higher nutrients transport,energy metabolism,antioxidant capacity,and intestinal physical barrier,while lower oxidative stress,inflammatory response,and pathogenic microbiota.展开更多
Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic bac...Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.展开更多
Photocatalytic oxidation techniques are promising for degradation of the highly ecotoxic and refractory isothiazolinone bactericides in relevant industrial wastewaters.However,low charge separation and directional tra...Photocatalytic oxidation techniques are promising for degradation of the highly ecotoxic and refractory isothiazolinone bactericides in relevant industrial wastewaters.However,low charge separation and directional transport efficiency under solar light radiation restrain their practical application.Here,we report a nanostructured photocatalyst doped with Gd and B in TiO_(2)with carbon incorporation and defect formation through incomplete calcination.The specific surface area,grain size,and hydrophilicity of TiO_(2)are improved,which is beneficial for the interfacial reaction between the photocatalyst and pollutants.The reduction of the bandgap,the broadening of the photo-absorption range,and the retarded electron-hole recombination promote the photocatalytic performance due to the improved oxygen vacancies based on the electron distribution modification.The difference in partial density of states(ΔPDOS)between the current catalyst and raw TiO_(2)indicates that the co-doping of Gd and B with incomplete calcination changes the electronic hybridization of conduction band and valence band near the Fermi level,and affects the band gap energy.It improved charge separation and directional transport efficiency and benefited the formation of main active species,including•OH and O_(2)•−,for the pollutant decomposition.The rate of photocatalytic removal of benzisothiazolinone(BIT)by the current photocatalyst reaches 1.25 h^(−1),being 4.31 times that of TiO_(2).The current work offers a constructive approach to the design and synthesis of nanostructured photocatalysts for the photocatalytic degradation of refractory organic pollutants.展开更多
Metalloproteins have inspired chemists for many years to synthesize artificial catalysts that mimic native enzymes.As a complementary approach to studying native enzymes or making synthetic models,biosynthetic approac...Metalloproteins have inspired chemists for many years to synthesize artificial catalysts that mimic native enzymes.As a complementary approach to studying native enzymes or making synthetic models,biosynthetic approach using small and stable proteins to model native enzymes has offered advantages of incorporating non-covalent secondary sphere interactions under physiological conditions.However,most biosynthetic models are restricted to natural amino acids.To overcome this limitation,incorporating unnatural amino acids into the biosynthetic models has shown promises.In this review,we summarize first synthetic,semisynthetic and biological methods of incorporates unnatural amino acids(UAAs)into proteins,followed by progress made in incorporating UAAs into both native metalloproteins and their biosynthetic models to fine-tune functional properties beyond native enzymes or their variants containing natural amino acids,such as reduction potentials of azurin,O_2 reduction rates and percentages of product formation of HCO models in Mb,the rate of radical transport in ribonucleotide reductase(RNR)and the proton and electron transfer pathways in photosystemⅡ(PSⅡ).We also discuss how this endeavour has allowed systematic investigations of precise roles of conserved residues in metalloproteins,such as Metl21 in azurin,Tyr244 that is cross-linked to one of the three His ligands to CuB in HCO,Tyr122,356,730 and 731 in RNR and TyrZ in PSⅡ.These examples have demonstrated that incorporating UAAs has provided a new dimension in our efforts to mimic native enzymes and in providing deeper insights into structural features responsible high enzymatic activity and reaction mechanisms,making it possible to design highly efficient artificial catalysts with similar or even higher activity than native enzymes.展开更多
Alumina supported Pd catalyst(Pd/Al_(2)O_(3)) is active for complete oxidation of methane, while often suffers transient deactivation during the cold down process. Herein, heating and cooling cycle tests between 200 a...Alumina supported Pd catalyst(Pd/Al_(2)O_(3)) is active for complete oxidation of methane, while often suffers transient deactivation during the cold down process. Herein, heating and cooling cycle tests between 200 and 900 ℃ and isothermal experiments at 650 ℃ were conducted to investigate the influence of NO_(x) on transient deactivation of Pd/θ-Al_(2)O_(3) catalyst during the methane oxidation. It was found that the co-fed of NO alleviated transient deactivation in the cooling ramp from 800 to 500 ℃, which was resulted from the in situ formation of NO_(2) during the process of methane oxidation. Over the Pd/θ-Al_(2)O_(3), thermogravimetric analysis and O_(2) temperature programmed oxidation measurements confirmed that transient deactivation was due to the decomposition of Pd O particles and the hysteresis of Pd reoxidation, while the metal Pd entities were less active for methane oxidation than the Pd O ones. CO pulse chemisorption and scanning transmission electron microscopy characterizations rule out the NO_(2) effect on Pd size change. Powder X-ray diffraction and X-ray photoelectron spectroscopy characterizations were used to obtain palladium status of Pd/θ-Al_(2)O_(3) before and after reactions, indicating that in lean conditions at 650 ℃, the presence of NO_(2) increases the content of active Pd O on the catalyst surface, thus benefits methane oxidation. Homogeneous reaction between CH 4, O_(2), and NO_(x) may be partially responsible for the alleviation above 650 ℃. The interesting research of alleviation in transient deactivation by NO_(x), the components co-existing in exhausts, are of great significance for the application.展开更多
基金supported by the National Key Research and Development Program(2021YFD1300400)Natural Science Foundation of Guangdong Province(2021A1515010944)Science and Technology Projects in Guangzhou(202201011730).
文摘Background The benefits of combining benzoic acid and essential oils(BAO)to mitigate intestinal impairment during the weaning process have been well established,while the detailed underlying mechanism has not been fully elucidated.Previous research has primarily focused on the reparative effects of BAO on intestinal injury,while neglecting its potential in enhancing intestinal stress resistance.Methods In this study,we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure.Piglets were pre-supplemented with BAO for 14 d,followed by a challenge with LPS or saline to collect blood and intestinal samples.Results Our findings demonstrated that BAO supplementation led to significant improvements in piglets’final weight,average daily gain,and feed intake/body gain ratio.Additionally,BAO supplementation positively influenced the composition of intestinal microbiota,increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota,Prevotella and Oscillospira.Furthermore,BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge.This was evidenced by elevated levels of T-AOC,SOD,and GSH,as well as decreased levels of MDA,TNF-α,and IL-6 in the plasma.Moreover,piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity,as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts.Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway.Additionally,the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO.Conclusions In summary,our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition,reinforcing the intestinal barrier,and enhancing antioxidative and anti-inflammatory capabilities.These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.
基金This research was funded by the Key Research and Development Plan of Jiangsu Province under grant BE2017735.Q.S.conceived the study and wrote the manuscript.Q.S.,C.C.,H.G.X.W.collected,analyzed,and interpreted the data.H.G.and X.W.contributed substantially to the development of ECG signal conversion Matlab software and remote automatic detection algorithm.J.L.,M.C.and C.L.revised the manuscript,evaluated and supervised the study.
文摘Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical events.Early diagnosis of arrhythmias,particularly AF and ventricular arrhythmias,is very important for the treatment and prognosis of patients.Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia.However,it has some shortcomings such as fixed detection timings,delayed report and inability of remote real-time detection.To deal with such problems,we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram(ECG)device with a remote cloud-based ECG platform and an expertsupporting system.In this study,31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded.In the H3-ECG group,ECG signals were transmitted using remote real-time modes,and confirmed reports were made by doctors in the remote expert-supporting system,while the traditional modes and detection systems were used in the Holter group.The results showed no significant differences between the two groups in 24-hour total heart rate(HR),averaged HR,maximum HR,minimum HR,premature atrial complexes(PACs)and premature ventricular complexes(PVCs)(P>0.05).The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs,PVCs,and AF by H3-ECG were 93%and 99%,98%and 99%,94%and 98%,respectively.Therefore,the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.
基金the Natural Science Foundation of Guangdong Province(2021A1515010944)the National Natural Science Foundation of China(31402082 and 32272894)。
文摘Background:Intrauterine growth restriction(IUGR)is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth(CUG)before weanling could significantly restore this negative influence.But there was limited knowledge about the underlying mechanism of CUG occurrence.Methods:Eighty litters of newborn piglets were divided into normal birth weight(NBW)and IUGR groups according to birth weight.At 26 d,those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG,and the piglets with IUGR still below average body weight were considered as NCUG.This study was conducted to systemically compare the intestinal difference among NBW,CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth.Results:The results indicated that the m RNA expression of nutrients(amino acids,glucose,and fatty acids)transporters,and mitochondrial electron transport chain(ETC)I were upregulated in CUG piglets'gut with improved morphology compared with those NCUG,as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism.Meanwhile,CUG piglet's gut showed higher antioxidative capacity with increased SOD and GSHPx activity,decreased MDA levels,as well as higher m RNA expressions of Nrf2,Keap1,SOD,and GSH-Px.Furthermore,inflammatory parameters including TNF-α,IL-1β,IL-6,and IL-12 factors,and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine,while the protein expression of ZO-1,Occludin and Claudin-1 was reduced.The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets,and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets.Conclusions:CUG piglet's intestine showed comprehensive restoration including higher nutrients transport,energy metabolism,antioxidant capacity,and intestinal physical barrier,while lower oxidative stress,inflammatory response,and pathogenic microbiota.
基金supported by the Natural Science Foundation of Jiangsu Province of China(Grant No.BK20160134 to LW and BK20191071 to CC)National Natural and Science Foundation of China(Grant No.81900295 to CC)Special Foundation for Clinical Science and Technology of Jiangsu Province(Grant No.BE2017754 to HWC).
文摘Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.
基金the National Key R&D Program of China(No.2021YFC2102205)the National Natural Science Foundation of China(No.51808312)the CNNC Key Laboratory on Uranium Extraction from Seawater(No.KLUES202207).
文摘Photocatalytic oxidation techniques are promising for degradation of the highly ecotoxic and refractory isothiazolinone bactericides in relevant industrial wastewaters.However,low charge separation and directional transport efficiency under solar light radiation restrain their practical application.Here,we report a nanostructured photocatalyst doped with Gd and B in TiO_(2)with carbon incorporation and defect formation through incomplete calcination.The specific surface area,grain size,and hydrophilicity of TiO_(2)are improved,which is beneficial for the interfacial reaction between the photocatalyst and pollutants.The reduction of the bandgap,the broadening of the photo-absorption range,and the retarded electron-hole recombination promote the photocatalytic performance due to the improved oxygen vacancies based on the electron distribution modification.The difference in partial density of states(ΔPDOS)between the current catalyst and raw TiO_(2)indicates that the co-doping of Gd and B with incomplete calcination changes the electronic hybridization of conduction band and valence band near the Fermi level,and affects the band gap energy.It improved charge separation and directional transport efficiency and benefited the formation of main active species,including•OH and O_(2)•−,for the pollutant decomposition.The rate of photocatalytic removal of benzisothiazolinone(BIT)by the current photocatalyst reaches 1.25 h^(−1),being 4.31 times that of TiO_(2).The current work offers a constructive approach to the design and synthesis of nanostructured photocatalysts for the photocatalytic degradation of refractory organic pollutants.
基金supported by the US National Science Foundation(CHE-1413328)the Major State Basic Research Program of China(2015CB856203)+1 种基金the National Natural Science Foundation of China (21325211,31500641)theTianjinMunicipalGrant(13ZCZDSY04800, 14ZCZDSY00059,14JCYBJC43400)
文摘Metalloproteins have inspired chemists for many years to synthesize artificial catalysts that mimic native enzymes.As a complementary approach to studying native enzymes or making synthetic models,biosynthetic approach using small and stable proteins to model native enzymes has offered advantages of incorporating non-covalent secondary sphere interactions under physiological conditions.However,most biosynthetic models are restricted to natural amino acids.To overcome this limitation,incorporating unnatural amino acids into the biosynthetic models has shown promises.In this review,we summarize first synthetic,semisynthetic and biological methods of incorporates unnatural amino acids(UAAs)into proteins,followed by progress made in incorporating UAAs into both native metalloproteins and their biosynthetic models to fine-tune functional properties beyond native enzymes or their variants containing natural amino acids,such as reduction potentials of azurin,O_2 reduction rates and percentages of product formation of HCO models in Mb,the rate of radical transport in ribonucleotide reductase(RNR)and the proton and electron transfer pathways in photosystemⅡ(PSⅡ).We also discuss how this endeavour has allowed systematic investigations of precise roles of conserved residues in metalloproteins,such as Metl21 in azurin,Tyr244 that is cross-linked to one of the three His ligands to CuB in HCO,Tyr122,356,730 and 731 in RNR and TyrZ in PSⅡ.These examples have demonstrated that incorporating UAAs has provided a new dimension in our efforts to mimic native enzymes and in providing deeper insights into structural features responsible high enzymatic activity and reaction mechanisms,making it possible to design highly efficient artificial catalysts with similar or even higher activity than native enzymes.
基金supported by the National Natural Science Foundation of China (Nos. U20B6004 and 22072179 )the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDA23010203)。
文摘Alumina supported Pd catalyst(Pd/Al_(2)O_(3)) is active for complete oxidation of methane, while often suffers transient deactivation during the cold down process. Herein, heating and cooling cycle tests between 200 and 900 ℃ and isothermal experiments at 650 ℃ were conducted to investigate the influence of NO_(x) on transient deactivation of Pd/θ-Al_(2)O_(3) catalyst during the methane oxidation. It was found that the co-fed of NO alleviated transient deactivation in the cooling ramp from 800 to 500 ℃, which was resulted from the in situ formation of NO_(2) during the process of methane oxidation. Over the Pd/θ-Al_(2)O_(3), thermogravimetric analysis and O_(2) temperature programmed oxidation measurements confirmed that transient deactivation was due to the decomposition of Pd O particles and the hysteresis of Pd reoxidation, while the metal Pd entities were less active for methane oxidation than the Pd O ones. CO pulse chemisorption and scanning transmission electron microscopy characterizations rule out the NO_(2) effect on Pd size change. Powder X-ray diffraction and X-ray photoelectron spectroscopy characterizations were used to obtain palladium status of Pd/θ-Al_(2)O_(3) before and after reactions, indicating that in lean conditions at 650 ℃, the presence of NO_(2) increases the content of active Pd O on the catalyst surface, thus benefits methane oxidation. Homogeneous reaction between CH 4, O_(2), and NO_(x) may be partially responsible for the alleviation above 650 ℃. The interesting research of alleviation in transient deactivation by NO_(x), the components co-existing in exhausts, are of great significance for the application.