Microwave-induced thermoacoustic imaging(MTAI)has advantages including the large imaging depth,high imaging resolution,high imaging contrast,and fast imaging speed.The thermoacoustic(TA)group of South China Normal Uni...Microwave-induced thermoacoustic imaging(MTAI)has advantages including the large imaging depth,high imaging resolution,high imaging contrast,and fast imaging speed.The thermoacoustic(TA)group of South China Normal University has dedicated to developing TA imaging for more than a decade and has made many breakthroughs.This review introduces these breakthroughs from two aspects including the improvement in techniques and the exploration of applications.On the technological level,there are ultrashort microwave pulse(USMP)-inducedTA imaging that can improve the imaging resolution,nonlinear thermoacoustic imaging(NTAI)that can improve the imaging contrast,polarized microwave-inducedthermoacoustic imaging(P-MTAI)that can obtain cellular-level alignment information,and more convenient and accurate handheld and multimodal probes.On the application side,the optimization and expansion have been carried out,mainly concentrating on breast and myocardial imaging.Finally,several current research directions are introduced,including the application of P-MTAI on joint imaging and research on whole-body imaging of small animals.展开更多
BACKGROUND Many natural products confer health benefits against diverse diseases through their antioxidant activities.Carbon tetrachloride(CCl4)is often used in animal experiments to study the effects of substances on...BACKGROUND Many natural products confer health benefits against diverse diseases through their antioxidant activities.Carbon tetrachloride(CCl4)is often used in animal experiments to study the effects of substances on liver injury and the related mechanisms of action,among which oxidative stress is a major pathogenic factor.AIM To compare antioxidant and hepatoprotective activities of ten herbs and identify and quantify phytochemicals for the one with strongest hepatoprotection.METHODS The antioxidant activity of ten medicinal herbs was determined by both ferricreducing antioxidant power and Trolox equivalent antioxidant capacity assays.The total phenolic and flavonoid contents were determined by Folin–Ciocalteu method and aluminum chloride colorimetry,respectively.Their effects on CCl4-induced oxidative liver injury were evaluated and compared in a mouse model by administrating each water extract(0.15 g/mL,10 mL/kg)once per day for seven consecutive days and a dose of CCl4 solution in olive oil(8%,v/v,10 mL/kg).The herb with the strongest hepatoprotective performance was analyzed for the detailed bioactive components by using high-performance liquid chromatography-electrospray ionization source-ion trap tandem mass spectrometry.RESULTS The results revealed that all tested herbs attenuated CCl4-induced oxidative liver injury;each resulted in significant decreases in levels of serum alanine transaminase,aspartate transaminase,alkaline phosphatase,and triacylglycerols.In addition,most herbs restored hepatic superoxide dismutase and catalase activities,glutathione levels,and reduced malondialdehyde levels.Sanguisorba officinalis(S.officinalis)L.,Coptis chinensis Franch.,and Pueraria lobata(Willd.)Ohwi root were the three most effective herbs,and S.officinalis L.exhibited the strongest hepatoprotective effect.Nine active components were identified in S.officinalis L.Gallic acid and(+)-catechin were quantified(7.86±0.45 mg/g and 8.19±0.57 mg/g dried weight,respectively).Furthermore,the tested herbs displayed a range of in vitro antioxidant activities proportional to their phenolic content;the strongest activities were also found for S.officinalis L.CONCLUSION This study is of value to assist the selection of more effective natural products for direct consumption and the development of nutraceuticals or therapeutics to manage oxidative stress-related diseases.展开更多
In the presence of energetic particles(EPs)from auxiliary heating and burning plasmas,fishbone instability and Alfvén modes can be excited and their transition can take place in certain overlapping regimes.Using ...In the presence of energetic particles(EPs)from auxiliary heating and burning plasmas,fishbone instability and Alfvén modes can be excited and their transition can take place in certain overlapping regimes.Using the hybrid kinetic-magnetohydrodynamic model in the NIMROD code,we have identified such a transition between the fishbone instability and theβ-induced Alfvén eigenmode(BAE)for the NBI heated plasmas on HL-2 A.When the safety factor at magnetic axis is well below one,typical kink-fishbone transition occurs as the EP fraction increases.When q0 is raised to approaching one,the fishbone mode is replaced with BAE for sufficient amount of EPs.When q0 is slightly above one,the toroidicity-induced Alfvén eigenmode dominates at lower EP pressure,whereas BAE dominates at higher EP pressure.展开更多
Objective: To investigate the weight losing, antihyperlipidemic and cardioprotective effects of the alkaloid fraction of Hunteria umbellata(H. umbellata) seed.Methods: Adult female Wistar rats(weight range: 120-150 g)...Objective: To investigate the weight losing, antihyperlipidemic and cardioprotective effects of the alkaloid fraction of Hunteria umbellata(H. umbellata) seed.Methods: Adult female Wistar rats(weight range: 120-150 g) were randomly divided into 4 and 5 treatment groups in the normal and triton-induced hyperlipidemic models, respectively. and were daily treated for 14 d before they were humanely sacrificed under inhaled diethyl ether anesthesia. About 5 mL of whole blood was obtained by cardiac puncture from each treated rat, from which serum for lipids assay was subsequently separated. Tissue samples of livers of treated rats were harvested and processed for histopathological analysis.Results: Repeated daily oral treatments of normal rats with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata resulted in significant(P<0.05 and P<0.001) and dose-dependent weight loss, and decreases in the serum triglyceride, total cholesterol and low density lipoprotein cholesterol, while significantly(P<0.001) increased the serum levels of high density lipoprotein cholesterol fraction. Similarly, oral pre-treatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata for 14 d before induction of hyperlipidemia with triton WR-1339 significantly(P<0.01, P<0.001) and dose-dependently attenuated increases in the average body weights, serum levels of triglyceride, total cholesterol and low density lipoprotein cholesterol while also significantly(P<0.01, P<0.001) and dose-dependently attenuated significant(P<0.001) decrease in the serum high-density lipoproteincholesterol levels when compared to the untreated control values. However, the results obtained for 50 mg/kg of alkaloid fraction of H. umbellata in both normal and triton WR-1339-induced hyperlipidemic rats were comparable to that recorded for 20 mg/kg of simvastatin. Similarly, oral pretreatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata significantly improved the histological lesions of fatty hepatic degeneration induced by triton WR-1339 treatment.Conclusions: Overall, results of this study showed that repeated oral treatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata elicited weight losing, antihyperlipidemic and cardioprotective effects in triton WR-1339 induced hyperlipidemic rats that were mediated via de novo cholesterol biosynthesis inhibition.展开更多
As a member of the inwardly rectifying channel (Kir) family, Kir2.1 allows to influx the cell more easily than to efflux, a biophysical phenomenon named inward rectification. The function of Kir2.1 is to set the resti...As a member of the inwardly rectifying channel (Kir) family, Kir2.1 allows to influx the cell more easily than to efflux, a biophysical phenomenon named inward rectification. The function of Kir2.1 is to set the resting membrane potential and modulate membrane excitability. It has been reported that residue E224 plays a key role in regulating inward rectification. The mutant Kir2.1 (E224G) displays weaker inward rectification than the WT channel. Gating of Kir2.1 depends on the membrane lipid, PIP<sub>2</sub>, such that the channel gates are closed in the absence of PIP<sub>2</sub>. Here we perform electrophysiological and computational approaches, and demonstrate that E224 also plays an important role in the PIP<sub>2</sub>-dependent activation of Kir2.1 in addition to its influence on inward rectification. The E224G mutant takes 4.5 times longer to be activated by PIP<sub>2</sub>. To probe the mechanism by which E224G slows the channel opening kinetics, we perform targeted molecular dynamics simulations and find that the mutant weakens the interactions between CD-loop and C-linker (H221-R189) and the adjacent G-loops (R312-E303) which are thought to stabilize the open state of the channel in our previous work. These data provide new insights into the regulation of Kir2.1 channel activity and suggest that a common mechanism may be involved in the distinct biophysical processes, such as inward rectification and PIP<sub>2</sub>-induced gating.展开更多
Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have ant...Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.展开更多
In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of su...In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of subcells on Cu(Inx,Ga1-x)Se2(CIGS)modules.In this way,we show that in-depth monitoring of material degradation in the vicinity of the ablation region and the identification of the underlying mechanisms can be accomplished.Specifically,by analyzing the standard P1 patterning line ablated before the CIGS deposition,we reveal an anomalous emission-quenching effect that follows the edge of the molybdenum groove underneath.We further rationalize the origins of this effect by comparing the topography of the P1 edge through a scanning electron microscope(SEM)cross-section,where a reduction of the photoemission cannot be explained by a thickness variation.We also investigate the laser-induced damage on P1 patterning lines performed after the deposition of CIGS.We then document,for the first time,the existence of a short-range damaged area,which is independent of the application of an optical aperture on the laser path.Our findings pave the way for a better understanding of P1-induced power losses and introduce new insights into the improvement of current strategies for industry-relevant module interconnection schemes.展开更多
The development of aqueous battery with dual mechanisms is now arousing more and more interest.The dual mechanisms of Zn^(2+)(de)intercalation and I^(-)/I_(2)redox bring unexpected effects.Herein,differing from previo...The development of aqueous battery with dual mechanisms is now arousing more and more interest.The dual mechanisms of Zn^(2+)(de)intercalation and I^(-)/I_(2)redox bring unexpected effects.Herein,differing from previous studies using Zn I_(2)additive,this work designs an aqueous Bi I_(3)-Zn battery with selfsupplied I^(-).Ex situ tests reveal the conversion of Bi I_(3)into Bi(discharge)and Bi OI(charge)at the 1st cycle and the dissolved I^(-)in electrolyte.The active I^(-)species enhances the specific capacity and discharge medium voltage of electrode as well as improves the generation of Zn dendrite and by-product.Furthermore,the porous hard carbon is introduced to enhance the electronic/ionic conductivity and adsorb iodine species,proven by experimental and theoretical studies.Accordingly,the well-designed Bi I_(3)-Zn battery delivers a high reversible capacity of 182 m A h g^(-1)at 0.2 A g^(-1),an excellent rate capability with 88 m A h g^(-1)at 10 A g^(-1),and an impressive cyclability with 63%capacity retention over 20 K cycles at 10 A g^(-1).An excellent electrochemical performance is obtained even at a high mass loading of 6 mg cm^(-2).Moreover,a flexible quasi-solid-state Bi I_(3)-Zn battery exhibits satisfactory battery performances.This work provides a new idea for designing high-performance aqueous battery with dual mechanisms.展开更多
BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidate...BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.展开更多
BACKGROUND Wnt1-inducible signaling pathway protein 1(WISP1)is upregulated in several types of human cancer,and has been implicated in cancer progression.However,its clinical implications in gastric cancer(GC)remain u...BACKGROUND Wnt1-inducible signaling pathway protein 1(WISP1)is upregulated in several types of human cancer,and has been implicated in cancer progression.However,its clinical implications in gastric cancer(GC)remain unclear.AIM To explore the expression pattern and clinical significance of WISP1 in GC.METHODS Public data portals,including Oncomine,The Cancer Genome Atlas database,Coexpedia,and Kaplan-Meier plotter,were analyzed for the expression and clinical significance of WISP1 mRNA levels in GC.One hundred and fifty patients who underwent surgery for GC between February 2010 and October 2012 at the Affiliated Hospital of Jiangnan University were selected for validation study.WISP1 levels were measured at both the mRNA and protein levels by RTqPCR,Western blot analysis,and immunohistochemistry(IHC).In addition,the in situ expression of WISP1 in the GC tissues was determined by IHC,and the patients were accordingly classified into high-and low-expression groups.The correlation of WISP1 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.WISP1 was knocked down by RNA interference.The 50%inhibitory concentration of oxaliplatin was detected by CellTiter-Blue assay.RESULTS WISP1 levels at both the mRNA and protein levels were remarkably upregulated in GC tissues compared to normal tissues.Moreover,IHC revealed that WISP1 expression was associated with T stage and chemotherapy outcome,but not with lymph node metastasis,age,gender,histological grade,or histological type.GC patients with high WISP1 expression showed a poor overall survival.Multivariate survival analysis indicated that WISP1 was an important prognostic factor for GC patients.Mechanistically,knock-down of WISP1 expression enhanced sensitivity to oxaliplatin by reducing DNA repair and enhancing DNA damage.CONCLUSION Significantly upregulated WISP1 expression is associated with cancer progression,chemotherapy outcome,and prognosis in GC.Mechanistically,knock-down of WISP1 expression enhances oxaliplatin sensitivity by reducing DNA repair and enhancing DNA damage.WISP1 may be a potential therapeutic target for GC treatment or a potential biomarker for diagnosis and prognosis.展开更多
Wnt1-inducible signaling pathway protein-1(WISP1),a member of the CCN family,is increasingly being recognized as a potential target for obesity and type 2 diabetes mellitus.Recent studies have shown that WISP1 can reg...Wnt1-inducible signaling pathway protein-1(WISP1),a member of the CCN family,is increasingly being recognized as a potential target for obesity and type 2 diabetes mellitus.Recent studies have shown that WISP1 can regulate low-grade inflammation in obese mice,and circulating WISP1 levels are associated with obesity and type 2 diabetes mellitus in adults.Herein,we measured serum WISP1 levels in obese youth and explored its relationships with pro-inflammatory cytokine interleukin 18(IL-18)and other metabolic indexes.Totally,44 normal-weight and 44 obese children and adolescents were enrolled.Physical and laboratory data were recorded,and then serum levels of WISP1 and IL-18 were determined by enzyme-linked immunosorbent assays.Results showed that serum levels of WISP1 were significantly higher in obese children and adolescents than in normal-weight healthy controls (1735.444-15.29 vs. 1364.084-18.69 pg/mL).WISP1 levels were significantly positively correlated with body mass index (BMI)and BMI z-score (r=0.392,P=0.008;r=0.474,P=0.001,respectively) in obese group;circulating IL-18 was increased in obese individuals (1229.064-29.42 vs. 295.874-13.30 pg/mL).Circulating WISP1 levels were significantly correlated with IL-18 (r=0.542,P<0.001),adiponectin (r=0.585,P<0.001)and leptin (r=0.592,P<0.001).The multivariate stepwise regression analysis showed that higher IL-18 levels represented the main determinant of increased WISP1 levels after adjusting for BMI,waist circumference, fasting insulin,homeostatic model assessment of insulin resistance (HOMA-IR)and HbAlc in obese individuals (β=0.542,P=0.000).WISP1 can be involved in glucose/lipid metabolism in obese youth,which may be modulated by IL-18.Increased WISP1 levels may be a risk factor of obesity and insulin resistance,and WISP1 has a potential therapeutic effect on insulin resistance in obese children and adolescents.展开更多
Background and aims:Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence.Pharmacological research is becoming increasingly focused on personalized treatment strategies.Drug ...Background and aims:Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence.Pharmacological research is becoming increasingly focused on personalized treatment strategies.Drug development based on glucokinase(GK)activation is an important strategy for lowering blood glucose.This study aimed to investigate the effect of GK activation on glucose and lipid metabolism in diet-induced obese mice.Materials and methods:Mice were fed with a high-fat diet(HFD)for 16 weeks to induce obesity,followed by a GK activator(GKA,AZD1656)or vehicle treatment by gavage for 4 weeks.The effect of GKA treatment on glucose metabolism was evaluated using glucose and insulin tolerance tests.Hepatic lipid accumulation was assessed by hematoxylin and eosin staining,Oil Red O staining,and transmission electron microscopy.The underlying mechanism of GK activation in glucose and lipid metabolism in the liver was studied using transcriptomic analysis,with a mechanistic study in mouse livers in vivo and AML12 cells in vitro.Results:GK activation by GKA treatment improved glucose tolerance in HFD-fed mice while increasing hepatic lipid accumulation.Transcriptomic analysis of liver tissues indicated the lipogenesis and protein kinase RNA-like endoplasmic reticulum kinase(PERK)-unfolded protein response(UPR)pathway activations in GKA-treated HFD-fed mice.Inhibition of the ACC activity,which is an important protein in lipogenesis,attenuated GKA treatment-induced lipid accumulation and PERK-UPR activation in vitro.Conclusions:GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation by increasing the lipogenic gene expression,which subsequently activated the hepatic PERK-UPR signaling pathway.展开更多
Objectives: To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STP) on Na2S2O4-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells. Methods: The cell viability and level...Objectives: To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STP) on Na2S2O4-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells. Methods: The cell viability and levels of mRNA and protein expression in H9c2 cells were determined following Na2S2O4-induced hypoxia using Hoechst staining, annexin V/propidium iodide(PI) flow cytometry, real-time polymerase chain reaction and Western blot analysis. Results: STP pretreatment signi?cantly increased the viability and inhibited aberrant morphological changes in H9c2 cardiomyoblast cells induced by Na2S2O4 treatment(P<0.05). In addition, STP pretreatment attenuated Na2S2O4-induced hypoxic damage, down-regulated the expression of pro-apoptotic Bax,and up-regulated the expression of anti-apoptotic Bcl-2 in H9c2 cells(P<0.05). Conclusions: STP was strongly cardioprotective in hypoxia-reoxygenation injury by preventing hypoxic damage and inhibiting cellular apoptosis.These results further support the use of STP as an effective drug for the treatment of ischemic heart disease.展开更多
Background: Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wipl) has been studied extensively in the context of cancer and the regulation of different types of stem cel...Background: Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wipl) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wipl in cardiac adaptation to M I is unknown. We investigated the significance of Wipl in a mouse model of MI. Methods: The study began in June 2014 and was completed in July 2016. We compared Wipl-knockout (Wipl-KO) mice and wild-type (WT) mice to deternline changes in cardiac function and survival in response to MI. The heart weight/body weight (HW/BW) ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending (LAD) coronary artery under 1.5% isoflurane anesthesia. After M1, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin (H&E) staining was used to determine the infarct size. Gene expression of interleukin-6 (IL-6), turnor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) was assessed by quantitative real-time polymerase chain reaction (qPCR), and the levels of signal transducers and activators of transcription 3 (stat3) and phosphor-stat3 (p-stat3) were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired l-test, and one-way analysis of variance (ANOVA) were used for statistical analyses. Results: Wipl-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac fiinction before LAD ligation. Alter MI, Wipl-deficient mice exhibited increased mortality (57.14% vs. 29.17%; n = 24 [WT], n - 35 [WipI-KO], P 〈 0.05), increased cardiac hypertrophy (HW/BW ratio: 7 days: 7.25±0.36 vs. 5.84 ± 0.18, n cross-sectional area: 7 days: 311.80 ± 8.29 vs. 268.90 ± 11.15, n P 〉 0.05), and reduced cardiac function (ejection fraction: 7 days 10, p〈 0.01, and 4 weeks: 6.05± 0.17 vs. 5.87 ±0.24, n= 10, P〉0.05; P 〈 0.05, and 4 weeks: 308.80 ± 11.26 vs. 317.00 ±13.55, n = 6 29.37± 1.38 vs. 34.72 ± 1.81, P 〈 0.05, and 4 weeks: 19.06 ± 2.07 vs 26.37 ± 2.95, P〈 0.05; fractional shortening: 7 days: 13.72 ± 0.71 vs. 16.50 ± 0.94, P〈 0.05, and 4 weeks: 8.79 ±1.00 vs. 12.48 ±1.48, P 〈 0.05; n = l0 [WT], n = 15 [Wipl-KO]). H&E staining revealed a larger infarct size in Wipl-KO mice than in WT mice (34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P 〈 0.01 ). The expression oflL-6 and p-stat3 was downregulated in Wipl-KO mice (IL-6:1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P 〈 0.01 ; and p-stat3/stat3:1.15 ±0.15 vs. 1.97 ± 0.23, n = 6, P 〈 0.05). Conclusion: The results suggest that Wipl could protect the heart from MI-induced ischemic injury.展开更多
The mechanism involving the effect of disorder/order transformation on the environmental embrittlement in gaseous H2 is summarized. It is shown that there is no hydrogen embrittlement in disordered state of Kurnakov t...The mechanism involving the effect of disorder/order transformation on the environmental embrittlement in gaseous H2 is summarized. It is shown that there is no hydrogen embrittlement in disordered state of Kurnakov type intermetallics in gaseous H2. However, the H2-induced environmental embrittlement for the ordered alloy having identical chemical composition becomes severer as the degree of the order increases. The results of testing on the ion gage turned on and off during tensile testing show that the more sensitive to H2-induced hydrogen embrittlement for ordered alloy than disordered one is attributed to the fact that atomic ordering may accelerate the kinetics of the catalytic reaction to produce more atomic hydrogen. The results on simultaneous hydrogen charging show that disordered alloys embrittled as hydrogen atoms are forced into the material implying that the embrittlement of ordered alloy in gaseous H2 is also due to the acceleration of the kinetics of catalytic reaction. The above suggestion was further verified by the adsorption tests of Ni3Fe intermetallics powder. It is shown that the amount of chemically adsorbed hydrogen in ordered state is significantly larger than that adsorbed by the disordered alloy, indicating that the more sensitive to H2-induced embrittlement in the ordered state of alloy is essentially due to the accelerated catalytic reaction.展开更多
Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and ...Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats. The effect of ET-1 on [Ca2+]i elevation was abolished in the presence of the ETA receptor blocker BQ123, but was not affected by the ETB receptor blocker BQ788. ET-1-induced an increase in [Ca2+]i, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETA receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.展开更多
Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection;however, the molecular regulation of NET formation remains poorly understood. In the current study,...Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection;however, the molecular regulation of NET formation remains poorly understood. In the current study, we found that inhibition of the wild-type p53-induced phosphatase 1 (Wip1) significantly suppressed the activity of Staphylococcus aureus (S. aureus) and accelerated abscess healing in S. aureus-induced abscess model mice by enhancing NET formation. A Wip1 inhibitor significantly enhanced NET formation in mouse and human neutrophils in vitro. High-resolution mass spectrometry and biochemical assays demonstrated that Coro1a is a substrate of Wip1. Further experiments also revealed that Wip1 preferentially and directly interacts with phosphorylated Coro1a than compared to unphosphorylated inactivated Coro1a. The phosphorylated Ser426 site of Coro1a and the 28–90 aa domain of Wip1 are essential for the direct interaction of Coro1a and Wip1 and for Wip1 dephosphorylation of p-Coro1a Ser426. Wip1 deletion or inhibition in neutrophils significantly upregulated the phosphorylation of Coro1a-Ser426, which activated phospholipase C and subsequently the calcium pathway, the latter of which promoted NET formation after infection or lipopolysaccharide stimulation. This study revealed Coro1a to be a novel substrate of Wip1 and showed that Wip1 is a negative regulator of NET formation during infection. These results support the potential application of Wip1 inhibitors to treat bacterial infections.展开更多
Daily snow data for 2300 climate stations covering the period from 1951 through 1980 have been used to monitor and diagnose secular variations,year-to-year fluctuations,and the spatial characteristics of snow variatio...Daily snow data for 2300 climate stations covering the period from 1951 through 1980 have been used to monitor and diagnose secular variations,year-to-year fluctuations,and the spatial characteristics of snow variation trends in China.An examination of time series reveals that there is a strong teleconnction to ENSO,to major volcanic eruptions, as well as to the CO_2-induced warming.The country-wide snow mass variations are positively correlated with global mean temperature,increasing during the current warming period and decreasing during the recent cooling period prior to the mid 1960s.A synchronous relationship exists between El Nino/Southern Oscillation and snowy winter in China. The year-to-year snow fluctuations seem to be generally out of phase with volcanic activity.The anomaly map shows that snow mass increased in high altitudes and moist regions,while it decreased in arid lowland and the southern bounda- ry zone during the warming period.The potential CO_2-induced changes in snow mass will further aggravate the regional differentiation between high mountains and lowlands,between moist and arid regions.The number of snow cover days will decrease in the northern lowlands,and snowfall will increase in the Qinghai-Xizang Plateau,high mountains,and the lower reaches of the Changjiang(Yangtze)River.展开更多
Mono-alkyl-functionalized pillar[5]arenes PI, P2, and P3 were synthesized by click reaction, which exhibited different self-assembly behavior in polar solvent DMSO. Stable pseudo[ 1 ]rotaxane was formed by the self-co...Mono-alkyl-functionalized pillar[5]arenes PI, P2, and P3 were synthesized by click reaction, which exhibited different self-assembly behavior in polar solvent DMSO. Stable pseudo[ 1 ]rotaxane was formed by the self-complexation from P1 or P2, whereas, concentration-dependent pseudorotaxane structures were generated by P3 which bearing more flexible side chain. Interestingly, the obtained pseudo[1]rotaxanes exhibited a dynamic fast assembly process upon adding NaBF4, resulting in the formation of Na+-induced pseudorotaxanes.展开更多
文摘Microwave-induced thermoacoustic imaging(MTAI)has advantages including the large imaging depth,high imaging resolution,high imaging contrast,and fast imaging speed.The thermoacoustic(TA)group of South China Normal University has dedicated to developing TA imaging for more than a decade and has made many breakthroughs.This review introduces these breakthroughs from two aspects including the improvement in techniques and the exploration of applications.On the technological level,there are ultrashort microwave pulse(USMP)-inducedTA imaging that can improve the imaging resolution,nonlinear thermoacoustic imaging(NTAI)that can improve the imaging contrast,polarized microwave-inducedthermoacoustic imaging(P-MTAI)that can obtain cellular-level alignment information,and more convenient and accurate handheld and multimodal probes.On the application side,the optimization and expansion have been carried out,mainly concentrating on breast and myocardial imaging.Finally,several current research directions are introduced,including the application of P-MTAI on joint imaging and research on whole-body imaging of small animals.
文摘BACKGROUND Many natural products confer health benefits against diverse diseases through their antioxidant activities.Carbon tetrachloride(CCl4)is often used in animal experiments to study the effects of substances on liver injury and the related mechanisms of action,among which oxidative stress is a major pathogenic factor.AIM To compare antioxidant and hepatoprotective activities of ten herbs and identify and quantify phytochemicals for the one with strongest hepatoprotection.METHODS The antioxidant activity of ten medicinal herbs was determined by both ferricreducing antioxidant power and Trolox equivalent antioxidant capacity assays.The total phenolic and flavonoid contents were determined by Folin–Ciocalteu method and aluminum chloride colorimetry,respectively.Their effects on CCl4-induced oxidative liver injury were evaluated and compared in a mouse model by administrating each water extract(0.15 g/mL,10 mL/kg)once per day for seven consecutive days and a dose of CCl4 solution in olive oil(8%,v/v,10 mL/kg).The herb with the strongest hepatoprotective performance was analyzed for the detailed bioactive components by using high-performance liquid chromatography-electrospray ionization source-ion trap tandem mass spectrometry.RESULTS The results revealed that all tested herbs attenuated CCl4-induced oxidative liver injury;each resulted in significant decreases in levels of serum alanine transaminase,aspartate transaminase,alkaline phosphatase,and triacylglycerols.In addition,most herbs restored hepatic superoxide dismutase and catalase activities,glutathione levels,and reduced malondialdehyde levels.Sanguisorba officinalis(S.officinalis)L.,Coptis chinensis Franch.,and Pueraria lobata(Willd.)Ohwi root were the three most effective herbs,and S.officinalis L.exhibited the strongest hepatoprotective effect.Nine active components were identified in S.officinalis L.Gallic acid and(+)-catechin were quantified(7.86±0.45 mg/g and 8.19±0.57 mg/g dried weight,respectively).Furthermore,the tested herbs displayed a range of in vitro antioxidant activities proportional to their phenolic content;the strongest activities were also found for S.officinalis L.CONCLUSION This study is of value to assist the selection of more effective natural products for direct consumption and the development of nutraceuticals or therapeutics to manage oxidative stress-related diseases.
基金supported by the National Magnetic Confinement Fusion Science Program of China(No.2019YFE03050004)National Natural Science Foundation of China(Nos.11875253,11775221,51821005)+3 种基金the Fundamental Research Funds for the Central Universities at University of Science and Technology of China(No.WK3420000004)Huazhong University of Science and Technology(No.2019kfy XJJS193)the Collaborative Innovation Program of Hefei Science Center,CAS(No.2019HSC-CIP015)the U.S.Department of Energy(Nos.DE-FG02-86ER53218 and DE-SC0018001)。
文摘In the presence of energetic particles(EPs)from auxiliary heating and burning plasmas,fishbone instability and Alfvén modes can be excited and their transition can take place in certain overlapping regimes.Using the hybrid kinetic-magnetohydrodynamic model in the NIMROD code,we have identified such a transition between the fishbone instability and theβ-induced Alfvén eigenmode(BAE)for the NBI heated plasmas on HL-2 A.When the safety factor at magnetic axis is well below one,typical kink-fishbone transition occurs as the EP fraction increases.When q0 is raised to approaching one,the fishbone mode is replaced with BAE for sufficient amount of EPs.When q0 is slightly above one,the toroidicity-induced Alfvén eigenmode dominates at lower EP pressure,whereas BAE dominates at higher EP pressure.
基金Supported by Institute of International Education(IIE ID:15101139)
文摘Objective: To investigate the weight losing, antihyperlipidemic and cardioprotective effects of the alkaloid fraction of Hunteria umbellata(H. umbellata) seed.Methods: Adult female Wistar rats(weight range: 120-150 g) were randomly divided into 4 and 5 treatment groups in the normal and triton-induced hyperlipidemic models, respectively. and were daily treated for 14 d before they were humanely sacrificed under inhaled diethyl ether anesthesia. About 5 mL of whole blood was obtained by cardiac puncture from each treated rat, from which serum for lipids assay was subsequently separated. Tissue samples of livers of treated rats were harvested and processed for histopathological analysis.Results: Repeated daily oral treatments of normal rats with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata resulted in significant(P<0.05 and P<0.001) and dose-dependent weight loss, and decreases in the serum triglyceride, total cholesterol and low density lipoprotein cholesterol, while significantly(P<0.001) increased the serum levels of high density lipoprotein cholesterol fraction. Similarly, oral pre-treatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata for 14 d before induction of hyperlipidemia with triton WR-1339 significantly(P<0.01, P<0.001) and dose-dependently attenuated increases in the average body weights, serum levels of triglyceride, total cholesterol and low density lipoprotein cholesterol while also significantly(P<0.01, P<0.001) and dose-dependently attenuated significant(P<0.001) decrease in the serum high-density lipoproteincholesterol levels when compared to the untreated control values. However, the results obtained for 50 mg/kg of alkaloid fraction of H. umbellata in both normal and triton WR-1339-induced hyperlipidemic rats were comparable to that recorded for 20 mg/kg of simvastatin. Similarly, oral pretreatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata significantly improved the histological lesions of fatty hepatic degeneration induced by triton WR-1339 treatment.Conclusions: Overall, results of this study showed that repeated oral treatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata elicited weight losing, antihyperlipidemic and cardioprotective effects in triton WR-1339 induced hyperlipidemic rats that were mediated via de novo cholesterol biosynthesis inhibition.
基金Supported by the National Natural Science Foundation for Distinguished Young Scholars of Hebei Province under Grant Nos C2015202340 and C2013202244the Foundation for Outstanding Talents of Hebei Province under Grant No C201400305+3 种基金the National Natural Science Foundation of China under Grant Nos 11247010,11175055,11475053,11347017,31400711 and 11647121the NIH R01 under Grant No HL059949-18the Foundation for the Science and Technology Program of Higher Education Institutions of Hebei Province under Grant No QN2016113the Scientific Innovation Fund for Excellent Young Scientists of Hebei University of Technology under Grant No 2015010
文摘As a member of the inwardly rectifying channel (Kir) family, Kir2.1 allows to influx the cell more easily than to efflux, a biophysical phenomenon named inward rectification. The function of Kir2.1 is to set the resting membrane potential and modulate membrane excitability. It has been reported that residue E224 plays a key role in regulating inward rectification. The mutant Kir2.1 (E224G) displays weaker inward rectification than the WT channel. Gating of Kir2.1 depends on the membrane lipid, PIP<sub>2</sub>, such that the channel gates are closed in the absence of PIP<sub>2</sub>. Here we perform electrophysiological and computational approaches, and demonstrate that E224 also plays an important role in the PIP<sub>2</sub>-dependent activation of Kir2.1 in addition to its influence on inward rectification. The E224G mutant takes 4.5 times longer to be activated by PIP<sub>2</sub>. To probe the mechanism by which E224G slows the channel opening kinetics, we perform targeted molecular dynamics simulations and find that the mutant weakens the interactions between CD-loop and C-linker (H221-R189) and the adjacent G-loops (R312-E303) which are thought to stabilize the open state of the channel in our previous work. These data provide new insights into the regulation of Kir2.1 channel activity and suggest that a common mechanism may be involved in the distinct biophysical processes, such as inward rectification and PIP<sub>2</sub>-induced gating.
基金supported by the Russian Foundation for Basic Research (Grant No. 20-04-00526А)
文摘Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.
基金the DFG research training group GRK 1896 at Erlangen University and from the Joint Project Helmholtz-Institute Erlangen-Nürnberg(HI-ERN)for Renewable Energy Production under Project DBF01253,respectivelyfinancial support through the“Aufbruch Bayern”initiative of the state of Bavaria(EnCN and Solar Factory of the Future)and the“Solar Factory of the Future”with the Energy Campus Nürnberg(EnCN).
文摘In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of subcells on Cu(Inx,Ga1-x)Se2(CIGS)modules.In this way,we show that in-depth monitoring of material degradation in the vicinity of the ablation region and the identification of the underlying mechanisms can be accomplished.Specifically,by analyzing the standard P1 patterning line ablated before the CIGS deposition,we reveal an anomalous emission-quenching effect that follows the edge of the molybdenum groove underneath.We further rationalize the origins of this effect by comparing the topography of the P1 edge through a scanning electron microscope(SEM)cross-section,where a reduction of the photoemission cannot be explained by a thickness variation.We also investigate the laser-induced damage on P1 patterning lines performed after the deposition of CIGS.We then document,for the first time,the existence of a short-range damaged area,which is independent of the application of an optical aperture on the laser path.Our findings pave the way for a better understanding of P1-induced power losses and introduce new insights into the improvement of current strategies for industry-relevant module interconnection schemes.
基金funding from National Natural Science Foundation of China(52103053,52102312)Huxiang Young Talents of Hunan Province(2022RC1004)+1 种基金Macao Young Scholars Program(AM2021011)Foundation of State Key Laboratory of Utilization of Woody Oil Resource(GZKF202126)。
文摘The development of aqueous battery with dual mechanisms is now arousing more and more interest.The dual mechanisms of Zn^(2+)(de)intercalation and I^(-)/I_(2)redox bring unexpected effects.Herein,differing from previous studies using Zn I_(2)additive,this work designs an aqueous Bi I_(3)-Zn battery with selfsupplied I^(-).Ex situ tests reveal the conversion of Bi I_(3)into Bi(discharge)and Bi OI(charge)at the 1st cycle and the dissolved I^(-)in electrolyte.The active I^(-)species enhances the specific capacity and discharge medium voltage of electrode as well as improves the generation of Zn dendrite and by-product.Furthermore,the porous hard carbon is introduced to enhance the electronic/ionic conductivity and adsorb iodine species,proven by experimental and theoretical studies.Accordingly,the well-designed Bi I_(3)-Zn battery delivers a high reversible capacity of 182 m A h g^(-1)at 0.2 A g^(-1),an excellent rate capability with 88 m A h g^(-1)at 10 A g^(-1),and an impressive cyclability with 63%capacity retention over 20 K cycles at 10 A g^(-1).An excellent electrochemical performance is obtained even at a high mass loading of 6 mg cm^(-2).Moreover,a flexible quasi-solid-state Bi I_(3)-Zn battery exhibits satisfactory battery performances.This work provides a new idea for designing high-performance aqueous battery with dual mechanisms.
文摘BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.
文摘BACKGROUND Wnt1-inducible signaling pathway protein 1(WISP1)is upregulated in several types of human cancer,and has been implicated in cancer progression.However,its clinical implications in gastric cancer(GC)remain unclear.AIM To explore the expression pattern and clinical significance of WISP1 in GC.METHODS Public data portals,including Oncomine,The Cancer Genome Atlas database,Coexpedia,and Kaplan-Meier plotter,were analyzed for the expression and clinical significance of WISP1 mRNA levels in GC.One hundred and fifty patients who underwent surgery for GC between February 2010 and October 2012 at the Affiliated Hospital of Jiangnan University were selected for validation study.WISP1 levels were measured at both the mRNA and protein levels by RTqPCR,Western blot analysis,and immunohistochemistry(IHC).In addition,the in situ expression of WISP1 in the GC tissues was determined by IHC,and the patients were accordingly classified into high-and low-expression groups.The correlation of WISP1 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.WISP1 was knocked down by RNA interference.The 50%inhibitory concentration of oxaliplatin was detected by CellTiter-Blue assay.RESULTS WISP1 levels at both the mRNA and protein levels were remarkably upregulated in GC tissues compared to normal tissues.Moreover,IHC revealed that WISP1 expression was associated with T stage and chemotherapy outcome,but not with lymph node metastasis,age,gender,histological grade,or histological type.GC patients with high WISP1 expression showed a poor overall survival.Multivariate survival analysis indicated that WISP1 was an important prognostic factor for GC patients.Mechanistically,knock-down of WISP1 expression enhanced sensitivity to oxaliplatin by reducing DNA repair and enhancing DNA damage.CONCLUSION Significantly upregulated WISP1 expression is associated with cancer progression,chemotherapy outcome,and prognosis in GC.Mechanistically,knock-down of WISP1 expression enhances oxaliplatin sensitivity by reducing DNA repair and enhancing DNA damage.WISP1 may be a potential therapeutic target for GC treatment or a potential biomarker for diagnosis and prognosis.
基金This study was supported by the National Natural Science Foundation of China (No.81670781)and program for Changjiang Scholars and Innovative Research Team in University (No.PCSIRT 1131).
文摘Wnt1-inducible signaling pathway protein-1(WISP1),a member of the CCN family,is increasingly being recognized as a potential target for obesity and type 2 diabetes mellitus.Recent studies have shown that WISP1 can regulate low-grade inflammation in obese mice,and circulating WISP1 levels are associated with obesity and type 2 diabetes mellitus in adults.Herein,we measured serum WISP1 levels in obese youth and explored its relationships with pro-inflammatory cytokine interleukin 18(IL-18)and other metabolic indexes.Totally,44 normal-weight and 44 obese children and adolescents were enrolled.Physical and laboratory data were recorded,and then serum levels of WISP1 and IL-18 were determined by enzyme-linked immunosorbent assays.Results showed that serum levels of WISP1 were significantly higher in obese children and adolescents than in normal-weight healthy controls (1735.444-15.29 vs. 1364.084-18.69 pg/mL).WISP1 levels were significantly positively correlated with body mass index (BMI)and BMI z-score (r=0.392,P=0.008;r=0.474,P=0.001,respectively) in obese group;circulating IL-18 was increased in obese individuals (1229.064-29.42 vs. 295.874-13.30 pg/mL).Circulating WISP1 levels were significantly correlated with IL-18 (r=0.542,P<0.001),adiponectin (r=0.585,P<0.001)and leptin (r=0.592,P<0.001).The multivariate stepwise regression analysis showed that higher IL-18 levels represented the main determinant of increased WISP1 levels after adjusting for BMI,waist circumference, fasting insulin,homeostatic model assessment of insulin resistance (HOMA-IR)and HbAlc in obese individuals (β=0.542,P=0.000).WISP1 can be involved in glucose/lipid metabolism in obese youth,which may be modulated by IL-18.Increased WISP1 levels may be a risk factor of obesity and insulin resistance,and WISP1 has a potential therapeutic effect on insulin resistance in obese children and adolescents.
基金This research was funded by Natural Science Foundation of Guangdong Province(2018B030311012)Natural Science Foundation of China(82070811,81770826)+2 种基金Sci-Tech Research Development Program of Guangzhou City(202201020497)National Key R&D Program of China(2017YFA0105803)Key Area R&D Program of Guangdong Province(2019B020227003).
文摘Background and aims:Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence.Pharmacological research is becoming increasingly focused on personalized treatment strategies.Drug development based on glucokinase(GK)activation is an important strategy for lowering blood glucose.This study aimed to investigate the effect of GK activation on glucose and lipid metabolism in diet-induced obese mice.Materials and methods:Mice were fed with a high-fat diet(HFD)for 16 weeks to induce obesity,followed by a GK activator(GKA,AZD1656)or vehicle treatment by gavage for 4 weeks.The effect of GKA treatment on glucose metabolism was evaluated using glucose and insulin tolerance tests.Hepatic lipid accumulation was assessed by hematoxylin and eosin staining,Oil Red O staining,and transmission electron microscopy.The underlying mechanism of GK activation in glucose and lipid metabolism in the liver was studied using transcriptomic analysis,with a mechanistic study in mouse livers in vivo and AML12 cells in vitro.Results:GK activation by GKA treatment improved glucose tolerance in HFD-fed mice while increasing hepatic lipid accumulation.Transcriptomic analysis of liver tissues indicated the lipogenesis and protein kinase RNA-like endoplasmic reticulum kinase(PERK)-unfolded protein response(UPR)pathway activations in GKA-treated HFD-fed mice.Inhibition of the ACC activity,which is an important protein in lipogenesis,attenuated GKA treatment-induced lipid accumulation and PERK-UPR activation in vitro.Conclusions:GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation by increasing the lipogenic gene expression,which subsequently activated the hepatic PERK-UPR signaling pathway.
基金Supported by the Foundation of Fujian University of Traditional Chinese Medicine(No.X2013026)the Developmental Fund of Chen Ke-ji Integrative Medicine(No.CKJ2013016)the Education Department of Fujian Province(No.JA14163)
文摘Objectives: To investigate the protective effects of Shexiang Tongxin Dropping Pill(麝香通心滴丸,STP) on Na2S2O4-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells. Methods: The cell viability and levels of mRNA and protein expression in H9c2 cells were determined following Na2S2O4-induced hypoxia using Hoechst staining, annexin V/propidium iodide(PI) flow cytometry, real-time polymerase chain reaction and Western blot analysis. Results: STP pretreatment signi?cantly increased the viability and inhibited aberrant morphological changes in H9c2 cardiomyoblast cells induced by Na2S2O4 treatment(P<0.05). In addition, STP pretreatment attenuated Na2S2O4-induced hypoxic damage, down-regulated the expression of pro-apoptotic Bax,and up-regulated the expression of anti-apoptotic Bcl-2 in H9c2 cells(P<0.05). Conclusions: STP was strongly cardioprotective in hypoxia-reoxygenation injury by preventing hypoxic damage and inhibiting cellular apoptosis.These results further support the use of STP as an effective drug for the treatment of ischemic heart disease.
文摘Background: Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wipl) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wipl in cardiac adaptation to M I is unknown. We investigated the significance of Wipl in a mouse model of MI. Methods: The study began in June 2014 and was completed in July 2016. We compared Wipl-knockout (Wipl-KO) mice and wild-type (WT) mice to deternline changes in cardiac function and survival in response to MI. The heart weight/body weight (HW/BW) ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending (LAD) coronary artery under 1.5% isoflurane anesthesia. After M1, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin (H&E) staining was used to determine the infarct size. Gene expression of interleukin-6 (IL-6), turnor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) was assessed by quantitative real-time polymerase chain reaction (qPCR), and the levels of signal transducers and activators of transcription 3 (stat3) and phosphor-stat3 (p-stat3) were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired l-test, and one-way analysis of variance (ANOVA) were used for statistical analyses. Results: Wipl-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac fiinction before LAD ligation. Alter MI, Wipl-deficient mice exhibited increased mortality (57.14% vs. 29.17%; n = 24 [WT], n - 35 [WipI-KO], P 〈 0.05), increased cardiac hypertrophy (HW/BW ratio: 7 days: 7.25±0.36 vs. 5.84 ± 0.18, n cross-sectional area: 7 days: 311.80 ± 8.29 vs. 268.90 ± 11.15, n P 〉 0.05), and reduced cardiac function (ejection fraction: 7 days 10, p〈 0.01, and 4 weeks: 6.05± 0.17 vs. 5.87 ±0.24, n= 10, P〉0.05; P 〈 0.05, and 4 weeks: 308.80 ± 11.26 vs. 317.00 ±13.55, n = 6 29.37± 1.38 vs. 34.72 ± 1.81, P 〈 0.05, and 4 weeks: 19.06 ± 2.07 vs 26.37 ± 2.95, P〈 0.05; fractional shortening: 7 days: 13.72 ± 0.71 vs. 16.50 ± 0.94, P〈 0.05, and 4 weeks: 8.79 ±1.00 vs. 12.48 ±1.48, P 〈 0.05; n = l0 [WT], n = 15 [Wipl-KO]). H&E staining revealed a larger infarct size in Wipl-KO mice than in WT mice (34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P 〈 0.01 ). The expression oflL-6 and p-stat3 was downregulated in Wipl-KO mice (IL-6:1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P 〈 0.01 ; and p-stat3/stat3:1.15 ±0.15 vs. 1.97 ± 0.23, n = 6, P 〈 0.05). Conclusion: The results suggest that Wipl could protect the heart from MI-induced ischemic injury.
基金Project supported by the National Natural Science Foundation of China (Grant Nos.50371050, 59895157, 59681002, 59771007)
文摘The mechanism involving the effect of disorder/order transformation on the environmental embrittlement in gaseous H2 is summarized. It is shown that there is no hydrogen embrittlement in disordered state of Kurnakov type intermetallics in gaseous H2. However, the H2-induced environmental embrittlement for the ordered alloy having identical chemical composition becomes severer as the degree of the order increases. The results of testing on the ion gage turned on and off during tensile testing show that the more sensitive to H2-induced hydrogen embrittlement for ordered alloy than disordered one is attributed to the fact that atomic ordering may accelerate the kinetics of the catalytic reaction to produce more atomic hydrogen. The results on simultaneous hydrogen charging show that disordered alloys embrittled as hydrogen atoms are forced into the material implying that the embrittlement of ordered alloy in gaseous H2 is also due to the acceleration of the kinetics of catalytic reaction. The above suggestion was further verified by the adsorption tests of Ni3Fe intermetallics powder. It is shown that the amount of chemically adsorbed hydrogen in ordered state is significantly larger than that adsorbed by the disordered alloy, indicating that the more sensitive to H2-induced embrittlement in the ordered state of alloy is essentially due to the accelerated catalytic reaction.
基金Supported by the National Natural Science Foundation of China (Grant No. 200830870910).
文摘Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats. The effect of ET-1 on [Ca2+]i elevation was abolished in the presence of the ETA receptor blocker BQ123, but was not affected by the ETB receptor blocker BQ788. ET-1-induced an increase in [Ca2+]i, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETA receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.
基金supported by grants from the National Natural Science Foundation for General and Key Programs(31930041,YZ)the National Key Research and Development Program of China(2017YFA0105002,2017YFA0104401,2017YFA0104402,YZ)+1 种基金the Knowledge Innovation Program of the Chinese Academy of Sciences(XDA16030301,YZ)the Doctoral Research Foundation Project of Affiliated Hospital of Guizhou Medical University(gyfybsky-2022-1,WZ)。
文摘Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection;however, the molecular regulation of NET formation remains poorly understood. In the current study, we found that inhibition of the wild-type p53-induced phosphatase 1 (Wip1) significantly suppressed the activity of Staphylococcus aureus (S. aureus) and accelerated abscess healing in S. aureus-induced abscess model mice by enhancing NET formation. A Wip1 inhibitor significantly enhanced NET formation in mouse and human neutrophils in vitro. High-resolution mass spectrometry and biochemical assays demonstrated that Coro1a is a substrate of Wip1. Further experiments also revealed that Wip1 preferentially and directly interacts with phosphorylated Coro1a than compared to unphosphorylated inactivated Coro1a. The phosphorylated Ser426 site of Coro1a and the 28–90 aa domain of Wip1 are essential for the direct interaction of Coro1a and Wip1 and for Wip1 dephosphorylation of p-Coro1a Ser426. Wip1 deletion or inhibition in neutrophils significantly upregulated the phosphorylation of Coro1a-Ser426, which activated phospholipase C and subsequently the calcium pathway, the latter of which promoted NET formation after infection or lipopolysaccharide stimulation. This study revealed Coro1a to be a novel substrate of Wip1 and showed that Wip1 is a negative regulator of NET formation during infection. These results support the potential application of Wip1 inhibitors to treat bacterial infections.
基金This work was supported by the National Natural Science Foundation of China through Grant No.4880019.
文摘Daily snow data for 2300 climate stations covering the period from 1951 through 1980 have been used to monitor and diagnose secular variations,year-to-year fluctuations,and the spatial characteristics of snow variation trends in China.An examination of time series reveals that there is a strong teleconnction to ENSO,to major volcanic eruptions, as well as to the CO_2-induced warming.The country-wide snow mass variations are positively correlated with global mean temperature,increasing during the current warming period and decreasing during the recent cooling period prior to the mid 1960s.A synchronous relationship exists between El Nino/Southern Oscillation and snowy winter in China. The year-to-year snow fluctuations seem to be generally out of phase with volcanic activity.The anomaly map shows that snow mass increased in high altitudes and moist regions,while it decreased in arid lowland and the southern bounda- ry zone during the warming period.The potential CO_2-induced changes in snow mass will further aggravate the regional differentiation between high mountains and lowlands,between moist and arid regions.The number of snow cover days will decrease in the northern lowlands,and snowfall will increase in the Qinghai-Xizang Plateau,high mountains,and the lower reaches of the Changjiang(Yangtze)River.
基金the financial support from the National Natural Science Foundation of China(Nos.21472089,21572101)the National Natural Science Foundation of Jiangsu(No.BK20140595)
文摘Mono-alkyl-functionalized pillar[5]arenes PI, P2, and P3 were synthesized by click reaction, which exhibited different self-assembly behavior in polar solvent DMSO. Stable pseudo[ 1 ]rotaxane was formed by the self-complexation from P1 or P2, whereas, concentration-dependent pseudorotaxane structures were generated by P3 which bearing more flexible side chain. Interestingly, the obtained pseudo[1]rotaxanes exhibited a dynamic fast assembly process upon adding NaBF4, resulting in the formation of Na+-induced pseudorotaxanes.