The development of aqueous zinc ion battery cathode materials with high capacity and high magnification is still a challenge.Herein,porous vanadium oxide/carbon(p-VO_(x)@C,mainly VO_(2) with a small amount of V_(2)O_(...The development of aqueous zinc ion battery cathode materials with high capacity and high magnification is still a challenge.Herein,porous vanadium oxide/carbon(p-VO_(x)@C,mainly VO_(2) with a small amount of V_(2)O_(3)) core/shell microspheres with oxygen vacancies are facilely fabricated by using a vanadium-based metal-organic framework(MIL-100(V)) as a sacrificial template.This unique structure can improve the conductivity of the VO_(x),accelerate electrolyte diffusion,and suppress structural collapse during circulation.Subsequently,H_(2)O molecules are introduced into the interlayer of VO_(x) through a highly efficient in-situ electrochemical activation process,facilitating the intercalation and diffusion of zinc ions.After the activation,an optimal sample exhibits a high specific capacity of 464.3 mA h g^(-1) at0.2 A g^(-1) and 395.2 mA h g^(-1) at 10 A g^(-1),indicating excellent rate performance.Moreover,the optimal sample maintains a capacity retention of about 89.3% after 2500 cycles at 10 A g^(-1).Density functional theory calculation demonstrates that the presence of oxygen vacancies and intercalated water molecules can significantly reduce the diffusion barrier for zinc ions.In addition,it is proved that the storage of zinc ions in the cathode is achieved by reversible intercalation/extraction during the charge and discharge process through various ex-situ analysis technologies.This work demonstrates that the p-VO_(x)@C has great potential for applications in aqueous ZIBs after electrochemical activation.展开更多
In the present research,the NaF assisted plasma electrolytic oxidation(PEO)is designed to fabricate the high-content ZnO nanoparti-cles doped coating on AZ31B alloy.The microstructure,phase constituents and corrosion ...In the present research,the NaF assisted plasma electrolytic oxidation(PEO)is designed to fabricate the high-content ZnO nanoparti-cles doped coating on AZ31B alloy.The microstructure,phase constituents and corrosion behavior of the PEO coatings are investigated systematically.The results reveal that the introduction of NaF promotes the formation of MgF2 nanophases in the passivation layer on Mg alloy,decreasing the breakdown voltage and discharge voltage.As a result,the continuous arcing caused by high discharge voltage is alleviated.With the increasing of NaF content,the Zn content in the PEO coating is enhanced and the pore size in the coating is decreased correspondingly.Due to the high-content ZnO doping,the PEO coating protected AZ31B alloy demonstrates the better corrosion resistance.Compared with the bare AZ31B alloy,the high-content ZnO doped PEO coated sample shows an increased corrosion potential from-1.465 V to-1.008 V,a decreased corrosion current density from 3.043×10^(-5) A·cm^(-2) to 3.960×10^(-8) A·cm^(-2) and an increased charge transfer resistance from 1.213×10^(2) ohm·cm^(2) to 2.598×10^(5) ohm·cm^(2).Besides,the high-content ZnO doped PEO coated sample also has the excellent corrosion resistance in salt solution,exhibiting no obvious corrosion after more than 2000 h neutral salt spraying and 28 days’immersion testing.The improved corrosion resistance can be ascribed to the relative uniform distribution of ZnO in PEO coating which can transform to Zn(OH)2 and form a continuous protective layer along the corrosion interface.展开更多
Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the...Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.展开更多
Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)reg...Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.展开更多
ROS1 and EGFR are primary oncogenic drivers in non-small cell lung cancer (NSCLC) pathogenesis. However, EGFR mutations and ROS1 fusions are generally mutually exclusive in NSCLC, leading to a negligible probability o...ROS1 and EGFR are primary oncogenic drivers in non-small cell lung cancer (NSCLC) pathogenesis. However, EGFR mutations and ROS1 fusions are generally mutually exclusive in NSCLC, leading to a negligible probability of their co-occurrence. Consequently, clinical data and treatment strategies for their simultaneous presence are remarkably scarce. This report details the first recorded case of a sarcomatoid, poorly differentiated lung adenocarcinoma harboring both a ROS1 fusion and an EGFR mutation, alongside ARID1A and NFKBIA gene mutations. Moreover, this case study encompasses a review of instances featuring concurrent ROS1 and EGFR mutations. The identified genetic alterations in ROS1, EGFR, ARID1A, and NFKBIA are pivotal in the etiology of NSCLC. These mutations significantly influence disease progression and are essential for the development of personalized therapeutic approaches. Recognizing the unique genetic profiles in patients permits healthcare providers to devise customized treatment regimens that target these specific mutations, thereby enhancing patient outcomes in NSCLC.展开更多
Primary liver cancer is a common and lethal malignancy in China.Transcatheter arterial chemoembolization(TACE)is globally recognized as the preferred treatment modality for the non-surgical resection of hepatocellular...Primary liver cancer is a common and lethal malignancy in China.Transcatheter arterial chemoembolization(TACE)is globally recognized as the preferred treatment modality for the non-surgical resection of hepatocellular carcinoma(HCC),while transcatheter arterial infusion(TAI)is another effective interventional treatment for HCC.In recent years,hepatic arterial infusion chemotherapy(HAIC)has gained increasing attention as an application-regulated modality for TAI.Owing to the current debate in the medical community regarding the use of HAIC and TACE for the treatment of HCC,the application of both approaches should be considered at a higher level,with a broader perspective and a more normative aspect.Accordingly,we aimed to define the rational combination of liver cancer TAI/HAIC with TACE as infusion transcatheter chemoembolization(iTACE),which suggests that the two interventions are not superior but lead to a mutually beneficial situation.In this review,we sought to discuss the development,specification,application,challenge and innovation,debate,and union of TAI/HAIC and TACE,and the clinical application and latest research on iTACE.We aimed to introduce new concepts of iTACE and expect new breakthroughs in the treatment of liver cancer owing to the combined use of the two major interventional tools.展开更多
Aluminum-ion batteries(AIBs)have been highlighted as a potential alternative to lithium-ion batteries for large-scale energy storage due to the abundant reserve,light weight,low cost,and good safety of Al.However,the ...Aluminum-ion batteries(AIBs)have been highlighted as a potential alternative to lithium-ion batteries for large-scale energy storage due to the abundant reserve,light weight,low cost,and good safety of Al.However,the development of AIBs faces challenges due to the usage of AlCl_(3)-based ionic liquid electrolytes,which are expensive,corrosive,and sensitive to humidity.Here,we develop a low-cost,non-corrosive,and air-stable hydrated eutectic electrolyte composed of aluminum perchlorate nonahydrate and methylurea(MU)ligand.Through optimizing the molar ratio to achieve the unique solvation structure,the formed Al(ClO_4)_(3)·9H_(2)O/MU hydrated deep eutectic electrolyte(AMHEE)with an average coordination number of 2.4 can facilely realize stable and reversible deposition/stripping of Al.When combining with vanadium oxide nanorods positive electrode,the Al-ion full battery delivers a high discharge capacity of 320 mAh g^(-1)with good capacity retention.The unique solvation structure with a low desolvation energy of the AMHEE enables Al^(3+)insertion/extraction during charge/discharge processes,which is evidenced by in situ synchrotron radiation X-ray diffraction.This work opens a new pathway of developing low-cost,safe,environmentally friendly and high-performance electrolytes for practical and sustainable AIBs.展开更多
In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunct...In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8<sup>+</sup> T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.展开更多
Ab initio molecular dynamics calculations have been carried out to search for the ground state structure of Fe_(n)Ti_(13-n)clusters and measure the thermal expansion of Fe_(n)Ti_(13-n).The volume of Fe_(n)Ti_(13-n)clu...Ab initio molecular dynamics calculations have been carried out to search for the ground state structure of Fe_(n)Ti_(13-n)clusters and measure the thermal expansion of Fe_(n)Ti_(13-n).The volume of Fe_(n)Ti_(13-n)clusters during thermal expansion is jointly determined by anharmonic interaction and magneto-volume effect.It has been found that Fe_(6)Ti_(7),Fe_9Ti_(4),Fe_(11)Ti_(2),and Fe_(13)clusters can exhibit the remarkable magneto-volume effect with abnormal volume behaviors and magnetic moment behaviors during thermal expansion.A prerequisite for the magneto-volume effect of Fe_(n)Ti_(13-n)clusters during thermal expansion has been revealed and the magnitude of the magneto-volume is also approximately determined.Furthermore,the magneto-volume behaviors of Fe_(n)Ti_(13-n)clusters are qualitatively characterized by the energy contour map.Our results shed light on the mechanism of the magneto-volume effect in Fe_(n)Ti_(13-n)clusters during thermal expansion,which can guide the design of nanomaterials with zero expansion or even controllable expansion properties.展开更多
We report the layering and liquid–liquid phase transition of liquid titanium confined between two parallel panel walls.Abnormal changes in the volume and the potential energy confirm the existence of the liquid–liqu...We report the layering and liquid–liquid phase transition of liquid titanium confined between two parallel panel walls.Abnormal changes in the volume and the potential energy confirm the existence of the liquid–liquid phase transition of the liquid titanium. The typical feature of the liquid–liquid phase transition is layering, which is induced by the slit size,pressure and temperature. We highlight the fact that the slit size and pressure will determine the number of layers. In addition, with the change in the slit size, the density of the confined liquid expresses a fluctuating law. The phase diagram of the layering transition is drawn to clearly understand the layering. This study provides insights into the liquid–liquid phase transition of liquid metal in a confined space.展开更多
The thermodynamic equilibrium of deoxidation reactions between molten slag and steel was calculated using a slag-steel coupling thermodynamic model and the mass conservation model based on the ion-molecular coexistenc...The thermodynamic equilibrium of deoxidation reactions between molten slag and steel was calculated using a slag-steel coupling thermodynamic model and the mass conservation model based on the ion-molecular coexistence theory.The study focused on the effects of slag composition and deoxidizer type on the oxygen content of low alloy steel during the electroslag remelting(ESR)process.The measured and predicted values of the oxygen content in remelted ingots,and the contents of FeO and MnO in slags were compared and analyzed.Results show that the measured content of total oxygen has a certain correlation with the trend of dissolved oxygen predicted by the model when using Ca-Si alloys as deoxidizer,but it is not correlated with the trend of dissolved oxygen predicted by the model when using Al as deoxidizer.The deoxidation mechanisms of Ca-Si and Al are different.Ca-Si alloy directly reacts with FeO and MnO in slag to reduce the oxygen potential of slag,hence it can inhibit the transfer of oxygen from the slag to molten steel.While,when Al deoxidizer is used,the oxygen content in steel is mainly reduced through floating up the alumina inclusions.Compared to Al,utilizing Ca-Si alloy as a deoxidizer is more effective in reducing the oxygen content and the amount of inclusions in ESR ingot.展开更多
With the changes in disease spectrum and the popularization of screening of low-dose spiral CT (CT) in the chest, more and more pulmonary nodules have been detected, most of which are bipulmonary multiple nodules. The...With the changes in disease spectrum and the popularization of screening of low-dose spiral CT (CT) in the chest, more and more pulmonary nodules have been detected, most of which are bipulmonary multiple nodules. The existence of multiple pulmonary nodules means that it may be a pathological state of benign and malignant co-existence. The origin and evolution of pulmonary nodules in different histopathological states have a great impact on the choice of treatment methods. In recent years, the rise of immunotherapy has brought a breakthrough in the treatment of refractory lung cancer. However, some patients are still ineffective in immunotherapy, which may be related to the immune microenvironment where nodules are proportioned in different components in different pathological states. This review article mainly predicts the development process of nodules by analyzing the origin of multiple pulmonary nodules and the immune microenvironment of nodules in different pathological conditions, so as to provide guidance for clinical treatment.展开更多
Identifying volcanic reservoir types and their distribution patterns in volcanic edifices is important for accurate prediction and exploration of hydrocarbon reservoirs.Herein,we analyzed the distribution patterns of ...Identifying volcanic reservoir types and their distribution patterns in volcanic edifices is important for accurate prediction and exploration of hydrocarbon reservoirs.Herein,we analyzed the distribution patterns of different reservoir levels in volcanic edifices,discussed controlling factors,and reclassified reservoir types.This was done using core observations,whole-rock geochemistry,and reservoir physical property analysis,combined with logging,drilling,seismic,and oil-gas test data.Reservoirs can be divided into three classes based on their physical properties.The Mesozoic intermediate and basic rocks formed ClassⅠreservoirs,most lithologies formed ClassⅡreservoirs,and diabase intrusions and tight volcanic rocks formed ClassⅢreservoirs.Reservoirs form in different lithologies in the Huanghua depression due to weathering.Tectonic faults deepen the influence of weathering leading to the formation of reservoirs in tight.Additionally,volcanic rhythms and fractures control the vertical distribution of Cenozoic basaltic reservoirs.Volcanic reservoirs are classified into five types based on the main controlling factors and distribution patterns in volcanic edifices:tectonic-alteration,vesiclefracture,weathered-effusive,weathered-eruptive,and weathered-tectonic types.Among these,the weathered-eruptive type can easily form ClassⅠreservoirs,making it the best target for exploration.Whereas the weathered-tectonic and vesicle-fracture types tend to develop ClassⅡreservoirs and can be potential targets.The new classification takes into account the relationship between reservoir levels and their distribution in volcanic edifices,it is more conducive to igneous reservoir prediction in the Huanghua depression.This study provides a novel idea for the classification and comparative study of igneous reservoirs in petroliferous basins.展开更多
背景急性胰腺炎(acute pancreatitis,AP)是常见的急腹症,不同类型预后不同.AP的免疫应答和失衡免疫与其严重程度有关,炎症因子和相关免疫细胞在AP发病机制中至关重要,因而寻找炎症细胞和新炎症免疫因子对精准治疗AP具有重要意义.目的探...背景急性胰腺炎(acute pancreatitis,AP)是常见的急腹症,不同类型预后不同.AP的免疫应答和失衡免疫与其严重程度有关,炎症因子和相关免疫细胞在AP发病机制中至关重要,因而寻找炎症细胞和新炎症免疫因子对精准治疗AP具有重要意义.目的探讨AP患者外周血CD14^+CD16^+单核细胞表达B7-H2的临床意义.方法A P患者63例[轻度A P(m i l dA P,M A P)25例、中度AP(moderately severe AP,MSAP)20例、重度AP(severe AP,SAP)18例],对照组为健康体检者20例,采用流式细胞仪检测CD14^+CD16^+细胞亚群上B7-H2表达情况,评价其与胰腺炎严重程度关联性及临床意义.结果AP患者发病24hCD14^+CD16^+细胞B7-H2出现异常高表达,显著高于健康对照组(t=11.10,P<0.001);A P各组B 7-H 2在C D 14^+C D 16^+细胞膜上表达明显高于CD14^+C D16^-细胞膜上表达(P<0.01);SAP组CD14^+C D 16^+和CD14^+C D 16^-细胞B7-H2表达(373.30±89.72和78.62±13.05)最高,M S A P组(279.55±76.95/44.92±12.44)其次,均高于M A P组(181.15±35.75/23.32±4.28),各组两两比较差异有显著性(P<0.01);MAP组、MSAP组发病24 h、48 h、72hCD14^+CD16^+和CD14^+CD16^-单核细胞膜B7-H2动态表达差异无显著性(P>0.05),然而,SAP组无论C D14^+C D16^+还是CD14^+C D16^-细胞膜B7-H2表达24h、48h、72h均呈明显上升趋势,差异有显著性(P<0.05).结论CD14^+CD16^+和CD14^+CD16^-单核细胞膜B7-H2在AP患者体内高表达,与AP严重程度密切相关,且SAP呈动态升高变化;同时B7-H2在AP患者CD14^+CD16^+单核细胞膜表达较CD14^+CD16^-单核细胞明显升高,为进一步认识AP免疫应答和失衡提供了新的线索,为AP精准靶向治疗提供参考.展开更多
基金supported by the National Natural Science Foundation of China(Nos.92163118,51972234)。
文摘The development of aqueous zinc ion battery cathode materials with high capacity and high magnification is still a challenge.Herein,porous vanadium oxide/carbon(p-VO_(x)@C,mainly VO_(2) with a small amount of V_(2)O_(3)) core/shell microspheres with oxygen vacancies are facilely fabricated by using a vanadium-based metal-organic framework(MIL-100(V)) as a sacrificial template.This unique structure can improve the conductivity of the VO_(x),accelerate electrolyte diffusion,and suppress structural collapse during circulation.Subsequently,H_(2)O molecules are introduced into the interlayer of VO_(x) through a highly efficient in-situ electrochemical activation process,facilitating the intercalation and diffusion of zinc ions.After the activation,an optimal sample exhibits a high specific capacity of 464.3 mA h g^(-1) at0.2 A g^(-1) and 395.2 mA h g^(-1) at 10 A g^(-1),indicating excellent rate performance.Moreover,the optimal sample maintains a capacity retention of about 89.3% after 2500 cycles at 10 A g^(-1).Density functional theory calculation demonstrates that the presence of oxygen vacancies and intercalated water molecules can significantly reduce the diffusion barrier for zinc ions.In addition,it is proved that the storage of zinc ions in the cathode is achieved by reversible intercalation/extraction during the charge and discharge process through various ex-situ analysis technologies.This work demonstrates that the p-VO_(x)@C has great potential for applications in aqueous ZIBs after electrochemical activation.
基金supported by the 2022 Shenzhen sustainable supporting funds for colleges and universities(20220810143642004)Shenzhen Basic Research Project(JCYJ20200109144608205 and JCYJ20210324120001003)+5 种基金Peking University Shenzhen Graduate School Research Startup Fund of Introducing Talent(No.1270110273)Shenzhen postdoctoral research fund project after outbound(No.2129933651)Shenzhen-Hong Kong Research and Development Fund(No.SGDX20201103095406024)City University of Hong Kong Strategic Research Grants(SRG)(Nos.7005264 and 7005505)Guangdong-Hong Kong Technology Cooperation Funding Scheme(TCFS)(No.GHP/085/18SZ)IER Foundation(IERF2020001 and IERF2019002).
文摘In the present research,the NaF assisted plasma electrolytic oxidation(PEO)is designed to fabricate the high-content ZnO nanoparti-cles doped coating on AZ31B alloy.The microstructure,phase constituents and corrosion behavior of the PEO coatings are investigated systematically.The results reveal that the introduction of NaF promotes the formation of MgF2 nanophases in the passivation layer on Mg alloy,decreasing the breakdown voltage and discharge voltage.As a result,the continuous arcing caused by high discharge voltage is alleviated.With the increasing of NaF content,the Zn content in the PEO coating is enhanced and the pore size in the coating is decreased correspondingly.Due to the high-content ZnO doping,the PEO coating protected AZ31B alloy demonstrates the better corrosion resistance.Compared with the bare AZ31B alloy,the high-content ZnO doped PEO coated sample shows an increased corrosion potential from-1.465 V to-1.008 V,a decreased corrosion current density from 3.043×10^(-5) A·cm^(-2) to 3.960×10^(-8) A·cm^(-2) and an increased charge transfer resistance from 1.213×10^(2) ohm·cm^(2) to 2.598×10^(5) ohm·cm^(2).Besides,the high-content ZnO doped PEO coated sample also has the excellent corrosion resistance in salt solution,exhibiting no obvious corrosion after more than 2000 h neutral salt spraying and 28 days’immersion testing.The improved corrosion resistance can be ascribed to the relative uniform distribution of ZnO in PEO coating which can transform to Zn(OH)2 and form a continuous protective layer along the corrosion interface.
基金supported by the National Natural Science Foundation of China(81870259,82170431,81903608,and U21A20339)the CAMS Innovation Fund for Medical Sciences(CIFMS+1 种基金2019-I2M-5-078)the Postdoctoral Research Foundation of Heilongjiang Province(LBH-Q20148).
文摘Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.
基金This work was supported in part by the National Natural Science Foundation of China(82370417,81970320,82270273)the Certificate of China Postdoctoral Science Foundation Grant(2021M693826)+1 种基金the postdoctoral funding from Heilongjiang Province(21042230046)the Hai Yan Youth Fund from Harbin Medical University Cancer Hospital(JJQN2021-09).
文摘Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.
文摘ROS1 and EGFR are primary oncogenic drivers in non-small cell lung cancer (NSCLC) pathogenesis. However, EGFR mutations and ROS1 fusions are generally mutually exclusive in NSCLC, leading to a negligible probability of their co-occurrence. Consequently, clinical data and treatment strategies for their simultaneous presence are remarkably scarce. This report details the first recorded case of a sarcomatoid, poorly differentiated lung adenocarcinoma harboring both a ROS1 fusion and an EGFR mutation, alongside ARID1A and NFKBIA gene mutations. Moreover, this case study encompasses a review of instances featuring concurrent ROS1 and EGFR mutations. The identified genetic alterations in ROS1, EGFR, ARID1A, and NFKBIA are pivotal in the etiology of NSCLC. These mutations significantly influence disease progression and are essential for the development of personalized therapeutic approaches. Recognizing the unique genetic profiles in patients permits healthcare providers to devise customized treatment regimens that target these specific mutations, thereby enhancing patient outcomes in NSCLC.
文摘Primary liver cancer is a common and lethal malignancy in China.Transcatheter arterial chemoembolization(TACE)is globally recognized as the preferred treatment modality for the non-surgical resection of hepatocellular carcinoma(HCC),while transcatheter arterial infusion(TAI)is another effective interventional treatment for HCC.In recent years,hepatic arterial infusion chemotherapy(HAIC)has gained increasing attention as an application-regulated modality for TAI.Owing to the current debate in the medical community regarding the use of HAIC and TACE for the treatment of HCC,the application of both approaches should be considered at a higher level,with a broader perspective and a more normative aspect.Accordingly,we aimed to define the rational combination of liver cancer TAI/HAIC with TACE as infusion transcatheter chemoembolization(iTACE),which suggests that the two interventions are not superior but lead to a mutually beneficial situation.In this review,we sought to discuss the development,specification,application,challenge and innovation,debate,and union of TAI/HAIC and TACE,and the clinical application and latest research on iTACE.We aimed to introduce new concepts of iTACE and expect new breakthroughs in the treatment of liver cancer owing to the combined use of the two major interventional tools.
基金supported by the National Natural Science Foundation of China(52274302)。
文摘Aluminum-ion batteries(AIBs)have been highlighted as a potential alternative to lithium-ion batteries for large-scale energy storage due to the abundant reserve,light weight,low cost,and good safety of Al.However,the development of AIBs faces challenges due to the usage of AlCl_(3)-based ionic liquid electrolytes,which are expensive,corrosive,and sensitive to humidity.Here,we develop a low-cost,non-corrosive,and air-stable hydrated eutectic electrolyte composed of aluminum perchlorate nonahydrate and methylurea(MU)ligand.Through optimizing the molar ratio to achieve the unique solvation structure,the formed Al(ClO_4)_(3)·9H_(2)O/MU hydrated deep eutectic electrolyte(AMHEE)with an average coordination number of 2.4 can facilely realize stable and reversible deposition/stripping of Al.When combining with vanadium oxide nanorods positive electrode,the Al-ion full battery delivers a high discharge capacity of 320 mAh g^(-1)with good capacity retention.The unique solvation structure with a low desolvation energy of the AMHEE enables Al^(3+)insertion/extraction during charge/discharge processes,which is evidenced by in situ synchrotron radiation X-ray diffraction.This work opens a new pathway of developing low-cost,safe,environmentally friendly and high-performance electrolytes for practical and sustainable AIBs.
文摘In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8<sup>+</sup> T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.
基金the support from the National Natural Science Foundation of China(Grant No.52171038)key R&D projects in Shandong Province(Grant No.2021SFGC1001)+1 种基金supported by the Special Funding in the Project of the Taishan Scholar Construction Engineering and the program of Jinan Science and Technology Bureau(Grant No.2020GXRC019)new material demonstration platform construction project from Ministry of Industry and Information Technology of China(Grant No.2020-370104-34-03-043952-01-11)。
文摘Ab initio molecular dynamics calculations have been carried out to search for the ground state structure of Fe_(n)Ti_(13-n)clusters and measure the thermal expansion of Fe_(n)Ti_(13-n).The volume of Fe_(n)Ti_(13-n)clusters during thermal expansion is jointly determined by anharmonic interaction and magneto-volume effect.It has been found that Fe_(6)Ti_(7),Fe_9Ti_(4),Fe_(11)Ti_(2),and Fe_(13)clusters can exhibit the remarkable magneto-volume effect with abnormal volume behaviors and magnetic moment behaviors during thermal expansion.A prerequisite for the magneto-volume effect of Fe_(n)Ti_(13-n)clusters during thermal expansion has been revealed and the magnitude of the magneto-volume is also approximately determined.Furthermore,the magneto-volume behaviors of Fe_(n)Ti_(13-n)clusters are qualitatively characterized by the energy contour map.Our results shed light on the mechanism of the magneto-volume effect in Fe_(n)Ti_(13-n)clusters during thermal expansion,which can guide the design of nanomaterials with zero expansion or even controllable expansion properties.
基金supported by the National Natural Science Foundation of China (Grant Nos. U1806219 and 52171038)the Special Funding in the Project of the Taishan Scholar Construction Engineering and the Program of Jinan Science and Technology Bureau (Grant No. 2020GXRC019)Key R&D Projects in Shandong Province, China (Grant No. 2021SFGC1001)。
文摘We report the layering and liquid–liquid phase transition of liquid titanium confined between two parallel panel walls.Abnormal changes in the volume and the potential energy confirm the existence of the liquid–liquid phase transition of the liquid titanium. The typical feature of the liquid–liquid phase transition is layering, which is induced by the slit size,pressure and temperature. We highlight the fact that the slit size and pressure will determine the number of layers. In addition, with the change in the slit size, the density of the confined liquid expresses a fluctuating law. The phase diagram of the layering transition is drawn to clearly understand the layering. This study provides insights into the liquid–liquid phase transition of liquid metal in a confined space.
文摘The thermodynamic equilibrium of deoxidation reactions between molten slag and steel was calculated using a slag-steel coupling thermodynamic model and the mass conservation model based on the ion-molecular coexistence theory.The study focused on the effects of slag composition and deoxidizer type on the oxygen content of low alloy steel during the electroslag remelting(ESR)process.The measured and predicted values of the oxygen content in remelted ingots,and the contents of FeO and MnO in slags were compared and analyzed.Results show that the measured content of total oxygen has a certain correlation with the trend of dissolved oxygen predicted by the model when using Ca-Si alloys as deoxidizer,but it is not correlated with the trend of dissolved oxygen predicted by the model when using Al as deoxidizer.The deoxidation mechanisms of Ca-Si and Al are different.Ca-Si alloy directly reacts with FeO and MnO in slag to reduce the oxygen potential of slag,hence it can inhibit the transfer of oxygen from the slag to molten steel.While,when Al deoxidizer is used,the oxygen content in steel is mainly reduced through floating up the alumina inclusions.Compared to Al,utilizing Ca-Si alloy as a deoxidizer is more effective in reducing the oxygen content and the amount of inclusions in ESR ingot.
文摘With the changes in disease spectrum and the popularization of screening of low-dose spiral CT (CT) in the chest, more and more pulmonary nodules have been detected, most of which are bipulmonary multiple nodules. The existence of multiple pulmonary nodules means that it may be a pathological state of benign and malignant co-existence. The origin and evolution of pulmonary nodules in different histopathological states have a great impact on the choice of treatment methods. In recent years, the rise of immunotherapy has brought a breakthrough in the treatment of refractory lung cancer. However, some patients are still ineffective in immunotherapy, which may be related to the immune microenvironment where nodules are proportioned in different components in different pathological states. This review article mainly predicts the development process of nodules by analyzing the origin of multiple pulmonary nodules and the immune microenvironment of nodules in different pathological conditions, so as to provide guidance for clinical treatment.
基金financially supported by the National Natural Science Foundation of China(No.42130309)the PetroChina Dagang Oilfield Company(No.DGTY-2018-JS-408)。
文摘Identifying volcanic reservoir types and their distribution patterns in volcanic edifices is important for accurate prediction and exploration of hydrocarbon reservoirs.Herein,we analyzed the distribution patterns of different reservoir levels in volcanic edifices,discussed controlling factors,and reclassified reservoir types.This was done using core observations,whole-rock geochemistry,and reservoir physical property analysis,combined with logging,drilling,seismic,and oil-gas test data.Reservoirs can be divided into three classes based on their physical properties.The Mesozoic intermediate and basic rocks formed ClassⅠreservoirs,most lithologies formed ClassⅡreservoirs,and diabase intrusions and tight volcanic rocks formed ClassⅢreservoirs.Reservoirs form in different lithologies in the Huanghua depression due to weathering.Tectonic faults deepen the influence of weathering leading to the formation of reservoirs in tight.Additionally,volcanic rhythms and fractures control the vertical distribution of Cenozoic basaltic reservoirs.Volcanic reservoirs are classified into five types based on the main controlling factors and distribution patterns in volcanic edifices:tectonic-alteration,vesiclefracture,weathered-effusive,weathered-eruptive,and weathered-tectonic types.Among these,the weathered-eruptive type can easily form ClassⅠreservoirs,making it the best target for exploration.Whereas the weathered-tectonic and vesicle-fracture types tend to develop ClassⅡreservoirs and can be potential targets.The new classification takes into account the relationship between reservoir levels and their distribution in volcanic edifices,it is more conducive to igneous reservoir prediction in the Huanghua depression.This study provides a novel idea for the classification and comparative study of igneous reservoirs in petroliferous basins.
文摘背景急性胰腺炎(acute pancreatitis,AP)是常见的急腹症,不同类型预后不同.AP的免疫应答和失衡免疫与其严重程度有关,炎症因子和相关免疫细胞在AP发病机制中至关重要,因而寻找炎症细胞和新炎症免疫因子对精准治疗AP具有重要意义.目的探讨AP患者外周血CD14^+CD16^+单核细胞表达B7-H2的临床意义.方法A P患者63例[轻度A P(m i l dA P,M A P)25例、中度AP(moderately severe AP,MSAP)20例、重度AP(severe AP,SAP)18例],对照组为健康体检者20例,采用流式细胞仪检测CD14^+CD16^+细胞亚群上B7-H2表达情况,评价其与胰腺炎严重程度关联性及临床意义.结果AP患者发病24hCD14^+CD16^+细胞B7-H2出现异常高表达,显著高于健康对照组(t=11.10,P<0.001);A P各组B 7-H 2在C D 14^+C D 16^+细胞膜上表达明显高于CD14^+C D16^-细胞膜上表达(P<0.01);SAP组CD14^+C D 16^+和CD14^+C D 16^-细胞B7-H2表达(373.30±89.72和78.62±13.05)最高,M S A P组(279.55±76.95/44.92±12.44)其次,均高于M A P组(181.15±35.75/23.32±4.28),各组两两比较差异有显著性(P<0.01);MAP组、MSAP组发病24 h、48 h、72hCD14^+CD16^+和CD14^+CD16^-单核细胞膜B7-H2动态表达差异无显著性(P>0.05),然而,SAP组无论C D14^+C D16^+还是CD14^+C D16^-细胞膜B7-H2表达24h、48h、72h均呈明显上升趋势,差异有显著性(P<0.05).结论CD14^+CD16^+和CD14^+CD16^-单核细胞膜B7-H2在AP患者体内高表达,与AP严重程度密切相关,且SAP呈动态升高变化;同时B7-H2在AP患者CD14^+CD16^+单核细胞膜表达较CD14^+CD16^-单核细胞明显升高,为进一步认识AP免疫应答和失衡提供了新的线索,为AP精准靶向治疗提供参考.