Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative patho...Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative pathogens.Previous studies reported that BAC-adapted Pseudomonas aeruginosa increased the tolerance to PB.Herein,we present the novel finding that the combination of BAC and PB exhibited synergistic antibacterial effects against P.aeruginosa.Time-killing assay demonstrated a significant reduction in bacterial cell viability.Scanning electron microscopy,zeta potential analysis,hydrophobicity measurements,and fluorescence probe analyses collectively revealed severe disruption of the cell envelope and membrane potential induced by the combination of BAC and PB.Transcriptomic analysis revealed that the BAC-PB combination notably downreg-ulated the expression of genes involved in lipid A modification and cell envelope production,including phoPQ,pmrAB,bamABCDE,lptABCDEG,lolB,yidC,and murJ.Additionally,the combination group exhibited augmented production of reactive oxygen species and diminished ATP synthesis.The expression of the genes associated with substance metabolism and energy generation was significantly impeded.This study provides significant implica-tions for the interactions of biocides and antibiotics on Gram-negative pathogens,while also addressing antibiotic resistance and developing the external treatment strategy for Pseudomonas-infected wounds and burns.展开更多
During the hyperacute phase of intracerebral hemorrhage(ICH),the mass effect and blood components mechanically lead to brain damage and neurotoxicity.Our findings revealed that the mass effect and transferrin precipit...During the hyperacute phase of intracerebral hemorrhage(ICH),the mass effect and blood components mechanically lead to brain damage and neurotoxicity.Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake,culminating in ferroptosis in neurons.M6A(N6-methyladenosine)modification,the most prevalent mRNA modification,plays a critical role in various cell death pathways.The Fto(fat mass and obesity-associated protein)demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels.Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis.Applying nanopore direct RNA sequencing,we identified voltage-dependent anion channel 3(Vdac3)as a potential target associated with ferroptosis.Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA.These findings elucidate the intricate interplay between Fto,Vdac3,m6A methylation,and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.展开更多
In 2018,Baige,Xizang,witnessed two consecutive large-scale landslides,causing significant damage and drawing widespread attention.From March 2011 to February 2018,the Baige landslide exhibited a 50-m displacement with...In 2018,Baige,Xizang,witnessed two consecutive large-scale landslides,causing significant damage and drawing widespread attention.From March 2011 to February 2018,the Baige landslide exhibited a 50-m displacement without complete failure,culminating in a collapse in October 2018.The mechanisms behind its resistance to failure despite substantial deformation and the influence of the complex geo-structure within the tectonic mélange belt remain unclear.To address these questions,this study utilized a multidisciplinary approach,integrating on-site geological field mapping,surface deformation monitoring,multielectrode resistivity method,and deep displacement analysis.The aim was to evaluate the impact of the intricate geo-structure within the tectonic mélange belt on the Baige landslide events.Findings reveal that the landslide's geo-structure consists of structurally fractured,mesh-like rock masses,including heterogeneous lenticular rock masses and intermittent brittle shear zones distributed around the lens-shaped rock masses.The study underscores that the inhomogeneous and weakly deformed lenticular rock masses function as natural locked segments,governing the stability of the Baige landslide.Specifically,the relatively intact and hard granodiorite porphyry play a crucial role in locking the landslide's deformation.Deep displacement analysis indicates that the brittle shear zones act as the sliding surfaces.The progressive destruction of the locked segments and the gradual penetration of brittle shear zones,driven by gravitational potential energy,contribute to the landslide occurrence.This research provides critical insights into the formation mechanisms of large-scale landslides within tectonic mélange belts.展开更多
The size and shape effect(SSE)of components has become a critical issue for mechanical properties,application reliability,and processing.In this study,the creep rupture life(CRL)of components with different wall thick...The size and shape effect(SSE)of components has become a critical issue for mechanical properties,application reliability,and processing.In this study,the creep rupture life(CRL)of components with different wall thicknesses and positions in a combustion chamber casing simulator made of K439B superalloy was investigated.The intrinsic mechanisms of the SSE were explored from the dendrite structure,volume fraction and size of theγ'phase,and element segregation,etc.It is shown that this casting exhibits a strong SSE of creep rupture life,characterized by a significant difference in the CRL values up to 60%with the variation of wall thickness and position in the casing.In terms of casting technology,the influence of SSE on CRL is actually determined by the cooling rate.The SSE on the creep rupture life originates from the dendrite structure(such as the secondary dendrite arm spacing),volume fraction size of theγ'phase in the dendrite trunk,and elements segregation rate.This work may have implications for the design and application of engineering components with large sizes and complex structures.展开更多
To investigate the effects of Al-Ti-B-RE grain refiner on microstructure and mechanical properties of Al-7.0Si-0.55Mg （A357） alloy, some novel Al-7.0Si-0.55Mg alloys added with different amount of Al-STi-1B-RE grain...To investigate the effects of Al-Ti-B-RE grain refiner on microstructure and mechanical properties of Al-7.0Si-0.55Mg （A357） alloy, some novel Al-7.0Si-0.55Mg alloys added with different amount of Al-STi-1B-RE grain refiner with different RE composition were prepared by vacuum-melting. The microstructure and fracture behavior of the AI-7.0Si-0.55Mg alloys with the grain refiners were observed by X-ray diffraction （XRD）, optical microscopy （OM）, scanning electron microscopy （SEM）, and the mechanical properties of the alloys were tested in mechanical testing machine at room temperature. The observation of AI-Ti-B-RE morphology and internal structure of the particles reveals that it exhibits a TiAl3/Ti2Al20RE core-shell structure via heterogeneous TiB2 nuclei. The tensile strength of Al-7.0Si-0.55Mg alloys with Al-5Ti-1B-3.0RE grain refiner reaches the peak value at the same addition （0.2%） of grain refiner.展开更多
The electroplastic effect in AZ31B magnesium alloy sheet was investigated through uniaxial tensile tests. In order to show the athermal effect of the electrical pulses, two types of uniaxial tensile tests at the same ...The electroplastic effect in AZ31B magnesium alloy sheet was investigated through uniaxial tensile tests. In order to show the athermal effect of the electrical pulses, two types of uniaxial tensile tests at the same testing temperature were carried out： uniaxial tension in environmental cabinet and uniaxial tension with electrical pulses. In addition, the distribution of temperature field in the cross-section area during uniaxial tension with electrical pulses was simulated. The results show that the distribution of temperature field along the cross-section area is homogeneous. By comparing the true stress？true strain curves of AZ31B alloy under uniaxial tensile tests, the athermal effect with electrical pulses was confirmed. The microstructure evolution after the uniaxial tension was studied by optical microscopy. The results indicate that the electrical pulses induced dynamic recrystallization plays an important role in the decrease of flow stress. Finally, a flow stress model of AZ31B sheet taking the influence of electroplastic effect into account was proposed and validated. The results demonstrate that the calculated data fit the experimental data well.展开更多
2022年中央一号文件《中共中央国务院关于做好2022年全面推进乡村振兴重点工作的意见》明确要求大力推进数字农业建设,推进智慧农业发展;2022年12月23日至24日中央农村工作会议上习近平总书记指出“产业振兴是乡村振兴的重中之重,要落...2022年中央一号文件《中共中央国务院关于做好2022年全面推进乡村振兴重点工作的意见》明确要求大力推进数字农业建设,推进智慧农业发展;2022年12月23日至24日中央农村工作会议上习近平总书记指出“产业振兴是乡村振兴的重中之重,要落实产业帮扶政策,做好‘土特产’文章,依托农业农村特色资源,向开发农业多种功能、挖掘乡村多元价值要效益,向一二三产业融合发展要效益,强龙头、补链条、兴业态、树品牌,推动乡村产业全链条升级,增强市场竞争力和可持续发展能力”。本文深刻领会习近平总书记、中央一号文件、中共浙江省委十五届二次全会精神,通过深入总结嘉兴与丽水近二十年开展“山海协作”的成功经验,并针对嘉兴与丽水联动发展特色农业产业链目前遇到的种养技术、销售模式、专家团队、高技能人才等瓶颈,提出构建“嘉兴农产品专业市场与丽水种养基地联动发展特色农业产业链的‘W2F+B2M’(Wholesale to Farmer+Business to Member,即嘉兴农产品专业市场与丽水种养基地+嘉兴专业市场商户与商户的会员联动)模式”,进一步完善嘉兴与丽水特色农业产业链的联动发展机制,助推嘉兴与丽水共同富裕。展开更多
The distribution of boron and the microstructure of grain boundary（GB） precipitates（M23（C,B） 6 and M 2B）have been analyzed with their effects on the susceptibility of ductility-dip-cracking（DDC） and tensile pr...The distribution of boron and the microstructure of grain boundary（GB） precipitates（M23（C,B） 6 and M 2B）have been analyzed with their effects on the susceptibility of ductility-dip-cracking（DDC） and tensile properties for NiCrFe-7 weld metal,using optical microscopy（OM）,secondary ion mass spectroscopy（SIMS）,scanning electron microscopy（SEM）,and transmission electron microscopy（TEM）.The results show that boron segregates at GBs in NiCrFe-7 weld metal during the welding process.The segregation of boron at GBs promotes the formation of continuous M23（C,B） 6 carbide chains and M 2B borides along GBs.The addition of boron aggravates GB embrittlement and causes more DDC in the weld metal,by its segregation at GBs presenting as an impurity,and promoting the formation of larger and continuous M 23（C,B） 6 carbides,and M 2B borides along GBs.DDC in the weld metal deteriorates the ductility and tensile strength of the weld metal simultaneously.展开更多
Dispatched by the Chinese government,a multidisciplinary team of 30 researchers collaborated with a team from Myanmar to conduct a 14-day on-site investigation.The work encompassed seismic intensity assessments,field ...Dispatched by the Chinese government,a multidisciplinary team of 30 researchers collaborated with a team from Myanmar to conduct a 14-day on-site investigation.The work encompassed seismic intensity assessments,field surveys,and loss evaluations.The paper focuses on the intensity distribution and structural damage characteristics of the 2025 M7.9 Myanmar earthquake,yielding the following key findings.(1)The seismogenic fault rupture propagated in a nearly N-S direction,with a surface rupture length of approximately 450 km.The seismic impact zone exhibited an elongated N-S distribution and a shorter E-W span,distributed like a belt around the seismogenic fault.(2)Within the seismic impact zones,existing buildings comprised five primary structural types,with timber(bamboo)structures constituting the largest proportion(≈80%in rural areas,≈50%in urban areas).The relatively low disaster losses and casualties were primarily attributable to the good seismic performance and low damage ratio of timber(bamboo)structures across varying intensity zones.(3)An anomalous zone of intensityⅨwas located at the boundary between intensityⅥandⅦregions in Nay Pyi Taw.Here,ridge topography combined with soft soil layers significantly amplified ground motion,exacerbating structural damage.(4)Directional effects of ground motion were observed,with the structural damage phenomena and peak ground acceleration(PGA)values in the N-S direction exceeding those in the E-W direction.This validates that the maximum PGA distribution of strike-slip fault earthquakes aligns with the fault strike.The research is expected to provide technical support for post-disaster reconstruction planning,site selection,and disaster mitigation strategies in Myanmar.展开更多
AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retro...AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.展开更多
BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many c...BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many complications.AIM To explore the protective effects of panax notoginseng saponin(PNS) against dextran sulfate sodium(DSS)-induced intestinal inflammatory injury through phosphoinositide-3-kinase protein kinase B(PI3K/AKT) signaling pathway inhibition in rats.METHODS Colitis rat models were generated via DSS induction, and rats were divided into control(no modeling), DSS, DSS + PNS 50 mg/k, and DSS + PNS 100 mg/kg groups. Then, the intestinal injury, oxidative stress parameters, inflammatory indices, tight junction proteins, apoptosis, macrophage polarization, and TLR4/AKT signaling pathway in colon tissues from rats in each of the groups were detected. The PI3 K/AKT signaling pathway in the colon tissue of rats was blocked using the PI3K/AKT signaling pathway inhibitor, LY294002.RESULTS Compared with rats in the control group, rats in the DSS group showed significantly shortened colon lengths, and significantly increased disease activity indices, oxidative stress reactions and inflammatory indices, as well as significantly decreased expression of tight junction-associated proteins. In addition, the DSS group showed significantly increased apoptotic cell numbers,and showed significantly increased M1 macrophages in spleen and colon tissues.They also showed significantly decreased M2 macrophages in colon tissues, as well as activation of the PI3K/AKT signaling pathway(all P < 0.05). Compared with rats in the DSS group, rats in the DSS + PNS group showed significantly lengthened colon lengths, decreased disease activity indices, and significantly alleviated oxidative stress reactions and inflammatory responses. In addition, this group showed significantly increased expression of tight junction-associated proteins, significantly decreased apoptotic cell numbers, and significantly decreased M1 macrophages in spleen and colon tissues. This group further showed significantly increased M2 macrophages in colon tissues, and significantly suppressed activation of the PI3K/AKT signaling pathway, as well as a dose dependency(all P < 0.05). When the PI3K/AKT signaling pathway was inhibited, the apoptosis rate of colon tissue cells in the DSS + LY294002 group was significantly lower than that of the DSS group(P < 0.05).CONCLUSION PNS can protect rats against DSS-induced intestinal inflammatory injury by inhibiting the PI3K/AKT signaling pathway, and therefore may be potentially used in the future as a drug for colitis.展开更多
BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate de...BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.展开更多
Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the different...Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.展开更多
Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytia...Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytial virus （RSV）. However, no antiviral agents with low toxicity and drug resistance are cur- rently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin （an ingredient of Rheum palmatum） against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum pal- matum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication in- hibition, virucidal and anti-absorption effects, by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tet- razolium bromide （MTT） assay and plaque reduction assay （PRA）. The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR （qPCR）. Cytokine （IFN-γ, TNF-α） mRNA expressions after emodin treatment （7.5, 15, 30 μmol/L） were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration （EC50） ranging from 13.06 to 14.27 μmol/L and selectivity index （SI） being 5.38-6.41 μmol/L. However, emodin couldn＇t directly inacti- vate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.展开更多
基金supported by the National Natural Science Foundation of China(No.32170121).
文摘Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative pathogens.Previous studies reported that BAC-adapted Pseudomonas aeruginosa increased the tolerance to PB.Herein,we present the novel finding that the combination of BAC and PB exhibited synergistic antibacterial effects against P.aeruginosa.Time-killing assay demonstrated a significant reduction in bacterial cell viability.Scanning electron microscopy,zeta potential analysis,hydrophobicity measurements,and fluorescence probe analyses collectively revealed severe disruption of the cell envelope and membrane potential induced by the combination of BAC and PB.Transcriptomic analysis revealed that the BAC-PB combination notably downreg-ulated the expression of genes involved in lipid A modification and cell envelope production,including phoPQ,pmrAB,bamABCDE,lptABCDEG,lolB,yidC,and murJ.Additionally,the combination group exhibited augmented production of reactive oxygen species and diminished ATP synthesis.The expression of the genes associated with substance metabolism and energy generation was significantly impeded.This study provides significant implica-tions for the interactions of biocides and antibiotics on Gram-negative pathogens,while also addressing antibiotic resistance and developing the external treatment strategy for Pseudomonas-infected wounds and burns.
基金supported by the National Key R&D Program of China(2022YFE0131000)the National Natural Science Foundation of China(82220108012,82271306,and 82071307)+1 种基金The Science and Education for Health Foundation of Suzhou for Youth(KJXW2023001)the Boxi Youth Natural Science Foundation(BXQN2023028).
文摘During the hyperacute phase of intracerebral hemorrhage(ICH),the mass effect and blood components mechanically lead to brain damage and neurotoxicity.Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake,culminating in ferroptosis in neurons.M6A(N6-methyladenosine)modification,the most prevalent mRNA modification,plays a critical role in various cell death pathways.The Fto(fat mass and obesity-associated protein)demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels.Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis.Applying nanopore direct RNA sequencing,we identified voltage-dependent anion channel 3(Vdac3)as a potential target associated with ferroptosis.Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA.These findings elucidate the intricate interplay between Fto,Vdac3,m6A methylation,and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
基金supported by the National Major Scientific Instruments and Equipment Development Projects of China(No.41827808)the Major Program of the National Natural Science Foundation of China(No.42090055)Supported by Science and Technology Projects of Xizang Autonomous Region,China(No.XZ202402ZD0001)。
文摘In 2018,Baige,Xizang,witnessed two consecutive large-scale landslides,causing significant damage and drawing widespread attention.From March 2011 to February 2018,the Baige landslide exhibited a 50-m displacement without complete failure,culminating in a collapse in October 2018.The mechanisms behind its resistance to failure despite substantial deformation and the influence of the complex geo-structure within the tectonic mélange belt remain unclear.To address these questions,this study utilized a multidisciplinary approach,integrating on-site geological field mapping,surface deformation monitoring,multielectrode resistivity method,and deep displacement analysis.The aim was to evaluate the impact of the intricate geo-structure within the tectonic mélange belt on the Baige landslide events.Findings reveal that the landslide's geo-structure consists of structurally fractured,mesh-like rock masses,including heterogeneous lenticular rock masses and intermittent brittle shear zones distributed around the lens-shaped rock masses.The study underscores that the inhomogeneous and weakly deformed lenticular rock masses function as natural locked segments,governing the stability of the Baige landslide.Specifically,the relatively intact and hard granodiorite porphyry play a crucial role in locking the landslide's deformation.Deep displacement analysis indicates that the brittle shear zones act as the sliding surfaces.The progressive destruction of the locked segments and the gradual penetration of brittle shear zones,driven by gravitational potential energy,contribute to the landslide occurrence.This research provides critical insights into the formation mechanisms of large-scale landslides within tectonic mélange belts.
基金financially supported by the National Science and Technology Major Project of China (No.J2019-VI-0004-0117)a Laboratory Fund Project (6142903220101)。
文摘The size and shape effect(SSE)of components has become a critical issue for mechanical properties,application reliability,and processing.In this study,the creep rupture life(CRL)of components with different wall thicknesses and positions in a combustion chamber casing simulator made of K439B superalloy was investigated.The intrinsic mechanisms of the SSE were explored from the dendrite structure,volume fraction and size of theγ'phase,and element segregation,etc.It is shown that this casting exhibits a strong SSE of creep rupture life,characterized by a significant difference in the CRL values up to 60%with the variation of wall thickness and position in the casing.In terms of casting technology,the influence of SSE on CRL is actually determined by the cooling rate.The SSE on the creep rupture life originates from the dendrite structure(such as the secondary dendrite arm spacing),volume fraction size of theγ'phase in the dendrite trunk,and elements segregation rate.This work may have implications for the design and application of engineering components with large sizes and complex structures.
基金Project(2012CB619503)supported by the Natioanl Basic Research Program of ChinaProject(2013AA031001)supported by the National High-tech Research and Development Program of ChinaProject(2012DFA50630)supported by the International Science&Technology Cooperation Program of China
文摘To investigate the effects of Al-Ti-B-RE grain refiner on microstructure and mechanical properties of Al-7.0Si-0.55Mg （A357） alloy, some novel Al-7.0Si-0.55Mg alloys added with different amount of Al-STi-1B-RE grain refiner with different RE composition were prepared by vacuum-melting. The microstructure and fracture behavior of the AI-7.0Si-0.55Mg alloys with the grain refiners were observed by X-ray diffraction （XRD）, optical microscopy （OM）, scanning electron microscopy （SEM）, and the mechanical properties of the alloys were tested in mechanical testing machine at room temperature. The observation of AI-Ti-B-RE morphology and internal structure of the particles reveals that it exhibits a TiAl3/Ti2Al20RE core-shell structure via heterogeneous TiB2 nuclei. The tensile strength of Al-7.0Si-0.55Mg alloys with Al-5Ti-1B-3.0RE grain refiner reaches the peak value at the same addition （0.2%） of grain refiner.
基金Projects(50975174,51275297)supported by the National Natural Science Foundation of ChinaProject(20100073110044)supported by the Education Ministry of China
文摘The electroplastic effect in AZ31B magnesium alloy sheet was investigated through uniaxial tensile tests. In order to show the athermal effect of the electrical pulses, two types of uniaxial tensile tests at the same testing temperature were carried out： uniaxial tension in environmental cabinet and uniaxial tension with electrical pulses. In addition, the distribution of temperature field in the cross-section area during uniaxial tension with electrical pulses was simulated. The results show that the distribution of temperature field along the cross-section area is homogeneous. By comparing the true stress？true strain curves of AZ31B alloy under uniaxial tensile tests, the athermal effect with electrical pulses was confirmed. The microstructure evolution after the uniaxial tension was studied by optical microscopy. The results indicate that the electrical pulses induced dynamic recrystallization plays an important role in the decrease of flow stress. Finally, a flow stress model of AZ31B sheet taking the influence of electroplastic effect into account was proposed and validated. The results demonstrate that the calculated data fit the experimental data well.
文摘2022年中央一号文件《中共中央国务院关于做好2022年全面推进乡村振兴重点工作的意见》明确要求大力推进数字农业建设,推进智慧农业发展;2022年12月23日至24日中央农村工作会议上习近平总书记指出“产业振兴是乡村振兴的重中之重,要落实产业帮扶政策,做好‘土特产’文章,依托农业农村特色资源,向开发农业多种功能、挖掘乡村多元价值要效益,向一二三产业融合发展要效益,强龙头、补链条、兴业态、树品牌,推动乡村产业全链条升级,增强市场竞争力和可持续发展能力”。本文深刻领会习近平总书记、中央一号文件、中共浙江省委十五届二次全会精神,通过深入总结嘉兴与丽水近二十年开展“山海协作”的成功经验,并针对嘉兴与丽水联动发展特色农业产业链目前遇到的种养技术、销售模式、专家团队、高技能人才等瓶颈,提出构建“嘉兴农产品专业市场与丽水种养基地联动发展特色农业产业链的‘W2F+B2M’(Wholesale to Farmer+Business to Member,即嘉兴农产品专业市场与丽水种养基地+嘉兴专业市场商户与商户的会员联动)模式”,进一步完善嘉兴与丽水特色农业产业链的联动发展机制,助推嘉兴与丽水共同富裕。
基金financial support by the National Natural Science Foundation of China (No.51474203)Key Research Program of the Chinese Academy of Sciences (No.KGZD-EW-XXX-2)
文摘The distribution of boron and the microstructure of grain boundary（GB） precipitates（M23（C,B） 6 and M 2B）have been analyzed with their effects on the susceptibility of ductility-dip-cracking（DDC） and tensile properties for NiCrFe-7 weld metal,using optical microscopy（OM）,secondary ion mass spectroscopy（SIMS）,scanning electron microscopy（SEM）,and transmission electron microscopy（TEM）.The results show that boron segregates at GBs in NiCrFe-7 weld metal during the welding process.The segregation of boron at GBs promotes the formation of continuous M23（C,B） 6 carbide chains and M 2B borides along GBs.The addition of boron aggravates GB embrittlement and causes more DDC in the weld metal,by its segregation at GBs presenting as an impurity,and promoting the formation of larger and continuous M 23（C,B） 6 carbides,and M 2B borides along GBs.DDC in the weld metal deteriorates the ductility and tensile strength of the weld metal simultaneously.
基金National Natural Science Foundation of China under Grant No.U2239252National Natural Science Foundation of China under Grant No.52279128Natural Science Foundation of Heilongjiang Province of China under Grant No.YQ2022E013。
文摘Dispatched by the Chinese government,a multidisciplinary team of 30 researchers collaborated with a team from Myanmar to conduct a 14-day on-site investigation.The work encompassed seismic intensity assessments,field surveys,and loss evaluations.The paper focuses on the intensity distribution and structural damage characteristics of the 2025 M7.9 Myanmar earthquake,yielding the following key findings.(1)The seismogenic fault rupture propagated in a nearly N-S direction,with a surface rupture length of approximately 450 km.The seismic impact zone exhibited an elongated N-S distribution and a shorter E-W span,distributed like a belt around the seismogenic fault.(2)Within the seismic impact zones,existing buildings comprised five primary structural types,with timber(bamboo)structures constituting the largest proportion(≈80%in rural areas,≈50%in urban areas).The relatively low disaster losses and casualties were primarily attributable to the good seismic performance and low damage ratio of timber(bamboo)structures across varying intensity zones.(3)An anomalous zone of intensityⅨwas located at the boundary between intensityⅥandⅦregions in Nay Pyi Taw.Here,ridge topography combined with soft soil layers significantly amplified ground motion,exacerbating structural damage.(4)Directional effects of ground motion were observed,with the structural damage phenomena and peak ground acceleration(PGA)values in the N-S direction exceeding those in the E-W direction.This validates that the maximum PGA distribution of strike-slip fault earthquakes aligns with the fault strike.The research is expected to provide technical support for post-disaster reconstruction planning,site selection,and disaster mitigation strategies in Myanmar.
文摘AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.
基金National Natural Science Foundation of China,No.81704059Scientific Research Project of Hebei Province Traditional Chinese Medicine Administration,No.2017130。
文摘BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many complications.AIM To explore the protective effects of panax notoginseng saponin(PNS) against dextran sulfate sodium(DSS)-induced intestinal inflammatory injury through phosphoinositide-3-kinase protein kinase B(PI3K/AKT) signaling pathway inhibition in rats.METHODS Colitis rat models were generated via DSS induction, and rats were divided into control(no modeling), DSS, DSS + PNS 50 mg/k, and DSS + PNS 100 mg/kg groups. Then, the intestinal injury, oxidative stress parameters, inflammatory indices, tight junction proteins, apoptosis, macrophage polarization, and TLR4/AKT signaling pathway in colon tissues from rats in each of the groups were detected. The PI3 K/AKT signaling pathway in the colon tissue of rats was blocked using the PI3K/AKT signaling pathway inhibitor, LY294002.RESULTS Compared with rats in the control group, rats in the DSS group showed significantly shortened colon lengths, and significantly increased disease activity indices, oxidative stress reactions and inflammatory indices, as well as significantly decreased expression of tight junction-associated proteins. In addition, the DSS group showed significantly increased apoptotic cell numbers,and showed significantly increased M1 macrophages in spleen and colon tissues.They also showed significantly decreased M2 macrophages in colon tissues, as well as activation of the PI3K/AKT signaling pathway(all P < 0.05). Compared with rats in the DSS group, rats in the DSS + PNS group showed significantly lengthened colon lengths, decreased disease activity indices, and significantly alleviated oxidative stress reactions and inflammatory responses. In addition, this group showed significantly increased expression of tight junction-associated proteins, significantly decreased apoptotic cell numbers, and significantly decreased M1 macrophages in spleen and colon tissues. This group further showed significantly increased M2 macrophages in colon tissues, and significantly suppressed activation of the PI3K/AKT signaling pathway, as well as a dose dependency(all P < 0.05). When the PI3K/AKT signaling pathway was inhibited, the apoptosis rate of colon tissue cells in the DSS + LY294002 group was significantly lower than that of the DSS group(P < 0.05).CONCLUSION PNS can protect rats against DSS-induced intestinal inflammatory injury by inhibiting the PI3K/AKT signaling pathway, and therefore may be potentially used in the future as a drug for colitis.
基金Supported by the National Natural Science Foundation of China,No.81070319the Beijing Natural Science Foundation of China,No.7102013the Beijing Municipal Education Commission Research Program,China,No.KM201610025004
文摘BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.
基金funded by the National Natural Science Foundation of China,No.81501185(to CR)the Key Research&Development Project of Shandong Province of China,No.2017GSF218043(to CR)the Science and Technology Planning Project of Yantai of China,No.2016WS017(to LNG),2017WS105(to HL)
文摘Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.
基金supported by grants from the National Mega Project on Major Drug Development(No.2009ZX09301-014-1)National Natural Science Foundation of China(No.81371865)
文摘Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytial virus （RSV）. However, no antiviral agents with low toxicity and drug resistance are cur- rently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin （an ingredient of Rheum palmatum） against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum pal- matum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication in- hibition, virucidal and anti-absorption effects, by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tet- razolium bromide （MTT） assay and plaque reduction assay （PRA）. The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR （qPCR）. Cytokine （IFN-γ, TNF-α） mRNA expressions after emodin treatment （7.5, 15, 30 μmol/L） were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration （EC50） ranging from 13.06 to 14.27 μmol/L and selectivity index （SI） being 5.38-6.41 μmol/L. However, emodin couldn＇t directly inacti- vate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.
