In a rapid cycling synchrotron(RCS),the magnetic field is synchronized with the beam energy,creating a highly dynamic magnetic environment.A ceramic chamber with a shielding layer(RF shield),composed of a series of co...In a rapid cycling synchrotron(RCS),the magnetic field is synchronized with the beam energy,creating a highly dynamic magnetic environment.A ceramic chamber with a shielding layer(RF shield),composed of a series of copper strips connected to a capacitor at either end,is typically employed as a vacuum chamber to mitigate eddy current effects and beam coupling impedance.Consequently,the ceramic chamber exhibits a thin-walled multilayered complex structure.Previous theoretical studies have suggested that the impedance of such a structure has a negligible impact on the beam.However,recent impedance measurements of the ceramic chamber in the China Spallation Neutron Source(CSNS)RCS revealed a resonance in the low-frequency range,which was confirmed by further theoretical analysis as a source of beam instability in the RCS.Currently,the magnitude of this impedance cannot be accurately assessed using theoretical calculations.In this study,we used the CST Microwave Studio to confirm the impedance of the ceramic chamber.Further simulations covering six different types of ceramic chambers were conducted to develop an impedance model in the RCS.Additionally,this study investigates the resonant characteristics of the ceramic chamber impedance,finding that the resonant frequency is closely related to the capacitance of the capacitors.This finding provides clear directions for further impedance optimization and is crucial for achieving a beam power of 500 kW for the CSNS Phase-Ⅱ project(CSNS-Ⅱ).However,careful attention must be paid to the voltage across the capacitors.展开更多
AIM: To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors (HDACIs) can sensitize hepatocellular carcinoma (HCC) cells to sorafenib treatment. METHODS: Bax, Bcl-2, ATG5-ATG12, p21, and p27 p...AIM: To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors (HDACIs) can sensitize hepatocellular carcinoma (HCC) cells to sorafenib treatment. METHODS: Bax, Bcl-2, ATG5-ATG12, p21, and p27 protein levels in Hep3B, HepG2, and PLC/PRF/5 cells were examined by Western blot. CCK8 and a fluoro-metric caspase-3 assay were used to examine cellular viability and apoptosis levels. The effect of Beclin-1 on sensitization of HCC cells to sorafenib was examined by transfecting Beclin-1 siRNA into Hep3B, HepG2, and PLC/PRF/5 cells. RESULTS: Autophagy inhibition enhances the inhibitory effects of vorinostat and sorafenib alone or in combination on HCC cell growth. Vorinostat and sorafenib synergistically induced apoptosis and cell cycle alterations. Western blot data indicated that HDACIs and Beclin- 1 knockdown increased the p53 acetylation level. The knockdown of Beclin-1 enhanced the synergistic effect of the combination of vorinostat with sorafenib. CONCLUSION: HDACIs can sensitize HCC cells to sorafenib treatment by regulating the acetylation level of Beclin-1. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.展开更多
We previously isolated a new species of the genus Phlebovirus from wild sandflies collected from Wuxiang County in central China,which named the Wuxiang virus(WUXV).In this study,we re-isolated the WUXV from wild sand...We previously isolated a new species of the genus Phlebovirus from wild sandflies collected from Wuxiang County in central China,which named the Wuxiang virus(WUXV).In this study,we re-isolated the WUXV from wild sandflies collected from two villages in Yangquan County,China in 2019.Four virus isolates that caused cytopathic effects in BHK-21 cells were successfully isolated from sandfly specimens collected from chicken pens and sheep pens.Phylogenetic analyses of the L,M and S gene segments of the viruses revealed that the four virus strains represented the previously isolated WUXV.The minimum infection rate(MIR)of the virus isolated from the sheep pen was 3.21,and the MIR of the virus isolated from the chicken pen was 3.45.The positive rates of Wuxiang virus neutralizing antibodies in serum samples of local healthy people and domestic chickens were 8.7%(4/46)and 100%(4/4),respectively,suggesting that Wuxiang virus can infect human and animal.In view of the fact that Wuxiang virus is infectious to humans and animals and has a relatively wide geographical distribution in China,it is of great public health significance to strengthen the investigation and study on the infection status of Wuxiang virus in humans and animals.展开更多
The traditional Chinese herb Astragalus membranaceus is a well-known treatment for neurological diseases and is considered to exhibit anti-dementia properties.This study investigated the synergistic effects of magnesi...The traditional Chinese herb Astragalus membranaceus is a well-known treatment for neurological diseases and is considered to exhibit anti-dementia properties.This study investigated the synergistic effects of magnesium ions and Astragalus membranaceus on global brain ischemia in rats.4＇-6-diamidino-2-phenylindole staining demonstrated that the number of living neurons was significantly greater in the rat hippocampus after administration of a combination of Astragalus membranaceus and magnesium,compared with a vehicle group,an Astragalus membranaceus alone group,and a magnesium alone group.Western blot assay revealed that cleaved Caspase-3 protein expression was significantly reduced in the rat hippocampus in the combined Astragalus membranaceus and magnesium group compared with the Astragalus membranaceus alone group and the magnesium alone group.The results suggested that the combination of Astragalus membranaceus and magnesium exhibits a stronger neuroprotective effect on global brain ischemia in rats compared with Astragalus membranaceus or magnesium alone.This effect was associated with decreased Caspase-3 expression.展开更多
BACKGROUND： Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown t...BACKGROUND： Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia. OBJECTIVE： To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein （CREB）, phosphorylated CREB （pCREB）, and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS： Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA. METHODS： A total of 42 female, Wistar rats were randomly assigned to the following groups： sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours. MAIN OUTCOME MEASURES： CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze. RESULTS： CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group （P 〈 0.01）. However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group （P 〈 0.01）. Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham operation group （P 〈 0.01）. Learning, memory, and behavior disorders were observed in the vascular cognitive impairment group. Sevoflurane treatment significantly improved these observed disorders. CONCLUSION： Sevoflurane improved cognitive impairment due to permanent bilateral occlusion of both common carotid arteries. Improved function was associated with increased CREB, pCREB, and Livin expression in the cortex and hippocampus.展开更多
BACKGROUND Persistent suspicion of prostate cancer(PCa)due to a rising prostate-specific antigen(PSA)level after repeated negative biopsies is a serious challenge in clinical practice.AIM To determine the role of Hira...BACKGROUND Persistent suspicion of prostate cancer(PCa)due to a rising prostate-specific antigen(PSA)level after repeated negative biopsies is a serious challenge in clinical practice.AIM To determine the role of Hiraoka’s transurethral detachment of the prostate(TUDP)combined with biopsy of the peripheral zone during the same session in patients with repeated negative biopsies in the diagnosis of PCa.METHODS We retrospectively evaluated the records of 10 patients who were eligible for inclusion in our hospital between December 2012 and August 2017.Patient demographics,a family history of PCa,the number of biopsies,prostate volume,pathological examination,and perioperative PSA level were obtained.RESULTS Two of 10 patients were pathologically diagnosed with PCa after surgery;the Gleason scores were 4+4 and 4+3,respectively.Both patients subsequently underwent laparoscopic radical prostatectomy.The median PSA levels preoperatively,and 3 mo and 1 year postoperatively in the other eight patients who were diagnosed with benign prostate hyperplasia after surgery were 19.10 ng/mL,1.10 ng/mL,and 1.15 ng/mL,respectively.The adjusted P values of the 3-mo and 1-year post-operative PSA level vs pre-operative PSA level were 0.003 and 0.026,respectively.None of the patients had increased PSA levels or PCa detected after a median 35 mo of follow-up.CONCLUSION TUDP combined with peripheral zone biopsy may improve the detection rate of PCa in patients with repeated negative biopsies.The PSA level declined rapidly in patients who had negative pathological examinations after TUDP,which remained stable 1 year after surgery.展开更多
Background:Diabetic foot ulcers(DBFU)are one of the main complications of diabetes.Platelet-rich plasma(PRP)treatment is a commonly used treatment option.Tibial transverse transport(TTT)also has a therapeutic effect o...Background:Diabetic foot ulcers(DBFU)are one of the main complications of diabetes.Platelet-rich plasma(PRP)treatment is a commonly used treatment option.Tibial transverse transport(TTT)also has a therapeutic effect on DBFU.Some studies have found that the TTT combined with PRP(TTT&PRP)has a significant effect on DBFU.Methods:PubMed,Cochrane Library,Web of Science,EMBASE,Chinese Biomedical Literature,CNKI,VIP,and Wanfang databases were used to find literature on the treatment of DBFUs using the TTT and PRP treatment according to the inclusion criteria.The specific inclusion criteria are as follows:(1)research type:clinical controlled trials,including retrospective cohort and randomized controlled studies;(2)diagnosis of DBFUs that does not include a definitively diagnosed traumatic ulcer;(3)original materials of Chinese and English literature published in full text.The exclusion criteria are:(1)the research group was not defined or grouped;(2)nonrandomized controlled trials,non-cohort studies,non-case-control studies,retrospective studies,and case reports;(3)repetitive research and animal experimentation;(4)ulcers caused by other diseases;(5)conservative treatment or no use of invasive treatment methods.Review Manager software(version 5.3)was used to conduct a meta-analysis of the included results.Result:The literature included 6 randomized controlled studies,including 508 patients,254 patients in the PRP treatment group,and 254 patients in the TTT&PRP group.The meta-analysis results showed that in terms of treatment efficacy,the TTT&PRP combined treatment group had a higher efficacy than the PRP group.After treatment,the TTT&PRP group had better treatment effects in psychological function,physiological function,and social function compared to the PRP group.After treatment,the TTT&PRP group showed a significant increase in serum epidermal growth factor(EGF),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and platelet-derived growth factor(PDGF)levels compared to the PRP group.In terms of wound healing after treatment,the TTT&PRP group performed better than the PRP group in terms of postoperative wound reduction rate,bacterial clearance rate,granulation tissue coverage rate,and granulation tissue growth thickness.Conclusion:TTT combined with PRP was more effective than PRP alone in treating DBFUs.展开更多
Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid ...Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.展开更多
Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating...Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.展开更多
BACKGROUND Colorectal cancer,one of the most common malignancies,is primarily treated through surgery.With the widespread use of laparoscopy,gastrointestinal reconstruction remains a key area of research.The choice be...BACKGROUND Colorectal cancer,one of the most common malignancies,is primarily treated through surgery.With the widespread use of laparoscopy,gastrointestinal reconstruction remains a key area of research.The choice between intraperitoneal anastomosis(IA)and extraperitoneal anastomosis(EA)remains a subject of considerable debate.This study uses intraperitoneal isoperistaltic side-to-side anastomosis(IISSA)with hand-sewn closure of the common opening to evaluate its safety and short-term outcomes.It is hypothesized that this technique may offer better short-term outcomes than EA.AIM To investigate the safety and short-term outcomes of IISSA with hand-sewn closure of the common opening compared to EA.METHODS Patients who underwent laparoscopic radical colon cancer surgery between January 2018 and June 2022 at the First Affiliated Hospital of Xiamen University were retrospectively analyzed.Surgical,postoperative,and pathological features of the IA and EA groups were observed before and after propensity score matching.Patients with right-sided and left-sided colon cancer were separated,each further divided into IA and EA groups(R-IA vs R-EA for right-sided,L-IA vs L-EA for left-sided),for stratified analysis of the aforementioned indicators.RESULTS After propensity score matching,63 pairs were matched in each group.In surgical characteristics,the IA group exhibited less blood loss and shorter incisions than the EA group.Regarding postoperative recovery,the IA group showed earlier recovery of gastrointestinal function.Pathologically,the IA group had greater lymph node clearance.Relative to the R-EA group,the R-IA group experienced reduced blood loss,shorter assisted incisions,earlier recovery of gastrointestinal functions and greater lymph node dissection.When compared to the L-EA group,the L-IA group demonstrated earlier postoperative anal exhaust and defecation,along with a reduced length of hospitalization.Regarding postoperative complications,no statistically significant differences were found between the groups either after matching or in the stratified analyses.CONCLUSION Compared to EA,IISSA with hand-sewn closure of the common opening is a safe and feasible option for laparoscopic radical colon cancer surgery.展开更多
Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as...Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as massive by-product,contribute to greenhouse effects and pose environmental challenges.Thus,the pursuit of nitrogen fixation through carbon–neutral pathways under benign conditions is a frontier of scientific topics,with the harnessing of solar energy emerging as an enticing and viable option.This review delves into the refinement strategies for scale-up mild photocatalytic nitrogen fixation,fields ripe with potential for innovation.The narrative is centered on enhancing the intrinsic capabilities of catalysts to surmount current efficiency barriers.Key focus areas include the in-depth exploration of fundamental mechanisms underpinning photocatalytic procedures,rational element selection,and functional planning,state-of-the-art experimental protocols for understanding photo-fixation processes,valid photocatalytic activity evaluation,and the rational design of catalysts.Furthermore,the review offers a suite of forward-looking recommendations aimed at propelling the advancement of mild nitrogen photo-fixation.It scrutinizes the existing challenges and prospects within this burgeoning domain,aspiring to equip researchers with insightful perspectives that can catalyze the evolution of cutting-edge nitrogen fixation methodologies and steer the development of next-generation photocatalytic systems.展开更多
AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from thr...AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N_(2)),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP group.Retinal neovascularization was observed by fluorescein angiography and quantified.Retinal thickness was evaluated by Hematoxylin and eosin(HE)stain.The expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western blot.IL-1βlevel in retina was analyzed using immunohistochemical staining.RESULTS:The increased area of neovascular clusters in OIR mice was significantly decreased by LBP.Retinal thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP group.Compared with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control group.Moreover,IL-1βwas reduced in retinal sections treated with LBP.In the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in migration.CONCLUSION:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt/mTOR signaling pathway.展开更多
BACKGROUND Acute variceal bleeding(AVB)in patients with cirrhosis remains life-threatening;moreover,the current risk stratification methods have certain limitations.Rebleeding and mortality after AVB remain major chal...BACKGROUND Acute variceal bleeding(AVB)in patients with cirrhosis remains life-threatening;moreover,the current risk stratification methods have certain limitations.Rebleeding and mortality after AVB remain major challenges.Although preemptive transjugular intrahepatic portosystemic shunt(p-TIPS)can improve outcomes,not all patients benefit equally.Accurate risk stratification is needed to guide treatment decisions and identify those most likely to benefit from p-TIPS.AIM To develop an artificial intelligence(AI)-driven model to guide AVB treatment decisions,and identify candidates eligible for p-TIPS.METHODS Patients with cirrhosis and AVB,from two multicenter retrospective cohorts in China,who received endoscopic variceal ligation plus pharmacotherapy(n=1227)or p-TIPS(n=1863)were included.Baseline data within 24 hours of hospital admission were obtained.The AI-AVB model,based on the six-week failure and one-year mortality rates,was developed to predict treatment efficacy and compared with standard risk scores.Outcomes and adverse events of the treatments were compared across the high-and low-risk subgroups stratified using the AI-AVB model.RESULTS The AI-AVB model demonstrated superior predictive performance compared to traditional risk stratification methods.In the internal validation cohort,the model achieved an area under the curve(AUC)of 0.842 for predicting six-week treatment failure and 0.954 for one-year mortality.In the external validation cohort,the AUCs were 0.814 and 0.889,respectively.The model effectively identified patients at high risk of first-line treatment failure who may benefit from aggressive interventions such as p-TIPS.In contrast,advancing the treatment strategy for low-risk patients did not notably improve the short-term prognosis.CONCLUSION The AI-AVB model can predict treatment outcomes,stratify the failure risk in cirrhotic patients with AVB,aid in clinical decisions,identify p-TIPS beneficiaries,and optimize personalized treatment strategies.展开更多
In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through top...In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through topological cues.An ideal TE scaffold should possess biomimetic cross-scale structures,similar to that of natural extracellular matrices,at the nano-to macro-scale level.Although freeform fabrication of TE scaffolds can be achieved through 3D printing,this method is limited in simultaneously building multiscale structures.To address this challenge,low-temperature fields were adopted in the traditional fabrication processes,such as casting and 3D printing.Ice crystals grow during scaffold fabrication and act as a template to control the nano-and micro-structures.These microstructures can be optimized by adjusting various parameters,such as the direction and magnitude of the low-temperature field.By preserving the macro-features fabricated using traditional methods,additional micro-structures with smaller scales can be incorporated simultaneously,realizing cross-scale structures that provide a better mimic of natural organs and tissues.In this paper,we present a state-of-the-art review of three low-temperature-field-assisted fabrication methods—freeze casting,cryogenic3D printing,and freeze spinning.Fundamental working principles,fabrication setups,processes,and examples of biomedical applications are introduced.The challenges and outlook for low-temperature-assisted fabrication are also discussed.展开更多
The rapid emergence and spread of colistin-resistant gram-negative bacteria has raised worldwide public health concerns,and phosphoethanolamine(PEtn)transferase modification-mediated colistin resistance has been widel...The rapid emergence and spread of colistin-resistant gram-negative bacteria has raised worldwide public health concerns,and phosphoethanolamine(PEtn)transferase modification-mediated colistin resistance has been widely documented in multiple gram-negative bacterial species.However,whether such a mechanism exists in the zoonotic pathogen Pasteurella multocida is still unknown.Recently,a novel PEtn transferase,PetL,was identified in P.multo-cida,but whether it is associated with colistin resistance remains to be elucidated.In this study,we found that PetL in P.multocida(PetL^(PM))exhibited structural characteristics similar to those of the mobile-colistin-resistant(MCR)protein and the PEtn transferase characterized in Neisseria meningitidis.The transformation of petLPM into E.coli or K.pneumoniae changed the phenotype of several tested strains from colistin sensitive to colistin resistant.Deletion of this gene decreased the colistin minimum inhibitory concentration(MIC)of P.multocida by 64-fold.Our extensive analysis by MALDI-TOF-MS demonstrated that PetLPM participated in the modification of bacterial lipopolysaccharide(LPS)-lipid A.Deletion of petL^(PM) led to an increase in membrane charge but a decrease in cell-surface hydrophobicity and cell permeability in P.multocida.The present study is the first to report the presence of PEtn transferase-mediated colistin resistance in the zoonotic pathogen P.multocida.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is notorious for its aggressive progression and dismal prognosis,with chromatin accessibility dynamics emerging as pivotal yet poorly understood drivers.AIM To dissect how multi...BACKGROUND Hepatocellular carcinoma(HCC)is notorious for its aggressive progression and dismal prognosis,with chromatin accessibility dynamics emerging as pivotal yet poorly understood drivers.AIM To dissect how multilayered chromatin regulation sustains oncogenic transcription and tumor-stroma crosstalk in HCC,we combined multiomics single cell analysis.METHODS We integrated single-cell RNA sequencing and paired single-cell assay for transposase-accessible chromatin with sequencing data of HCC samples,complemented by bulk RNA sequencing validation across The Cancer Genome Atlas,Liver Cancer Institute,and GSE25907 cohorts.Cell type-specific chromatin architectures were resolved via ArchR,with regulatory hubs identified through peak-to-gene linkages and coaccessibility networks.Functional validation employed A485-mediated histone 3 lysine 27 acetylation suppression and small interfering RNA targeting DGAT1.RESULTS Malignant hepatocytes exhibited expanded chromatin accessibility profiles,characterized by increased numbers of accessible peaks and larger physical regions despite reduced peak intensity.Enhancer-like peaks enriched in malignant regulation,forming long-range hubs.Eighteen enhancer-like peak-related genes showed tumor-specific overexpression and diagnostic accuracy,correlating with poor prognosis.Intercellular coaccessibility analysis revealed tumor-stroma symbiosis via shared chromatin states.Pharmacological histone 3 lysine 27 acetylation inhibition paradoxically downregulated DGAT1,the hub gene most strongly regulated by chromatin accessibility.DGAT1 knockdown suppressed cell proliferation.CONCLUSION Multilayered chromatin reprogramming sustains HCC progression through tumor-stroma crosstalk and DGAT1-related oncogenic transcription,defining targetable epigenetic vulnerabilities.展开更多
The wide application of smart contracts allows industry companies to implement some complex distributed collaborative businesses,which involve the calculation of complex functions,such as matrix operations.However,com...The wide application of smart contracts allows industry companies to implement some complex distributed collaborative businesses,which involve the calculation of complex functions,such as matrix operations.However,complex functions such as matrix operations are difficult to implement on Ethereum Virtual Machine(EVM)-based smart contract platforms due to their distributed security environment limitations.Existing off-chain methods often result in a significant reduction in contract execution efficiency,thus a platform software development kit interface implementation method has become a feasible way to reduce overheads,but this method cannot verify operation correctness and may leak sensitive user data.To solve the above problems,we propose a verifiable EVM-based smart contract cross-language implementation scheme for complex operations,especially matrix operations,which can guarantee operation correctness and user privacy while ensuring computational efficiency.In this scheme,a verifiable interaction process is designed to verify the computation process and results,and a matrix blinding technology is introduced to protect sensitive user data in the calculation process.The security analysis and performance tests show that the proposed scheme can satisfy the correctness and privacy of the cross-language implementation of smart contracts at a small additional efficiency cost.展开更多
Active and poisoning-resistant Ru-based electrocatalysts for the hydrogen oxidation reaction(HOR)are designed and fabricated by integrating Cu/Ru dual single atoms and alloy CuRu nanoparticles(N-(CuRu)_(NP+SA)@NC)thro...Active and poisoning-resistant Ru-based electrocatalysts for the hydrogen oxidation reaction(HOR)are designed and fabricated by integrating Cu/Ru dual single atoms and alloy CuRu nanoparticles(N-(CuRu)_(NP+SA)@NC)through a strategy involving weak chemical reduction and ammonia-assisted gas-phase nitridation.The resultant N-(CuRu)_(NP+SA)@NC electrocatalysts feature nitrogen atoms coordinated to both Cu and Ru metal atoms via strong N-metal interactions.Density functional theory calculations revealed that alloyed CuRu nanoparticles and monodispersed Cu atoms are vital for altering the electronic configuration of the host Ru elements.This finely tuned structure enhanced the adsorption of H and OH and promoted CO oxidation over the N-(CuRu)_(NP+SA)@NC electrocatalyst,resulting in high alkaline HOR activity,as evidenced by the higher exchange current density of 3.74 mA cm^(-2)and high mass activity of 3.28 mAμg_(Ru)^(-1),which are far superior to those of most Ru-based catalysts reported to date.Moreover,the N-(CuRu)_(NP+SA)@NC electrocatalysts are resistant to CO poisoning and can be used at a high concentration of 1000 ppm CO with no distinct decay in the activity,in stark contrast to the commercial Pt/C catalyst under the same conditions.展开更多
The evolution of fretting wear behavior of zirconium alloy cladding tubes mated with dimples under the gross slip regime(GSR)was investigated.The findings revealed that the primary wear mechanisms under GSR were delam...The evolution of fretting wear behavior of zirconium alloy cladding tubes mated with dimples under the gross slip regime(GSR)was investigated.The findings revealed that the primary wear mechanisms under GSR were delamination,surface fatigue wear and abrasive wear,and the fretting damage rate mainly depends on delamination.The cross-sectional microstructure of the worn area could be divided into the third-body layer,tribologically transformed structure layer,and general deformation layer,with their formation mechanisms analyzed.Furthermore,the mechanism of wear-induced grain refinement was identified as dynamic recrystallization(DRX),including both continuous DRX and discontinuous DRX.Additionally,the processes of fretting wear and DRX were discussed.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation,China(No.2021B1515140007).
文摘In a rapid cycling synchrotron(RCS),the magnetic field is synchronized with the beam energy,creating a highly dynamic magnetic environment.A ceramic chamber with a shielding layer(RF shield),composed of a series of copper strips connected to a capacitor at either end,is typically employed as a vacuum chamber to mitigate eddy current effects and beam coupling impedance.Consequently,the ceramic chamber exhibits a thin-walled multilayered complex structure.Previous theoretical studies have suggested that the impedance of such a structure has a negligible impact on the beam.However,recent impedance measurements of the ceramic chamber in the China Spallation Neutron Source(CSNS)RCS revealed a resonance in the low-frequency range,which was confirmed by further theoretical analysis as a source of beam instability in the RCS.Currently,the magnitude of this impedance cannot be accurately assessed using theoretical calculations.In this study,we used the CST Microwave Studio to confirm the impedance of the ceramic chamber.Further simulations covering six different types of ceramic chambers were conducted to develop an impedance model in the RCS.Additionally,this study investigates the resonant characteristics of the ceramic chamber impedance,finding that the resonant frequency is closely related to the capacitance of the capacitors.This finding provides clear directions for further impedance optimization and is crucial for achieving a beam power of 500 kW for the CSNS Phase-Ⅱ project(CSNS-Ⅱ).However,careful attention must be paid to the voltage across the capacitors.
基金Supported by Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University
文摘AIM: To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors (HDACIs) can sensitize hepatocellular carcinoma (HCC) cells to sorafenib treatment. METHODS: Bax, Bcl-2, ATG5-ATG12, p21, and p27 protein levels in Hep3B, HepG2, and PLC/PRF/5 cells were examined by Western blot. CCK8 and a fluoro-metric caspase-3 assay were used to examine cellular viability and apoptosis levels. The effect of Beclin-1 on sensitization of HCC cells to sorafenib was examined by transfecting Beclin-1 siRNA into Hep3B, HepG2, and PLC/PRF/5 cells. RESULTS: Autophagy inhibition enhances the inhibitory effects of vorinostat and sorafenib alone or in combination on HCC cell growth. Vorinostat and sorafenib synergistically induced apoptosis and cell cycle alterations. Western blot data indicated that HDACIs and Beclin- 1 knockdown increased the p53 acetylation level. The knockdown of Beclin-1 enhanced the synergistic effect of the combination of vorinostat with sorafenib. CONCLUSION: HDACIs can sensitize HCC cells to sorafenib treatment by regulating the acetylation level of Beclin-1. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
基金supported by the Ministry of Science and Technology of the People’s Republic of China(2018ZX10711001,2018ZX10734-404-003)National Key Research and Development Program(No.2018YFA0900800)+4 种基金National Science and Technology Major Project(2018ZX10102001)National Natural Science Foundation of China(31900156)Key Research and Development(R&D)Projects of Shanxi Province,China(201803D31205)the United States National Institutes of Health U01 AI151810Development Grant of the State Key Laboratory of Infectious Disease Prevention and Control(2014SKLID103,2015SKLID505)。
文摘We previously isolated a new species of the genus Phlebovirus from wild sandflies collected from Wuxiang County in central China,which named the Wuxiang virus(WUXV).In this study,we re-isolated the WUXV from wild sandflies collected from two villages in Yangquan County,China in 2019.Four virus isolates that caused cytopathic effects in BHK-21 cells were successfully isolated from sandfly specimens collected from chicken pens and sheep pens.Phylogenetic analyses of the L,M and S gene segments of the viruses revealed that the four virus strains represented the previously isolated WUXV.The minimum infection rate(MIR)of the virus isolated from the sheep pen was 3.21,and the MIR of the virus isolated from the chicken pen was 3.45.The positive rates of Wuxiang virus neutralizing antibodies in serum samples of local healthy people and domestic chickens were 8.7%(4/46)and 100%(4/4),respectively,suggesting that Wuxiang virus can infect human and animal.In view of the fact that Wuxiang virus is infectious to humans and animals and has a relatively wide geographical distribution in China,it is of great public health significance to strengthen the investigation and study on the infection status of Wuxiang virus in humans and animals.
基金the National Natural Science Foundation of China, No. 81000498the Natural Science Foundation of Nanjing Medical University, No. 09MJMUM107
文摘The traditional Chinese herb Astragalus membranaceus is a well-known treatment for neurological diseases and is considered to exhibit anti-dementia properties.This study investigated the synergistic effects of magnesium ions and Astragalus membranaceus on global brain ischemia in rats.4＇-6-diamidino-2-phenylindole staining demonstrated that the number of living neurons was significantly greater in the rat hippocampus after administration of a combination of Astragalus membranaceus and magnesium,compared with a vehicle group,an Astragalus membranaceus alone group,and a magnesium alone group.Western blot assay revealed that cleaved Caspase-3 protein expression was significantly reduced in the rat hippocampus in the combined Astragalus membranaceus and magnesium group compared with the Astragalus membranaceus alone group and the magnesium alone group.The results suggested that the combination of Astragalus membranaceus and magnesium exhibits a stronger neuroprotective effect on global brain ischemia in rats compared with Astragalus membranaceus or magnesium alone.This effect was associated with decreased Caspase-3 expression.
文摘BACKGROUND： Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia. OBJECTIVE： To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein （CREB）, phosphorylated CREB （pCREB）, and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS： Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA. METHODS： A total of 42 female, Wistar rats were randomly assigned to the following groups： sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours. MAIN OUTCOME MEASURES： CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze. RESULTS： CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group （P 〈 0.01）. However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group （P 〈 0.01）. Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham operation group （P 〈 0.01）. Learning, memory, and behavior disorders were observed in the vascular cognitive impairment group. Sevoflurane treatment significantly improved these observed disorders. CONCLUSION： Sevoflurane improved cognitive impairment due to permanent bilateral occlusion of both common carotid arteries. Improved function was associated with increased CREB, pCREB, and Livin expression in the cortex and hippocampus.
基金Supported by Shengjing Hospital Science and Technology Program,No.MC05.
文摘BACKGROUND Persistent suspicion of prostate cancer(PCa)due to a rising prostate-specific antigen(PSA)level after repeated negative biopsies is a serious challenge in clinical practice.AIM To determine the role of Hiraoka’s transurethral detachment of the prostate(TUDP)combined with biopsy of the peripheral zone during the same session in patients with repeated negative biopsies in the diagnosis of PCa.METHODS We retrospectively evaluated the records of 10 patients who were eligible for inclusion in our hospital between December 2012 and August 2017.Patient demographics,a family history of PCa,the number of biopsies,prostate volume,pathological examination,and perioperative PSA level were obtained.RESULTS Two of 10 patients were pathologically diagnosed with PCa after surgery;the Gleason scores were 4+4 and 4+3,respectively.Both patients subsequently underwent laparoscopic radical prostatectomy.The median PSA levels preoperatively,and 3 mo and 1 year postoperatively in the other eight patients who were diagnosed with benign prostate hyperplasia after surgery were 19.10 ng/mL,1.10 ng/mL,and 1.15 ng/mL,respectively.The adjusted P values of the 3-mo and 1-year post-operative PSA level vs pre-operative PSA level were 0.003 and 0.026,respectively.None of the patients had increased PSA levels or PCa detected after a median 35 mo of follow-up.CONCLUSION TUDP combined with peripheral zone biopsy may improve the detection rate of PCa in patients with repeated negative biopsies.The PSA level declined rapidly in patients who had negative pathological examinations after TUDP,which remained stable 1 year after surgery.
基金supported by the Zhejiang Province Traditional Chinese Medicine Science and Technology Program Project(grant no.:2023ZL429).
文摘Background:Diabetic foot ulcers(DBFU)are one of the main complications of diabetes.Platelet-rich plasma(PRP)treatment is a commonly used treatment option.Tibial transverse transport(TTT)also has a therapeutic effect on DBFU.Some studies have found that the TTT combined with PRP(TTT&PRP)has a significant effect on DBFU.Methods:PubMed,Cochrane Library,Web of Science,EMBASE,Chinese Biomedical Literature,CNKI,VIP,and Wanfang databases were used to find literature on the treatment of DBFUs using the TTT and PRP treatment according to the inclusion criteria.The specific inclusion criteria are as follows:(1)research type:clinical controlled trials,including retrospective cohort and randomized controlled studies;(2)diagnosis of DBFUs that does not include a definitively diagnosed traumatic ulcer;(3)original materials of Chinese and English literature published in full text.The exclusion criteria are:(1)the research group was not defined or grouped;(2)nonrandomized controlled trials,non-cohort studies,non-case-control studies,retrospective studies,and case reports;(3)repetitive research and animal experimentation;(4)ulcers caused by other diseases;(5)conservative treatment or no use of invasive treatment methods.Review Manager software(version 5.3)was used to conduct a meta-analysis of the included results.Result:The literature included 6 randomized controlled studies,including 508 patients,254 patients in the PRP treatment group,and 254 patients in the TTT&PRP group.The meta-analysis results showed that in terms of treatment efficacy,the TTT&PRP combined treatment group had a higher efficacy than the PRP group.After treatment,the TTT&PRP group had better treatment effects in psychological function,physiological function,and social function compared to the PRP group.After treatment,the TTT&PRP group showed a significant increase in serum epidermal growth factor(EGF),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and platelet-derived growth factor(PDGF)levels compared to the PRP group.In terms of wound healing after treatment,the TTT&PRP group performed better than the PRP group in terms of postoperative wound reduction rate,bacterial clearance rate,granulation tissue coverage rate,and granulation tissue growth thickness.Conclusion:TTT combined with PRP was more effective than PRP alone in treating DBFUs.
基金funded by the National Key Research and Development Program of China(No.2022YFC2804101)the Guangdong Provincial Key R&D Program(No.2023B1111050011)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515010432)the Guangzhou Basic and Applied Basic Research Foundation(No.202201010305)the High-Level Talents Special Program of Zhejiang(No.2022R52036)。
文摘Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.
基金Dean's Office Howard University College of Medicine,Grant/Award Number:Bridge Fund/Pilot Study AwardNational Center on Minority Health and Health Disparities,Grant/Award Number:RCMI/IDC Award U54MD007597National Institute of Child Health and Human Development,Grant/Award Number:R03HD095417 and R16HD116702。
文摘Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.
基金Bethune Charitable Foundation Project,No.HZB-20190528-10Natural Science Foundation of Fujian Province,No.2020J011230.
文摘BACKGROUND Colorectal cancer,one of the most common malignancies,is primarily treated through surgery.With the widespread use of laparoscopy,gastrointestinal reconstruction remains a key area of research.The choice between intraperitoneal anastomosis(IA)and extraperitoneal anastomosis(EA)remains a subject of considerable debate.This study uses intraperitoneal isoperistaltic side-to-side anastomosis(IISSA)with hand-sewn closure of the common opening to evaluate its safety and short-term outcomes.It is hypothesized that this technique may offer better short-term outcomes than EA.AIM To investigate the safety and short-term outcomes of IISSA with hand-sewn closure of the common opening compared to EA.METHODS Patients who underwent laparoscopic radical colon cancer surgery between January 2018 and June 2022 at the First Affiliated Hospital of Xiamen University were retrospectively analyzed.Surgical,postoperative,and pathological features of the IA and EA groups were observed before and after propensity score matching.Patients with right-sided and left-sided colon cancer were separated,each further divided into IA and EA groups(R-IA vs R-EA for right-sided,L-IA vs L-EA for left-sided),for stratified analysis of the aforementioned indicators.RESULTS After propensity score matching,63 pairs were matched in each group.In surgical characteristics,the IA group exhibited less blood loss and shorter incisions than the EA group.Regarding postoperative recovery,the IA group showed earlier recovery of gastrointestinal function.Pathologically,the IA group had greater lymph node clearance.Relative to the R-EA group,the R-IA group experienced reduced blood loss,shorter assisted incisions,earlier recovery of gastrointestinal functions and greater lymph node dissection.When compared to the L-EA group,the L-IA group demonstrated earlier postoperative anal exhaust and defecation,along with a reduced length of hospitalization.Regarding postoperative complications,no statistically significant differences were found between the groups either after matching or in the stratified analyses.CONCLUSION Compared to EA,IISSA with hand-sewn closure of the common opening is a safe and feasible option for laparoscopic radical colon cancer surgery.
基金financially supported by the National Natural Science Foundation of China(No.21675131)the Volkswagen Foundation(Freigeist Fellowship No.89592)+1 种基金the Natural Science Foundation of Chongqing(No.2020jcyj-zdxmX0003,CSTB2023NSCQ-MSX0924)the National Research Foundation,Singapore,and A*STAR(Agency for Science Technology and Research)under its LCER Phase 2 Programme Hydrogen&Emerging Technologies FI,Directed Hydrogen Programme(Award No.U2305D4003).
文摘Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as massive by-product,contribute to greenhouse effects and pose environmental challenges.Thus,the pursuit of nitrogen fixation through carbon–neutral pathways under benign conditions is a frontier of scientific topics,with the harnessing of solar energy emerging as an enticing and viable option.This review delves into the refinement strategies for scale-up mild photocatalytic nitrogen fixation,fields ripe with potential for innovation.The narrative is centered on enhancing the intrinsic capabilities of catalysts to surmount current efficiency barriers.Key focus areas include the in-depth exploration of fundamental mechanisms underpinning photocatalytic procedures,rational element selection,and functional planning,state-of-the-art experimental protocols for understanding photo-fixation processes,valid photocatalytic activity evaluation,and the rational design of catalysts.Furthermore,the review offers a suite of forward-looking recommendations aimed at propelling the advancement of mild nitrogen photo-fixation.It scrutinizes the existing challenges and prospects within this burgeoning domain,aspiring to equip researchers with insightful perspectives that can catalyze the evolution of cutting-edge nitrogen fixation methodologies and steer the development of next-generation photocatalytic systems.
基金Supported by the Tianjin Health Research Project(No.ZC20069No.TJWJ2022MS040)+1 种基金the Foundation of the Committee of Integrated Traditional Chinese and Western Medicine(No.2021011)the Science and Technology Foundation of Tianjin Eye Hospital(No.YKYB1901).
文摘AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N_(2)),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP group.Retinal neovascularization was observed by fluorescein angiography and quantified.Retinal thickness was evaluated by Hematoxylin and eosin(HE)stain.The expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western blot.IL-1βlevel in retina was analyzed using immunohistochemical staining.RESULTS:The increased area of neovascular clusters in OIR mice was significantly decreased by LBP.Retinal thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP group.Compared with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control group.Moreover,IL-1βwas reduced in retinal sections treated with LBP.In the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in migration.CONCLUSION:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt/mTOR signaling pathway.
基金Supported by Key Research and Development Program of Jiangsu Province,No.BE2023767Xuzhou Key Research and Development Program under Grant,No.KC23273+1 种基金Affiliated Hospital of Xuzhou Medical University,No.2022ZL26Construction Project of High-Level Hospital of Jiangsu Province,No.GSPSJ20240802.
文摘BACKGROUND Acute variceal bleeding(AVB)in patients with cirrhosis remains life-threatening;moreover,the current risk stratification methods have certain limitations.Rebleeding and mortality after AVB remain major challenges.Although preemptive transjugular intrahepatic portosystemic shunt(p-TIPS)can improve outcomes,not all patients benefit equally.Accurate risk stratification is needed to guide treatment decisions and identify those most likely to benefit from p-TIPS.AIM To develop an artificial intelligence(AI)-driven model to guide AVB treatment decisions,and identify candidates eligible for p-TIPS.METHODS Patients with cirrhosis and AVB,from two multicenter retrospective cohorts in China,who received endoscopic variceal ligation plus pharmacotherapy(n=1227)or p-TIPS(n=1863)were included.Baseline data within 24 hours of hospital admission were obtained.The AI-AVB model,based on the six-week failure and one-year mortality rates,was developed to predict treatment efficacy and compared with standard risk scores.Outcomes and adverse events of the treatments were compared across the high-and low-risk subgroups stratified using the AI-AVB model.RESULTS The AI-AVB model demonstrated superior predictive performance compared to traditional risk stratification methods.In the internal validation cohort,the model achieved an area under the curve(AUC)of 0.842 for predicting six-week treatment failure and 0.954 for one-year mortality.In the external validation cohort,the AUCs were 0.814 and 0.889,respectively.The model effectively identified patients at high risk of first-line treatment failure who may benefit from aggressive interventions such as p-TIPS.In contrast,advancing the treatment strategy for low-risk patients did not notably improve the short-term prognosis.CONCLUSION The AI-AVB model can predict treatment outcomes,stratify the failure risk in cirrhotic patients with AVB,aid in clinical decisions,identify p-TIPS beneficiaries,and optimize personalized treatment strategies.
基金National Natural Science Foundation Council of China(Grant No.52305359)Hubei Provincial Natural Science Foundation of China(Grant No.2023AFB141)National Medical Products Administration Key Laboratory for Dental Materials(PKUSS20240401)。
文摘In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through topological cues.An ideal TE scaffold should possess biomimetic cross-scale structures,similar to that of natural extracellular matrices,at the nano-to macro-scale level.Although freeform fabrication of TE scaffolds can be achieved through 3D printing,this method is limited in simultaneously building multiscale structures.To address this challenge,low-temperature fields were adopted in the traditional fabrication processes,such as casting and 3D printing.Ice crystals grow during scaffold fabrication and act as a template to control the nano-and micro-structures.These microstructures can be optimized by adjusting various parameters,such as the direction and magnitude of the low-temperature field.By preserving the macro-features fabricated using traditional methods,additional micro-structures with smaller scales can be incorporated simultaneously,realizing cross-scale structures that provide a better mimic of natural organs and tissues.In this paper,we present a state-of-the-art review of three low-temperature-field-assisted fabrication methods—freeze casting,cryogenic3D printing,and freeze spinning.Fundamental working principles,fabrication setups,processes,and examples of biomedical applications are introduced.The challenges and outlook for low-temperature-assisted fabrication are also discussed.
基金supported in part by the Hubei Provincial Natural Science Foundation of China(grant no.2023AFA094)the Yingzi Tech&Huazhong Agricultural University Intelligent Research Institute of Food Health(No.IRIFH202209)+1 种基金Fundamental Research Funds for the Central Universities(Project 2662023PY005)the Hubei Hongshan Laboratory&Huazhong Agricultural University Start-up Fund.
文摘The rapid emergence and spread of colistin-resistant gram-negative bacteria has raised worldwide public health concerns,and phosphoethanolamine(PEtn)transferase modification-mediated colistin resistance has been widely documented in multiple gram-negative bacterial species.However,whether such a mechanism exists in the zoonotic pathogen Pasteurella multocida is still unknown.Recently,a novel PEtn transferase,PetL,was identified in P.multo-cida,but whether it is associated with colistin resistance remains to be elucidated.In this study,we found that PetL in P.multocida(PetL^(PM))exhibited structural characteristics similar to those of the mobile-colistin-resistant(MCR)protein and the PEtn transferase characterized in Neisseria meningitidis.The transformation of petLPM into E.coli or K.pneumoniae changed the phenotype of several tested strains from colistin sensitive to colistin resistant.Deletion of this gene decreased the colistin minimum inhibitory concentration(MIC)of P.multocida by 64-fold.Our extensive analysis by MALDI-TOF-MS demonstrated that PetLPM participated in the modification of bacterial lipopolysaccharide(LPS)-lipid A.Deletion of petL^(PM) led to an increase in membrane charge but a decrease in cell-surface hydrophobicity and cell permeability in P.multocida.The present study is the first to report the presence of PEtn transferase-mediated colistin resistance in the zoonotic pathogen P.multocida.
基金Supported by the Science and Technology Planning Project of Guangzhou,No.2024A03J0102the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar,No.2022B1515020024+1 种基金National Natural Science Foundation of China,No.82070574the Key Research and Development Program of Guangzhou,No.2023B03J1298.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is notorious for its aggressive progression and dismal prognosis,with chromatin accessibility dynamics emerging as pivotal yet poorly understood drivers.AIM To dissect how multilayered chromatin regulation sustains oncogenic transcription and tumor-stroma crosstalk in HCC,we combined multiomics single cell analysis.METHODS We integrated single-cell RNA sequencing and paired single-cell assay for transposase-accessible chromatin with sequencing data of HCC samples,complemented by bulk RNA sequencing validation across The Cancer Genome Atlas,Liver Cancer Institute,and GSE25907 cohorts.Cell type-specific chromatin architectures were resolved via ArchR,with regulatory hubs identified through peak-to-gene linkages and coaccessibility networks.Functional validation employed A485-mediated histone 3 lysine 27 acetylation suppression and small interfering RNA targeting DGAT1.RESULTS Malignant hepatocytes exhibited expanded chromatin accessibility profiles,characterized by increased numbers of accessible peaks and larger physical regions despite reduced peak intensity.Enhancer-like peaks enriched in malignant regulation,forming long-range hubs.Eighteen enhancer-like peak-related genes showed tumor-specific overexpression and diagnostic accuracy,correlating with poor prognosis.Intercellular coaccessibility analysis revealed tumor-stroma symbiosis via shared chromatin states.Pharmacological histone 3 lysine 27 acetylation inhibition paradoxically downregulated DGAT1,the hub gene most strongly regulated by chromatin accessibility.DGAT1 knockdown suppressed cell proliferation.CONCLUSION Multilayered chromatin reprogramming sustains HCC progression through tumor-stroma crosstalk and DGAT1-related oncogenic transcription,defining targetable epigenetic vulnerabilities.
基金supported in part by the National Natural Science Foundation of China under Grant 62272007,U23B2002in part by the Excellent Young Talents Project of the Beijing Municipal University Teacher Team Construction Support Plan under Grant BPHR202203031+1 种基金in part by the Yunnan Key Laboratory of Blockchain Application Technology under Grant 2021105AG070005(YNB202102)in part by the Open Topics of Key Laboratory of Blockchain Technology and Data Security,The Ministry of Industry and Information Technology of the People’s Republic of China under Grant 20243222。
文摘The wide application of smart contracts allows industry companies to implement some complex distributed collaborative businesses,which involve the calculation of complex functions,such as matrix operations.However,complex functions such as matrix operations are difficult to implement on Ethereum Virtual Machine(EVM)-based smart contract platforms due to their distributed security environment limitations.Existing off-chain methods often result in a significant reduction in contract execution efficiency,thus a platform software development kit interface implementation method has become a feasible way to reduce overheads,but this method cannot verify operation correctness and may leak sensitive user data.To solve the above problems,we propose a verifiable EVM-based smart contract cross-language implementation scheme for complex operations,especially matrix operations,which can guarantee operation correctness and user privacy while ensuring computational efficiency.In this scheme,a verifiable interaction process is designed to verify the computation process and results,and a matrix blinding technology is introduced to protect sensitive user data in the calculation process.The security analysis and performance tests show that the proposed scheme can satisfy the correctness and privacy of the cross-language implementation of smart contracts at a small additional efficiency cost.
文摘Active and poisoning-resistant Ru-based electrocatalysts for the hydrogen oxidation reaction(HOR)are designed and fabricated by integrating Cu/Ru dual single atoms and alloy CuRu nanoparticles(N-(CuRu)_(NP+SA)@NC)through a strategy involving weak chemical reduction and ammonia-assisted gas-phase nitridation.The resultant N-(CuRu)_(NP+SA)@NC electrocatalysts feature nitrogen atoms coordinated to both Cu and Ru metal atoms via strong N-metal interactions.Density functional theory calculations revealed that alloyed CuRu nanoparticles and monodispersed Cu atoms are vital for altering the electronic configuration of the host Ru elements.This finely tuned structure enhanced the adsorption of H and OH and promoted CO oxidation over the N-(CuRu)_(NP+SA)@NC electrocatalyst,resulting in high alkaline HOR activity,as evidenced by the higher exchange current density of 3.74 mA cm^(-2)and high mass activity of 3.28 mAμg_(Ru)^(-1),which are far superior to those of most Ru-based catalysts reported to date.Moreover,the N-(CuRu)_(NP+SA)@NC electrocatalysts are resistant to CO poisoning and can be used at a high concentration of 1000 ppm CO with no distinct decay in the activity,in stark contrast to the commercial Pt/C catalyst under the same conditions.
基金supported by the National Natural Science Foundation of China(No.52105221)the Postdoctoral Fellowship Program(Grade C)of China Postdoctoral Science Foundation(No.GZC20232749)+1 种基金the Youth Innovation Promotion Assessment CAS(No.2022187)the IMR Innovation Fund(No.2024-PY13).
文摘The evolution of fretting wear behavior of zirconium alloy cladding tubes mated with dimples under the gross slip regime(GSR)was investigated.The findings revealed that the primary wear mechanisms under GSR were delamination,surface fatigue wear and abrasive wear,and the fretting damage rate mainly depends on delamination.The cross-sectional microstructure of the worn area could be divided into the third-body layer,tribologically transformed structure layer,and general deformation layer,with their formation mechanisms analyzed.Furthermore,the mechanism of wear-induced grain refinement was identified as dynamic recrystallization(DRX),including both continuous DRX and discontinuous DRX.Additionally,the processes of fretting wear and DRX were discussed.
