Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AF...Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.展开更多
Objective To screen the target genes that are associated with survival of breast cancer(BRCA) and explore their prognostic values and immune correlations with BRCA using multiple databases..Methods The microarray expr...Objective To screen the target genes that are associated with survival of breast cancer(BRCA) and explore their prognostic values and immune correlations with BRCA using multiple databases..Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database(GEO) and analyzed to obtain differentially expressed genes(DEGs). Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs. The key gene was determined using R language, STRING, and Cytoscape, and the differential expression of the key gene was verified using external datasets The Cancer Genome Atlas(TCGA) and quantitative real-time PCR(q RT-PCR) for BRCA tissues of 37 patients. The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language, TIMER, and Gene Set Enrichment Analysis(GSEA).Results Of 10 hub genes seleceed from 302 DEGS, UBE2C was identified as the gene associated with BRCA survival. The expression of UBE2C was differentially upregulated in BRCA, as verified by TCGA and q RT-PCR. Prognostic analysis revealed that UBE2C served as an independent prognostic factor. High expression of UBE2C was associated with decreased immune infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, and myeloid dendritic cells in BRCA tissue. The expression of UBE2C in BRCA showed a significant correlation with immune checkpoints genes PDCD1, CD274, and CTLA4 expressions. There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability. GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues is closely related to the BRCA immune microenvironment and showes predictive values on the survivals and prognosis of BRCA patients and the effecacy of immunotherapy. UBE2C may be an potential immune-related prognostic biomarker for BRCA.展开更多
Inverted perovskite solar cells(PSCs) have attracted broad research and industrial interest owing to their suppressed hysteresis,cost-effectiveness,and easy-fabrication.However,the issue of non-radiative recombination...Inverted perovskite solar cells(PSCs) have attracted broad research and industrial interest owing to their suppressed hysteresis,cost-effectiveness,and easy-fabrication.However,the issue of non-radiative recombination losses at the n-type interface between the perovskite and fullerene has impeded further improvement of photovoltaic performance.Here,we modify the n-type interface of FAPbI_(3) perovskite films by constructing a stereochemical two-dimensional(2D) perovskite interlayer,in which the organic cations comprise both pyridine and ammonium groups.The pyridine N donor can create stable bonding with the surface-uncoordinated Pb on the perovskite,thereby passivating the shallow-level defects and enhancing the air stability of the film.Furthermore,the pyridine N donor also offers a positive polar interface to decrease the surface work function of the perovskite film,enabling n-type modification.Ultimately,we employ a p-i-n photovoltaic(PV) device with the positive dipole interlayer at perovskite/fullerene contact and achieve remarkable photoelectric conversion efficiency(PCE) of 22.0%.展开更多
Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the...Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.展开更多
The Mesoproterozoic rifts are developed in the Ordos Basin located in the western margin of the North China Plate.Based on the latest 3D seismic data and previous research results,this study intends to discuss the zon...The Mesoproterozoic rifts are developed in the Ordos Basin located in the western margin of the North China Plate.Based on the latest 3D seismic data and previous research results,this study intends to discuss the zonal differential deformation characteristics and genetic mechanism of the Mesoproterozoic rifts in the Ordos Basin.NE-trending rifts are developed in the Mesoproterozoic in the south-central Ordos Basin,the main part of which are located near the western margin of the North China Plate.NNW-trending rifts are developed in the north of the basin,while NW-NNW rifts in the Mesoproterozoic in Hangjinqi area.The genetic mechanism of the Mesoproterozoic rifts is related to regional extensional stress field,plate boundary conditions and internal preexisting structures.The main extensional stress direction strikes NWW-SSE(120°)in the western margin of the North China Plate,based on the forward rift trend of the northern Mesoproterozoic.In Hangjinqi area,the reactivation of the existing NWtrending Wulansu fault and NW-NW-trending Daolao fault,results in dextral shear stress field.The boundary between the western margin of the North China Plate and its adjacent plates forms a nearly NS-trending preexisting basement tectonic belt,which intersects with the NWW-SSE(120°)extensional stress at an acute angle of 60°.Therefore,the western margin of the North China Plate is formed by oblique normal faults under oblique extension.Due to the long time span of Columbia Supercontinent breakup(1.8e1.6 Ga),the oblique rift in the south-central Ordos Basin is formed under the continuous oblique extension at the western margin of the North China Plate.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.展开更多
This study constructs an integrated model of user experience in smart home applications(apps)to deeply explore the impact of cognitive dissonance on users’emotional responses,subsequent behaviors,and experiential out...This study constructs an integrated model of user experience in smart home applications(apps)to deeply explore the impact of cognitive dissonance on users’emotional responses,subsequent behaviors,and experiential outcomes.The research emphasizes the importance of addressing emotional management in the design and development of smart home apps.The findings indicate that emotional response plays a critical mediating role in the user experience of these apps,offering new insights for further optimization.By understanding users’emotional reactions and behavioral patterns under cognitive dissonance,developers can more effectively improve interface design and enhance the overall user experience.展开更多
In recent years, perovskite solar cells(PSCs) have propelled into the limelight owing to rapid development of efficiency;however, the abundant defects at the perovskite grain boundaries result in unwanted energy loss ...In recent years, perovskite solar cells(PSCs) have propelled into the limelight owing to rapid development of efficiency;however, the abundant defects at the perovskite grain boundaries result in unwanted energy loss and structural degradation. Here, the grain boundaries of perovskite polycrystalline films have been found to act as nanocapillaries for capturing perovskite quantum dots(PQDs), which enable the conformal assemble of PQDs at the top interspace between perovskite grains. The existence of PQDs passivated the surface defects, optimized the interfacial band alignments, and ultimately improved the power conversion efficiency from 19.27% to 22.47% in inverted PSCs. Our findings open up the possibility of selective assembly and structural modulation of the perovskite nanostructures towards efficient and stable PSCs.展开更多
A ZrV_(2)alloy is typically susceptible to poisoning by impurity gases,which causes a considerable reduction in the hydrogen storage properties of the alloy.In this study,the adsorption characteristics of oxygen on Zr...A ZrV_(2)alloy is typically susceptible to poisoning by impurity gases,which causes a considerable reduction in the hydrogen storage properties of the alloy.In this study,the adsorption characteristics of oxygen on ZrV_(2)surfaces doped with Hf,Ti,and Pd are investigated,and the effect of oxygen on the hydrogen storage performance of the alloy was discussed.Subsequently,the adsorption energy,bond-length change,density of states,and differential charge density of the alloy before and after doping are analyzed using the first-principles method.The theoretical results show that Ti doping has a limited effect on the adsorption of oxygen atoms on the ZrV_(2)surface,whereas Hf doping decreases the adsorption energy of oxygen on the ZrV_(2)surface.Oxygen atoms are more difficult to adsorb at most adsorption sites on Pd-substituting surfaces,which indicates that Pd has the best anti-poisoning properties,followed by Hf.The analysis of the differential charge density and partial density of states show that the electron interaction between the oxygen atom and surface atom of the alloys is weakened,and the total energy is reduced after Hf and Pd doping.Based on theoretical calculations,the hydrogen absorption kinetics of ZrV_(2),Zr_(0.9)Hf_(0.1)V_(2),and Zr(V_(0.9)Pd_(0.1))_(2) alloys are studied in a hydrogen-oxygen mixture of 0.5 vol%O_(2) at 25℃.The experimental results show that the hydrogen storage capacities of ZrV_(2),Zr_(0.9)Hf_(0.1)V_(2),and Zr(V_(0.9)Pd_(0.1))_(2) decrease to 19%,69%,and 80%of their original values,respectively.The order of alloy resistance to 0.5 vol%O_(2) poisoning is Zr(V_(0.9)Pd_(0.1))_(2)>Zr_(0.9)Hf_(0.1)V_(2)>ZrV_(2).Pd retains its original hydrogen absorption performance to a greater extent than undoped surfaces,and it has the strongest resistance to poisoning,which is consistent with previous theoretical calculations.展开更多
Objective The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family.Among these,P2X3 is a type of P2X receptor which is specifically expressed on nerves,especi...Objective The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family.Among these,P2X3 is a type of P2X receptor which is specifically expressed on nerves,especially on pre-ganglionic sensory fibers.This study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial infarction.Methods The Sprague-Dawley rats were divided randomly into three groups:sham group-myocardial infarction group,and myocardial infarction with gefapixant treatment group.Myocardial infarction was induced by left anterior descending branch ligation.The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin(HE)staining and myocardial injury biomarkers.Conditions of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen III.The sympathetic innervation was detected by norepinephrine concentration(pg/mL),in-vivo electrophysiology,and typical sympathetic biomarkers.Inflammatory cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology,quantitative realtime PCR(qPCR)and Western blotting.Results It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ratio.Furthermore,gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS,and decreased LVIDd and LVIDs.The expression levels of collagen I and collagen III,and TNF-αwere all decreased by P2X3 inhibition.Mechanistically,the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3(NLRP3)inflammasome and subsequent cleavage of caspase-1 which modulated interleukin-1β(IL-1β)and IL-18 level in heart after gefapixant treatment were associated with the suppressed cardiac inflammation.Conclusion It is suggested that P2X3 inhibition by gefapixant ameliorates post-infarct autonomic nervous imbalance,cardiac dysfunction,and remodeling possibly via inactivating NLRP3 inflammasome.展开更多
Family resilience is not the sum of the individual psychological resilience of each of the family members,but the family itself as a unit of resilience research.The representative models of family stress tolerance the...Family resilience is not the sum of the individual psychological resilience of each of the family members,but the family itself as a unit of resilience research.The representative models of family stress tolerance theory mainly include Mc Cubbin's series of family stress tolerance models and Walsh's family stress tolerance framework,which are widely used in the practice of family therapy.In the future,empirical studies on family resilience should be strengthened,measurement tools with high reliability and validity should be established,and the combination of family resilience theory and community-based practice should be promoted.展开更多
To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on ch...To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular展开更多
BACKGROUND There are many types of treatments for calcaneal fractures,including conservative treatment,conventional surgical treatment,and minimally invasive surgery.The choice of specific treatment options is still c...BACKGROUND There are many types of treatments for calcaneal fractures,including conservative treatment,conventional surgical treatment,and minimally invasive surgery.The choice of specific treatment options is still controversial.Open reduction and internal fixation are currently the most commonly used surgical procedures in the clinic.A good fracture reduction effect can be achieved by using the lateral extension incision of the calcaneus;however,many studies have reported a high incidence of postoperative incision complications.Although there are many methods for the classification of intra-articular calcaneal fractures,it is generally believed that the computed tomography(CT)classification proposed by Sanders has high application value in the selection of treatment methods and evaluation of prognosis of calcaneal fractures.However,this method has no clear guiding significance for the choice of surgical incision and surgical plan.AIM To explore the application and clinical efficacy of medial column classification in the treatment of intra-articular calcaneal fractures.METHODS From July 2017 to July 2018,91 patients,including 60 males and 31 females aged 27 to 60 years,were enrolled.All participants had closed intra-articular calcaneal fracture,and their surgical options were selected under the guidance of medial column classification.The patients'fractures were classified according to the Sanders classification:Type II,35 cases;Type III,33 cases;and Type IV,23 cases.Among them,53 patients had medial column displacement(shortened varus)and underwent open reduction and internal fixation with L-lateral incision of the calcaneus;38 patients had no displacement of the medial column and underwent open reduction and internal fixation with tarsal sinus incision.The calcaneus Bohler angle,Gissane angle,length,width,height,and step thickness of the articular surface were evaluated by X-ray and three-dimensional CT before and after surgery and at the last follow-up.Foot function recovery was assessed by the Maryland foot scoring criteria.RESULTS All patients were followed for 5 to 14 mo,with an average of 10.5±2.9 mo.The fractures of all patients healed,and the healing time was 10 to 19 wk,with an average of 10.8±1.5 wk.One patient developed wound infection 1 wk after surgery and was actively debrided and implanted with antibiotic calcium sulfate to control the infection.The patient's fracture healed 5 mo after surgery.One patient developed a sural nerve injury,and the symptoms disappeared 3 mo after surgery.The patients were assessed according to the Maryland foot scoring system:Excellent in 77 cases,good in 10,and fair in 4.The excellent and good rate was 95.6%.CONCLUSION Medial column classification can effectively guide the surgical selection for intraarticular fractures of the calcaneus.展开更多
BACKGROUND Constipation is one of the most important nonmotor symptoms in Parkinson's disease(PD)patients,and constipation of different severities is closely related to the pathogenesis of PD.PD with constipation(...BACKGROUND Constipation is one of the most important nonmotor symptoms in Parkinson's disease(PD)patients,and constipation of different severities is closely related to the pathogenesis of PD.PD with constipation(PDC)is considered a unique type of constipation,but its mechanism of formation and factors affecting its severity have been less reported.Understanding the gastrointestinal motility characteristics and constipation classification of PDC patients is essential to guide the treatment of PDC.In this study,the colonic transit test and high-resolution anorectal manometry were used to identify the intestinal motility of PDC to provide a basis for the treatment of PDC.AIM To investigate the clinical classification of PDC,to clarify its characteristics of colonic motility and rectal anal canal pressure,and to provide a basis for further research on the pathogenesis of PDC.METHODS Twenty PDC patients and 20 patients with functional constipation(FC)who were treated at Xuanwu Hospital of Capital Medical University from August 6,2018 to December 2,2019 were included.A colonic transit test and high-resolution anorectal manometry were performed to compare the differences in colonic transit time,rectal anal canal pressure,and constipation classification between the two groups.RESULTS There were no statistically significant differences in sex,age,body mass index,or duration of constipation between the two groups.It was found that more patients in the PDC group exhibited difficulty in defecating than in the FC group,and the difference was statistically significant.The rectal resting pressure,anal sphincter resting pressure,intrarectal pressure,and anal relaxation rate in the PDC group were significantly lower than those in the FC group.The proportion of paradoxical contractions in the PDC group was significantly higher than that in the FC group.There was a statistically significant difference in the type composition ratio of defecatory disorders between the two groups(P<0.05).The left colonic transit time,rectosigmoid colonic transit time(RSCTT),and total colonic transit time were prolonged in PDC and FC patients compared to normal values.The patients with FC had a significantly longer right colonic transit time and a significantly shorter RSCTT than patients with PDC(P<0.05).Mixed constipation predominated in PDC patients and FC patients,and no significant difference was observed.CONCLUSION Patients with PDC and FC have severe functional dysmotility of the colon and rectum,but there are certain differences in segmental colonic transit time and rectal anal canal pressure between the two groups.展开更多
基金funded by Suzhou Science and Technology Council(SNG201907)Universities Natural Science Foundation of Jiangsu Province(20KJB330002)+6 种基金General Program of China Postdoctoral Science Foundation(2022M711369)the Startup Funding of Soochow University,Jiangsu Province-Suzhou Science and Technology Planning Project(SL T201917)National Natural Science Foundation of China(32172922,31972741)Natural Science Foundation of Jiangsu Province of China(BK20211216,BK20221091)the Startup Funding of Hefei University of Technology(1302003712022058)China-CEEC Joint University Education Project(202010)the Excellence Project PrF UHK(2217/2022-2023)。
文摘Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.
文摘Objective To screen the target genes that are associated with survival of breast cancer(BRCA) and explore their prognostic values and immune correlations with BRCA using multiple databases..Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database(GEO) and analyzed to obtain differentially expressed genes(DEGs). Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs. The key gene was determined using R language, STRING, and Cytoscape, and the differential expression of the key gene was verified using external datasets The Cancer Genome Atlas(TCGA) and quantitative real-time PCR(q RT-PCR) for BRCA tissues of 37 patients. The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language, TIMER, and Gene Set Enrichment Analysis(GSEA).Results Of 10 hub genes seleceed from 302 DEGS, UBE2C was identified as the gene associated with BRCA survival. The expression of UBE2C was differentially upregulated in BRCA, as verified by TCGA and q RT-PCR. Prognostic analysis revealed that UBE2C served as an independent prognostic factor. High expression of UBE2C was associated with decreased immune infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, and myeloid dendritic cells in BRCA tissue. The expression of UBE2C in BRCA showed a significant correlation with immune checkpoints genes PDCD1, CD274, and CTLA4 expressions. There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability. GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues is closely related to the BRCA immune microenvironment and showes predictive values on the survivals and prognosis of BRCA patients and the effecacy of immunotherapy. UBE2C may be an potential immune-related prognostic biomarker for BRCA.
基金financially supported by the National Ten Thousand Talent Program for Young Top-notch Talent,China,the National Natural Science Fund for Excellent Young Scholars,China(52022030)the National Natural Science Foundation of China,China(51972111,52203330)+7 种基金the Shanghai Pilot Program for Basic Research,China(22TQ1400100-5)the “Dawn”Program of Shanghai Education Commission,China(22SG28)the Shanghai Municipal Natural Science Foundation,China(22ZR1418000)the Science and Technology Innovation Plan of Shanghai Science and Technology Commission,China(22YF1410000)the Postdoctoral Research Foundation of China,China(2021M701190)the Fundamental Research Funds for the Central Universities,China(JKD01231632,JKVD1231041)the Major Science and Technology Projects of Inner Mongolia Autonomous Region,China(2021ZD0042)the Shanghai Engineering Research Center of Hierarchical Nanomaterials,China(18DZ2252400)。
文摘Inverted perovskite solar cells(PSCs) have attracted broad research and industrial interest owing to their suppressed hysteresis,cost-effectiveness,and easy-fabrication.However,the issue of non-radiative recombination losses at the n-type interface between the perovskite and fullerene has impeded further improvement of photovoltaic performance.Here,we modify the n-type interface of FAPbI_(3) perovskite films by constructing a stereochemical two-dimensional(2D) perovskite interlayer,in which the organic cations comprise both pyridine and ammonium groups.The pyridine N donor can create stable bonding with the surface-uncoordinated Pb on the perovskite,thereby passivating the shallow-level defects and enhancing the air stability of the film.Furthermore,the pyridine N donor also offers a positive polar interface to decrease the surface work function of the perovskite film,enabling n-type modification.Ultimately,we employ a p-i-n photovoltaic(PV) device with the positive dipole interlayer at perovskite/fullerene contact and achieve remarkable photoelectric conversion efficiency(PCE) of 22.0%.
基金supported by the National Natural Science Foundation of China(81870259,82170431,81903608,and U21A20339)the CAMS Innovation Fund for Medical Sciences(CIFMS+1 种基金2019-I2M-5-078)the Postdoctoral Research Foundation of Heilongjiang Province(LBH-Q20148).
文摘Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.
文摘The Mesoproterozoic rifts are developed in the Ordos Basin located in the western margin of the North China Plate.Based on the latest 3D seismic data and previous research results,this study intends to discuss the zonal differential deformation characteristics and genetic mechanism of the Mesoproterozoic rifts in the Ordos Basin.NE-trending rifts are developed in the Mesoproterozoic in the south-central Ordos Basin,the main part of which are located near the western margin of the North China Plate.NNW-trending rifts are developed in the north of the basin,while NW-NNW rifts in the Mesoproterozoic in Hangjinqi area.The genetic mechanism of the Mesoproterozoic rifts is related to regional extensional stress field,plate boundary conditions and internal preexisting structures.The main extensional stress direction strikes NWW-SSE(120°)in the western margin of the North China Plate,based on the forward rift trend of the northern Mesoproterozoic.In Hangjinqi area,the reactivation of the existing NWtrending Wulansu fault and NW-NW-trending Daolao fault,results in dextral shear stress field.The boundary between the western margin of the North China Plate and its adjacent plates forms a nearly NS-trending preexisting basement tectonic belt,which intersects with the NWW-SSE(120°)extensional stress at an acute angle of 60°.Therefore,the western margin of the North China Plate is formed by oblique normal faults under oblique extension.Due to the long time span of Columbia Supercontinent breakup(1.8e1.6 Ga),the oblique rift in the south-central Ordos Basin is formed under the continuous oblique extension at the western margin of the North China Plate.
基金Natural Science Foundation of Chongqing,China,No.cstc2021jcyj-msxmX0501Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2022QNXM074.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.
文摘This study constructs an integrated model of user experience in smart home applications(apps)to deeply explore the impact of cognitive dissonance on users’emotional responses,subsequent behaviors,and experiential outcomes.The research emphasizes the importance of addressing emotional management in the design and development of smart home apps.The findings indicate that emotional response plays a critical mediating role in the user experience of these apps,offering new insights for further optimization.By understanding users’emotional reactions and behavioral patterns under cognitive dissonance,developers can more effectively improve interface design and enhance the overall user experience.
基金financially supported by the National Ten Thousand Talent Program for Young Top-notch Talentthe National Natural Science Fund for Excellent Young Scholars (52022030)+8 种基金the National Natural Science Foundation of China (51972111,52203330)the Shanghai Pilot Program for Basic Research(22TQ1400100-5)the “Dawn” Program of Shanghai Education Commission (22SG28)the Shanghai Municipal Natural Science Foundation (22ZR1418000)the Science and Technology Innovation Plan of Shanghai Science and Technology Commission(22YF1410000)the Postdoctoral Research Foundation of China(2021M701190)the Fundamental Research Funds for the Central Universities (JKM01221621, JKM01221678)the Major Science and Technology Projects of Inner Mongolia Autonomous Region(2021ZD0042)Shanghai Engineering Research Center of Hierarchical Nanomaterials (18DZ2252400)。
文摘In recent years, perovskite solar cells(PSCs) have propelled into the limelight owing to rapid development of efficiency;however, the abundant defects at the perovskite grain boundaries result in unwanted energy loss and structural degradation. Here, the grain boundaries of perovskite polycrystalline films have been found to act as nanocapillaries for capturing perovskite quantum dots(PQDs), which enable the conformal assemble of PQDs at the top interspace between perovskite grains. The existence of PQDs passivated the surface defects, optimized the interfacial band alignments, and ultimately improved the power conversion efficiency from 19.27% to 22.47% in inverted PSCs. Our findings open up the possibility of selective assembly and structural modulation of the perovskite nanostructures towards efficient and stable PSCs.
基金the Youth Innovation Promotion Association,Chinese Academy of Science(No.2019263)the National Natural Science Foundation of China(No.12105355).
文摘A ZrV_(2)alloy is typically susceptible to poisoning by impurity gases,which causes a considerable reduction in the hydrogen storage properties of the alloy.In this study,the adsorption characteristics of oxygen on ZrV_(2)surfaces doped with Hf,Ti,and Pd are investigated,and the effect of oxygen on the hydrogen storage performance of the alloy was discussed.Subsequently,the adsorption energy,bond-length change,density of states,and differential charge density of the alloy before and after doping are analyzed using the first-principles method.The theoretical results show that Ti doping has a limited effect on the adsorption of oxygen atoms on the ZrV_(2)surface,whereas Hf doping decreases the adsorption energy of oxygen on the ZrV_(2)surface.Oxygen atoms are more difficult to adsorb at most adsorption sites on Pd-substituting surfaces,which indicates that Pd has the best anti-poisoning properties,followed by Hf.The analysis of the differential charge density and partial density of states show that the electron interaction between the oxygen atom and surface atom of the alloys is weakened,and the total energy is reduced after Hf and Pd doping.Based on theoretical calculations,the hydrogen absorption kinetics of ZrV_(2),Zr_(0.9)Hf_(0.1)V_(2),and Zr(V_(0.9)Pd_(0.1))_(2) alloys are studied in a hydrogen-oxygen mixture of 0.5 vol%O_(2) at 25℃.The experimental results show that the hydrogen storage capacities of ZrV_(2),Zr_(0.9)Hf_(0.1)V_(2),and Zr(V_(0.9)Pd_(0.1))_(2) decrease to 19%,69%,and 80%of their original values,respectively.The order of alloy resistance to 0.5 vol%O_(2) poisoning is Zr(V_(0.9)Pd_(0.1))_(2)>Zr_(0.9)Hf_(0.1)V_(2)>ZrV_(2).Pd retains its original hydrogen absorption performance to a greater extent than undoped surfaces,and it has the strongest resistance to poisoning,which is consistent with previous theoretical calculations.
基金supported by the National Natural Science Foundation of China(No.81370282).
文摘Objective The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family.Among these,P2X3 is a type of P2X receptor which is specifically expressed on nerves,especially on pre-ganglionic sensory fibers.This study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial infarction.Methods The Sprague-Dawley rats were divided randomly into three groups:sham group-myocardial infarction group,and myocardial infarction with gefapixant treatment group.Myocardial infarction was induced by left anterior descending branch ligation.The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin(HE)staining and myocardial injury biomarkers.Conditions of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen III.The sympathetic innervation was detected by norepinephrine concentration(pg/mL),in-vivo electrophysiology,and typical sympathetic biomarkers.Inflammatory cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology,quantitative realtime PCR(qPCR)and Western blotting.Results It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ratio.Furthermore,gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS,and decreased LVIDd and LVIDs.The expression levels of collagen I and collagen III,and TNF-αwere all decreased by P2X3 inhibition.Mechanistically,the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3(NLRP3)inflammasome and subsequent cleavage of caspase-1 which modulated interleukin-1β(IL-1β)and IL-18 level in heart after gefapixant treatment were associated with the suppressed cardiac inflammation.Conclusion It is suggested that P2X3 inhibition by gefapixant ameliorates post-infarct autonomic nervous imbalance,cardiac dysfunction,and remodeling possibly via inactivating NLRP3 inflammasome.
基金supported by Scientific research fund project of Binzhou Medical University(No.20SKNY13)Binzhou 2023 social science planning project(No.23-SKGH-189)innovation program of university students(No.202210440071)。
文摘Family resilience is not the sum of the individual psychological resilience of each of the family members,but the family itself as a unit of resilience research.The representative models of family stress tolerance theory mainly include Mc Cubbin's series of family stress tolerance models and Walsh's family stress tolerance framework,which are widely used in the practice of family therapy.In the future,empirical studies on family resilience should be strengthened,measurement tools with high reliability and validity should be established,and the combination of family resilience theory and community-based practice should be promoted.
基金supported by the Chinese High-Tech Program(863)Chinese Key Basic Research Project(973)the National Natural Science Foundation of China.Gratitude was extended to Prof.Zhu CHEN for his suggestion and direction of this work.
文摘To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular
文摘BACKGROUND There are many types of treatments for calcaneal fractures,including conservative treatment,conventional surgical treatment,and minimally invasive surgery.The choice of specific treatment options is still controversial.Open reduction and internal fixation are currently the most commonly used surgical procedures in the clinic.A good fracture reduction effect can be achieved by using the lateral extension incision of the calcaneus;however,many studies have reported a high incidence of postoperative incision complications.Although there are many methods for the classification of intra-articular calcaneal fractures,it is generally believed that the computed tomography(CT)classification proposed by Sanders has high application value in the selection of treatment methods and evaluation of prognosis of calcaneal fractures.However,this method has no clear guiding significance for the choice of surgical incision and surgical plan.AIM To explore the application and clinical efficacy of medial column classification in the treatment of intra-articular calcaneal fractures.METHODS From July 2017 to July 2018,91 patients,including 60 males and 31 females aged 27 to 60 years,were enrolled.All participants had closed intra-articular calcaneal fracture,and their surgical options were selected under the guidance of medial column classification.The patients'fractures were classified according to the Sanders classification:Type II,35 cases;Type III,33 cases;and Type IV,23 cases.Among them,53 patients had medial column displacement(shortened varus)and underwent open reduction and internal fixation with L-lateral incision of the calcaneus;38 patients had no displacement of the medial column and underwent open reduction and internal fixation with tarsal sinus incision.The calcaneus Bohler angle,Gissane angle,length,width,height,and step thickness of the articular surface were evaluated by X-ray and three-dimensional CT before and after surgery and at the last follow-up.Foot function recovery was assessed by the Maryland foot scoring criteria.RESULTS All patients were followed for 5 to 14 mo,with an average of 10.5±2.9 mo.The fractures of all patients healed,and the healing time was 10 to 19 wk,with an average of 10.8±1.5 wk.One patient developed wound infection 1 wk after surgery and was actively debrided and implanted with antibiotic calcium sulfate to control the infection.The patient's fracture healed 5 mo after surgery.One patient developed a sural nerve injury,and the symptoms disappeared 3 mo after surgery.The patients were assessed according to the Maryland foot scoring system:Excellent in 77 cases,good in 10,and fair in 4.The excellent and good rate was 95.6%.CONCLUSION Medial column classification can effectively guide the surgical selection for intraarticular fractures of the calcaneus.
文摘BACKGROUND Constipation is one of the most important nonmotor symptoms in Parkinson's disease(PD)patients,and constipation of different severities is closely related to the pathogenesis of PD.PD with constipation(PDC)is considered a unique type of constipation,but its mechanism of formation and factors affecting its severity have been less reported.Understanding the gastrointestinal motility characteristics and constipation classification of PDC patients is essential to guide the treatment of PDC.In this study,the colonic transit test and high-resolution anorectal manometry were used to identify the intestinal motility of PDC to provide a basis for the treatment of PDC.AIM To investigate the clinical classification of PDC,to clarify its characteristics of colonic motility and rectal anal canal pressure,and to provide a basis for further research on the pathogenesis of PDC.METHODS Twenty PDC patients and 20 patients with functional constipation(FC)who were treated at Xuanwu Hospital of Capital Medical University from August 6,2018 to December 2,2019 were included.A colonic transit test and high-resolution anorectal manometry were performed to compare the differences in colonic transit time,rectal anal canal pressure,and constipation classification between the two groups.RESULTS There were no statistically significant differences in sex,age,body mass index,or duration of constipation between the two groups.It was found that more patients in the PDC group exhibited difficulty in defecating than in the FC group,and the difference was statistically significant.The rectal resting pressure,anal sphincter resting pressure,intrarectal pressure,and anal relaxation rate in the PDC group were significantly lower than those in the FC group.The proportion of paradoxical contractions in the PDC group was significantly higher than that in the FC group.There was a statistically significant difference in the type composition ratio of defecatory disorders between the two groups(P<0.05).The left colonic transit time,rectosigmoid colonic transit time(RSCTT),and total colonic transit time were prolonged in PDC and FC patients compared to normal values.The patients with FC had a significantly longer right colonic transit time and a significantly shorter RSCTT than patients with PDC(P<0.05).Mixed constipation predominated in PDC patients and FC patients,and no significant difference was observed.CONCLUSION Patients with PDC and FC have severe functional dysmotility of the colon and rectum,but there are certain differences in segmental colonic transit time and rectal anal canal pressure between the two groups.
