Due to the novel applications of flexible pipes conveying fluid in the field of soft robotics and biomedicine,the investigations on the mechanical responses of the pipes have attracted considerable attention.The fluid...Due to the novel applications of flexible pipes conveying fluid in the field of soft robotics and biomedicine,the investigations on the mechanical responses of the pipes have attracted considerable attention.The fluid-structure interaction(FSI)between the pipe with a curved shape and the time-varying internal fluid flow brings a great challenge to the revelation of the dynamical behaviors of flexible pipes,especially when the pipe is highly flexible and usually undergoes large deformations.In this work,the geometrically exact model(GEM)for a curved cantilevered pipe conveying pulsating fluid is developed based on the extended Hamilton's principle.The stability of the curved pipe with three different subtended angles is examined with the consideration of steady fluid flow.Specific attention is concentrated on the large-deformation resonance of circular pipes conveying pulsating fluid,which is often encountered in practical engineering.By constructing bifurcation diagrams,oscillating shapes,phase portraits,time traces,and Poincarémaps,the dynamic responses of the curved pipe under various system parameters are revealed.The mean flow velocity of the pulsating fluid is chosen to be either subcritical or supercritical.The numerical results show that the curved pipe conveying pulsating fluid can exhibit rich dynamical behaviors,including periodic and quasi-periodic motions.It is also found that the preferred instability type of a cantilevered curved pipe conveying steady fluid is mainly in the flutter of the second mode.For a moderate value of the mass ratio,however,a third-mode flutter may occur,which is quite different from that of a straight pipe system.展开更多
Liver transplantation is the optimal treatment for patients with end-stage liver disease,metabolic liver diseases,and hepatic malignancies that are not amenable to resection.Hepatic ischemia-reperfusion injury(IRI)is ...Liver transplantation is the optimal treatment for patients with end-stage liver disease,metabolic liver diseases,and hepatic malignancies that are not amenable to resection.Hepatic ischemia-reperfusion injury(IRI)is the main problem in liver transplantation and liver resection,leading to parenchymal cell injury and organ dysfunction.The damage of liver sinusoidal endothelial cells(LSECs)is a critical event in IRI.LSECs work as an important regulating factor of liver regeneration after partial hepatectomy.This review primarily describes the mechanisms of LSECs injury in IRI and explores the roles of LSECs in liver regeneration,and briefly introduces the protective strategies targeting LSECs damaged in IRI.展开更多
Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and th...Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve(B.breve).A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing.The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography(micro-CT).Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay(ELISA).The senescence and biological functions were tested in oral mucosal stem cells(OMSCs)treated with sunitinib.Ligated loop experiments were used to investigate the effect of oral B.breve.Neutralizing antibody for interleukin-10(IL-10)was used to prove the critical role of IL-10 in the pro-healing process derived from B.breve.Results showed that sunitinib caused oral mucosal wound healing impairment in mice.In vitro,sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation,migration,and differentiation.Oral administration of B.breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells(DCs)-derived IL-10.IL-10 reversed cellular senescence caused by sunitinib in OMSCs,and IL-10 neutralizing antibody blocked the ameliorative effect of B.breve on oral mucosal wound healing under sunitinib treatment conditions.In conclusion,sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B.breve could improve wound healing impairment via intestinal DCs-derived IL-10.展开更多
Objective Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck,but its occurrence and progression mechanisms remain unclear.In addition-there is a lack of effective targeting drugs...Objective Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck,but its occurrence and progression mechanisms remain unclear.In addition-there is a lack of effective targeting drugs.The second major subunit of DNA polymerase(POLE2)catalyzes the prolongation of new strand replication and modifies exonuclease domain activity.Our previous study found that POLE2 was associated with OSCC progression,but the mechanism remains unclear.Methods The expression of POLE2 in OSCC tissues was detected using immunological assays.Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC.POLE2 expression was inhibited in OSCC cells,and the effects of gene and protein expression were detected using RT-PCR and Western blotting.The POLE2 knockout model was constructed by transfecting a lentiviral vector.Cell proliferation,apoptosis,and migration were detected using various assays including colony formation,MTT,flow cytometry,wound healing assay,Transwell assay,and the Human Apoptosis Antibody Array.The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice.After 30 days,tumors were removed under anesthesia and tumor weight and dimension were recorded.Tumor cell proliferation was analyzed using Ki67 staining.Results POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues.In addition,POLE2 gene levels were statistically correlated with tumor classification and prognosis.Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro.Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation.We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3,CD40,CD40L,DR6,Fas,IGFBP-6,p21,and SMAC.In addition,POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway.Conclusion POLE2 is closely related to the progression of OSCC.Thus,POLE2 may be a potential target for OSCC treatment.展开更多
High pressure science and technology is a vast area of inter-disciplinary research that encompasses the fields of physics,chem-istry,geoscience,and materials science and in which the science of ordinary matter is only...High pressure science and technology is a vast area of inter-disciplinary research that encompasses the fields of physics,chem-istry,geoscience,and materials science and in which the science of ordinary matter is only a special case under ambient condi-tions.Pressure,the physical variable of force exerted on the chem-ical bonding of a material,directly controls the material’s phys-ical and chemical properties.展开更多
The linkage between Qi and mitochondria was investigated by exploring the effect of Traditional Chinese Medicine (TCM) Qi-invigorating herbs on mitochondrial function at the biochemical and molecular levels. Three Chi...The linkage between Qi and mitochondria was investigated by exploring the effect of Traditional Chinese Medicine (TCM) Qi-invigorating herbs on mitochondrial function at the biochemical and molecular levels. Three Chinese herbs (<i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;">,</span><i><span style="font-family:Verdana;"> Herba cistanche</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Panax ginseng</span></i><span style="font-family:Verdana;"></i>) were used to treat cultured mouse kidney cells and the generation of adenosine triphosphate (ATP) was measured. The Qi-invigorating herb, <i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;"></i>, was selected for further </span></span><span style="font-family:""><span style="font-family:Verdana;">study using additional biological and molecular parameters, including ATP, reactive oxygen species (ROS), mitochondrial membrane potential (MMP),</span><span><span style="font-family:Verdana;"> mtDNA copies, superoxide dismutase (SOD), glutathione (GSH), cell growth, cell viability and transcriptomes. We also chose two concentrations of <i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;"></i> to study the hormetic effect. The results indicated that: 1) Qi-invigorating herbs have significant effects on the function of mitochondria, with ATP production and the antioxidant capacity being significantly enhanced, and ROS le</span></span><span style="font-family:Verdana;">vels being reduced, allowing for a more optimal oxidation environment. The effect of the herbs followed a hormetic curve with a stimulating effect at lower</span><span> </span><span style="font-family:Verdana;">doses but an inhibiting effect at high doses;2) The growth of the cells was not</span><span> </span><span style="font-family:Verdana;">affected despite numerous biochemical changes associated with mitochondrial</span><span> </span><span style="font-family:Verdana;">function, indicating the powerful ability of mitochondria to maintain cellular homeostasis;3) The up-regulation of NOCT gene, related to nicotinamide adenine dinucleotide (NADH) synthesis, offers a molecular basis for the ATP-promoting effect of the Qi-invigorating herbs. This work provides additional insight into the efficacy of TCM herbs from a western perspective.展开更多
<div style="text-align:justify;"> Titanium alloy materials are widely used in the marine and aviation fields due to their excellent properties. The submersible sailing on the water surface is faster th...<div style="text-align:justify;"> Titanium alloy materials are widely used in the marine and aviation fields due to their excellent properties. The submersible sailing on the water surface is faster than underwater diving, so once an accident occurs, the consequences are unimaginable. Based on the failure criterion of the J-K model, this paper uses finite element simulation software to study the impact of impact velocity and impact angle on the collision response of a titanium alloy cylindrical pressure shell, providing a reference for the deep sea titanium alloy pressure shell. </div>展开更多
<i><span style="font-family:Verdana;">Astragali Radix </span></i><span style="font-family:Verdana;">(AR), the dried root of legumes, belongs to the Qi-invigorating<...<i><span style="font-family:Verdana;">Astragali Radix </span></i><span style="font-family:Verdana;">(AR), the dried root of legumes, belongs to the Qi-invigorating</span><span style="font-family:""> <span style="font-family:Verdana;">herbs in traditional Chinese medicine and plays an important role in the</span><span style="font-family:Verdana;"> treatment of many diseases. In order to understand the mechanism of action of AR extract. We used AR extract to treat M-1, mouse kidney cells, and used transcriptome sequencing technology to detect the genomic transcription level of the cells under the action of AR at different concentrations and times. The results showed that after a low concentration of AR treatments on the cells, the expression of genes related to cell growth and cellular immune response changed significantly, among which multiple genes are related to mitochondrial function, while high concentrations of AR affected the expression of histones and disease-related genes. It showed that the low concentration of AR extract can achieve the effect of invigorating Qi by regulating the function of mitochondria. In addition, several important genes and pathways were identified as potential targets of AR activation. The research not only clarified the main molecular biological mechanism of AR invigorating Qi, but also provided experimental basis and cellular physiology reference for the further clinical application of AR.展开更多
Apricot has a long history of cultivation and has many varieties and types. The traditional variety identification methods are timeconsuming and labor-consuming, posing grand challenges to apricot resource management....Apricot has a long history of cultivation and has many varieties and types. The traditional variety identification methods are timeconsuming and labor-consuming, posing grand challenges to apricot resource management. Tool development in this regard will help researchers quickly identify variety information. This study photographed apricot fruits outdoors and indoors and constructed a dataset that can precisely classify the fruits using a U-net model (F-score:99%), which helps to obtain the fruit's size, shape, and color features. Meanwhile, a variety search engine was constructed, which can search and identify variety from the database according to the above features. Besides, a mobile and web application (ApricotView) was developed, and the construction mode can be also applied to other varieties of fruit trees.Additionally, we have collected four difficult-to-identify seed datasets and used the VGG16 model for training, with an accuracy of 97%, which provided an important basis for ApricotView. To address the difficulties in data collection bottlenecking apricot phenomics research, we developed the first apricot database platform of its kind (ApricotDIAP, http://apricotdiap.com/) to accumulate, manage, and publicize scientific data of apricot.展开更多
A reasonable heat treatment process for TC4 ELI titanium alloy is crucial to tune microstructures to improve its explosion resistance.However,there is limited investigation on tuning microstructures of TC4 ELI to impr...A reasonable heat treatment process for TC4 ELI titanium alloy is crucial to tune microstructures to improve its explosion resistance.However,there is limited investigation on tuning microstructures of TC4 ELI to improve explosion resistance.Moreover,the current challenge is quantifying microstructural changes'effects on explosion resistance and incorporating microstructural changes into finite element models.This work aims to tune microstructures to improve explosion resistance and elucidate their anti-explosion mechanism,and find a suitable method to incorporate microstructural changes into finite element models.In this work,we systematically study the deformation and failure characteristics of TC4 ELI plates with varying microstructures using an air explosion test and LS-DYNA finite element modeling.The Johnson-Cook(JC)constitutive parameters are used to quantify the effects of microstructural changes on explosion resistance and incorporate microstructural changes into finite element models.Because of the heat treatment,one plate has equiaxed microstructure and the other has bimodal microstructure.The convex of the plate after the explosion has a quadratic relationship with the charge mass,and the simulation results demonstrate high reliability,with the error less than 17.5%.Therefore,it is feasible to obtain corresponding JC constitutive parameters based on the differences in microstructures and mechanical properties and characterize the effects of microstructural changes on explosion resistance.The bimodal target exhibits excellent deformation resistance.The response of bimodal microstructure to the shock wave may be more intense under explosive loading.The well-coordinated structure of the bimodal target enhances its resistance to deformation.展开更多
Identification of the S genotype of Malus plants will greatly promote the discovery of new genes,the cultivation and production of apple,the breeding of new varieties,and the origin and evolution of self-incompatibili...Identification of the S genotype of Malus plants will greatly promote the discovery of new genes,the cultivation and production of apple,the breeding of new varieties,and the origin and evolution of self-incompatibility in Malus plants.In this experiment,88 Malus germplasm resources,such as Aihuahong,Xishuhaitang,and Reguanzi,were used as materials.Seven gene-specific primer combinations were used in the genotype identification.PCR amplification using leaf DNA produced a single S-RNase gene fragment in all materials.The results revealed that 70 of the identified materials obtained a complete S-RNase genotype,while only one S-RNase gene was found in 18 of them.Through homology comparison and analysis,13 S-RNase genotypes were obtained:S_(1)S_(2)(Aihuahong,etc.),S_(1)S_(28)(Xixian Haitang,etc.),S_(1)S_(51)(Hebei Pingdinghaitang),S_(1)S_(3)(Xiangyangcun Daguo,etc.),S_(2)S_(3)(Zhaiyehaitang,etc.),S_(3)S_(51)(Xishan 1),S_(3)S_(28)(Huangselihaerde,etc.),S_(2)S_(28)(Honghaitang,etc.),S_(4)S_(28)(Bo 11),S_(7)S_(28)(Jiuquan Shaguo),S_(10)S_e(Dongchengguan 13),S_(10)S_(21)(Dongxiangjiao)and S_(3)S_(51)(Xiongyue Haitang).Simultaneously,the frequency of the S gene in the tested materials was analyzed.The findings revealed that different S genes had varying frequencies in Malus resources,as well as varying frequencies between intraspecific and interspecific.S_(3) had the highest frequency of 68.18%,followed by S_(1)(42.04%).In addition,the phylogenetic tree and origin evolution analysis revealed that the S gene differentiation was completed prior to the formation of various apple species,that cultivated species also evolved new S genes,and that the S_(50) gene is the oldest S allele in Malus plants.The S_(1),S_(29),and S_(33) genes in apple-cultivated species,on the other hand,may have originated in M.sieversii,M.hupehensis,and M.kansuensis,respectively.In addition to M.sieversii,M.kansuensis and M.sikkimensis may have also played a role in the origin and evolution of some Chinese apples.展开更多
In the boreal summer and autumn of 2023,the globe experienced an extremely hot period across both oceans and continents.The consecutive record-breaking mean surface temperature has caused many to speculate upon how th...In the boreal summer and autumn of 2023,the globe experienced an extremely hot period across both oceans and continents.The consecutive record-breaking mean surface temperature has caused many to speculate upon how the global temperature will evolve in the coming 2023/24 boreal winter.In this report,as shown in the multi-model ensemble mean(MME)prediction released by the Institute of Atmospheric Physics at the Chinese Academy of Sciences,a medium-to-strong eastern Pacific El Niño event will reach its mature phase in the following 2−3 months,which tends to excite an anomalous anticyclone over the western North Pacific and the Pacific-North American teleconnection,thus serving to modulate the winter climate in East Asia and North America.Despite some uncertainty due to unpredictable internal atmospheric variability,the global mean surface temperature(GMST)in the 2023/24 winter will likely be the warmest in recorded history as a consequence of both the El Niño event and the long-term global warming trend.Specifically,the middle and low latitudes of Eurasia are expected to experience an anomalously warm winter,and the surface air temperature anomaly in China will likely exceed 2.4 standard deviations above climatology and subsequently be recorded as the warmest winter since 1991.Moreover,the necessary early warnings are still reliable in the timely updated mediumterm numerical weather forecasts and sub-seasonal-to-seasonal prediction.展开更多
Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,m...Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated the expression of myocardial JunB/c-Fos,which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.Conclusion The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK(p38 and ERK1/2)pathway.展开更多
BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify geno...BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.展开更多
AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investiga...AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway. TGF-β_1, TβRⅠ, TβRⅡ, Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-β_1, Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-β_1, TβRⅠ , TβRⅡ , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, signifi cantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P < 0.05). The positiveexpression ratio of Smad7 in cases with benign biliary stricture was 70.0%, higher than that in normal bile duct, but this difference is not statistically signifi cant 70.0% vs 50%, P > 0.05). There was a positive correlation between positive expression of TGF-β_1, Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-β/Smad/ CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.展开更多
Objective: To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma(DLBCL).Methods: A retrospective study of 37 patients with primary testicular DLBCL was ca...Objective: To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma(DLBCL).Methods: A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed.Results: During a median follow-up period of 39.8 months(5.4-93.0 months), the median progression-free survival(PFS) was 26.2 months(95% CI: 0-65 months) and the 3-year overall survival(OS) rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage(stage I/II), lactate dehydrogenase(LDH) ≤245 U/L, international prognostic index(IPI) ≤1, primary tumor diameter <7.5 cm, and patients who had complete response(CR) and received doxorubicin-contained chemotherapy(P<0.05). There was a trend toward superior outcome for patients who received combined therapy(surgery/chemotherapy/radiotherapy)(P=0.055). Patients who had CR, primary tumor diameter <7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis.Conclusions: Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy(RT) seemed to improve survival.展开更多
AIM:To examine the correlation of phosphatidylinositol3-kinase(PIK3)CB expression with preoperative radiotherapy response in patients with stageⅡ/Ⅲrectal adenocarcinoma.METHODS:PIK3CB immunoexpression was retrospect...AIM:To examine the correlation of phosphatidylinositol3-kinase(PIK3)CB expression with preoperative radiotherapy response in patients with stageⅡ/Ⅲrectal adenocarcinoma.METHODS:PIK3CB immunoexpression was retrospectively assessed in pretreatment biopsies from 208 patients with clinical stageⅡ/Ⅲrectal adenocarcinoma,who underwent radical surgery after 30-Gy/10-fractionpreoperative radiotherapy.The relation between PIK3CB expression and tumor regression grade,clinicopathological characteristics,and survival time was statistically analyzed.Western blotting and in vitro clonogenic formation assay were used to detect PIK3CB expression in four colorectal cancer cell lines(HCT116,HT29,Lo Vo,and LS174T)treated with 6-Gy ionizing radiation.Pharmacological assays were used to evaluate the therapeutic relevance of TGX-221(a PIK3CB-specific inhibitor)in the four colorectal cancer cell lines.RESULTS:Immunohistochemical staining indicated that PIK3CB was more abundant in rectal adenocarcinoma tissues with poor response to preoperative radiotherapy.High expression of PIK3CB was closely correlated with tumor height(P<0.05),yp T stage(P<0.05),and high-degree tumor regression grade(P<0.001).High expression of PIK3CB was a potential prognostic factor for local recurrence-free survival(P<0.05)and metastasis-free survival(P<0.05).High expression of PIK3CB was also associated with poor therapeutic response and adverse outcomes in rectal adenocarcinoma patients treated with 30-Gy/10-fraction preoperative radiotherapy.In vitro,PIK3CB expression was upregulated in all four colorectal cancer cell lines concurrently treated with 6-Gy ionizing radiation,and the PIK3CB-specific inhibitor TGX-221 effectively inhibited the clonogenic formation of these four colorectal cancer cell lines.CONCLUSION:PIK3CB is critically involved in response to preoperative radiotherapy and may serve as a novel target for therapeutic intervention.展开更多
Cervicogenic headache(CEH)has been recognized as a unique category of headache that can be difficult to diagnose and treat.In China,CEH patients are managed by many different specialties,and the treatment plans remain...Cervicogenic headache(CEH)has been recognized as a unique category of headache that can be difficult to diagnose and treat.In China,CEH patients are managed by many different specialties,and the treatment plans remain controversial.Therefore,there is a great need for comprehensive evidence-based Chinese experts’recommendations for the management of CEH.The Chinese Association for the Study of Pain asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with CEH.A group of multidisciplinary Chinese Association for the Study of Pain experts identified the clinically relevant topics in CEH.A systematic review of the literature was performed,and evidence supporting the benefits and harms for the management of CEH was summarized.Twenty-four recommendations were finally developed through expert consensus voting for evidence quality and recommendation strength.We hope this guideline provides direction for clinicians and patients making treatment decisions for the management of CEH.展开更多
In this study,the nonplanar post-buckling behavior of a simply supported fluid-conveying pipe with an axially sliding downstream end is investigated within the framework of a three-dimensional(3 D)theoretical model.Th...In this study,the nonplanar post-buckling behavior of a simply supported fluid-conveying pipe with an axially sliding downstream end is investigated within the framework of a three-dimensional(3 D)theoretical model.The complete nonlinear governing equations are discretized via Galerkin’s method and then numerically solved by the use of a fourth-order Runge-Kutta integration algorithm.Different initial conditions are chosen for calculations to show the nonplanar buckling characteristics of the pipe in two perpendicular lateral directions.A detailed parametric analysis is performed in order to study the influence of several key system parameters such as the mass ratio,the flow velocity,and the gravity parameter on the post-buckling behavior of the pipe.Typical results are presented in the form of bifurcation diagrams when the flow velocity is selected as the variable parameter.It is found that the pipe will stay at its original straight equilibrium position until the critical flow velocity is reached.Just beyond the critical flow velocity,the pipe would lose stability by static divergence via a pitchfork bifurcation,and two possible nonzero equilibrium positions are generated.It is shown that the buckling and post-buckling behaviors of the pipe cannot be influenced by the mass ratio parameter.Unlike a pipe with two immovable ends,however,the pinned-pinned pipe with an axially sliding downstream end shows some different features regarding post-buckling behaviors.The most important feature is that the buckling amplitude of the pipe with an axially sliding downstream end would increase first and then decrease with the increase in the flow velocity.In addition,the buckled shapes of the pipe varying with the flow velocity are displayed in order to further show the new post-buckling features of the pipe with an axially sliding downstream end.展开更多
Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell line.Methods: First, we employed a quantitative proteomics approach bas...Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell line.Methods: First, we employed a quantitative proteomics approach based on stable isotope labeling by amino acids in cell culture(SILAC) to identify the different proteins expressed in HepG2 liver cancer cells upon exposure to ABA. Next, bioinformatics analyses through DAVID and STRING on-line tools were used to predict the pathways involved. Finally, we applied functional validation including cell cycle analysis and Western blotting for apoptosis and mTOR pathway-related proteins to confirm the bioinformatics predictions.Results: We identified 330 different proteins with the SILAC-based quantitative proteomics approach. The bioinformatics analysis and the functional validation revealed that the mTOR pathway, ribosome biogenesis, cell cycle, and apoptosis pathways were differentially regulated by ABA. G1 cell cycle arrest, apoptosis and mTOR inhibition were confirmed.Conclusions: ABA, a potential mTOR inhibitor, induces the disruption of ribosomal biogenesis. It also affects the mTOR-MRP axis to cause G1 cell cycle arrest and finally leads to cancer cell apoptosis.展开更多
基金Project supported by the National Natural Science Foundation of China (Nos.12072119,12325201,and 52205594)the China National Postdoctoral Program for Innovative Talents (No.BX20220118)。
文摘Due to the novel applications of flexible pipes conveying fluid in the field of soft robotics and biomedicine,the investigations on the mechanical responses of the pipes have attracted considerable attention.The fluid-structure interaction(FSI)between the pipe with a curved shape and the time-varying internal fluid flow brings a great challenge to the revelation of the dynamical behaviors of flexible pipes,especially when the pipe is highly flexible and usually undergoes large deformations.In this work,the geometrically exact model(GEM)for a curved cantilevered pipe conveying pulsating fluid is developed based on the extended Hamilton's principle.The stability of the curved pipe with three different subtended angles is examined with the consideration of steady fluid flow.Specific attention is concentrated on the large-deformation resonance of circular pipes conveying pulsating fluid,which is often encountered in practical engineering.By constructing bifurcation diagrams,oscillating shapes,phase portraits,time traces,and Poincarémaps,the dynamic responses of the curved pipe under various system parameters are revealed.The mean flow velocity of the pulsating fluid is chosen to be either subcritical or supercritical.The numerical results show that the curved pipe conveying pulsating fluid can exhibit rich dynamical behaviors,including periodic and quasi-periodic motions.It is also found that the preferred instability type of a cantilevered curved pipe conveying steady fluid is mainly in the flutter of the second mode.For a moderate value of the mass ratio,however,a third-mode flutter may occur,which is quite different from that of a straight pipe system.
基金supported by grants from the National Key Re-search and Development Program of China(2021YFA1100500 and 2016YFA0102100)。
文摘Liver transplantation is the optimal treatment for patients with end-stage liver disease,metabolic liver diseases,and hepatic malignancies that are not amenable to resection.Hepatic ischemia-reperfusion injury(IRI)is the main problem in liver transplantation and liver resection,leading to parenchymal cell injury and organ dysfunction.The damage of liver sinusoidal endothelial cells(LSECs)is a critical event in IRI.LSECs work as an important regulating factor of liver regeneration after partial hepatectomy.This review primarily describes the mechanisms of LSECs injury in IRI and explores the roles of LSECs in liver regeneration,and briefly introduces the protective strategies targeting LSECs damaged in IRI.
基金supported by the Clinical Medicine Plus X-Young Scholars Project of Peking University of the Fundamental Research Funds for the Central Universities (PKU2023LCXQ035)the Chinese Academy of Medical Sciences Central Public-Interest Scientific Institution Basal Research Fund (2022-JKCS-27)+3 种基金the National clinical key discipline construction project (PKUSSNKP-202114)China Postdoctoral Science Foundation (2022M720289)Chinese Stomatological Association Clinical Research Fund (CSA-SIS2022-01)National Natural Science Foundation of China (82301024)
文摘Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve(B.breve).A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing.The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography(micro-CT).Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay(ELISA).The senescence and biological functions were tested in oral mucosal stem cells(OMSCs)treated with sunitinib.Ligated loop experiments were used to investigate the effect of oral B.breve.Neutralizing antibody for interleukin-10(IL-10)was used to prove the critical role of IL-10 in the pro-healing process derived from B.breve.Results showed that sunitinib caused oral mucosal wound healing impairment in mice.In vitro,sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation,migration,and differentiation.Oral administration of B.breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells(DCs)-derived IL-10.IL-10 reversed cellular senescence caused by sunitinib in OMSCs,and IL-10 neutralizing antibody blocked the ameliorative effect of B.breve on oral mucosal wound healing under sunitinib treatment conditions.In conclusion,sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B.breve could improve wound healing impairment via intestinal DCs-derived IL-10.
基金the National Natural Science Foundation of China(No.82203418)the Natural Science Foundation of Hubei Province(No.2022CFB286 and No.2021CFB589).
文摘Objective Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck,but its occurrence and progression mechanisms remain unclear.In addition-there is a lack of effective targeting drugs.The second major subunit of DNA polymerase(POLE2)catalyzes the prolongation of new strand replication and modifies exonuclease domain activity.Our previous study found that POLE2 was associated with OSCC progression,but the mechanism remains unclear.Methods The expression of POLE2 in OSCC tissues was detected using immunological assays.Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC.POLE2 expression was inhibited in OSCC cells,and the effects of gene and protein expression were detected using RT-PCR and Western blotting.The POLE2 knockout model was constructed by transfecting a lentiviral vector.Cell proliferation,apoptosis,and migration were detected using various assays including colony formation,MTT,flow cytometry,wound healing assay,Transwell assay,and the Human Apoptosis Antibody Array.The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice.After 30 days,tumors were removed under anesthesia and tumor weight and dimension were recorded.Tumor cell proliferation was analyzed using Ki67 staining.Results POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues.In addition,POLE2 gene levels were statistically correlated with tumor classification and prognosis.Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro.Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation.We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3,CD40,CD40L,DR6,Fas,IGFBP-6,p21,and SMAC.In addition,POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway.Conclusion POLE2 is closely related to the progression of OSCC.Thus,POLE2 may be a potential target for OSCC treatment.
基金H.K.Mao is supported by the National Natural Science Foundation of China under Grant No.U1930401.
文摘High pressure science and technology is a vast area of inter-disciplinary research that encompasses the fields of physics,chem-istry,geoscience,and materials science and in which the science of ordinary matter is only a special case under ambient condi-tions.Pressure,the physical variable of force exerted on the chem-ical bonding of a material,directly controls the material’s phys-ical and chemical properties.
文摘The linkage between Qi and mitochondria was investigated by exploring the effect of Traditional Chinese Medicine (TCM) Qi-invigorating herbs on mitochondrial function at the biochemical and molecular levels. Three Chinese herbs (<i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;">,</span><i><span style="font-family:Verdana;"> Herba cistanche</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Panax ginseng</span></i><span style="font-family:Verdana;"></i>) were used to treat cultured mouse kidney cells and the generation of adenosine triphosphate (ATP) was measured. The Qi-invigorating herb, <i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;"></i>, was selected for further </span></span><span style="font-family:""><span style="font-family:Verdana;">study using additional biological and molecular parameters, including ATP, reactive oxygen species (ROS), mitochondrial membrane potential (MMP),</span><span><span style="font-family:Verdana;"> mtDNA copies, superoxide dismutase (SOD), glutathione (GSH), cell growth, cell viability and transcriptomes. We also chose two concentrations of <i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;"></i> to study the hormetic effect. The results indicated that: 1) Qi-invigorating herbs have significant effects on the function of mitochondria, with ATP production and the antioxidant capacity being significantly enhanced, and ROS le</span></span><span style="font-family:Verdana;">vels being reduced, allowing for a more optimal oxidation environment. The effect of the herbs followed a hormetic curve with a stimulating effect at lower</span><span> </span><span style="font-family:Verdana;">doses but an inhibiting effect at high doses;2) The growth of the cells was not</span><span> </span><span style="font-family:Verdana;">affected despite numerous biochemical changes associated with mitochondrial</span><span> </span><span style="font-family:Verdana;">function, indicating the powerful ability of mitochondria to maintain cellular homeostasis;3) The up-regulation of NOCT gene, related to nicotinamide adenine dinucleotide (NADH) synthesis, offers a molecular basis for the ATP-promoting effect of the Qi-invigorating herbs. This work provides additional insight into the efficacy of TCM herbs from a western perspective.
文摘<div style="text-align:justify;"> Titanium alloy materials are widely used in the marine and aviation fields due to their excellent properties. The submersible sailing on the water surface is faster than underwater diving, so once an accident occurs, the consequences are unimaginable. Based on the failure criterion of the J-K model, this paper uses finite element simulation software to study the impact of impact velocity and impact angle on the collision response of a titanium alloy cylindrical pressure shell, providing a reference for the deep sea titanium alloy pressure shell. </div>
文摘<i><span style="font-family:Verdana;">Astragali Radix </span></i><span style="font-family:Verdana;">(AR), the dried root of legumes, belongs to the Qi-invigorating</span><span style="font-family:""> <span style="font-family:Verdana;">herbs in traditional Chinese medicine and plays an important role in the</span><span style="font-family:Verdana;"> treatment of many diseases. In order to understand the mechanism of action of AR extract. We used AR extract to treat M-1, mouse kidney cells, and used transcriptome sequencing technology to detect the genomic transcription level of the cells under the action of AR at different concentrations and times. The results showed that after a low concentration of AR treatments on the cells, the expression of genes related to cell growth and cellular immune response changed significantly, among which multiple genes are related to mitochondrial function, while high concentrations of AR affected the expression of histones and disease-related genes. It showed that the low concentration of AR extract can achieve the effect of invigorating Qi by regulating the function of mitochondria. In addition, several important genes and pathways were identified as potential targets of AR activation. The research not only clarified the main molecular biological mechanism of AR invigorating Qi, but also provided experimental basis and cellular physiology reference for the further clinical application of AR.
基金supported by the Fundamental Research Funds for the Central Non-profit Research Institution of the Chinese Academy of Forestry (Grant No.CAFYBB2020ZY003)the Key S&T Project of Inner Mongolia (Grant No.2021ZD0041-001-002)the Central Public-interest Scientific Institution Basal Research Fund (Grant No.11024316000202300001)。
文摘Apricot has a long history of cultivation and has many varieties and types. The traditional variety identification methods are timeconsuming and labor-consuming, posing grand challenges to apricot resource management. Tool development in this regard will help researchers quickly identify variety information. This study photographed apricot fruits outdoors and indoors and constructed a dataset that can precisely classify the fruits using a U-net model (F-score:99%), which helps to obtain the fruit's size, shape, and color features. Meanwhile, a variety search engine was constructed, which can search and identify variety from the database according to the above features. Besides, a mobile and web application (ApricotView) was developed, and the construction mode can be also applied to other varieties of fruit trees.Additionally, we have collected four difficult-to-identify seed datasets and used the VGG16 model for training, with an accuracy of 97%, which provided an important basis for ApricotView. To address the difficulties in data collection bottlenecking apricot phenomics research, we developed the first apricot database platform of its kind (ApricotDIAP, http://apricotdiap.com/) to accumulate, manage, and publicize scientific data of apricot.
基金National Key Laboratory of Science and Technology on Materials under Shock and Impact(Grant No.WDZC2022-4)to provide fund for conducting experiments。
文摘A reasonable heat treatment process for TC4 ELI titanium alloy is crucial to tune microstructures to improve its explosion resistance.However,there is limited investigation on tuning microstructures of TC4 ELI to improve explosion resistance.Moreover,the current challenge is quantifying microstructural changes'effects on explosion resistance and incorporating microstructural changes into finite element models.This work aims to tune microstructures to improve explosion resistance and elucidate their anti-explosion mechanism,and find a suitable method to incorporate microstructural changes into finite element models.In this work,we systematically study the deformation and failure characteristics of TC4 ELI plates with varying microstructures using an air explosion test and LS-DYNA finite element modeling.The Johnson-Cook(JC)constitutive parameters are used to quantify the effects of microstructural changes on explosion resistance and incorporate microstructural changes into finite element models.Because of the heat treatment,one plate has equiaxed microstructure and the other has bimodal microstructure.The convex of the plate after the explosion has a quadratic relationship with the charge mass,and the simulation results demonstrate high reliability,with the error less than 17.5%.Therefore,it is feasible to obtain corresponding JC constitutive parameters based on the differences in microstructures and mechanical properties and characterize the effects of microstructural changes on explosion resistance.The bimodal target exhibits excellent deformation resistance.The response of bimodal microstructure to the shock wave may be more intense under explosive loading.The well-coordinated structure of the bimodal target enhances its resistance to deformation.
基金financially supported by the Agricultural Science and Technology Innovation Program(CAASASTIP-2021-RIP-02)。
文摘Identification of the S genotype of Malus plants will greatly promote the discovery of new genes,the cultivation and production of apple,the breeding of new varieties,and the origin and evolution of self-incompatibility in Malus plants.In this experiment,88 Malus germplasm resources,such as Aihuahong,Xishuhaitang,and Reguanzi,were used as materials.Seven gene-specific primer combinations were used in the genotype identification.PCR amplification using leaf DNA produced a single S-RNase gene fragment in all materials.The results revealed that 70 of the identified materials obtained a complete S-RNase genotype,while only one S-RNase gene was found in 18 of them.Through homology comparison and analysis,13 S-RNase genotypes were obtained:S_(1)S_(2)(Aihuahong,etc.),S_(1)S_(28)(Xixian Haitang,etc.),S_(1)S_(51)(Hebei Pingdinghaitang),S_(1)S_(3)(Xiangyangcun Daguo,etc.),S_(2)S_(3)(Zhaiyehaitang,etc.),S_(3)S_(51)(Xishan 1),S_(3)S_(28)(Huangselihaerde,etc.),S_(2)S_(28)(Honghaitang,etc.),S_(4)S_(28)(Bo 11),S_(7)S_(28)(Jiuquan Shaguo),S_(10)S_e(Dongchengguan 13),S_(10)S_(21)(Dongxiangjiao)and S_(3)S_(51)(Xiongyue Haitang).Simultaneously,the frequency of the S gene in the tested materials was analyzed.The findings revealed that different S genes had varying frequencies in Malus resources,as well as varying frequencies between intraspecific and interspecific.S_(3) had the highest frequency of 68.18%,followed by S_(1)(42.04%).In addition,the phylogenetic tree and origin evolution analysis revealed that the S gene differentiation was completed prior to the formation of various apple species,that cultivated species also evolved new S genes,and that the S_(50) gene is the oldest S allele in Malus plants.The S_(1),S_(29),and S_(33) genes in apple-cultivated species,on the other hand,may have originated in M.sieversii,M.hupehensis,and M.kansuensis,respectively.In addition to M.sieversii,M.kansuensis and M.sikkimensis may have also played a role in the origin and evolution of some Chinese apples.
基金the Key Research Program of Frontier Sciences,CAS(Grant No.ZDBS-LYDQC010)the National Natural Science Foundation of China(Grant No.42175045).
文摘In the boreal summer and autumn of 2023,the globe experienced an extremely hot period across both oceans and continents.The consecutive record-breaking mean surface temperature has caused many to speculate upon how the global temperature will evolve in the coming 2023/24 boreal winter.In this report,as shown in the multi-model ensemble mean(MME)prediction released by the Institute of Atmospheric Physics at the Chinese Academy of Sciences,a medium-to-strong eastern Pacific El Niño event will reach its mature phase in the following 2−3 months,which tends to excite an anomalous anticyclone over the western North Pacific and the Pacific-North American teleconnection,thus serving to modulate the winter climate in East Asia and North America.Despite some uncertainty due to unpredictable internal atmospheric variability,the global mean surface temperature(GMST)in the 2023/24 winter will likely be the warmest in recorded history as a consequence of both the El Niño event and the long-term global warming trend.Specifically,the middle and low latitudes of Eurasia are expected to experience an anomalously warm winter,and the surface air temperature anomaly in China will likely exceed 2.4 standard deviations above climatology and subsequently be recorded as the warmest winter since 1991.Moreover,the necessary early warnings are still reliable in the timely updated mediumterm numerical weather forecasts and sub-seasonal-to-seasonal prediction.
基金supported by grants from the National Natural Science Foundation of China(No.81874434 and No.81804053)Yangtze River Delta Traditional Chinese Medicine Endocrinology and Metabolic Disease Specialist Alliance(No.ZY2021-2023-0302).
文摘Objective Diabetic cardiomyopathy(DCM)represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus(DM).DCM typically manifests as myocardial fibrosis,myocardial hypertrophy,and impaired left ventricular diastolic function.While the clinical utility of the Jianpi Qinghua(JPQH)formula has been established in treating diabetes and insulin resistance,its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain.This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula(JPQHF)in ameliorating myocardial injury in nonobese diabetic rats,specifically focusing on apoptosis and inflammation.Methods Wistar rats were assigned as the normal control group(CON),while Goto-Kakizaki(GK)rats were randomly divided into three groups:DM,DM treated with the JPQHF,and DM treated with metformin(MET).Following a 4-week treatment regimen,various biochemical markers related to glucose metabolism,cardiac function,cardiac morphology,and myocardial ultrastructure in GK rats were assessed.RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets.In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells.Cell viability was evaluated using CCK-8 assay,apoptosis was monitored via flow cytometry,and the production of inflammatory cytokines was measured using quantitative real-time PCR(qPCR)and ELISA.Protein expression levels were determined by Western blotting analysis.The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.Results The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole(IVSs)and left ventricular internal diameter at end-systole and end-diastole(LVIDs and LVIDd).JPQHF effectively suppressed high glucose-induced activation of IL-1βand caspase 3 in cardiomyocytes.Furthermore,JPQHF downregulated the expression of myocardial JunB/c-Fos,which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.Conclusion The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK(p38 and ERK1/2)pathway.
文摘BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.
基金The grant from Shaanxi Science and Technology Project, No. 2002K10-G8
文摘AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway. TGF-β_1, TβRⅠ, TβRⅡ, Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-β_1, Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-β_1, TβRⅠ , TβRⅡ , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, signifi cantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P < 0.05). The positiveexpression ratio of Smad7 in cases with benign biliary stricture was 70.0%, higher than that in normal bile duct, but this difference is not statistically signifi cant 70.0% vs 50%, P > 0.05). There was a positive correlation between positive expression of TGF-β_1, Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-β/Smad/ CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.
文摘Objective: To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma(DLBCL).Methods: A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed.Results: During a median follow-up period of 39.8 months(5.4-93.0 months), the median progression-free survival(PFS) was 26.2 months(95% CI: 0-65 months) and the 3-year overall survival(OS) rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage(stage I/II), lactate dehydrogenase(LDH) ≤245 U/L, international prognostic index(IPI) ≤1, primary tumor diameter <7.5 cm, and patients who had complete response(CR) and received doxorubicin-contained chemotherapy(P<0.05). There was a trend toward superior outcome for patients who received combined therapy(surgery/chemotherapy/radiotherapy)(P=0.055). Patients who had CR, primary tumor diameter <7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis.Conclusions: Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy(RT) seemed to improve survival.
基金Supported by Grants from the National Natural Science Foundation of China No.30872923the Peking University People’s Hospital Research and Development Fund No.RDB2007-47,No.RDK2008-01 and No.RDB2011-25
文摘AIM:To examine the correlation of phosphatidylinositol3-kinase(PIK3)CB expression with preoperative radiotherapy response in patients with stageⅡ/Ⅲrectal adenocarcinoma.METHODS:PIK3CB immunoexpression was retrospectively assessed in pretreatment biopsies from 208 patients with clinical stageⅡ/Ⅲrectal adenocarcinoma,who underwent radical surgery after 30-Gy/10-fractionpreoperative radiotherapy.The relation between PIK3CB expression and tumor regression grade,clinicopathological characteristics,and survival time was statistically analyzed.Western blotting and in vitro clonogenic formation assay were used to detect PIK3CB expression in four colorectal cancer cell lines(HCT116,HT29,Lo Vo,and LS174T)treated with 6-Gy ionizing radiation.Pharmacological assays were used to evaluate the therapeutic relevance of TGX-221(a PIK3CB-specific inhibitor)in the four colorectal cancer cell lines.RESULTS:Immunohistochemical staining indicated that PIK3CB was more abundant in rectal adenocarcinoma tissues with poor response to preoperative radiotherapy.High expression of PIK3CB was closely correlated with tumor height(P<0.05),yp T stage(P<0.05),and high-degree tumor regression grade(P<0.001).High expression of PIK3CB was a potential prognostic factor for local recurrence-free survival(P<0.05)and metastasis-free survival(P<0.05).High expression of PIK3CB was also associated with poor therapeutic response and adverse outcomes in rectal adenocarcinoma patients treated with 30-Gy/10-fraction preoperative radiotherapy.In vitro,PIK3CB expression was upregulated in all four colorectal cancer cell lines concurrently treated with 6-Gy ionizing radiation,and the PIK3CB-specific inhibitor TGX-221 effectively inhibited the clonogenic formation of these four colorectal cancer cell lines.CONCLUSION:PIK3CB is critically involved in response to preoperative radiotherapy and may serve as a novel target for therapeutic intervention.
文摘Cervicogenic headache(CEH)has been recognized as a unique category of headache that can be difficult to diagnose and treat.In China,CEH patients are managed by many different specialties,and the treatment plans remain controversial.Therefore,there is a great need for comprehensive evidence-based Chinese experts’recommendations for the management of CEH.The Chinese Association for the Study of Pain asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with CEH.A group of multidisciplinary Chinese Association for the Study of Pain experts identified the clinically relevant topics in CEH.A systematic review of the literature was performed,and evidence supporting the benefits and harms for the management of CEH was summarized.Twenty-four recommendations were finally developed through expert consensus voting for evidence quality and recommendation strength.We hope this guideline provides direction for clinicians and patients making treatment decisions for the management of CEH.
基金Project supported by the National Natural Science Foundation of China(Nos.11622216,11602090,and 11672115)the Natural Science Foundation of Hubei Province(No.2017CFB429)the fundamental Research Funds for the Central Universities of China(No.2017KFYXJJ135)
文摘In this study,the nonplanar post-buckling behavior of a simply supported fluid-conveying pipe with an axially sliding downstream end is investigated within the framework of a three-dimensional(3 D)theoretical model.The complete nonlinear governing equations are discretized via Galerkin’s method and then numerically solved by the use of a fourth-order Runge-Kutta integration algorithm.Different initial conditions are chosen for calculations to show the nonplanar buckling characteristics of the pipe in two perpendicular lateral directions.A detailed parametric analysis is performed in order to study the influence of several key system parameters such as the mass ratio,the flow velocity,and the gravity parameter on the post-buckling behavior of the pipe.Typical results are presented in the form of bifurcation diagrams when the flow velocity is selected as the variable parameter.It is found that the pipe will stay at its original straight equilibrium position until the critical flow velocity is reached.Just beyond the critical flow velocity,the pipe would lose stability by static divergence via a pitchfork bifurcation,and two possible nonzero equilibrium positions are generated.It is shown that the buckling and post-buckling behaviors of the pipe cannot be influenced by the mass ratio parameter.Unlike a pipe with two immovable ends,however,the pinned-pinned pipe with an axially sliding downstream end shows some different features regarding post-buckling behaviors.The most important feature is that the buckling amplitude of the pipe with an axially sliding downstream end would increase first and then decrease with the increase in the flow velocity.In addition,the buckled shapes of the pipe varying with the flow velocity are displayed in order to further show the new post-buckling features of the pipe with an axially sliding downstream end.
基金supported by the National Natural Science Foundation of China (No. NSFC-81502406, 81673320)Education Scientific Research Project for young teachers, 2018 (No. JT180013)
文摘Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell line.Methods: First, we employed a quantitative proteomics approach based on stable isotope labeling by amino acids in cell culture(SILAC) to identify the different proteins expressed in HepG2 liver cancer cells upon exposure to ABA. Next, bioinformatics analyses through DAVID and STRING on-line tools were used to predict the pathways involved. Finally, we applied functional validation including cell cycle analysis and Western blotting for apoptosis and mTOR pathway-related proteins to confirm the bioinformatics predictions.Results: We identified 330 different proteins with the SILAC-based quantitative proteomics approach. The bioinformatics analysis and the functional validation revealed that the mTOR pathway, ribosome biogenesis, cell cycle, and apoptosis pathways were differentially regulated by ABA. G1 cell cycle arrest, apoptosis and mTOR inhibition were confirmed.Conclusions: ABA, a potential mTOR inhibitor, induces the disruption of ribosomal biogenesis. It also affects the mTOR-MRP axis to cause G1 cell cycle arrest and finally leads to cancer cell apoptosis.
