A Comparative Study on the Post-Buckling Behavior of Reinforced Thermoplastic Pipes(RTPs)Under External Pressure Considering Progressive Failure

The collapse pressure is a key parameter when RTPs are applied in harsh deep-water environments.To investigate the collapse of RTPs,numerical simulations and hydrostatic pressure tests are conducted.For the numerical simulations,the eigenvalue analysis and Riks analysis are combined,in which the Hashin failure criterion and fracture energy stiffness degradation model are used to simulate the progressive failure of composites,and the“infinite”boundary conditions are applied to eliminate the boundary effects.As for the hydrostatic pressure tests,RTP specimens were placed in a hydrostatic chamber after filled with water.It has been observed that the cross-section of the middle part collapses when it reaches the maximum pressure.The collapse pressure obtained from the numerical simulations agrees well with that in the experiment.Meanwhile,the applicability of NASA SP-8007 formula on the collapse pressure prediction was also discussed.It has a relatively greater difference because of the ignorance of the progressive failure of composites.For the parametric study,it is found that RTPs have much higher first-ply-failure pressure when the winding angles are between 50°and 70°.Besides,the effect of debonding and initial ovality,and the contribution of the liner and coating are also discussed.

Viscoelastic stress change from the 1931 M_(w)7.8 Fuyun earthquake and its impacts on seismic activity around the Altai mountains

The 1931 M_(w)7.8 Fuyun earthquake occurred around the Altai mountains, an intracontinental deformation belt with limited active strain-rate accumulation. To explore whether seismic activity in this deformation belt was affected by stress interaction among different active faults, we calculate the Coulomb failure stress change(ΔCFS) induced by the Fuyun earthquake due to coseismic deformation of the elastic crust and postseismic viscoelastic relaxation of the lower crust and upper mantle. Numerical results show that the total ΔCFS at a 10-km depth produced by the Fuyun earthquake attains approximately 0.015-0.134 bar near the epicenter, and just before the occurrence of the 2003 M_(w)7.2 Chuya earthquake, which distances about 400 km away from the Fuyun earthquake. Among the increased ΔCFS,viscoelastic relaxation from 1931 to 2003 contributes to approximately 0.014-0.131 bar, accounting for>90% of the total ΔCFS. More importantly, we find that for the recorded seismicity in the region with a radius of about 270 km to the Fuyun earthquake from 1970 to 2018, the percentage of earthquakes that fall in positive lobes of ΔCFS resolved on the NNW-SSE Fuyun strike-slip fault, on the NWW-SEE Irtysh strike-slip fault, and on the NW-SE Kurti reverse fault is up to 67.22%-91.36%. Therefore, the predictedΔCFS suggests that the impact of the 1931 M_(w)7.8 Fuyun earthquake on seismic activity around the Altai mountains is still significant as to hasten occurrence of the 2003 M_(w)7.2 Chuya earthquake at a relatively far distance and to trigger its aftershocks in the near-field even after several decades of the mainshock.

Comparison of engineering failures and seismic responses of 500 kV transformer-bushing systems in the 2022 Luding earthquake

Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.

Bioinformatics Analysis of the Relationship between Dilated Cardiomyopathy and Chronic Heart Failure

Objective: To screen and analyze the differentially expressed genes between dilated cardiomyopathy (DCM) and chronic heart failure (CHF) based on bioinformatics methods. Methods: The Gene Expression Omnibus (GEO) database was used for data retrieval, and the chip data GSE3585 was downloaded, which was the original data of DCM and normal control group. At the same time, the chip data GSE76701 was downloaded, which was the original data of CHF and control group. Differentially expressed mRNAs (DEmRNAs) were screened by R language limma package, the data were standardized, and the common differentially expressed genes were screened. GO function and KEGG pathway enrichment analysis were performed on the common differentially expressed genes. String11.0 online tool was used for data analysis to obtain differentially expressed genes, and the results were imported into Cytoscape 3.9.1 software. The results were imported into Cytoscape 3.9.1 software, and the common expression gene module was obtained by MOCDE algorithm. Nine Hub genes were obtained by 10 algorithms such as MCC. Results: A total of 248 differentially expressed genes were screened. GO analysis showed that differentially expressed genes were mainly concentrated in 9 different physiological and pathological processes. KEGG analysis showed that the main signaling pathways involved in differentially expressed genes were 2, and 9 key differentially expressed genes were predicted: NPPB, NPPA, MYH6, FRZB, ASPN, SFRP4, RPS4Y1, DDX3Y. Conclusion: This study preliminarily explored the molecular mechanism of DCM and CHF, and obtained the common differentially expressed genes of the two diseases. Further experimental studies are needed to verify the correlation between gene expression and clinicopathological features. Provide new ideas for clinical drug treatment research.

Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty

Objective The study sought to investigate the clinical predictive value of quantitative flow ratio(QFR)for the long-term target vessel failure(TVF)outcome in patients with in-stent restenosis(ISR)by using drug-coated balloon(DCB)treatment after a long-term follow-up.Methods This was a retrospective study.A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled.The QFR of the entire target vessel was measured offline.The primary endpoint was TVF,including target vessel-cardiac death(TV-CD),target vessel-myocardial infarction(TV-MI),and clinically driven-target vessel revascularization(CD-TVR).Results The follow-up time was 3.09±1.53 years,and 50 patients had TVF.The QFR immediately after percutaneous coronary intervention(PCI)was significantly lower in the TVF group than in the no-TVF group.Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up[hazard ratio(HR):5.15×10−5(6.13×10−8−0.043);P<0.01].Receiver-operating characteristic(ROC)curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925(area under the curve:0.886,95%confidence interval:0.834–0.938;sensitivity:83.40%,specificity:88.00;P<0.01).In addition,QFR≤0.925 post-PCI was strongly correlated with the TVF,including TV-MI and CD-TVR(P<0.01).Conclusion The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty.A lower QFR immediately after PCI was associated with a worse TVF outcome.

Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles:Sequential Embryo Transfer or Double-blastocyst Transfer?

Objective Both sequential embryo transfer(SeET)and double-blastocyst transfer(DBT)can serve as embryo transfer strategies for women with recurrent implantation failure(RIF).This study aims to compare the effects of SeET and DBT on pregnancy outcomes.Methods Totally,261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis.According to different embryo quality and transfer strategies,they were divided into four groups:group A,good-quality SeET(GQ-SeET,n=38 cycles);group B,poor-quality or mixed-quality SeET(PQ/MQ-SeET,n=31 cycles);group C,good-quality DBT(GQ-DBT,n=121 cycles);and group D,poor-quality or mixed-quality DBT(PQ/MQ-DBT,n=71 cycles).The main outcome,clinical pregnancy rate,was compared,and the generalized estimating equation(GEE)model was used to correct potential confounders that might impact pregnancy outcomes.Results GQ-DBT achieved a significantly higher clinical pregnancy rate(aOR 2.588,95%CI 1.267–5.284,P=0.009)and live birth rate(aOR 3.082,95%CI 1.482–6.412,P=0.003)than PQ/MQ-DBT.Similarly,the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET(aOR 4.047,95%CI 1.218–13.450,P=0.023).The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT,and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT.Conclusion SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups.Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos,no matter whether in SeET or DBT.Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

Interrelationships between Length of the Day, Moon Distance, Phanerozoic Geodynamic Cycles, Tidal Dissipation and Earth’s Core: Review and Analysis

The rotation of the Earth and the related length of the day (LOD) are predominantly affected by tidal dissipation through the Moon and the growth of the Earth’s core. Due to the increased concentration of mass around the rotation axis of the spinning Earth during the growth of the core the rotation should have been accelerated. Controversially the tidal dissipation by the Moon, which is mainly dependent on the availability of open shallow seas and the kind of Moon escape from a nearby position, acts towards a deceleration of the rotating Earth. Measurements of LOD for Phanerozoic and Precambrian times open ways to solve questions concerning the geodynamical history of the Earth. These measurements encompass investigations of growth patterns in fossils and depositional patterns in sediments (Cyclostratigraphy, Tidalites, Stromatolites, Rhythmites). These patterns contain information on the LOD and on the changing distance between Earth and Moon and can be used as well for a discussion about the growth of the Earth’s core. By updating an older paper with its simple approach as well as incorporating newly published results provided by the geoscientific community, a moderate to fast growth of the core in a hot early Earth will be favored controversially to the assumption of a delayed development of the core in an originally cold Earth. Core development with acceleration of Earth’s rotation and the contemporaneous slowing down due to tidal dissipation during the filling of the ocean may significantly interrelate.

Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome

BACKGROUND Chronic heart failure is a complex clinical syndrome.The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure;however,the underlying molecular mechanism is still not clear.AIM To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure.METHODS The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target genes of chronic heart failure were searched in the Genecards database.The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drugdisease targets,which were then used to construct a key chemical componenttarget network using Cytoscape 3.7.2 software.The protein-protein interaction network was constructed using the String database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database.Finally,our previously published relevant articles were searched to verify the results obtained via network pharmacology.RESULTS A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified,of which quercetin,kaempferol,7-methoxy-2-methyl isoflavone,formononetin,and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3,MAPK3,AKT1,JUN,MAPK1,TP53,TNF,HSP90AA1,p65,MAPK8,MAPK14,IL6,EGFR,EDN1,FOS,and other proteins.The pathways identified by KEGG enrichment analysis include pathways in cancer,IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,calcium signaling pathway,cAMP signaling pathway,NF-kappaB signaling pathway,AMPK signaling pathway,etc.Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α,IL-6,MAPK,cAMP,and AMPK pathways to affect the mitochondrial structure of myocardial cells,oxidative stress,and energy metabolism,thus achieving the therapeutic effects on chronic heart failure.CONCLUSION The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes,oxidative stress,energy metabolism,and other processes.Future studies are warranted to investigate the role of the IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Investigating the Correlation between Patient Education on Web-Based Portal Functionality and the Reduction in 30-Day Hospital Readmission Rates

Background: The growing use of web-based patient portals offers patients valuable tools for accessing health information, communicating with healthcare providers, and engaging in self-management. However, the influence of educating patients on these portals’ functionality on clinical outcomes, such as all-cause readmission rates, remains underexplored. Objective: This research proposal tested the hypothesis that educating a subset of patients with Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF), on how to effectively access and utilize the functionality of web-based patient portals can reduce all-cause readmission rates. Methods: We performed a prospective, quasi-experimental study at Bon Secours St. Mary’s Hospital in Richmond, Virginia, USA;dividing participants into an intervention group, receiving education about accessing and navigating “My Chart”, the Bon Secours Web based portal, and a control group, receiving standard care. We then compared 30-day readmission rates, patient engagement, and self-management behaviors between the groups. Data was analyzed using statistical tests to assess the intervention’s impact. Results: We projected that educated patients will exhibit lower readmission rates, improved engagement, and better self-management. The results of the study showed that there was a significant decrease in 30-day readmissions in the intervention group in comparison with the control group (22.7% and 40.9%, respectively). This reduction of 18. 2% of readmissions evaluated here for a trial of meaningful clinical effect is statistically insignificant (p = 0. 184). The practical significance of the intervention is considered small-to-moderate (Cramer V = 0. 20) suggesting that the observed difference has a potential clinical importance even though the difference was not statistically significant. Conclusion: These results imply that the proposed educational intervention might have a positive impact on readmissions;nonetheless, the patient’s characteristics that make him or her capable of readmission cannot be changed and are assessed by the RoR (Risk of Readmission) score. The potential impact of the intervention may be offset, in part, by these baseline risk factors. The study’s power may be limited by sample size, potentially affecting the detection of significant differences. Future studies with larger, multi-center samples and longer follow-up periods are recommended to confirm these findings.

Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure:a mediated Mendelian randomization study

Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by network Mendelian randomization(MR).Methods:Genome-wide analysis of DBP,HRDRF,and HF was downloaded from the public database(Genome-Wide Analysis Study[GWAS])and was used to analyze the results and to conduct mediated MR analysis.Results:Analysis showed that DBP was positively correlated with HRDRF(OR=1.0002,95%CI:1.0001–1.0003,P=1.8076e-05)and DBP was positively correlated with HF(OR=1.0295,95%CI:1.0221–1.0370,P=2.5292e-15).HF and HRDRF had a positive causal effect(OR=1.0001,95%CI:1.0000–1.0001,P=0.0152).Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%.Conclusions:DBP can increase the risk of renal disease with renal failure,and HF may play an impor tant role in mediating this causal relationship.

A Comparison between Forming Behaviours of Two Pre-Consolidated Woven Thermoplastic Composites

This paper presents the results of an investigation on stretch forming behaviour of two consolidated woven thermoplastic composites: a self-reinforced polypropylene (SRPP) and a glass-fibre reinforced polypropylene (GRPP) composite. A custom-built press with a hemispherical punch was employed to deform composites’ specimens possessing different aspect ratios into an open die. The induced strains on the outer surface of specimens were measured continuously through two high speed, high resolution CCD cameras by employing a Digital Image Correlation (DIC) technique. The strain paths at three different locations on the surface of specimens were compared to elucidate the effect of fibre and matrix on the formability of a woven composite. The fractured surface of specimens was investigated to reveal the effect of fibre mechanical properties on failure morphologies in woven composites. It was found out that the main mode of failure in GRPP is fibre fracture while observed failure morphologies in SRPP were a complex combination of different failure mechanisms. It was revealed that the combination of applied boundary conditions and specimen’s width determines the effective forming mechanisms.

Impacts of Sea Surface Temperature on the Interannual Variability of Winter Haze Days in Guangdong Province

The impact of sea surface temperature(SST)on winter haze in Guangdong province(WHDGD)was analyzed on the interannual scale.It was pointed out that the northern Indian Ocean and the northwest Pacific SST play a leading role in the variation of WHDGD.Cold(warm)SST anomalies over the northern Indian Ocean and the Northwest Pacific stimulate the eastward propagation of cold(warm)Kelvin waves through the Gill forced response,causing Ekman convergence(divergence)in the western Pacific,inducing abnormal cyclonic(anticyclonic)circulation.It excites the positive(negative)Western Pacific teleconnection pattern(WP),which results in the temperature and the precipitation decrease(increase)in Guangdong and forms the meteorological variables conditions that are conducive(not conducive)to the formation of haze.ENSO has an asymmetric influence on WHDGD.In El Niño(La Niña)winters,there are strong(weak)coordinated variations between the northern Indian Ocean,the northwest Pacific,and the eastern Pacific,which stimulate the negative(positive)phase of WP teleconnection.In El Niño winters,the enhanced moisture is attributed to the joint effects of the horizontal advection from the surrounding ocean,vertical advection from the moisture convergence,and the increased atmospheric apparent moisture sink(Q2)from soil evaporation.The weakening of the atmospheric apparent heat source(Q1)in the upper layer is not conducive to the formation of inversion stratification.In contrast,in La Niña winters,the reduced moisture is attributed to the reduced upward water vapor transport and Q2 loss.Due to the Q1 increase in the upper layer,the temperature inversion forms and suppresses the diffusion of haze.

Seasonal Prediction of Extreme High-Temperature Days in Southwestern China Based on the Physical Precursors

Extreme high temperatures frequently occur in southwestern China,significantly impacting the local ecological system and economic development.However,accurate prediction of extreme high-temperature days(EHDs)in this region is still an unresolved challenge.Based on the spatiotemporal characteristics of EHDs over China,a domain-averaged EHD index over southwestern China(SWC-EHDs)during April-May is defined.The simultaneous dynamic and thermodynamic fields associated with the increased SWC-EHDs are a local upper-level anticyclonic(high-pressure)anomaly and wavy geopotential height anomaly patterns over Eurasia.In tracing the origins of the lower boundary anomalies,two physically meaningful precursors are detected for SWC-EHDs.They are the tripolar SST change tendency from December-January to February-March in the northern Atlantic and the February-March mean snow depth in central Asia.Using these two selected predictors,a physics-based empirical model prediction was applied to the training period of 1961–2005 to obtain a skillful prediction of the EHDs index,attaining a correlation coefficient of 0.76 in the independent prediction period(2006–19),suggesting that 58%of the total SWC-EHDs variability is predictable.This study provides an estimate for the lower bound of the seasonal predictability of EHDs as well as for the hydrological drought over southwestern China.

Research on the Voltage Supporting Capability of Multi-VSC-HVDC Subsystems Operation Strategy to Receiving-end LCC-HVDC Network in Weak AC Grid

For the hybrid multi-infeed HVDC system in which the receiving-end grid is a strong AC grid including LCC-HVDC subsystems and multiple VSC-HVDC subsystems,it has higher voltage support capability.However,for weak AC grid,the voltage support capability of the multi-VSC-HVDC subsystems to the LCC-HVDC subsystem(voltage support capability-mVSCs-LCC)can resist the risk of commutation failure.Based on this consideration,this paper proposes an evaluation index called Dynamic Voltage Support Strength Factor(DVSF)for the hybrid multi-infeed system,and uses this index to qualitatively judge the voltage support capability-mVSCs-LCC in weak AC grid.In addition,the proposed evaluation index can also indirectly judge the ability of the LCC-HVDC subsystem to suppress commutation failure.Firstly,the mathematical model of the power flow of the LCC and VSC networks in the steady-state is analyzed,and the concept of DVSF applied to hybrid multi-infeed system is proposed.Furthermore,the DVSF index is also used to qualitatively judge the voltage support capability-mVSCs-LCC.Secondly,the influence of multiple VSC-HVDC subsystems with different operation strategies on the DVSF is analyzed with reference to the concept of DVSF.Finally,the indicators proposed in this paper are compared with other evaluation indicators through MATLAB simulation software to verify its effectiveness.More importantly,the effects of multi-VSC-HVDC subsystems using different coordinated control strategies on the voltage support capability of the receiving-end LCC-HVDC subsystem are also verified.

Paraneoplastic myopathy-related rhabdomyolysis and pancreatic cancer:A case report and review of the literature

BACKGROUND Rhabdomyolysis is a life-threatening condition,often leading to progressive renal failure and death.It is caused by destruction of skeletal muscle and the release of myoglobin and other intracellular contents into the circulation.The most frequent cause of this condition is“crush syndrome”,although several others have been described and paraneoplastic inflammatory myopathies associated with various types of cancer are repeatedly reported.CASE SUMMARY We describe a rare case of a patient with pancreatic cancer who developed rhabdomyolysis early on,possibly due to paraneoplastic myositis leading to acute renal failure and eventually to rapid death.A 78-year-old Caucasian woman was referred to our hospital for obstructive jaundice and weight loss due to a lesion in the pancreatic head.She presented increasingly severe renal insufficiency with anuria,a dramatic increase in creatine phosphokinase(36000 U/L,n.v.20-180 U/L)and myoglobin(>120000μg/L,n.v.12-70μg/L).On clinical examination,the patient showed increasing pain in the lower limbs associated with muscle weakness which was severe enough to immobilize her.Paraneoplastic myopathy linked to the malignant lesion of the pancreatic head was suspected.The patient was treated with hemodialysis and intravenous methylprednisolone.Despite all the efforts to prepare the patient for surgery,her general condition rapidly deteriorated and she eventually died 30 d after hospital admission.CONCLUSION The possible causes of rhabdomyolysis in this patient with pancreatic cancer are discussed,the development of paraneoplastic myopathy being the most likely.Clinicians should bear in mind that these syndromes may become clinically manifest at any stage of the cancer course and their early diagnosis and treatment could improve the patient’s prognosis.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway

Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.

Time series prediction of reservoir bank landslide failure probability considering the spatial variability of soil properties

Historically,landslides have been the primary type of geological disaster worldwide.Generally,the stability of reservoir banks is primarily affected by rainfall and reservoir water level fluctuations.Moreover,the stability of reservoir banks changes with the long-term dynamics of external disastercausing factors.Thus,assessing the time-varying reliability of reservoir landslides remains a challenge.In this paper,a machine learning(ML)based approach is proposed to analyze the long-term reliability of reservoir bank landslides in spatially variable soils through time series prediction.This study systematically investigated the prediction performances of three ML algorithms,i.e.multilayer perceptron(MLP),convolutional neural network(CNN),and long short-term memory(LSTM).Additionally,the effects of the data quantity and data ratio on the predictive power of deep learning models are considered.The results show that all three ML models can accurately depict the changes in the time-varying failure probability of reservoir landslides.The CNN model outperforms both the MLP and LSTM models in predicting the failure probability.Furthermore,selecting the right data ratio can improve the prediction accuracy of the failure probability obtained by ML models.

Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure:A multicenter study

BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/cirrhosis.It was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF.This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction model.AIM To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model.METHODS This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022.Within 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other conditions.Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram.Nomogram performance was validated further.The diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)score.RESULTS A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this study.The independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total bilirubin.Better diagnostic performance of the nomogram was obtained in the training[area under receiver operating characteristic curve(AUC):0.833;95%confidence interval(95%CI):0.792-0.873;sensitivity:83.1%;specificity:73.5%]and validation(AUC:0.802;95%CI:0.684-0.920;sensitivity:95.5%;specificity:52.5%)cohorts compared with the MELD score and the ALBI score.CONCLUSION This PHLF nomogram,mainly based on LS by 2D-SWE and SPA,was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Investigation of the block toppling evolution of a layered model slope by centrifuge test and discrete element modeling

Primary toppling usually occurs in layered rock slopes with large anti-dip angles.In this paper,the block toppling evolution was explored using a large-scale centrifuge system.Each block column in the layered model slope was made of cement mortar.Some artificial cracks perpendicular to the block column were prefabricated.Strain gages,displacement gages,and high-speed camera measurements were employed to monitor the deformation and failure processes of the model slope.The centrifuge test results show that the block toppling evolution can be divided into seven stages,i.e.layer compression,formation of major tensile crack,reverse bending of the block column,closure of major tensile crack,strong bending of the block column,formation of failure zone,and complete failure.Block toppling is characterized by sudden large deformation and occurs in stages.The wedge-shaped cracks in the model incline towards the slope.Experimental observations show that block toppling is mainly caused by bending failure rather than by shear failure.The tensile strength also plays a key factor in the evolution of block toppling.The simulation results from discrete element method(DEM)is in line with the testing results.Tensile stress exists at the backside of rock column during toppling deformation.Stress concentration results in the fragmented rock column and its degree is the most significant at the slope toe.