Many conventional methods of testing strong and pulsed electromagnetic fields,the ones used in radars for example,had deficiencies due to the difficulty in obtaining simultaneous information about the electromagnetic ...Many conventional methods of testing strong and pulsed electromagnetic fields,the ones used in radars for example,had deficiencies due to the difficulty in obtaining simultaneous information about the electromagnetic field's peak both in the time domain and in the frequency domain.With regard to this problem,after analyzing the time-domain and the frequency-domain characteristics of radar pulsed signals,we propose a new time-frequency combination test method based on the correction of the test parameters,as well as its correction method at different bandwidths.The test method is applied in a quick test of a high-power pulsed radar signal,and the corrected results have error less than 1 dB in both the time domain and the frequency domain,which indicates that the proposed time-frequency combined method is effective in testing strong and pulsed electromagnetic fields.展开更多
The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with...The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.展开更多
With the increasingly complex and changeable electromagnetic environment,wireless communication systems are facing jamming and abnormal signal injection,which significantly affects the normal operation of a communicat...With the increasingly complex and changeable electromagnetic environment,wireless communication systems are facing jamming and abnormal signal injection,which significantly affects the normal operation of a communication system.In particular,the abnormal signals may emulate the normal signals,which makes it very challenging for abnormal signal recognition.In this paper,we propose a new abnormal signal recognition scheme,which combines time-frequency analysis with deep learning to effectively identify synthetic abnormal communication signals.Firstly,we emulate synthetic abnormal communication signals including seven jamming patterns.Then,we model an abnormal communication signals recognition system based on the communication protocol between the transmitter and the receiver.To improve the performance,we convert the original signal into the time-frequency spectrogram to develop an image classification algorithm.Simulation results demonstrate that the proposed method can effectively recognize the abnormal signals under various parameter configurations,even under low signal-to-noise ratio(SNR)and low jamming-to-signal ratio(JSR)conditions.展开更多
Seismic time-frequency(TF)transforms are essential tools in reservoir interpretation and signal processing,particularly for characterizing frequency variations in non-stationary seismic data.Recently,sparse TF trans-f...Seismic time-frequency(TF)transforms are essential tools in reservoir interpretation and signal processing,particularly for characterizing frequency variations in non-stationary seismic data.Recently,sparse TF trans-forms,which leverage sparse coding(SC),have gained significant attention in the geosciences due to their ability to achieve high TF resolution.However,the iterative approaches typically employed in sparse TF transforms are computationally intensive,making them impractical for real seismic data analysis.To address this issue,we propose an interpretable convolutional sparse coding(CSC)network to achieve high TF resolution.The proposed model is generated based on the traditional short-time Fourier transform(STFT)transform and a modified UNet,named ULISTANet.In this design,we replace the conventional convolutional layers of the UNet with learnable iterative shrinkage thresholding algorithm(LISTA)blocks,a specialized form of CSC.The LISTA block,which evolves from the traditional iterative shrinkage thresholding algorithm(ISTA),is optimized for extracting sparse features more effectively.Furthermore,we create a synthetic dataset featuring complex frequency-modulated signals to train ULISTANet.Finally,the proposed method’s performance is subsequently validated using both synthetic and field data,demonstrating its potential for enhanced seismic data analysis.展开更多
Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effec...Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.展开更多
Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease in...Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.展开更多
Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and ...Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.展开更多
To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-dec...To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-decomposition associated with kernel-based-extreme-learningmachine optimized by the whale optimization algorithm(VMD-WOA-KELM)is proposed in this paper.Firstly,the displacement is decomposed by VMD to three IMF components and a residual component of different fluctuation characteristics.The key impact factors of each IMF component are selected according to Copula model,and the corresponding WOA-KELM is established to conduct point prediction.Subsequently,the parametric method(PM)and non-parametric method(NPM)are used to estimate the prediction error probability density distribution(PDF)of each component,whose prediction interval(PI)under the 95%confidence level is also obtained.By means of the differential evolution algorithm(DE),a weighted combination model based on the PIs is built to construct the combination-interval(CI).Finally,the CIs of each component are added to generate the total PI.A comparative case study shows that the CIPM performs better in constructing landslide displacement PI with high performance.展开更多
A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that r...A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that regulates heading date,plant height and grain number.Here,we investigated the relationship between Ghd7 and florigen genes Hd3a and RFT1,to determine their roles in regulating heading date and grain number under different photoperiods.Our results revealed that under long-day(LD)conditions,Hd3a acts prior to RFT1 to promote heading while negatively regulating plant height and grain number.In contrast,Ghd7 positively regulates heading date,plant height,and grain number by inhibiting both Hd3a and RFT1.Under short-day(SD)conditions,the functions of Hd3a and RFT1 remain consistent with those under LD conditions,but Ghd7 does not inhibit their expression,resulting in a weaker phenotypic effect compared to Hd3a.Additionally,under both LD and SD conditions,increased Ghd7 expression enhances its inhibitory effect on Hd3a and RFT1,leading to later heading and increased grain number;however,once the heading date exceeds 94 d,grain number no longer increases.Moreover,the gn1a allele increased grain number by 16.5%to 42.5%,while combinations of the elite alleles from Ghd7,Hd3a,RFT1,and Gn1a significantly increased grain number by up to 240.9%.Therefore,we propose a new breeding strategy to optimize the heading date and grain number using the Ghd7Hd3aRFT1gn1a combination of Ghd7,Hd3a,RFT1,and Gn1a under LD conditions,and the Ghd7hd3aRFT1gn1a combination under SD conditions.This strategy improved the yield of the high-quality Northeast variety Kongyu 131(KY131)by 69.1%in Beijing and 93.7%in Hainan.This strategy will greatly improve the efficiency of north-to-south adaptation in rice,providing theoretical guidance for expanding the geographical adaptability of rice varieties.展开更多
Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances m...Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances made in recent years with regard to immunotherapy in both basic research and clinical practice,there remains scope for further improvement,particularly with respect to its efficacy against solid tumors.With advancements in nanotechnology,tumor nanovaccines hold immense potential for preventing tumor recurrence and treating metastatic tumors.Nevertheless,the considerable heterogeneity of tumor immunogenicity presents a number of significant challenges in the development of nanometrescale vaccines targeting solid tumors.Recent findings indicate that immune checkpoint inhibitor(ICI)therapy can improve the immunosuppressive microenvironment within tumors,while nanovaccines can also augment tumor sensitivity toward ICIs.Consequently,combining tumor nanovaccine with ICI therapy holds promise for effectively eradicating tumors or controlling their recurrence and metastasis during cancer treatment.This review delves into the mechanism behind combining tumor nanovaccine with ICI while focusing on factors influencing this combined therapy approach.Moreover,it offers an overview of the current research status regarding the combination of tumor nanovaccines with chemotherapy,radiotherapy,photothermal therapy,and sonodynamic therapy,as well as prospects for future developments in this field.展开更多
BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of a...BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of albumin-bound paclitaxel(nab-ptx)combined with the small molecule vascular endothelial growth factor inhibitor anlotinib in secondline and beyond treatment of AGC.METHODS We collected data from AGC patients at our hospital who experienced disease progression after first-line chemotherapy and received anlotinib combined with nab-ptx.The primary endpoints included overall survival(OS)and progressionfree survival(PFS),while the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and adverse events(AEs).RESULTS Preliminary results indicated that anlotinib combined with nab-ptx can provide significant efficacy in second-line or above treatment for AGC(median PFS=6.0 months,median OS=12.0 months),with an ORR of 42%and a DCR of 78%.Further analysis revealed that patients who experienced hypertension,proteinuria,and hand-foot syndrome during treatment had better efficacy compared to those who did not experience these AEs.Mechanistic studies suggest that this regimen likely exerts synergistic anti-tumor effects by activating the immune response through the reduction of regulatory T-cell proportions.Common adverse reactions included bone marrow suppression,peripheral neuropathy,hypertension,proteinuria,and hand-foot syndrome,which were manageable and resolved with appropriate interventions,indicating the promising application of this regimen in second-line or above treatment for AGC.CONCLUSION The combination of anlotinib and nab-ptx shows promising efficacy with fewer toxicities in AGC treatment.The regimen holds promise as a second-line treatment of AGC;however,its specific clinical value requires further research.展开更多
Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.Howe...Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.However,emerging evidence indicates that unintended pro-metastatic effects may offset the therapeutic benefits of HDACis.Chen et al elucidate this paradox,demonstrating that TSA-induced hyperacetylation activates the BRD4/c-Myc/ER-stress axis,thereby promoting epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma(ESCC).Furthermore,they clarify the clinical significance of histone acetylation in the prognostic evaluation of ESCC.Their findings underscore the complexity of epigenetic therapies and highlight the necessity of reevaluating the associated risks and combinatorial therapeutic strategies with HDACi-based treatments.Here,we summarize the potential risks of HDACis therapy and discuss feasible combination therapeutic strategies.展开更多
BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain lim...BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain limited.AIM To examine the predictive value of endoscopic findings of primary tumors for responses to neoadjuvant immunotherapy.METHODS This retrospective study,conducted at a tertiary center in China,evaluated 74 patients with colorectal cancer,including 17 with deficient mismatch repair(dMMR)and 15 with proficient mismatch repair(pMMR)tumors.Patients underwent neoadjuvant immunotherapy followed by surgery.Endoscopic findings before and after neoadjuvant immunotherapy were reviewed and compared with the pathology of the resected specimens.RESULTS In the pMMR group(n=57 evaluable patients),endoscopy identified 11/17 patients who achieved a complete response(CR),while misidentifying 1/40 patients with residual disease as CR(64.7%vs 2.5%,P<0.01).Conversely,22/40 patients with residual disease were accurately identified as achieving a partial response(PR),with 1/17 patients who achieved CR misclassified as PR(55.0%vs 5.9%,P<0.01).The sensitivity,specificity,and accuracy of endoscopic diagnosis for pathological CR were 64.7%,97.5%,and 87.7%,respectively.In the dMMR cohort,endoscopy classified 9/17 patients as CR and 2 of the remaining patients with residual tumors as PR(64.3%vs 66.7%,P=0.73).The method demonstrated 100%sensitivity and 82.4%accuracy in diagnosing pathological CR.CONCLUSION Endoscopic evidence of CR or PR was well correlated with postoperative pathological outcomes in the pMMR cohort.Despite endoscopic indications of tumor residue,a complete pathological response post-surgery was possible in the dMMR cohort.展开更多
Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,an...Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,and based onμ-CT three-dimensional reconstruction imaging and finite element analysis(FEA)techniques,the stress distribution and potential failure mechanism at the cement-sandstone bonding interface under axial loading were analyzed.The key findings are as follows:(1)stress concentrations are highly likely to form at the gap between the cement and sandstone interface and around interfacial voids,with Von Mises stress reaching critical levels of 18.0-20.0 MPa at these locations,significantly exceeding the stress magnitudes in well-bonded regions;(2)the phenomenon of local stress concentration driven by interfacial defects can be identified as the main basis for predicting damage location in interfacial debonding and continuous shear under axial load;(3)ensuring tight cementation at the cement-sandstone interface and minimizing interfacial voids are paramount for preventing stress-induced failure;(4)the critical Von Mises stress value of 20 MPa at the interface defect can be used as a benchmark for material selection and designed to ensure long-term integrity in oil and gas well applications subjected to similar axial loads.These findings contribute to a more accurate understanding of the failure mechanism of the cement-sandstone interface and to the precise design of material properties,thereby ensuring the long-term integrity of oil and gas well applications subjected to similar axial loads.展开更多
Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference...Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference is compact on the weighted Bergman space in the unit disk.Motivated by the subtle connection of composition operator theory on the weighted Bergman spaces,Korenblum spaces and bounded holomorphic function spaces,we first explore the rigid phenomenon which also holds on the Korenblum space over the unit ball.Furthermore,we discuss which difference of composition operators is compact when the compact combination of composition operators does not satisfy the condition(CNC)on Korenblum spaces and bounded holomorphic function spaces over the unit ball setting.展开更多
Understanding the mechanical properties of coal-rock-bolt(CRB)combinations at high strain rates and the anchoring mechanism of bolts is crucial for ensuring the safety of coal mining operations.However,the dynamic beh...Understanding the mechanical properties of coal-rock-bolt(CRB)combinations at high strain rates and the anchoring mechanism of bolts is crucial for ensuring the safety of coal mining operations.However,the dynamic behaviors of these combinations,especially the mechanism of action of prestressed bolts,still need to be further investigated.This study carried out split Hopkinson pressure bar(SHPB)tests on three sets of coal-rock(CR),CRB,and coal-rock-prestressed bolt(CRPB)combinations with different interface angles(β=15°,30°,45°,and 60°).The dynamic properties of the combinations were analyzed based on the stress-strain curve,energy dissipation,dynamic strength,fractal dimension of cracks,and failure mode of bolts.The test results show that a larger β will affect the stress transfer and anti-sliding ability of CR,resulting in a decrease in CR strength.The anchoring force of the bolt effectively suppresses the slip feature of CRB at the yield stage.As the strain rate increases,CRB shows a more pronounced'sudden increase'in strength,and the bolt significantly enhances its dynamic strength.The prestressed bolts enhance the dynamic strength of CRPB while weaken the effect of β.The fractal dimension of the macrocracks increases with strain rate,with smaller variations in CRB and CRPB,indicating that the bolt reduces the complexity degree of CRB and CRPB.The anchoring force of CRB depends on bolt strength,which reduces the slip along the interface.The anchoring force of CRPB balances the coal-rock slip and suppresses crack formation,resulting in a more cohesive response under dynamic load.展开更多
Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,...Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,thus contributing to the development of vascular disorders,especially atherosclerotic diseases.Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis.It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes(T2DM)complicated with atherosclerotic diseases.Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor,which could offer additional vascular benefits and reduce the risk of atherosclerotic complications.Likewise,combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia,whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits.Moreover,co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies.For instance,a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications.However,these potential benefits remain need validation by the evidence from clinical studies.Despite the limitations,such as heterogeneity across different patient populations,and deficiency in long-term outcomes,such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.展开更多
Purpose–To systematically characterize and objectively evaluate basic railway safety management capability,creating a closed-loop management approach which allows continuous improvement and optimization.Design/method...Purpose–To systematically characterize and objectively evaluate basic railway safety management capability,creating a closed-loop management approach which allows continuous improvement and optimization.Design/methodology/approach–A basic railway safety management capability evaluation index system based on a comprehensive analysis of national safety management standards,railway safety rules and regulations and existing safety data from railway transport enterprises is presented.The system comprises a guideline layer including safety committee formation,work safety responsibility,safety management organization and safety rules and regulations as its components,along with an index layer consisting of 12 quantifiable indexes.Game theory combination weighting is utilized to integrate subjective and objective weight values derived using AHP and CRITIC methods and further combined using the TOPSIS method in order to construct a comprehensive basic railway safety management capability evaluation model.Findings–The case study presented demonstrates that this evaluation index system and comprehensive evaluation model are capable of effectively characterizing and evaluating basic railway safety management capability and providing directional guidance for its sustained improvement.Originality/value–Construction of an evaluation index system that is quantifiable,generalizable and accessible,accurately reflects the main aspects of railway transportation enterprises’basic safety management capability and provides interoperability across various railway transportation enterprises.The application of the game theoretic combination weighting method to derive composite weights which combine experts’subjective evaluations with the objectivity of data.展开更多
The essence of the outburst-rock burst compound dynamic disaster is the disaster behavior of the"gas-coal-surrounding rock"system under the comprehensive action of the stress field and the seepage field.Base...The essence of the outburst-rock burst compound dynamic disaster is the disaster behavior of the"gas-coal-surrounding rock"system under the comprehensive action of the stress field and the seepage field.Based on the geological occurrence characteristics of coal and rock in the roof,coal,and floor,this study combinedexperimental research and theoretical analysis to explore the effects of confining pressure,gas pressure,and axial loading rate on the mechanical behavior of gasbearing rock-coal-rock combination structures("RCR combination").The results show that both decreasing gas pressure and increasing confining pressure can improve the deformation capacity and bearing capacity of the RCR combination.When the gas pressure decreases from 1.5 to 0.5 MPa and the confining pressure increases from 3 to 9 MPa,the peak stress of the RCR combination increases by 15.83% and 184.02%,respectively.On increasing the axial loading rate,the peak stress of the RCR combination first increases and then decreases,and the elastic modulus continues to decrease.There is a good correspondence between stress and acoustic emission counts(AE),which can be used as a predictive index for judging rock fracture instability.Compared with rock,coal exerts much greater influence on the mechanical strength of the RCR combination.The theoretical analysis shows that the parameters m and F_0 mainly affect the peak stress of the RCR combination,and the speed of stress reduction after the peak of the RCR combination is influenced by the parameter m.The coal elastic modulus exerts greater influence on the bearing capacity of the RCR combination than the rock elastic modulus.When the elastic modulus of rocks increases from 10 to 25 GPa and that of coal increases from 2 to 5 GPa,the peak stress of the RCR combination increases by 9.87% and 8.97%,respectively.展开更多
BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immu...BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immunotherapy and other therapeutic methods have provided new treatment options for middle and advanced HCC(aHCC).Predicting the effect of targeted combined immunotherapy has become a hot topic in current research.AIM To explore the relationship between nodule enhancement in hepatobiliary phase and the efficacy of combined targeted immunotherapy for aHCC.METHODS Data from 56 patients with aHCC for magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid were retrospectively collected.Signal intensity of intrahepatic nodules was measured,and the hepatobiliary relative enhancement ratio(RER)was calculated.Progression-free survival(PFS)of patients with high and low reinforcement of HCC nodules was compared.The model was validated using receiver operating characteristic curves.Univariate and multivariate logistic regression and Kaplan-Meier analysis were performed to explore factors influencing the efficacy of targeted immunization and PFS.RESULTS Univariate and multivariate analyses revealed that the RER,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and prognostic nutritional index were significantly associated with the efficacy of tyrosine kinase inhibitors combined with immunotherapy(P<0.05).The area under the curve of the RER for predicting the efficacy of tyrosine kinase inhibitors combined with anti-programmed death 1 antibody in patients with aHCC was 0.876(95%confidence interval:0.781-0.971,P<0.05),the optimal cutoff value was 0.904,diagnostic sensitivity was 87.5%,and specificity was 79.2%.Kaplan-Meier analysis showed that neutrophil-to-lymphocyte ratio<5,plateletto-lymphocyte ratio<300,prognostic nutritional index<45,and RER<0.9 significantly improved PFS.CONCLUSION AHCC nodules enhancement in the hepatobiliary stage was significantly correlated with PFS.Imaging information and immunological indicators had high predictive efficacy for targeted combined immunotherapy and were associated with PFS.展开更多
文摘Many conventional methods of testing strong and pulsed electromagnetic fields,the ones used in radars for example,had deficiencies due to the difficulty in obtaining simultaneous information about the electromagnetic field's peak both in the time domain and in the frequency domain.With regard to this problem,after analyzing the time-domain and the frequency-domain characteristics of radar pulsed signals,we propose a new time-frequency combination test method based on the correction of the test parameters,as well as its correction method at different bandwidths.The test method is applied in a quick test of a high-power pulsed radar signal,and the corrected results have error less than 1 dB in both the time domain and the frequency domain,which indicates that the proposed time-frequency combined method is effective in testing strong and pulsed electromagnetic fields.
基金National Natural Science Foundation of China under Grant No.51578463。
文摘The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.
基金supported by Natural Science Foundation of China(No.62371231)Natural Science Foundation on Frontier Leading Technology Basic Research Project of Jiangsu under Grant BK20222001Jiangsu Provincial Key Research and Development Program(No.BE2023027).
文摘With the increasingly complex and changeable electromagnetic environment,wireless communication systems are facing jamming and abnormal signal injection,which significantly affects the normal operation of a communication system.In particular,the abnormal signals may emulate the normal signals,which makes it very challenging for abnormal signal recognition.In this paper,we propose a new abnormal signal recognition scheme,which combines time-frequency analysis with deep learning to effectively identify synthetic abnormal communication signals.Firstly,we emulate synthetic abnormal communication signals including seven jamming patterns.Then,we model an abnormal communication signals recognition system based on the communication protocol between the transmitter and the receiver.To improve the performance,we convert the original signal into the time-frequency spectrogram to develop an image classification algorithm.Simulation results demonstrate that the proposed method can effectively recognize the abnormal signals under various parameter configurations,even under low signal-to-noise ratio(SNR)and low jamming-to-signal ratio(JSR)conditions.
基金supported by the National Natural Science Foundation of China under Grant 42474139the Key Research and Development Program of Shaanxi under Grant 2024GX-YBXM-067.
文摘Seismic time-frequency(TF)transforms are essential tools in reservoir interpretation and signal processing,particularly for characterizing frequency variations in non-stationary seismic data.Recently,sparse TF trans-forms,which leverage sparse coding(SC),have gained significant attention in the geosciences due to their ability to achieve high TF resolution.However,the iterative approaches typically employed in sparse TF transforms are computationally intensive,making them impractical for real seismic data analysis.To address this issue,we propose an interpretable convolutional sparse coding(CSC)network to achieve high TF resolution.The proposed model is generated based on the traditional short-time Fourier transform(STFT)transform and a modified UNet,named ULISTANet.In this design,we replace the conventional convolutional layers of the UNet with learnable iterative shrinkage thresholding algorithm(LISTA)blocks,a specialized form of CSC.The LISTA block,which evolves from the traditional iterative shrinkage thresholding algorithm(ISTA),is optimized for extracting sparse features more effectively.Furthermore,we create a synthetic dataset featuring complex frequency-modulated signals to train ULISTANet.Finally,the proposed method’s performance is subsequently validated using both synthetic and field data,demonstrating its potential for enhanced seismic data analysis.
基金supported by the National Natural Science Foundation of China(No.82173947).
文摘Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
基金supported by grants from the National Natural Science Foundation of China(U21A20400,81973789,82004327).
文摘Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.
基金supported by the Shaanxi Qinchuang Yuan“scientist+engineer”team construction(No.2023KXJ-080)Shaanxi Chiral Drug Engineering Technology Research Center(Department of Science and Technology of Shaanxi Province.No.[2011]-251).
文摘Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.
基金financially supported by the National Natural Science Foundation of China(Nos.42277149,41502299,41372306)the Research Planning of Sichuan Education Department,China(No.16ZB0105)+3 种基金the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection Independent Research Project(Nos.SKLGP2016Z007,SKLGP2018Z017,SKLGP2020Z009)Chengdu University of Technology Young and Middle Aged Backbone Program(No.KYGG201720)Sichuan Provincial Science and Technology Department Program(No.19YYJC2087)China Scholarship Council。
文摘To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-decomposition associated with kernel-based-extreme-learningmachine optimized by the whale optimization algorithm(VMD-WOA-KELM)is proposed in this paper.Firstly,the displacement is decomposed by VMD to three IMF components and a residual component of different fluctuation characteristics.The key impact factors of each IMF component are selected according to Copula model,and the corresponding WOA-KELM is established to conduct point prediction.Subsequently,the parametric method(PM)and non-parametric method(NPM)are used to estimate the prediction error probability density distribution(PDF)of each component,whose prediction interval(PI)under the 95%confidence level is also obtained.By means of the differential evolution algorithm(DE),a weighted combination model based on the PIs is built to construct the combination-interval(CI).Finally,the CIs of each component are added to generate the total PI.A comparative case study shows that the CIPM performs better in constructing landslide displacement PI with high performance.
基金supported by grants from the Chinese Academy of Sciences(XDA24010101)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Key Research and Development Program of China(2023YFF1001200)Natural Science Foundation of Zhejiang Province(LD24C130001)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS。
文摘A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that regulates heading date,plant height and grain number.Here,we investigated the relationship between Ghd7 and florigen genes Hd3a and RFT1,to determine their roles in regulating heading date and grain number under different photoperiods.Our results revealed that under long-day(LD)conditions,Hd3a acts prior to RFT1 to promote heading while negatively regulating plant height and grain number.In contrast,Ghd7 positively regulates heading date,plant height,and grain number by inhibiting both Hd3a and RFT1.Under short-day(SD)conditions,the functions of Hd3a and RFT1 remain consistent with those under LD conditions,but Ghd7 does not inhibit their expression,resulting in a weaker phenotypic effect compared to Hd3a.Additionally,under both LD and SD conditions,increased Ghd7 expression enhances its inhibitory effect on Hd3a and RFT1,leading to later heading and increased grain number;however,once the heading date exceeds 94 d,grain number no longer increases.Moreover,the gn1a allele increased grain number by 16.5%to 42.5%,while combinations of the elite alleles from Ghd7,Hd3a,RFT1,and Gn1a significantly increased grain number by up to 240.9%.Therefore,we propose a new breeding strategy to optimize the heading date and grain number using the Ghd7Hd3aRFT1gn1a combination of Ghd7,Hd3a,RFT1,and Gn1a under LD conditions,and the Ghd7hd3aRFT1gn1a combination under SD conditions.This strategy improved the yield of the high-quality Northeast variety Kongyu 131(KY131)by 69.1%in Beijing and 93.7%in Hainan.This strategy will greatly improve the efficiency of north-to-south adaptation in rice,providing theoretical guidance for expanding the geographical adaptability of rice varieties.
基金financially supported by the Key Scientific Research Project of Henan Provincial Universities in 2024(No.24A350013)the Project of Basic Research Fund of Henan Institute of Medical and Pharmaceutical Sciences(No.2024BP0202)+1 种基金the Key Scientific and Technological Project of Henan Province(No.242102311213)the Henan Province Postdoctoral Program(No.343915)。
文摘Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances made in recent years with regard to immunotherapy in both basic research and clinical practice,there remains scope for further improvement,particularly with respect to its efficacy against solid tumors.With advancements in nanotechnology,tumor nanovaccines hold immense potential for preventing tumor recurrence and treating metastatic tumors.Nevertheless,the considerable heterogeneity of tumor immunogenicity presents a number of significant challenges in the development of nanometrescale vaccines targeting solid tumors.Recent findings indicate that immune checkpoint inhibitor(ICI)therapy can improve the immunosuppressive microenvironment within tumors,while nanovaccines can also augment tumor sensitivity toward ICIs.Consequently,combining tumor nanovaccine with ICI therapy holds promise for effectively eradicating tumors or controlling their recurrence and metastasis during cancer treatment.This review delves into the mechanism behind combining tumor nanovaccine with ICI while focusing on factors influencing this combined therapy approach.Moreover,it offers an overview of the current research status regarding the combination of tumor nanovaccines with chemotherapy,radiotherapy,photothermal therapy,and sonodynamic therapy,as well as prospects for future developments in this field.
基金Supported by Natural Science Foundation of Hubei Province,No.2019CFC929.
文摘BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of albumin-bound paclitaxel(nab-ptx)combined with the small molecule vascular endothelial growth factor inhibitor anlotinib in secondline and beyond treatment of AGC.METHODS We collected data from AGC patients at our hospital who experienced disease progression after first-line chemotherapy and received anlotinib combined with nab-ptx.The primary endpoints included overall survival(OS)and progressionfree survival(PFS),while the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and adverse events(AEs).RESULTS Preliminary results indicated that anlotinib combined with nab-ptx can provide significant efficacy in second-line or above treatment for AGC(median PFS=6.0 months,median OS=12.0 months),with an ORR of 42%and a DCR of 78%.Further analysis revealed that patients who experienced hypertension,proteinuria,and hand-foot syndrome during treatment had better efficacy compared to those who did not experience these AEs.Mechanistic studies suggest that this regimen likely exerts synergistic anti-tumor effects by activating the immune response through the reduction of regulatory T-cell proportions.Common adverse reactions included bone marrow suppression,peripheral neuropathy,hypertension,proteinuria,and hand-foot syndrome,which were manageable and resolved with appropriate interventions,indicating the promising application of this regimen in second-line or above treatment for AGC.CONCLUSION The combination of anlotinib and nab-ptx shows promising efficacy with fewer toxicities in AGC treatment.The regimen holds promise as a second-line treatment of AGC;however,its specific clinical value requires further research.
基金Supported by National Natural Science Foundation of China,No.32270768,No.82273970,No.32070726 and No.82370715Hubei Natural Science Foundation of China,No.2024AFB218+1 种基金National Key R&D Program of China,No.2023YFC2507904Doctoral Startup Foundation of Hubei University of Technology,No.XJ2022003901.
文摘Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.However,emerging evidence indicates that unintended pro-metastatic effects may offset the therapeutic benefits of HDACis.Chen et al elucidate this paradox,demonstrating that TSA-induced hyperacetylation activates the BRD4/c-Myc/ER-stress axis,thereby promoting epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma(ESCC).Furthermore,they clarify the clinical significance of histone acetylation in the prognostic evaluation of ESCC.Their findings underscore the complexity of epigenetic therapies and highlight the necessity of reevaluating the associated risks and combinatorial therapeutic strategies with HDACi-based treatments.Here,we summarize the potential risks of HDACis therapy and discuss feasible combination therapeutic strategies.
基金Supported by the National Natural Science Foundation of China,No.82072732.
文摘BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain limited.AIM To examine the predictive value of endoscopic findings of primary tumors for responses to neoadjuvant immunotherapy.METHODS This retrospective study,conducted at a tertiary center in China,evaluated 74 patients with colorectal cancer,including 17 with deficient mismatch repair(dMMR)and 15 with proficient mismatch repair(pMMR)tumors.Patients underwent neoadjuvant immunotherapy followed by surgery.Endoscopic findings before and after neoadjuvant immunotherapy were reviewed and compared with the pathology of the resected specimens.RESULTS In the pMMR group(n=57 evaluable patients),endoscopy identified 11/17 patients who achieved a complete response(CR),while misidentifying 1/40 patients with residual disease as CR(64.7%vs 2.5%,P<0.01).Conversely,22/40 patients with residual disease were accurately identified as achieving a partial response(PR),with 1/17 patients who achieved CR misclassified as PR(55.0%vs 5.9%,P<0.01).The sensitivity,specificity,and accuracy of endoscopic diagnosis for pathological CR were 64.7%,97.5%,and 87.7%,respectively.In the dMMR cohort,endoscopy classified 9/17 patients as CR and 2 of the remaining patients with residual tumors as PR(64.3%vs 66.7%,P=0.73).The method demonstrated 100%sensitivity and 82.4%accuracy in diagnosing pathological CR.CONCLUSION Endoscopic evidence of CR or PR was well correlated with postoperative pathological outcomes in the pMMR cohort.Despite endoscopic indications of tumor residue,a complete pathological response post-surgery was possible in the dMMR cohort.
基金supported by the National Natural Science Foundation of China(No.52274026)the National Key Research and Development Program(No.2022YFC2806504)the CNOOC Research Project(No.KJGG-2022-17-04 and NO.KJGG-2022-17-05).
文摘Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,and based onμ-CT three-dimensional reconstruction imaging and finite element analysis(FEA)techniques,the stress distribution and potential failure mechanism at the cement-sandstone bonding interface under axial loading were analyzed.The key findings are as follows:(1)stress concentrations are highly likely to form at the gap between the cement and sandstone interface and around interfacial voids,with Von Mises stress reaching critical levels of 18.0-20.0 MPa at these locations,significantly exceeding the stress magnitudes in well-bonded regions;(2)the phenomenon of local stress concentration driven by interfacial defects can be identified as the main basis for predicting damage location in interfacial debonding and continuous shear under axial load;(3)ensuring tight cementation at the cement-sandstone interface and minimizing interfacial voids are paramount for preventing stress-induced failure;(4)the critical Von Mises stress value of 20 MPa at the interface defect can be used as a benchmark for material selection and designed to ensure long-term integrity in oil and gas well applications subjected to similar axial loads.These findings contribute to a more accurate understanding of the failure mechanism of the cement-sandstone interface and to the precise design of material properties,thereby ensuring the long-term integrity of oil and gas well applications subjected to similar axial loads.
基金supported by National Science Foundations of China(Grant No.11771340,12171373).
文摘Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference is compact on the weighted Bergman space in the unit disk.Motivated by the subtle connection of composition operator theory on the weighted Bergman spaces,Korenblum spaces and bounded holomorphic function spaces,we first explore the rigid phenomenon which also holds on the Korenblum space over the unit ball.Furthermore,we discuss which difference of composition operators is compact when the compact combination of composition operators does not satisfy the condition(CNC)on Korenblum spaces and bounded holomorphic function spaces over the unit ball setting.
基金Financial support from the National Natural Science Foundation of China(Grant No.52374119)the Province Education Department of Liaoning(Grant No.LJ212410146068)the opening fund of State Key Laboratory of Performance Monitoring and Protecting of Rail Transit Infrastructure,East China Jiaotong University(Grant No.HJGZ2023103).
文摘Understanding the mechanical properties of coal-rock-bolt(CRB)combinations at high strain rates and the anchoring mechanism of bolts is crucial for ensuring the safety of coal mining operations.However,the dynamic behaviors of these combinations,especially the mechanism of action of prestressed bolts,still need to be further investigated.This study carried out split Hopkinson pressure bar(SHPB)tests on three sets of coal-rock(CR),CRB,and coal-rock-prestressed bolt(CRPB)combinations with different interface angles(β=15°,30°,45°,and 60°).The dynamic properties of the combinations were analyzed based on the stress-strain curve,energy dissipation,dynamic strength,fractal dimension of cracks,and failure mode of bolts.The test results show that a larger β will affect the stress transfer and anti-sliding ability of CR,resulting in a decrease in CR strength.The anchoring force of the bolt effectively suppresses the slip feature of CRB at the yield stage.As the strain rate increases,CRB shows a more pronounced'sudden increase'in strength,and the bolt significantly enhances its dynamic strength.The prestressed bolts enhance the dynamic strength of CRPB while weaken the effect of β.The fractal dimension of the macrocracks increases with strain rate,with smaller variations in CRB and CRPB,indicating that the bolt reduces the complexity degree of CRB and CRPB.The anchoring force of CRB depends on bolt strength,which reduces the slip along the interface.The anchoring force of CRPB balances the coal-rock slip and suppresses crack formation,resulting in a more cohesive response under dynamic load.
基金Supported by the Natural Science Research Project of Anhui Province,No.2023AH053172National Natural Science Foundation of Anhui Province,No.2408085QH260+1 种基金Projects of Administration of Traditional Chinese Medicine of Anhui Province,No.2024CCCX082National Natural Science Foundation Incubation Program of The Second Hospital of Anhui Medical University,No.2022GMFY08.
文摘Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,thus contributing to the development of vascular disorders,especially atherosclerotic diseases.Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis.It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes(T2DM)complicated with atherosclerotic diseases.Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor,which could offer additional vascular benefits and reduce the risk of atherosclerotic complications.Likewise,combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia,whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits.Moreover,co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies.For instance,a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications.However,these potential benefits remain need validation by the evidence from clinical studies.Despite the limitations,such as heterogeneity across different patient populations,and deficiency in long-term outcomes,such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.
基金supported by the China National Railway Group Co.,Ltd.Research and Development Project(P2023T002).
文摘Purpose–To systematically characterize and objectively evaluate basic railway safety management capability,creating a closed-loop management approach which allows continuous improvement and optimization.Design/methodology/approach–A basic railway safety management capability evaluation index system based on a comprehensive analysis of national safety management standards,railway safety rules and regulations and existing safety data from railway transport enterprises is presented.The system comprises a guideline layer including safety committee formation,work safety responsibility,safety management organization and safety rules and regulations as its components,along with an index layer consisting of 12 quantifiable indexes.Game theory combination weighting is utilized to integrate subjective and objective weight values derived using AHP and CRITIC methods and further combined using the TOPSIS method in order to construct a comprehensive basic railway safety management capability evaluation model.Findings–The case study presented demonstrates that this evaluation index system and comprehensive evaluation model are capable of effectively characterizing and evaluating basic railway safety management capability and providing directional guidance for its sustained improvement.Originality/value–Construction of an evaluation index system that is quantifiable,generalizable and accessible,accurately reflects the main aspects of railway transportation enterprises’basic safety management capability and provides interoperability across various railway transportation enterprises.The application of the game theoretic combination weighting method to derive composite weights which combine experts’subjective evaluations with the objectivity of data.
基金Natural Science Foundation of Henan Province,Grant/Award Number:232300420331Open Research Fund of Key Laboratory of Safety and High-efficiency Coal Mining,Ministry of Education,Grant/Award Number:JYBSYS202303+4 种基金National Natural Science Foundation of China,Grant/Award Numbers:52130409,52374249Innovation Training Program for College Students,Grant/Award Number:202312026National Key Research and Development Program of China,Grant/Award Number:2023YFC3009003Open Research Fund of Key Laboratory of Xinjiang Coal Resources Green Mining,Ministry of Education,Grant/Award Number:KLXGY-KB2421Fundamental Research Funds for the Central Universities,Grant/Award Number:2024JCCXAQ01。
文摘The essence of the outburst-rock burst compound dynamic disaster is the disaster behavior of the"gas-coal-surrounding rock"system under the comprehensive action of the stress field and the seepage field.Based on the geological occurrence characteristics of coal and rock in the roof,coal,and floor,this study combinedexperimental research and theoretical analysis to explore the effects of confining pressure,gas pressure,and axial loading rate on the mechanical behavior of gasbearing rock-coal-rock combination structures("RCR combination").The results show that both decreasing gas pressure and increasing confining pressure can improve the deformation capacity and bearing capacity of the RCR combination.When the gas pressure decreases from 1.5 to 0.5 MPa and the confining pressure increases from 3 to 9 MPa,the peak stress of the RCR combination increases by 15.83% and 184.02%,respectively.On increasing the axial loading rate,the peak stress of the RCR combination first increases and then decreases,and the elastic modulus continues to decrease.There is a good correspondence between stress and acoustic emission counts(AE),which can be used as a predictive index for judging rock fracture instability.Compared with rock,coal exerts much greater influence on the mechanical strength of the RCR combination.The theoretical analysis shows that the parameters m and F_0 mainly affect the peak stress of the RCR combination,and the speed of stress reduction after the peak of the RCR combination is influenced by the parameter m.The coal elastic modulus exerts greater influence on the bearing capacity of the RCR combination than the rock elastic modulus.When the elastic modulus of rocks increases from 10 to 25 GPa and that of coal increases from 2 to 5 GPa,the peak stress of the RCR combination increases by 9.87% and 8.97%,respectively.
基金Supported by Natural Science Foundation of Henan Province,No.242300421286the research and practice project of higher education reform in Henan Province,No.2023SJGLX124Ythe research and practice project of higher education reform of Zhengzhou University,No.2023ZZUJGXM114.
文摘BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immunotherapy and other therapeutic methods have provided new treatment options for middle and advanced HCC(aHCC).Predicting the effect of targeted combined immunotherapy has become a hot topic in current research.AIM To explore the relationship between nodule enhancement in hepatobiliary phase and the efficacy of combined targeted immunotherapy for aHCC.METHODS Data from 56 patients with aHCC for magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid were retrospectively collected.Signal intensity of intrahepatic nodules was measured,and the hepatobiliary relative enhancement ratio(RER)was calculated.Progression-free survival(PFS)of patients with high and low reinforcement of HCC nodules was compared.The model was validated using receiver operating characteristic curves.Univariate and multivariate logistic regression and Kaplan-Meier analysis were performed to explore factors influencing the efficacy of targeted immunization and PFS.RESULTS Univariate and multivariate analyses revealed that the RER,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and prognostic nutritional index were significantly associated with the efficacy of tyrosine kinase inhibitors combined with immunotherapy(P<0.05).The area under the curve of the RER for predicting the efficacy of tyrosine kinase inhibitors combined with anti-programmed death 1 antibody in patients with aHCC was 0.876(95%confidence interval:0.781-0.971,P<0.05),the optimal cutoff value was 0.904,diagnostic sensitivity was 87.5%,and specificity was 79.2%.Kaplan-Meier analysis showed that neutrophil-to-lymphocyte ratio<5,plateletto-lymphocyte ratio<300,prognostic nutritional index<45,and RER<0.9 significantly improved PFS.CONCLUSION AHCC nodules enhancement in the hepatobiliary stage was significantly correlated with PFS.Imaging information and immunological indicators had high predictive efficacy for targeted combined immunotherapy and were associated with PFS.
