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
Arrhythmias are a frequently occurring phenomenon in clinical practice,but how to accurately dis-tinguish subtle rhythm abnormalities remains an ongoing difficulty faced by the entire research community when conductin...Arrhythmias are a frequently occurring phenomenon in clinical practice,but how to accurately dis-tinguish subtle rhythm abnormalities remains an ongoing difficulty faced by the entire research community when conducting ECG-based studies.From a review of existing studies,two main factors appear to contribute to this problem:the uneven distribution of arrhythmia classes and the limited expressiveness of features learned by current models.To overcome these limitations,this study proposes a dual-path multimodal framework,termed DM-EHC(Dual-Path Multimodal ECG Heartbeat Classifier),for ECG-based heartbeat classification.The proposed framework links 1D ECG temporal features with 2D time–frequency features.By setting up the dual paths described above,the model can process more dimensions of feature information.The MIT-BIH arrhythmia database was selected as the baseline dataset for the experiments.Experimental results show that the proposed method outperforms single modalities and performs better for certain specific types of arrhythmias.The model achieved mean precision,recall,and F1 score of 95.14%,92.26%,and 93.65%,respectively.These results indicate that the framework is robust and has potential value in automated arrhythmia classification.展开更多
Fault features in mechanical systems often manifest as transient impulses,which can be effectively analyzed using time-frequency analysis(TFA)methods.Recently,a new TFA technique known as the time-reassigned multi-syn...Fault features in mechanical systems often manifest as transient impulses,which can be effectively analyzed using time-frequency analysis(TFA)methods.Recently,a new TFA technique known as the time-reassigned multi-synchrosqueezing transform(TMssT)was proposed to capture these transient impulses for fault diagnosis.However,the TMSST,which is based on the short-time Fourier transform(STFT),suffers from unclear high-frequency re-presentations owing to the fixed sliding window used in the STFT.To address this limitation,the current study combined TMSST with the S-transform and a local maximum method to enhance the time-frequency representation for improved signal analysis.Furthermore,an extractive reconstruction algorithm that binds the maximum value of the spectral envelope is proposed for spectral decomposition.To validate the proposed technique,a simulated noise-added signal and four experimental bearing defect datasets were used.The results demonstrate that the proposed technique can effectively and accurately extract fault features from bearing signals regardless of whether the bearings operate under constant or varying speed conditions.This study offers a novel and efficient approach for fault diagnosis in mechanical systems with complex dynamic behaviors.展开更多
The state-of-the-art optical atomic clocks and the time-frequency signal transmission open a fresh field for gravity potential(geopotential)determination.Various methods,including optical fiber frequency transfer,sate...The state-of-the-art optical atomic clocks and the time-frequency signal transmission open a fresh field for gravity potential(geopotential)determination.Various methods,including optical fiber frequency transfer,satellite two-way,satellite common-view,satellite carrier phase,VLBI,tri-frequency combination,and dual-frequency combination,were developed to determine the geopotential differences using optical atomic clocks and then determine the geopotential at station B based on the geopotential at station A.This review elaborates the principles,methods,scientific objectives,applications,and relevant research trends of geopotential determination based on time-frequency signals.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
Urban forests are highly multifunctional and provide numerous ecological functions.Plant functional traits individually or jointly influence the ecological multifunctionality of tree species(TS-EMF)and can also modify...Urban forests are highly multifunctional and provide numerous ecological functions.Plant functional traits individually or jointly influence the ecological multifunctionality of tree species(TS-EMF)and can also modify TSEMF in response to environmental changes.However,there has been limited exploration of multitrait combinations for predicting TS-EMF across seasons and of trait thresholds that enhance TS-EMF.Here,for 10 dominant tree species in urban forests of Northeast China,14 traits were measured and four aboveground and three belowground ecological functions assessed in three seasons.Ecological functions and TS-EMF differed significantly throughout the seasons(P<0.05).Synergistic relationships were found between carbon sequestration and oxygen release,between cooling and humidification,and between organic carbon accumulation and nutrient cycling.Notably,aboveground multifunctionality played a leading role in TS-EMF.With seasonal changes,resource allocation shifted toward traits related to resource acquisition rather than conservation to maintain TS-EMF.The combination of traits that predicted TS-EMF varied by type,accounting for up to 66.45%of the variation.TS-EMF was primarily driven by leaf structure in spring and by nutrient accumulation in autumn.Leaf carbon content(LCC)consistently served as a stabilizing factor for predicting TS-EMF across seasons.At 36.5-36.8 mg g^(-1),LCC had its optimal effect on TS-EMF.Other traits in combination that positively influence total TS-EMF include leaf nitrogen content(3.43-3.45 mg g^(-1)),leaf phosphorus content(0.80-0.83 mg g^(-1)),and leaf area(65.86-68.43 cm^(2)).Within these specified trait thresholds,Morus alba and Quercus mongolica were identified as key species.These findings suggest that the trade-off between various ecological functions can be managed by altering plant traits across seasons.This approach could provide a theoretical foundation for enhancing the TS-EMF of urban forests through trait-based management,offering practical guidance for selecting tree species.展开更多
The aim of this paper is to present a new method for flight flutter modal parameter identification in noisy environment. This method employs a time-frequency （TF） filter to reduce the noise before identification, wh...The aim of this paper is to present a new method for flight flutter modal parameter identification in noisy environment. This method employs a time-frequency （TF） filter to reduce the noise before identification, which depends on the localization property of sweep excitation in TF domain. Then, a generalized total least square （GTLS） identification algorithm based on stochastic framework is applied to the enhanced data. System identification with noisy data is transformed into a generalized total least square problem, and the solution is carried out by the generalized singular value decomposition （GSVD） to avoid the intensive nonlinear optimization computation. A nearly maximum likelihood property can be achieved by ＇optimally＇ weighted generalized total least square. Finally, the efficiency of the method is illustrated by means of flight test data.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
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
Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergist...Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergistic drug combination discovery,their applications remain constrained by experimental data fragmentation,high costs,and extensive combinatorial space.Recent developments in artificial intelligence(AI),encompassing traditional machine learning and deep learning algorithms,have been extensively applied in NPDC identification.Through the integration of multi-source heterogeneous data and autonomous feature extraction,prediction accuracy has markedly improved,offering a robust technical approach for novel NPDC discovery.This review comprehensively examines recent advances in AI-driven NPDC prediction,presents relevant data resources and algorithmic frameworks,and evaluates current limitations and future prospects.AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.展开更多
The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated t...The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated to reveal the main controlling factors of shale oil occurrence under different lamina combinations.The differential enrichment mechanisms and patterns of shale oil were discussed using the shale oil micro-migration characterization and evaluation methods from the perspectives of relay hydrocarbon supply,stepwise migration,and multi-stage differentiation.The results are obtained in five aspects.First,Chang 73 shale mainly develops five types of lamina combination,i.e.non-laminated shale,sandy laminated shale,tuffaceous laminated shale,mixed laminated shale,and organic-rich laminated shale.Second,shales with different lamina combinations are obviously different in the reservoir space.Specifically,shales with sandy laminae and tuffaceous laminae have a large number of intergranular pores,dissolution pores and hydrocarbon generation-induced fractures.The multi-scale pore and fracture system constitutes the main place for liquid hydrocarbon occurrence.Third,the occurrence and distribution of shale oil in shale with different lamina combinations are jointly controlled by organic matter abundance,reservoir property,thermal evolution degree,mineral composition and laminae scale.The micro-nano-scale pore-fracture networks within shales containing rigid laminae,particularly sandy and tuffaceous laminations,primarily contain free-state light hydrocarbon components.In contrast,adsorption-phase heavy hydrocarbon components predominantly occupy surfaces of organic matter assemblages,clay mineral matrices,and framework mineral particulates.Fourth,there is obvious shale oil micro-migration between shales with different lamina combinations in Chang 73.Generally,such micro-migration is stepwise in a sequence of organic-rich laminated shale→tuffaceous laminated shale→mixed laminated shale→sandy lamiated shale→non-laminated shale.Fifth,the relay hydrocarbon supply of organic matter under the control of the spatial superposition of shales with various laminae,the stepwise migration via multi-scale pore and fracture network,and the multi-differentiation in shales with different lamina combinations under the control of organic-inorganic interactions fundamentally decide the differences of shale oil components between shales with different lamina combinations.展开更多
Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are expose...Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are exposed to ultrasound (US) irradiation. Methods: The combined time-frequency analysis was applied to the original signals instead of the traditional Fourier spectral analysis technique. Results: The results obtained from simulation as well as experiment showed that the subharmonic, 2nd harmonic and ultra harmonic of the microbubbles occurred during the oscillation and varied with time. The dependence on the incident ultrasonic amplitude and microbubble parameters were established. Conclusion: The transient echoes backscattered from the ultrasound agent in the evaluation of the blood perfusion can be analyzed thoroughly by the technique of combined-frequency analysis and the time detail of the frequency contents can be revealed.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
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
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
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
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
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
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
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supported by the Innovative Human Resource Development for Local Intel-lectualization program through the Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korea government(MSIT)(No.IITP-2026-2020-0-01741)the research fund of Hanyang University(HY-2025-1110).
文摘Arrhythmias are a frequently occurring phenomenon in clinical practice,but how to accurately dis-tinguish subtle rhythm abnormalities remains an ongoing difficulty faced by the entire research community when conducting ECG-based studies.From a review of existing studies,two main factors appear to contribute to this problem:the uneven distribution of arrhythmia classes and the limited expressiveness of features learned by current models.To overcome these limitations,this study proposes a dual-path multimodal framework,termed DM-EHC(Dual-Path Multimodal ECG Heartbeat Classifier),for ECG-based heartbeat classification.The proposed framework links 1D ECG temporal features with 2D time–frequency features.By setting up the dual paths described above,the model can process more dimensions of feature information.The MIT-BIH arrhythmia database was selected as the baseline dataset for the experiments.Experimental results show that the proposed method outperforms single modalities and performs better for certain specific types of arrhythmias.The model achieved mean precision,recall,and F1 score of 95.14%,92.26%,and 93.65%,respectively.These results indicate that the framework is robust and has potential value in automated arrhythmia classification.
基金Supported by National Natural Science Foundation of China(Grant No.62271230)Shandong Provincial Central Guidance on Local Science and Technology Development Fund(Grant No.YDZX2022178).
文摘Fault features in mechanical systems often manifest as transient impulses,which can be effectively analyzed using time-frequency analysis(TFA)methods.Recently,a new TFA technique known as the time-reassigned multi-synchrosqueezing transform(TMssT)was proposed to capture these transient impulses for fault diagnosis.However,the TMSST,which is based on the short-time Fourier transform(STFT),suffers from unclear high-frequency re-presentations owing to the fixed sliding window used in the STFT.To address this limitation,the current study combined TMSST with the S-transform and a local maximum method to enhance the time-frequency representation for improved signal analysis.Furthermore,an extractive reconstruction algorithm that binds the maximum value of the spectral envelope is proposed for spectral decomposition.To validate the proposed technique,a simulated noise-added signal and four experimental bearing defect datasets were used.The results demonstrate that the proposed technique can effectively and accurately extract fault features from bearing signals regardless of whether the bearings operate under constant or varying speed conditions.This study offers a novel and efficient approach for fault diagnosis in mechanical systems with complex dynamic behaviors.
基金National Natural Science Foundation of China(Grant Nos.42388102,42030105,42192535)the Open Fund of State Key Laboratory of Precision Geodesy,Innovation Academy for Precision Measurement Science and Technology,Chinese Academy of Sciences(Grant No.SKLPG2025-1-5)。
文摘The state-of-the-art optical atomic clocks and the time-frequency signal transmission open a fresh field for gravity potential(geopotential)determination.Various methods,including optical fiber frequency transfer,satellite two-way,satellite common-view,satellite carrier phase,VLBI,tri-frequency combination,and dual-frequency combination,were developed to determine the geopotential differences using optical atomic clocks and then determine the geopotential at station B based on the geopotential at station A.This review elaborates the principles,methods,scientific objectives,applications,and relevant research trends of geopotential determination based on time-frequency signals.
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supported by the National Natural Science Foundation(32130068,32271634,and 32071597)CAS Key Laboratory of Forest Ecology and Silviculture,Institute of Applied Ecology,Chinese Academy of Sciences(KLFES-2025)。
文摘Urban forests are highly multifunctional and provide numerous ecological functions.Plant functional traits individually or jointly influence the ecological multifunctionality of tree species(TS-EMF)and can also modify TSEMF in response to environmental changes.However,there has been limited exploration of multitrait combinations for predicting TS-EMF across seasons and of trait thresholds that enhance TS-EMF.Here,for 10 dominant tree species in urban forests of Northeast China,14 traits were measured and four aboveground and three belowground ecological functions assessed in three seasons.Ecological functions and TS-EMF differed significantly throughout the seasons(P<0.05).Synergistic relationships were found between carbon sequestration and oxygen release,between cooling and humidification,and between organic carbon accumulation and nutrient cycling.Notably,aboveground multifunctionality played a leading role in TS-EMF.With seasonal changes,resource allocation shifted toward traits related to resource acquisition rather than conservation to maintain TS-EMF.The combination of traits that predicted TS-EMF varied by type,accounting for up to 66.45%of the variation.TS-EMF was primarily driven by leaf structure in spring and by nutrient accumulation in autumn.Leaf carbon content(LCC)consistently served as a stabilizing factor for predicting TS-EMF across seasons.At 36.5-36.8 mg g^(-1),LCC had its optimal effect on TS-EMF.Other traits in combination that positively influence total TS-EMF include leaf nitrogen content(3.43-3.45 mg g^(-1)),leaf phosphorus content(0.80-0.83 mg g^(-1)),and leaf area(65.86-68.43 cm^(2)).Within these specified trait thresholds,Morus alba and Quercus mongolica were identified as key species.These findings suggest that the trade-off between various ecological functions can be managed by altering plant traits across seasons.This approach could provide a theoretical foundation for enhancing the TS-EMF of urban forests through trait-based management,offering practical guidance for selecting tree species.
文摘The aim of this paper is to present a new method for flight flutter modal parameter identification in noisy environment. This method employs a time-frequency （TF） filter to reduce the noise before identification, which depends on the localization property of sweep excitation in TF domain. Then, a generalized total least square （GTLS） identification algorithm based on stochastic framework is applied to the enhanced data. System identification with noisy data is transformed into a generalized total least square problem, and the solution is carried out by the generalized singular value decomposition （GSVD） to avoid the intensive nonlinear optimization computation. A nearly maximum likelihood property can be achieved by ＇optimally＇ weighted generalized total least square. Finally, the efficiency of the method is illustrated by means of flight test data.
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 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supported by National Natural Science Foundation of China(Nos.82404511,82373790)Central Guidance on Local Science and Technology Development Fund of Hebei Province(No.226Z2605G)Program for Young Scientists in the Field of Natural Science of Hebei Medical University(No.CYCZ2023011).
文摘Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergistic drug combination discovery,their applications remain constrained by experimental data fragmentation,high costs,and extensive combinatorial space.Recent developments in artificial intelligence(AI),encompassing traditional machine learning and deep learning algorithms,have been extensively applied in NPDC identification.Through the integration of multi-source heterogeneous data and autonomous feature extraction,prediction accuracy has markedly improved,offering a robust technical approach for novel NPDC discovery.This review comprehensively examines recent advances in AI-driven NPDC prediction,presents relevant data resources and algorithmic frameworks,and evaluates current limitations and future prospects.AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
基金Supported by the National Natural Science Foundation of China(42302184)Innovation Group Project of Basic Research in Gansu Province,China(22JR5RA045)。
文摘The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated to reveal the main controlling factors of shale oil occurrence under different lamina combinations.The differential enrichment mechanisms and patterns of shale oil were discussed using the shale oil micro-migration characterization and evaluation methods from the perspectives of relay hydrocarbon supply,stepwise migration,and multi-stage differentiation.The results are obtained in five aspects.First,Chang 73 shale mainly develops five types of lamina combination,i.e.non-laminated shale,sandy laminated shale,tuffaceous laminated shale,mixed laminated shale,and organic-rich laminated shale.Second,shales with different lamina combinations are obviously different in the reservoir space.Specifically,shales with sandy laminae and tuffaceous laminae have a large number of intergranular pores,dissolution pores and hydrocarbon generation-induced fractures.The multi-scale pore and fracture system constitutes the main place for liquid hydrocarbon occurrence.Third,the occurrence and distribution of shale oil in shale with different lamina combinations are jointly controlled by organic matter abundance,reservoir property,thermal evolution degree,mineral composition and laminae scale.The micro-nano-scale pore-fracture networks within shales containing rigid laminae,particularly sandy and tuffaceous laminations,primarily contain free-state light hydrocarbon components.In contrast,adsorption-phase heavy hydrocarbon components predominantly occupy surfaces of organic matter assemblages,clay mineral matrices,and framework mineral particulates.Fourth,there is obvious shale oil micro-migration between shales with different lamina combinations in Chang 73.Generally,such micro-migration is stepwise in a sequence of organic-rich laminated shale→tuffaceous laminated shale→mixed laminated shale→sandy lamiated shale→non-laminated shale.Fifth,the relay hydrocarbon supply of organic matter under the control of the spatial superposition of shales with various laminae,the stepwise migration via multi-scale pore and fracture network,and the multi-differentiation in shales with different lamina combinations under the control of organic-inorganic interactions fundamentally decide the differences of shale oil components between shales with different lamina combinations.
文摘Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are exposed to ultrasound (US) irradiation. Methods: The combined time-frequency analysis was applied to the original signals instead of the traditional Fourier spectral analysis technique. Results: The results obtained from simulation as well as experiment showed that the subharmonic, 2nd harmonic and ultra harmonic of the microbubbles occurred during the oscillation and varied with time. The dependence on the incident ultrasonic amplitude and microbubble parameters were established. Conclusion: The transient echoes backscattered from the ultrasound agent in the evaluation of the blood perfusion can be analyzed thoroughly by the technique of combined-frequency analysis and the time detail of the frequency contents can be revealed.
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(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 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 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 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.
