Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none o...Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.展开更多
BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erl...BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.展开更多
To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior in...To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior information with other sensor information in the form of constraints.Firstly,the train precise track constraint method of the train is proposed,and the plane position constraint and train motion state constraints are analysed.A model for combining prior information with constraints is established.Then an adaptive H∞filter with combination constraints is derived based on the adaptive adjustment method of the robustness factor.Finally,the positioning effect of the proposed algorithm is simulated and analysed under the conditions of a straight track and a curved track.The results show that the positioning accuracy of the algorithm with constrained filtering is significantly better than that of the algorithm without constrained filtering and that the algorithm with constrained filtering can achieve better performance when combined with track and condition information,which can significantly reduce the train positioning error.The effectiveness of the proposed algorithm is verified.展开更多
The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarr...The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.展开更多
Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered ...Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered combination kit, containing 2 g secnidazole, 1 g azithromycin and 150 mg fluconazole (Azimyn FS Kit), has been successfully evaluated in clinical trials and used in several countries for management syndromic vaginal discharge due to infections. Methods: This is a longitudinal study which aimed to verify the clinical efficacy of the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit<sup><sup>®</sup></sup>) in the syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultations in Kinshasa/DR Congo from March to September 2023. Results: Majority of patients had whitish vaginal discharge (51.6%) of average abundance (56.2%), accompanied by pruritus in 72.1% of cases, and dyspareunia in 23.5% of cases and hypogastralgia in 40.2% of cases. One week after treatment with the Azimyn FS<sup><sup>®</sup></sup> combined kit, at the greatest majority of patients (97.3%), abnormal vaginal discharge had decreased by more than 50% (84.1%). Two weeks after treatment with the Azimyn FS<sup><sup>®</sup></sup> combined kit, almost all patients (97.3%) no longer had abnormal vaginal discharge which had completely disappeared. Conclusion: A single dose of secnidazole, azithromycin and fluconazole in the form of an oral combi-kit (Azimyn FS Kit) has shown excellent therapeutic effectiveness in the syndromic treatment of abnormal vaginal discharge wherein patients were treated without diagnostic confirmation.展开更多
Background:Small cell lung cancer(SCLC)is an aggressive malignant tumor with strong immunosuppressive effects,characterized by rapid doubling time and poor prognosis.Currently,effective therapeutic options are urgentl...Background:Small cell lung cancer(SCLC)is an aggressive malignant tumor with strong immunosuppressive effects,characterized by rapid doubling time and poor prognosis.Currently,effective therapeutic options are urgently needed for Extensive-stage small-cell lung Cancer.Case description:In the present case,a combination therapy of anlotinib,envolizumab,and etoposide was administered to treat an 80-year-old female patient with extensive-stage SCLC accompanied by mediastinal lymph node and bone metastasis.After two cycles of treatment,the tumor lesions in the right lungs decreased from 5.04*3.44 cm to 1.65*1.42 cm.As of now,no significant mass is seen there and no serious adverse reactions in this patient.Until September 2023,she has survived for 18 months with no disease progression.Conclusions:Research shows that Alectinib,in combination with evolocumab plus etoposide,could be an original,viable therapeutic option for the treatment option of patients with extensive-stage SCLC.展开更多
Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the...Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.展开更多
Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contr...Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.展开更多
In this study, lambda-cyhalothrin(LC) loaded polyurea microcapsules(MCs) with different particle sizes were fabricated.All of the MCs showed varying degrees of physical collapse, which was more obvious among those wit...In this study, lambda-cyhalothrin(LC) loaded polyurea microcapsules(MCs) with different particle sizes were fabricated.All of the MCs showed varying degrees of physical collapse, which was more obvious among those with smaller particle sizes. MCs with particle sizes of 1.38 μm(MC-S), 5.13 μm(MC-M) and 10.05 μm(MC-L) had shell thicknesses of 39.6,50.3 and 150.1 nm, respectively. MCs with smaller particles tended to have significantly faster release profiles, and the MC-S group had much higher bioactivity against Agrotis ipsilon and better foliar affinity on the peanut leaves(indicated by rainfastness) than MC-M and MC-L. All of the MCs exhibited light-enhanced release profiles and had much slower degradation compared with the emulsifiable concentrate(EC) group, among which MC-L had the slowest degradation.To generate MCs with both favorable quick efficacy and long-lasting efficacy, binary mixtures of MC-S, MC-M and MC-L were produced by mixing them in pairs at ratios of 2:1, 1:1 and 1:2. The mixture of MC-S:MC-L at 1:2 showed the best comprehensive efficacy in the peanut foliar spray scenario among the nine tested combinations, and its effective duration was three times longer than that of EC. Overall, the precise combination of MCs with different particle sizes can regulate the efficacy of pesticide control and serve as a strategy for the better utilization of pesticides.展开更多
Recovery of the coal buried under buildings,railways and water bodies and the residual coal in irregularly arranged fully mechanized mining faces is a common engineering problem facing underground coal mining.In this ...Recovery of the coal buried under buildings,railways and water bodies and the residual coal in irregularly arranged fully mechanized mining faces is a common engineering problem facing underground coal mining.In this study,a mining technology of continuous driving and gangue backfilling(CDGB)was proposed.The technology,which can not only alleviate ground subsidence and gangue discharge,but also release the above-mentioned coals,contributes to green and efficient sustainable development of mining.The stability of the system of the solidified body-reserved coal pillar combination(S-C combination)is crucial to the CDGB technology.Therefore,it is of great significance to explore the mechanical and damage characteristics of S-C combination in the synergistic bearing process.First,four sets of differentshaped S-C combination specimens were fabricated and a S-C combination bearing structure in CDGB was constructed to explore the differences in mechanical characteristics and damage modes of different-shaped S-C combination specimens during CDGB.Subsequently,their surface strain field evolutions and acoustic emission(AE)response characteristics in the load-bearing process were obtained with the aid of the digital image correlation technique and the AE signal monitoring system.Furthermore,a damage evolution model based on AE parameters and mechanical parameters was established to clarify the damage evolution law.The following results were obtained:(1)The free area of S-C combination can serve as a quantitative index to evaluate the stability of the overburden control system;(2)The concept of critical value k of the free area was first proposed.When the free area exceeds the critical value k(free area ratio greater than 1.13),the deformation resistance and the free area changes becomes negatively correlated;(3)As the free area expands,the failure of the S-C combination specimen evolves from tensile failure to shear failure.The distribution characteristics of the axial strain field also verified such a change in the failure mode;(4)When the free area expands,the peak AE count gradually changes from“double peaks”to“a single peak”.In this process,the expansion of free area shortens the time for accumulating and releasing energy during loading.Micro cracks generated in the specimen change from a phased steep growth to a continuous increase,and the process in which micro cracks develop,converge,intersect and connect to form macro cracks accelerates.The damage evolution law concluded based on AE parameters and mechanical parameters can well characterize the damage evolution process of S-C combination,providing certain reference for the study on the synergistic bearing of S-C combination during CDGB.展开更多
The electromagnetic time-reversal(TR)technique has the characteristics of spatiotemporal focusing in a time-reversal cavity(TRC),which can be used for pulse compression,thus forming an electromagnetic pulse with high ...The electromagnetic time-reversal(TR)technique has the characteristics of spatiotemporal focusing in a time-reversal cavity(TRC),which can be used for pulse compression,thus forming an electromagnetic pulse with high peak power.A time-reversed pulse-compression method in a single channel has high pulse compression gain.However,single channel pulse compression can only generate limited gain.This paper proposes a novel TR power-combination method in a multichannel TRC to obtain higher peak power based on TR pulse-compression theory.First,the TR power-combination model is given,and the crosstalk properties of the associated channel and the influence of the reversal performance are studied.Then,the power-combination performances for the TR pulse compression,such as combined signal to noise ratio(SNR)and combined compression gain,are analyzed by numerical simulation and experimental methods.The results show that the proposed method has obvious advantages over pulse-compression methods using a single channel cavity,and is more convenient for power combination.展开更多
Objective:To investigate the potential activity of novel herbal combination and novel herbal formulation(syrup)in female Sprague Dawley rats with letrozole-induced polycystic ovary syndrome(PCOS).Methods:Forty-two rat...Objective:To investigate the potential activity of novel herbal combination and novel herbal formulation(syrup)in female Sprague Dawley rats with letrozole-induced polycystic ovary syndrome(PCOS).Methods:Forty-two rats were randomly divided into seven groups with six rats in each group.Group 1 received 0.5%carboxy methylcellulose orally for 37 days and served as the normal control group.Group 2 was orally administered with letrozole of 1 mg/kg for 21 days and served as the PCOS induction group without treatment.Group 3 to 7 were administered with letrozole of 1 mg/kg for 21 days orally to induce PCOS,and then respectively received clomiphene citrate at 1 mg/kg,100 and 200 mg/kg of novel herbal combination,200 mg/kg of novel herbal formulation(syrup),and 400 mg/kg of marketed formulation of Pushyanuga churna,once daily for 15 days.Effects of the novel herbal combination and its syrup formulation were evaluated on the hormonal profile,the levels of antioxidants,the lipid profile and on the ovarian morphology,using letrozole-induced PCOS model in rats.Results:Letrozole caused alterations in hormonal levels and lipid levels similar to PCOS and ovarian histology showed presence of ovarian cysts confirming the induction of PCOS in rats.On treatment with the novel herbal combination and its syrup formulation in PCOS-induced rats,the altered hormonal and lipid profiles showed significant recovery to normal levels.Ovarian histology confirmed the restoration of folliculogenesis in the PCOS-induced rats.The treatment with the syrup formulation of novel herbal combination was found to be more effective than novel herbal combination and showed better recovery in various parameters evaluated.The results of the study,however,suggested that treatment with novel herbal combination and its syrup formulation provided minimal protection against oxidative stress caused due to the induction of PCOS.Conclusions:The integrated approach for management of PCOS is to counterbalance the limitations associated with modern therapy.Both the novel herbal combination and the syrup formulation of novel herbal combination show efficacy in the management of PCOS in rats and restore folliculogenesis in the ovary.The syrup formulation of novel herbal combination is most effective in the management of PCOS and shows potential to be developed as an adjuvant therapeutic agent.展开更多
Sucrose nonfermenting-related protein kinase 1(SnRK1)is one of the critical serine/threonine protein kinases.It commonly mediates plant growth and development,cross-talks with metabolism processes and physiological re...Sucrose nonfermenting-related protein kinase 1(SnRK1)is one of the critical serine/threonine protein kinases.It commonly mediates plant growth and development,cross-talks with metabolism processes and physiological responses to biotic or abiotic stresses.It plays a key role in distributing carbohydrates and sugar signal transporting.In the present study,eight SnRK1 coding genes were identified in sorghum(Sorghum bicolor L.)via sequences alignment,with three forαsubunits(SnRK1α1 to SnRK1α3),three forβ(SnRK1β1 to SnRK1β3),and one for bothγ(SnRK1γ)andβγ(SnRK1βγ).These eight corresponding genes located on five chromosomes(Chr)of Chr1–3,Chr7,and Chr9 and presented collinearities to SnRK1s from maize and rice,exhibiting highly conserved domains within the same subunits from the three kinds of cereals.Expression results via qRT-PCR showed that different coding genes of SnRK1s in sorghum possessed similar expression patterns except for SnRK1α3 with a low expression level in grains and SnRK1β2 with a relatively high expression level in inflorescences.Results of subcellular localization in sorghum leaf protoplast showed that SnRK1α1/α2/α3/γmainly located on organelles,while the rest four of SnRK1β1/β2/β3/βγlocated on both membranes and some organelles.Besides,three combinations were discovered among eight SnRK1 subunits in sorghum through yeast two hybrid,includingα1-β2-βγ,α2-β3-γ,andα3-β3-γ.These results provide informative references for the following functional dissection of SnRK1 subunits in sorghum.展开更多
Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constru...Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib(Gefi),ferrocene(Fc)and dihydroartemisinin(DHA)for the combined therapy of both ferroptosis and apoptosis.In the tumor microenvironment,this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH.Interestingly,the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc,further executing tumor cell death with concomitant chemotherapy by Gefi.More importantly,this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis,as well as no noticeable side-effects during treatments.This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.展开更多
AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,...AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,randomized,prospective crossover study on fourty primary open angle glaucoma patients.Two weeks of washout period were followed by randomization to either once daily(OD,group A)or twice daily dosing(BD,group B)of LTFC for 4wk.After another 2-week washout period,the patients’treatment dose was crossed-over for another 4wk.IOP reduction alongside ocular and systemic side effects were evaluated.RESULTS:Mean baseline IOP was 18.57±2.93 and 17.8±3.01 mm Hg before OD and BD dose respectively,(P=0.27).Mean IOP after BD dose was statistically lower(12.49±1.59 mm Hg)compared to OD(13.48±1.81 mm Hg,P=0.017).Although IOP reduction after BD dose was more(5.32±3.24 mm Hg,29.89%)than after OD dosing(5.04 mm Hg,27.14%),it did not reach statistical significance(P=0.68).Patients switched from OD to BD(group A)showed mean IOP reduction by 0.69 mm Hg[95%confidence interval(CI):-0.09 to 1.48 mm Hg,P=0.078];but patients switched from BD to OD(group B)had significantly higher mean IOP by 1.25 mm Hg(95%CI:-2.04 to-0.46 mm Hg,P=0.006).BD dose had more ocular side effects albeit mild.CONCLUSION:Mean IOP after LTFC dosed twice daily is statistically lower,with additional mild side effects.展开更多
Pedo-spectroscopy has the potential to provide valuable information about soil physical,chemical,and biological properties.Nowadays,wemay predict soil properties usingVNIRfield imaging spectra(IS)such as Prisma satell...Pedo-spectroscopy has the potential to provide valuable information about soil physical,chemical,and biological properties.Nowadays,wemay predict soil properties usingVNIRfield imaging spectra(IS)such as Prisma satellite data or laboratory spectra(LS).The primary goal of this study is to investigate machine learning models namely Partial Least Squares Regression(PLSR)and Support Vector Regression(SVR)for the prediction of several soil properties,including clay,sand,silt,organic matter,nitrate NO3-,and calcium carbonate CaCO_(3),using five VNIR spectra dataset combinations(%IS,%LS)as follows:C1(0%IS,100%LS),C2(20%IS,80%LS),C3(50%IS,50%LS),C4(80%IS,20%LS)and C5(100%IS,0%LS).Soil samples were collected at bare soils and at the upper(0–30 cm)layer.The data set has been split into a training dataset 80%of the collected data(n=248)and a validation dataset 20%of the collected data(n=61).The proposed PLSR and SVR models were trained then tested for each dataset combination.According to our results,SVR outperforms PLSR for both:C1(0%IS,100%LS)and C5(100%IS,0%LS).For Soil Organic Matter(SOM)prediction,it achieves(R^(2)=0.79%,RMSE=1.42%)and(R^(2)=0.76%,RMSE=1.3%),respectively.The data fusion has improved the soil property prediction.The highest improvement was obtained for the SOM property(R^(2)=0.80%,RMSE=1.39)when using the SVR model and applying the second Combination C2(20% of IS and 80%LS).展开更多
Influenced by its training corpus,the performance of different machine translation systems varies greatly.Aiming at achieving higher quality translations,system combination methods combine the translation results of m...Influenced by its training corpus,the performance of different machine translation systems varies greatly.Aiming at achieving higher quality translations,system combination methods combine the translation results of multiple systems through statistical combination or neural network combination.This paper proposes a new multi-system translation combination method based on the Transformer architecture,which uses a multi-encoder to encode source sentences and the translation results of each system in order to realize encoder combination and decoder combination.The experimental verification on the Chinese-English translation task shows that this method has 1.2-2.35 more bilingual evaluation understudy(BLEU)points compared with the best single system results,0.71-3.12 more BLEU points compared with the statistical combination method,and 0.14-0.62 more BLEU points compared with the state-of-the-art neural network combination method.The experimental results demonstrate the effectiveness of the proposed system combination method based on Transformer.展开更多
Immunotherapy targets the dysfunctional immune system to induce cancer cell killing by CD8-positive T cells.Immune checkpoint inhibitors(ICIs),specifically anti-PD-1 antibodies,anti-PD-L1 antibodies,and anti-CTLA4 ant...Immunotherapy targets the dysfunctional immune system to induce cancer cell killing by CD8-positive T cells.Immune checkpoint inhibitors(ICIs),specifically anti-PD-1 antibodies,anti-PD-L1 antibodies,and anti-CTLA4 antibodies,have revolutionized the management of many malignancies due to their significant role in generating a durable clinical response.However,clinical data suggest that response rates to ICI monotherapy are low due to the immunologically silent characteristics of breast cancer(BC).Chemotherapy,surgery,radiotherapy,and targeted therapy were recently reported to alter the tumor microenvironment and enhance the ICI response.Some clinical studies supported that ICIs,in combination with other treatment strategies,show superior efficacy in BC control,especially triple-negative breast cancer.Therefore,seeking a reasonable combination therapy is a promising way to improve ICI response.The present review highlights the clinical efficacy of ICIs treatment options in combination with standard-of-care therapies,such as chemotherapy and targeted therapy。展开更多
With the development of Global Navigation Satellite Systems(GNSS),geodetic GNSS receivers have been utilized to monitor sea levels using GNSS-Interferometry Reflectometry(GNSS-IR)technology.The multi-mode,multi-freque...With the development of Global Navigation Satellite Systems(GNSS),geodetic GNSS receivers have been utilized to monitor sea levels using GNSS-Interferometry Reflectometry(GNSS-IR)technology.The multi-mode,multi-frequency signals of GPS,GLONASS,Galileo,and Beidou can be used for GNSS-IR sea level retrieval,but combining these retrievals remains problematic.To address this issue,a GNSS-IR sea level retrieval combination system has been developed,which begins by analyzing error sources in GNSS-IR sea level retrieval and establishing and solving the GNSS-IR retrieval equation.This paper focuses on two key points:time window selection and equation stability.The stability of the retrieval combination equations is determined by the condition number of the coefficient matrix within the time window.The impact of ill-conditioned coefficient matrices on the retrieval results is demonstrated using an extreme case of SNR data with only ascending or descending trajectories.After determining the time window and removing ill-conditioned equations,the multi-mode,multi-frequency GNSS-IR retrieval is performed.Results from three International GNSS Service(IGS)stations show that the combination method produces high-precision,high-resolution,and high-reliability sea level retrieval combination sequences.展开更多
BACKGROUND A transjugular intrahepatic portosystemic shunt(TIPS)is widely placed to treat portal hypertension.Because the Viatorr®stent(W.L.Gore and Associates,Flagstaff,AZ,United States)is not available in all h...BACKGROUND A transjugular intrahepatic portosystemic shunt(TIPS)is widely placed to treat portal hypertension.Because the Viatorr®stent(W.L.Gore and Associates,Flagstaff,AZ,United States)is not available in all hospitals in China,the bare metal stent(BMS)/stent-graft combination technique is still popular for TIPS construction.Stent fracture is a complication after TIPS placement using this technique,with limited available literature focusing on it.AIM To assess the incidence of stent fracture after TIPS placement using the BMS/stent-graft combination technique and to identify the risk factors for stent fracture.We proposed technique modifications to improve the clinical results of TIPS placement with the BMS/stent-graft combination technique.METHODS We retrospectively analyzed the computed tomography(CT)data of all patients with portal hypertension who underwent the TIPS procedure between June 2011 and December 2021 in a single center.Patients implanted with the BMS/stent graft and had follow-up imaging data available were included.We identified patients with stent fracture and analyzed their characteristics.Multivariable logistic regression was applied to identify the potential predictors of stent fracture.RESULTS Of the 68 included patients,stent fracture occurred in seven(10.3%)patients.Based on CT images,the stent fractures were categorized into three types.Our study consisted of four(57.1%)type I fractures,one(14.3%)type II fracture,one(14.3%)type IIIa fracture,and one(14.3%)type IIIb fracture.After adjusting for covariates,multivariable logistic regression revealed that the risk factors for stent fracture were the implantation of a greater number of stents[adjusted odds ratio(aOR)=22.2,95%confidence interval(CI):1.2-415.4,P=0.038]and a larger proximal sagittal stent bending angle(aOR=1.1,95%CI:1.0-1.3,P=0.020).CONCLUSION Stent fracture occurred in approximately 10%of patients with portal hypertension who underwent TIPS with the BMS/stent-graft combination technique.The number of implanted stents and stent bending angle at the inferior vena cava end were predictors of stent fracture,which suggests that the incidence of stent fracture could potentially be reduced by procedural modifications.展开更多
基金supported by the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,No.2020LKSFG02C(to Qiang Fang and SG)the National Natural Science Foundation of China,No.82201511(to SG)+1 种基金the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515110873(to SG),2022A1515110139(to TW)the Medical Scientific Research Foundation of Guangdong Province,No.A2022077(to SG)。
文摘Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.
基金Supported by NIH/National Cancer Institute Grant,No.R01CA138441 and No.R01CA269452UW Madison Centene Pancreas Cancer Collaborative Award,No.21-8568.
文摘BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.
基金the National Natural Science Fund of China(61471080)Training Plan for Young Backbone Teachers in Colleges and Universities of Henan Province(2018GGJS171).
文摘To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior information with other sensor information in the form of constraints.Firstly,the train precise track constraint method of the train is proposed,and the plane position constraint and train motion state constraints are analysed.A model for combining prior information with constraints is established.Then an adaptive H∞filter with combination constraints is derived based on the adaptive adjustment method of the robustness factor.Finally,the positioning effect of the proposed algorithm is simulated and analysed under the conditions of a straight track and a curved track.The results show that the positioning accuracy of the algorithm with constrained filtering is significantly better than that of the algorithm without constrained filtering and that the algorithm with constrained filtering can achieve better performance when combined with track and condition information,which can significantly reduce the train positioning error.The effectiveness of the proposed algorithm is verified.
基金supported by Zanjan University of Medical Sciences,Zanjan,Iran(Grant Number:A-12-1244-16&Ethical Code:IR.ZUMS.REC.1399.316).
文摘The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.
文摘Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered combination kit, containing 2 g secnidazole, 1 g azithromycin and 150 mg fluconazole (Azimyn FS Kit), has been successfully evaluated in clinical trials and used in several countries for management syndromic vaginal discharge due to infections. Methods: This is a longitudinal study which aimed to verify the clinical efficacy of the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit<sup><sup>®</sup></sup>) in the syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultations in Kinshasa/DR Congo from March to September 2023. Results: Majority of patients had whitish vaginal discharge (51.6%) of average abundance (56.2%), accompanied by pruritus in 72.1% of cases, and dyspareunia in 23.5% of cases and hypogastralgia in 40.2% of cases. One week after treatment with the Azimyn FS<sup><sup>®</sup></sup> combined kit, at the greatest majority of patients (97.3%), abnormal vaginal discharge had decreased by more than 50% (84.1%). Two weeks after treatment with the Azimyn FS<sup><sup>®</sup></sup> combined kit, almost all patients (97.3%) no longer had abnormal vaginal discharge which had completely disappeared. Conclusion: A single dose of secnidazole, azithromycin and fluconazole in the form of an oral combi-kit (Azimyn FS Kit) has shown excellent therapeutic effectiveness in the syndromic treatment of abnormal vaginal discharge wherein patients were treated without diagnostic confirmation.
文摘Background:Small cell lung cancer(SCLC)is an aggressive malignant tumor with strong immunosuppressive effects,characterized by rapid doubling time and poor prognosis.Currently,effective therapeutic options are urgently needed for Extensive-stage small-cell lung Cancer.Case description:In the present case,a combination therapy of anlotinib,envolizumab,and etoposide was administered to treat an 80-year-old female patient with extensive-stage SCLC accompanied by mediastinal lymph node and bone metastasis.After two cycles of treatment,the tumor lesions in the right lungs decreased from 5.04*3.44 cm to 1.65*1.42 cm.As of now,no significant mass is seen there and no serious adverse reactions in this patient.Until September 2023,she has survived for 18 months with no disease progression.Conclusions:Research shows that Alectinib,in combination with evolocumab plus etoposide,could be an original,viable therapeutic option for the treatment option of patients with extensive-stage SCLC.
基金supported by the National Key Research and Development Programs of China(Grant No.2018YFA0209700)National Natural Science Foundation of China(Grant No.22077073)+1 种基金Frontiers Science Center for New Organic Matter,Nankai University(Grant No.63181206)the Fundamental Research Funds for the Central Universities,Nankai University(Grant No.63206015)。
文摘Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.
基金by the National Natural Science Foundation of China(No.81700453).
文摘Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.
基金funded by grants from the Modern Agricultural Industry Technology System for Vegetables in Shandong Province, China (SDAIT-05)the National Natural Science Foundation of China (32001953)。
文摘In this study, lambda-cyhalothrin(LC) loaded polyurea microcapsules(MCs) with different particle sizes were fabricated.All of the MCs showed varying degrees of physical collapse, which was more obvious among those with smaller particle sizes. MCs with particle sizes of 1.38 μm(MC-S), 5.13 μm(MC-M) and 10.05 μm(MC-L) had shell thicknesses of 39.6,50.3 and 150.1 nm, respectively. MCs with smaller particles tended to have significantly faster release profiles, and the MC-S group had much higher bioactivity against Agrotis ipsilon and better foliar affinity on the peanut leaves(indicated by rainfastness) than MC-M and MC-L. All of the MCs exhibited light-enhanced release profiles and had much slower degradation compared with the emulsifiable concentrate(EC) group, among which MC-L had the slowest degradation.To generate MCs with both favorable quick efficacy and long-lasting efficacy, binary mixtures of MC-S, MC-M and MC-L were produced by mixing them in pairs at ratios of 2:1, 1:1 and 1:2. The mixture of MC-S:MC-L at 1:2 showed the best comprehensive efficacy in the peanut foliar spray scenario among the nine tested combinations, and its effective duration was three times longer than that of EC. Overall, the precise combination of MCs with different particle sizes can regulate the efficacy of pesticide control and serve as a strategy for the better utilization of pesticides.
基金the National Natural Science Foundation of China(Nos.U21A20108,52322403,52174108,and 51974105)the Support Plan for Science&Technology Innovation Talents in Universities of Henan Province(No.21HASTIT024)+1 种基金the Scientific and technological innovation research team of Henan Polytechnic University(No.T2021-5)the Henan Excellent Youth Science Foundation(No.222300420045).
文摘Recovery of the coal buried under buildings,railways and water bodies and the residual coal in irregularly arranged fully mechanized mining faces is a common engineering problem facing underground coal mining.In this study,a mining technology of continuous driving and gangue backfilling(CDGB)was proposed.The technology,which can not only alleviate ground subsidence and gangue discharge,but also release the above-mentioned coals,contributes to green and efficient sustainable development of mining.The stability of the system of the solidified body-reserved coal pillar combination(S-C combination)is crucial to the CDGB technology.Therefore,it is of great significance to explore the mechanical and damage characteristics of S-C combination in the synergistic bearing process.First,four sets of differentshaped S-C combination specimens were fabricated and a S-C combination bearing structure in CDGB was constructed to explore the differences in mechanical characteristics and damage modes of different-shaped S-C combination specimens during CDGB.Subsequently,their surface strain field evolutions and acoustic emission(AE)response characteristics in the load-bearing process were obtained with the aid of the digital image correlation technique and the AE signal monitoring system.Furthermore,a damage evolution model based on AE parameters and mechanical parameters was established to clarify the damage evolution law.The following results were obtained:(1)The free area of S-C combination can serve as a quantitative index to evaluate the stability of the overburden control system;(2)The concept of critical value k of the free area was first proposed.When the free area exceeds the critical value k(free area ratio greater than 1.13),the deformation resistance and the free area changes becomes negatively correlated;(3)As the free area expands,the failure of the S-C combination specimen evolves from tensile failure to shear failure.The distribution characteristics of the axial strain field also verified such a change in the failure mode;(4)When the free area expands,the peak AE count gradually changes from“double peaks”to“a single peak”.In this process,the expansion of free area shortens the time for accumulating and releasing energy during loading.Micro cracks generated in the specimen change from a phased steep growth to a continuous increase,and the process in which micro cracks develop,converge,intersect and connect to form macro cracks accelerates.The damage evolution law concluded based on AE parameters and mechanical parameters can well characterize the damage evolution process of S-C combination,providing certain reference for the study on the synergistic bearing of S-C combination during CDGB.
基金Project supported by the National Key R&D Program of China(Grant No.2021YFC2203503)。
文摘The electromagnetic time-reversal(TR)technique has the characteristics of spatiotemporal focusing in a time-reversal cavity(TRC),which can be used for pulse compression,thus forming an electromagnetic pulse with high peak power.A time-reversed pulse-compression method in a single channel has high pulse compression gain.However,single channel pulse compression can only generate limited gain.This paper proposes a novel TR power-combination method in a multichannel TRC to obtain higher peak power based on TR pulse-compression theory.First,the TR power-combination model is given,and the crosstalk properties of the associated channel and the influence of the reversal performance are studied.Then,the power-combination performances for the TR pulse compression,such as combined signal to noise ratio(SNR)and combined compression gain,are analyzed by numerical simulation and experimental methods.The results show that the proposed method has obvious advantages over pulse-compression methods using a single channel cavity,and is more convenient for power combination.
基金supported by DST-SERB,Government of India via sanction No.EMR/2017/001106。
文摘Objective:To investigate the potential activity of novel herbal combination and novel herbal formulation(syrup)in female Sprague Dawley rats with letrozole-induced polycystic ovary syndrome(PCOS).Methods:Forty-two rats were randomly divided into seven groups with six rats in each group.Group 1 received 0.5%carboxy methylcellulose orally for 37 days and served as the normal control group.Group 2 was orally administered with letrozole of 1 mg/kg for 21 days and served as the PCOS induction group without treatment.Group 3 to 7 were administered with letrozole of 1 mg/kg for 21 days orally to induce PCOS,and then respectively received clomiphene citrate at 1 mg/kg,100 and 200 mg/kg of novel herbal combination,200 mg/kg of novel herbal formulation(syrup),and 400 mg/kg of marketed formulation of Pushyanuga churna,once daily for 15 days.Effects of the novel herbal combination and its syrup formulation were evaluated on the hormonal profile,the levels of antioxidants,the lipid profile and on the ovarian morphology,using letrozole-induced PCOS model in rats.Results:Letrozole caused alterations in hormonal levels and lipid levels similar to PCOS and ovarian histology showed presence of ovarian cysts confirming the induction of PCOS in rats.On treatment with the novel herbal combination and its syrup formulation in PCOS-induced rats,the altered hormonal and lipid profiles showed significant recovery to normal levels.Ovarian histology confirmed the restoration of folliculogenesis in the PCOS-induced rats.The treatment with the syrup formulation of novel herbal combination was found to be more effective than novel herbal combination and showed better recovery in various parameters evaluated.The results of the study,however,suggested that treatment with novel herbal combination and its syrup formulation provided minimal protection against oxidative stress caused due to the induction of PCOS.Conclusions:The integrated approach for management of PCOS is to counterbalance the limitations associated with modern therapy.Both the novel herbal combination and the syrup formulation of novel herbal combination show efficacy in the management of PCOS in rats and restore folliculogenesis in the ovary.The syrup formulation of novel herbal combination is most effective in the management of PCOS and shows potential to be developed as an adjuvant therapeutic agent.
基金supported by the National Natural Science Foundation of China(32001607)the Fundamental Research Funds for the Central Universities of Southwest University,China(SWU118087)。
文摘Sucrose nonfermenting-related protein kinase 1(SnRK1)is one of the critical serine/threonine protein kinases.It commonly mediates plant growth and development,cross-talks with metabolism processes and physiological responses to biotic or abiotic stresses.It plays a key role in distributing carbohydrates and sugar signal transporting.In the present study,eight SnRK1 coding genes were identified in sorghum(Sorghum bicolor L.)via sequences alignment,with three forαsubunits(SnRK1α1 to SnRK1α3),three forβ(SnRK1β1 to SnRK1β3),and one for bothγ(SnRK1γ)andβγ(SnRK1βγ).These eight corresponding genes located on five chromosomes(Chr)of Chr1–3,Chr7,and Chr9 and presented collinearities to SnRK1s from maize and rice,exhibiting highly conserved domains within the same subunits from the three kinds of cereals.Expression results via qRT-PCR showed that different coding genes of SnRK1s in sorghum possessed similar expression patterns except for SnRK1α3 with a low expression level in grains and SnRK1β2 with a relatively high expression level in inflorescences.Results of subcellular localization in sorghum leaf protoplast showed that SnRK1α1/α2/α3/γmainly located on organelles,while the rest four of SnRK1β1/β2/β3/βγlocated on both membranes and some organelles.Besides,three combinations were discovered among eight SnRK1 subunits in sorghum through yeast two hybrid,includingα1-β2-βγ,α2-β3-γ,andα3-β3-γ.These results provide informative references for the following functional dissection of SnRK1 subunits in sorghum.
基金financial supports from National Natural Science Foundation of China(32000992,21977081,32101124)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR23C100001)+1 种基金Wenzhou Medical University(KYYW201901)Zhejiang Qianjiang Talent Plan(QJD20020224)
文摘Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib(Gefi),ferrocene(Fc)and dihydroartemisinin(DHA)for the combined therapy of both ferroptosis and apoptosis.In the tumor microenvironment,this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH.Interestingly,the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc,further executing tumor cell death with concomitant chemotherapy by Gefi.More importantly,this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis,as well as no noticeable side-effects during treatments.This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.
基金Anis Baidura Azal holds a Masters scholarship funded by the Government of MalaysiaNorshamsiah Md Din receives funding from the UKMMC Fundamental Research Fund(No.FF-2019-058)。
文摘AIM:To evaluate whether latanoprost/timolol fixed combination(LTFC)dosed twice daily may provide further intraocular pressure(IOP)reduction and evaluate the safety profile at this dose.METHODS:This is an open-labeled,randomized,prospective crossover study on fourty primary open angle glaucoma patients.Two weeks of washout period were followed by randomization to either once daily(OD,group A)or twice daily dosing(BD,group B)of LTFC for 4wk.After another 2-week washout period,the patients’treatment dose was crossed-over for another 4wk.IOP reduction alongside ocular and systemic side effects were evaluated.RESULTS:Mean baseline IOP was 18.57±2.93 and 17.8±3.01 mm Hg before OD and BD dose respectively,(P=0.27).Mean IOP after BD dose was statistically lower(12.49±1.59 mm Hg)compared to OD(13.48±1.81 mm Hg,P=0.017).Although IOP reduction after BD dose was more(5.32±3.24 mm Hg,29.89%)than after OD dosing(5.04 mm Hg,27.14%),it did not reach statistical significance(P=0.68).Patients switched from OD to BD(group A)showed mean IOP reduction by 0.69 mm Hg[95%confidence interval(CI):-0.09 to 1.48 mm Hg,P=0.078];but patients switched from BD to OD(group B)had significantly higher mean IOP by 1.25 mm Hg(95%CI:-2.04 to-0.46 mm Hg,P=0.006).BD dose had more ocular side effects albeit mild.CONCLUSION:Mean IOP after LTFC dosed twice daily is statistically lower,with additional mild side effects.
基金supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R196),Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘Pedo-spectroscopy has the potential to provide valuable information about soil physical,chemical,and biological properties.Nowadays,wemay predict soil properties usingVNIRfield imaging spectra(IS)such as Prisma satellite data or laboratory spectra(LS).The primary goal of this study is to investigate machine learning models namely Partial Least Squares Regression(PLSR)and Support Vector Regression(SVR)for the prediction of several soil properties,including clay,sand,silt,organic matter,nitrate NO3-,and calcium carbonate CaCO_(3),using five VNIR spectra dataset combinations(%IS,%LS)as follows:C1(0%IS,100%LS),C2(20%IS,80%LS),C3(50%IS,50%LS),C4(80%IS,20%LS)and C5(100%IS,0%LS).Soil samples were collected at bare soils and at the upper(0–30 cm)layer.The data set has been split into a training dataset 80%of the collected data(n=248)and a validation dataset 20%of the collected data(n=61).The proposed PLSR and SVR models were trained then tested for each dataset combination.According to our results,SVR outperforms PLSR for both:C1(0%IS,100%LS)and C5(100%IS,0%LS).For Soil Organic Matter(SOM)prediction,it achieves(R^(2)=0.79%,RMSE=1.42%)and(R^(2)=0.76%,RMSE=1.3%),respectively.The data fusion has improved the soil property prediction.The highest improvement was obtained for the SOM property(R^(2)=0.80%,RMSE=1.39)when using the SVR model and applying the second Combination C2(20% of IS and 80%LS).
基金Supported by the National Key Research and Development Program of China(No.2019YFA0707201)the Fund of the Institute of Scientific and Technical Information of China(No.ZD2021-17).
文摘Influenced by its training corpus,the performance of different machine translation systems varies greatly.Aiming at achieving higher quality translations,system combination methods combine the translation results of multiple systems through statistical combination or neural network combination.This paper proposes a new multi-system translation combination method based on the Transformer architecture,which uses a multi-encoder to encode source sentences and the translation results of each system in order to realize encoder combination and decoder combination.The experimental verification on the Chinese-English translation task shows that this method has 1.2-2.35 more bilingual evaluation understudy(BLEU)points compared with the best single system results,0.71-3.12 more BLEU points compared with the statistical combination method,and 0.14-0.62 more BLEU points compared with the state-of-the-art neural network combination method.The experimental results demonstrate the effectiveness of the proposed system combination method based on Transformer.
文摘Immunotherapy targets the dysfunctional immune system to induce cancer cell killing by CD8-positive T cells.Immune checkpoint inhibitors(ICIs),specifically anti-PD-1 antibodies,anti-PD-L1 antibodies,and anti-CTLA4 antibodies,have revolutionized the management of many malignancies due to their significant role in generating a durable clinical response.However,clinical data suggest that response rates to ICI monotherapy are low due to the immunologically silent characteristics of breast cancer(BC).Chemotherapy,surgery,radiotherapy,and targeted therapy were recently reported to alter the tumor microenvironment and enhance the ICI response.Some clinical studies supported that ICIs,in combination with other treatment strategies,show superior efficacy in BC control,especially triple-negative breast cancer.Therefore,seeking a reasonable combination therapy is a promising way to improve ICI response.The present review highlights the clinical efficacy of ICIs treatment options in combination with standard-of-care therapies,such as chemotherapy and targeted therapy。
基金National Natural Science Foundation of China(No.42004018)。
文摘With the development of Global Navigation Satellite Systems(GNSS),geodetic GNSS receivers have been utilized to monitor sea levels using GNSS-Interferometry Reflectometry(GNSS-IR)technology.The multi-mode,multi-frequency signals of GPS,GLONASS,Galileo,and Beidou can be used for GNSS-IR sea level retrieval,but combining these retrievals remains problematic.To address this issue,a GNSS-IR sea level retrieval combination system has been developed,which begins by analyzing error sources in GNSS-IR sea level retrieval and establishing and solving the GNSS-IR retrieval equation.This paper focuses on two key points:time window selection and equation stability.The stability of the retrieval combination equations is determined by the condition number of the coefficient matrix within the time window.The impact of ill-conditioned coefficient matrices on the retrieval results is demonstrated using an extreme case of SNR data with only ascending or descending trajectories.After determining the time window and removing ill-conditioned equations,the multi-mode,multi-frequency GNSS-IR retrieval is performed.Results from three International GNSS Service(IGS)stations show that the combination method produces high-precision,high-resolution,and high-reliability sea level retrieval combination sequences.
文摘BACKGROUND A transjugular intrahepatic portosystemic shunt(TIPS)is widely placed to treat portal hypertension.Because the Viatorr®stent(W.L.Gore and Associates,Flagstaff,AZ,United States)is not available in all hospitals in China,the bare metal stent(BMS)/stent-graft combination technique is still popular for TIPS construction.Stent fracture is a complication after TIPS placement using this technique,with limited available literature focusing on it.AIM To assess the incidence of stent fracture after TIPS placement using the BMS/stent-graft combination technique and to identify the risk factors for stent fracture.We proposed technique modifications to improve the clinical results of TIPS placement with the BMS/stent-graft combination technique.METHODS We retrospectively analyzed the computed tomography(CT)data of all patients with portal hypertension who underwent the TIPS procedure between June 2011 and December 2021 in a single center.Patients implanted with the BMS/stent graft and had follow-up imaging data available were included.We identified patients with stent fracture and analyzed their characteristics.Multivariable logistic regression was applied to identify the potential predictors of stent fracture.RESULTS Of the 68 included patients,stent fracture occurred in seven(10.3%)patients.Based on CT images,the stent fractures were categorized into three types.Our study consisted of four(57.1%)type I fractures,one(14.3%)type II fracture,one(14.3%)type IIIa fracture,and one(14.3%)type IIIb fracture.After adjusting for covariates,multivariable logistic regression revealed that the risk factors for stent fracture were the implantation of a greater number of stents[adjusted odds ratio(aOR)=22.2,95%confidence interval(CI):1.2-415.4,P=0.038]and a larger proximal sagittal stent bending angle(aOR=1.1,95%CI:1.0-1.3,P=0.020).CONCLUSION Stent fracture occurred in approximately 10%of patients with portal hypertension who underwent TIPS with the BMS/stent-graft combination technique.The number of implanted stents and stent bending angle at the inferior vena cava end were predictors of stent fracture,which suggests that the incidence of stent fracture could potentially be reduced by procedural modifications.
