The joint roughness coefficient(JRC) is one of the key parameters for evaluating the shear strength of rock joints.Because of the scale effect in the JRC,reliable JRC values are of great importance for most rock engin...The joint roughness coefficient(JRC) is one of the key parameters for evaluating the shear strength of rock joints.Because of the scale effect in the JRC,reliable JRC values are of great importance for most rock engineering projects.During the collection process of JRC samples,the redundancy or insufficiency of representative rock joint surface topography(RJST) information in serial length JRC samples is the essential reason that affects the reliability of the scale effect results.Therefore,this paper proposes an adaptive sampling method,in which we use the entropy consistency measure Q(a) to evaluate the consistency of the joint morphology information contained in adjacent JRC samples.Then the sampling interval is automatically adjusted according to the threshold Q(at) of the entropy consistency measure to ensure that the degree of change of RJST information between JRC samples is the same,and ultimately makes the representative RJST information in the collected JRC samples more balanced.The application results of actual cases show that the proposed method can obtain the scale effect in the JRC efficiently and reliably.展开更多
A mixed adaptive dynamic programming(ADP)scheme based on zero-sum game theory is developed to address optimal control problems of autonomous underwater vehicle(AUV)systems subject to disturbances and safe constraints....A mixed adaptive dynamic programming(ADP)scheme based on zero-sum game theory is developed to address optimal control problems of autonomous underwater vehicle(AUV)systems subject to disturbances and safe constraints.By combining prior dynamic knowledge and actual sampled data,the proposed approach effectively mitigates the defect caused by the inaccurate dynamic model and significantly improves the training speed of the ADP algorithm.Initially,the dataset is enriched with sufficient reference data collected based on a nominal model without considering modelling bias.Also,the control object interacts with the real environment and continuously gathers adequate sampled data in the dataset.To comprehensively leverage the advantages of model-based and model-free methods during training,an adaptive tuning factor is introduced based on the dataset that possesses model-referenced information and conforms to the distribution of the real-world environment,which balances the influence of model-based control law and data-driven policy gradient on the direction of policy improvement.As a result,the proposed approach accelerates the learning speed compared to data-driven methods,concurrently also enhancing the tracking performance in comparison to model-based control methods.Moreover,the optimal control problem under disturbances is formulated as a zero-sum game,and the actor-critic-disturbance framework is introduced to approximate the optimal control input,cost function,and disturbance policy,respectively.Furthermore,the convergence property of the proposed algorithm based on the value iteration method is analysed.Finally,an example of AUV path following based on the improved line-of-sight guidance is presented to demonstrate the effectiveness of the proposed method.展开更多
Objective:Mycophenolate mofetil(MMF)is frequently prescribed to pediatric patients with nephrotic syndrome(NS);however,information on the active metabolite mycophenolic acid(MPA)in this population is limited.Method:Us...Objective:Mycophenolate mofetil(MMF)is frequently prescribed to pediatric patients with nephrotic syndrome(NS);however,information on the active metabolite mycophenolic acid(MPA)in this population is limited.Method:Using ultra-high performance liquid chromatography–tandem mass spectrometry(UHPLC–MS/MS),we validated a rapid and simple approach to measure MPA in accordance with the Bioanalytical Method Validation Guidance issued by the relevant regulatory authorities.Statistical analyses were performed on 69 pediatric patients with frequently relapsing/steroid-dependent nephrotic syndrome(FRNS/SDNS)who received corticosteroids plus MMF.Results:Forty-two patients achieved the endpoints and reported adverse events(AEs).The area under the concentration–time curve of MPA in the AE group was further distributed.Monitoring blood MPA concentrations is critical to prevent AEs during MMF administration in children with FRNS/SDNS.Conclusion:UHPLC–MS/MS offers a more accurate reference than immunoassays.展开更多
A novel environmentally benign biphasic system composed of propylene carbonate(PC) and aqueous solution of p-toluenesulfonic acid(p-TsOH aq) was designed for the efficient valorization of lignocellulosic bamboo residu...A novel environmentally benign biphasic system composed of propylene carbonate(PC) and aqueous solution of p-toluenesulfonic acid(p-TsOH aq) was designed for the efficient valorization of lignocellulosic bamboo residues, resulting in more than 95.5% of hemicellulose and 97.2% of lignin digested under mild conditions of 130°C for 1 h. Meanwhile, 91.9% of cellulose was retained with loose structure, followed by 95.8% enzyme hydrolysis yield and 347.9 mg g-1of glucose yield. Notably, the synergistic effect between PC and p-TsOH on efficiency and selectivity was proposed by a control group experiment and subsequently verified, which is believed to be responsible for the simultaneous degradation and separation of lignin and hemicelluloses into oligomeric phenols and pentose, also facilitating subsequent valorization.Furthermore, the novel PC/p-TsOH aq biphasic system demonstrated excellent retrievability and adaptability to different feedstocks, offering a promising green strategy for the efficient valorization of lignocellulosic biomass in industrial biorefineries.展开更多
The hydrothermal signatures of mid-ocean ridge sediments are crucial geochemical data providing insights into investigating hydrothermal anomalies and locating seafloor massive sulfide deposits.This paper outlines the...The hydrothermal signatures of mid-ocean ridge sediments are crucial geochemical data providing insights into investigating hydrothermal anomalies and locating seafloor massive sulfide deposits.This paper outlines the geochemical features of 24 surface sediments and one sediment core(26 V-GC 01,294 cm)along the South Mid-Atlantic Ridge(SMAR)from 18°S to 22°S,an area where hydrothermal active fields have yet to be discovered.The surface sediments mainly consist of biogenic carbonates,aluminosilicates,and hydrothermal Fe-Mn(oxy)oxides.The core sediments primarily comprise organic matter,detrital materials,hydrothermal components,and substances scavenged from seawater.The rare Earth element(REE)patterns suggest the presence of hydrothermal contributions within the surface and core sediments.The enrichment factors for Fe,Mn,Cu,and Zn in surface sediments suggest these metals are concentrated at the 19°S,21°S,and 21.5°S segments,further indicating their potential as hydrothermal active fields.Downcore variations of Fe,Mn,P,Cu,Pb,V,and Co suggest at least six episodes of hydrothermal activity.The impact of hydrothermal processes on the sediments from SMAR 18°S to 22°S indicates that the study area has the potential to host a significant number of hydrothermal active fields.展开更多
Metal ions trigger Fenton/Fenton-like reactions,generating highly toxic hydroxyl radicals(•OH)for chemodynamic therapy(CDT),which is crucial in inducing lethal oxidative DNA damage and subsequent cell apoptosis.Howeve...Metal ions trigger Fenton/Fenton-like reactions,generating highly toxic hydroxyl radicals(•OH)for chemodynamic therapy(CDT),which is crucial in inducing lethal oxidative DNA damage and subsequent cell apoptosis.However,tumor cells can counteract this damage through repair pathways,particularly MutT homolog 1(MTH1)protein attenuation of oxidative DNA damage.Suppression of MTH1 can enhance CDT efficacy,therefore,orderly integrating Fenton/Fenton-like agents with an MTH1 inhibitor is expected to significantly augment CDT effectiveness.Carrier-free CuTH@CD,self-assembled through the supramolecular orchestration ofγ-cyclodextrin(γ-CD)with Cu^(2+)and the MTH1 inhibitor TH588,effectively overcoming tumor resistance by greatly amplifying oxidative damage capability.Without additional carriers and mediated by multiple supramolecular regulatory effects,CuTH@CD enables high drug loading content,stability,and uniform size distribution.Upon internalization by tumor cells,CuTH@CD invalidates repair pathways through Cu^(2+)-mediated glutathione(GSH)depletion and TH588-mediated MTH1 inhibition.Meanwhile,both generated Cu^(+)ions and existing ones within the nanoassembly initiate a Fentonlike reaction,leading to the accumulation of•OH.This strategy enhances CDT efficiency with minimal side effects,improving oxidative damage potency and advancing self-delivery nanoplatforms for developing effective chemodynamic tumor therapies.展开更多
Microorganisms play a critical role in the biotransformation of arsenic and the form which it exists in the environment. In this study, a methyl parathion-degrading bacterium Caballeronia jiangsuensis, isolated from a...Microorganisms play a critical role in the biotransformation of arsenic and the form which it exists in the environment. In this study, a methyl parathion-degrading bacterium Caballeronia jiangsuensis, isolated from an abandoned pesticide manufacturing plant, was used to analyze arsenic accumulation and transformation. The accumulation of trivalent organoarsenic compounds in C. jiangsuensis occurred to a greater extent than that of their pentavalent counterparts. The chromosome of C. jiangsuensis contains an arsenic gene island whose GC content is significantly lower than that of the genome, suggesting that the island was acquired via horizontal gene transfer. There was approximately 90%-99% similarity between the proteins encoded by the gene island and the corresponding sequence of the plasmid pkk5 from Burkholderia sp. KK1. The biotransformation of different arsenic species by C. jiangsuensis was subsequently analyzed. The results revealed that monomethylarsenic acid(MAs(Ⅴ)) was rapidly demethylated to arsenate with very small amounts of intermediate monomethylarsonous acid(MAs(Ⅲ)), whereas MAs(Ⅲ) was largely oxidized to MAs(Ⅴ) despite the occurrence of the gene arsI probably responsible for aerobic demethylation of MAs(Ⅲ) in C. jiangsuensis. In addition, dimethylarsenic acid was partly demethylated to arsenate. Horizontal gene transfer of ars operon from a plasmid to other bacteria represents an adaptation to a specific environment. This study provides a new perspective for understanding arsenic biogeochemical cycling.展开更多
Objective:To observe the clinical effect of modified Yu Rong San gel eye mask in the treatment of dark circles.Methods:96 cases of patients with dark circles were randomly divided into treatment group and control grou...Objective:To observe the clinical effect of modified Yu Rong San gel eye mask in the treatment of dark circles.Methods:96 cases of patients with dark circles were randomly divided into treatment group and control group.In the control group and the treatment group,the common eye mask and the modified Yu Rong San gel eye mask were applied to the black circle area respectively.After 15min,water was used to wash the face,the application of the mask for one time a day,four weeks,one course,and three courses were observed.Results:After three courses of treatment,the total effective rate of the treatment group was higher than that of the control group(P<0.05);the area of black eye circles in the treatment group was smaller than that before treatment(P<0.05);compared with the control group,the score of black eye circles was lower than that before treatment,the difference was statistically significant(P<0.05).Conclusions Addition and reduction of Yu Rong San gel eye mask is effective in the treatment of dark circles.展开更多
Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,in...Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.展开更多
Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effect...Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.展开更多
Converting carbohydrates into 5-hydroxymethylfurfural(5-HMF) is an attractive and promising route for value-added utilization of agricultural and forestry biomass resource. As an important platform compound, 5-HMF pos...Converting carbohydrates into 5-hydroxymethylfurfural(5-HMF) is an attractive and promising route for value-added utilization of agricultural and forestry biomass resource. As an important platform compound, 5-HMF possesses high active furan structure with hydroxymethyl and aldehyde group for production of various bio-chemicals and materials, meanwhile, which suffer from low stability and poor yield during the industrial biorefinery process. Hence, selective production of 5-HMF with high-yield and low-cost has attracted extensive attention from scientific and industrial researchers. This review sorted and described the latest advanced research on solvent and catalyst system, as well as energy field effect for production of 5-HMF with different feedstock in detail, emphatically discussing the solvent effect and its synergistic effect with other aspects. Besides, the future prospects and challenges for production of 5-HMF from carbohydrates were also presented, which provide a profound insight into industrial 5-HMF process with economic and environmental feature.展开更多
BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model...BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.展开更多
Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therape...Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high heterogeneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell proliferation,differentiation,and disease progression.Significant associations between tumor grade,prognosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry...Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.展开更多
Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac...Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.展开更多
BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To asses...BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.展开更多
AIM To investigate whether serum interleukin(IL)-34 levels are correlated with hepatic inflammation and fibrosis in patients with chronic hepatitis B virus(HBV) infection. METHODS In this study, serum IL-34 levels wer...AIM To investigate whether serum interleukin(IL)-34 levels are correlated with hepatic inflammation and fibrosis in patients with chronic hepatitis B virus(HBV) infection. METHODS In this study, serum IL-34 levels were assessed by enzyme-linked immunosorbent assay in 19 healthy controls and 175 patients with chronic HBV infection undergoing biopsy. The frequently used serological markers of liver fibrosis were based on laboratory indexes measured at the Clinical Laboratory of the Second Affiliated Hospital of Anhui Medical University. Liver stiffness was detected by transient elastography with Fibro Touch. The relationships of non-invasive makers of liver fibrosis and IL-34 levels with inflammation and fibrosis were analyzed. The diagnostic value of IL-34 and other liver fibrosis makers wereevaluated using areas under the receiver operating characteristic curves, sensitivity and specificity.RESULTS Serum IL-34 levels were associated with inflammatory activity in the liver, and IL-34 levels differed among phases of chronic HBV infection(P = 0.001). By comparing serum IL-34 levels among patients with various stages of liver fibrosis determined by liver biopsy, we found that IL-34 levels ≥ 15.83 pg/m L had a high sensitivity of 86.6% and a specificity of 78.7% for identifying severe fibrosis(S3-S4). Furthermore, we showed that IL-34 is superior to the fibrosis-4 score, one of the serum makers of liver fibrosis, in identifying severe liver fibrosis and early cirrhosis in patients with HBV-related liver fibrosis in China.CONCLUSION Our results indicate that IL-34, a cytokine involved in the induction of activation of profibrogenic macrophages, can be an indicator of liver inflammation and fibrosis in patients with chronic HBV infection.展开更多
In arid and semi-arid regions, freshwater scarcity and high water salinity are serious and chronic problems for crop production and sustainable agriculture development. We conducted a field experiment to evaluate the ...In arid and semi-arid regions, freshwater scarcity and high water salinity are serious and chronic problems for crop production and sustainable agriculture development. We conducted a field experiment to evaluate the effect of irrigation water salinity and nitrogen（N） application rate on soil salinity and cotton yield under drip irrigation during the 2011 and 2012 growing seasons. The experimental design was a 3×4 factorial with three irrigation water salinity levels（0.35, 4.61 and 8.04 dS/m） and four N application rates（0, 240, 360 and 480 kg N/hm2）. Results showed that soil water content increased as the salinity of the irrigation water increased, but decreased as the N application rate increased. Soil salinity increased as the salinity of the irrigation water increased. Specifically, soil salinity measured in 1：5 soil：water extracts was 218% higher in the 4.61 dS/m treatment and 347% higher in the 8.04 dS/m treatment than in the 0.35 dS/m treatment. Nitrogen fertilizer application had relatively little effect on soil salinity, increasing salinity by only 3%–9% compared with the unfertilized treatment. Cotton biomass, cotton yield and evapotranspiration（ET） decreased significantly in both years as the salinity of irrigation water increased, and increased as the N application rate increased regardless of irrigation water salinity; however, the positive effects of N application were reduced when the salinity of the irrigation water was 8.04 dS/m. Water use efficiency（WUE） was significantly higher by 11% in the 0.35 dS/m treatment than in the 8.04 dS/m treatment. There was no significant difference in WUE between the 0.35 dS/m treatment and the 4.61 dS/m treatment. The WUE was also significantly affected by the N application rate. The WUE was highest in the 480 kg N/hm2 treatment, being 31% higher than that in the 0 kg N/hm2 treatment and 12% higher than that in the 240 kg N/hm2 treatment. There was no significant difference between the 360 and 480 kg N/hm2 treatments. The N use efficiency（NUE） was significantly lower in the 8.04 dS/m treatment than in either the 4.61 dS/m or the 0.35 dS/m treatment. There was no significant difference in NUE between the latter two treatments. These results suggest that irrigation water with salinity 〈4.61 dS/m does not have an obvious negative effect on cotton production, WUE or NUE under the experimental conditions. Application of N fertilizer（0–360 kg N/hm2） could alleviate salt damage, promote cotton growth, and increase both cotton yield and water use efficiency.展开更多
Objective:To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.Methods:Cell counting and MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3-carbo...Objective:To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.Methods:Cell counting and MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium,inner salt) method were used to monitor the effects of cordycepin on cell proliferation.Flow cytometry(FCM) was used to analyze the effects of cordycepin on the cell cycle progress.Annexin V-fluorescein isothiocyanate(FITC) analysis was used to detect apoptosis at a very early stage.Caspase-Glo was used to determine caspase activity and Western blot was used to measure protein expression levels of c-Jun N-terminal kinase(JNK),p38,and Bcl-2 pro-apoptosis family.Results:The numbers of viable SW480 and SW620 cells and the proliferation of these cells were significantly reduced with increases in cordycepin concentration(P<0.01).The cell cycle progression of SW480 and SW620 was arrested at the G0/G1 phase by the addition of cordycepin,and apoptosis rates of cordycepin treatments were increased compared with the control group.Cordycepin-treated cells showed phosphatidylserine valgus,suggesting the existence of early apoptosis.Caspase-3/7 and-9 activity significantly increased and the protein expression levels of JNK,p38,and Bax,Bid,Bim,and Puma from Bcl-2 pro-apoptosis molecules also increased after the treatment with cordycepin.Conclusions:Cordycepin can inhibit SW480 and SW620 cell proliferation and induce apoptosis.Apoptosis might be induced by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules.展开更多
基金supported by the National Natural Science Foundation of China(No.42207175)。
文摘The joint roughness coefficient(JRC) is one of the key parameters for evaluating the shear strength of rock joints.Because of the scale effect in the JRC,reliable JRC values are of great importance for most rock engineering projects.During the collection process of JRC samples,the redundancy or insufficiency of representative rock joint surface topography(RJST) information in serial length JRC samples is the essential reason that affects the reliability of the scale effect results.Therefore,this paper proposes an adaptive sampling method,in which we use the entropy consistency measure Q(a) to evaluate the consistency of the joint morphology information contained in adjacent JRC samples.Then the sampling interval is automatically adjusted according to the threshold Q(at) of the entropy consistency measure to ensure that the degree of change of RJST information between JRC samples is the same,and ultimately makes the representative RJST information in the collected JRC samples more balanced.The application results of actual cases show that the proposed method can obtain the scale effect in the JRC efficiently and reliably.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFC2801700Defense Industrial Technology Development Program,Grant/Award Numbers:JCKY2021110B024,JCKY2022110C072+6 种基金Science and Technology Innovation 2030-“New Generation Artificial Intelligence”Major Project,Grant/Award Number:2022ZD0116305Natural Science Foundation of Hefei,China,Grant/Award Number:202321National Natural Science Foundation of China,Grant/Award Numbers:U2013601,U20A20225Yangtze River Delta S&T Innovation Community Joint Research Project,Grant/Award Number:2022CSJGG0900Anhui Province Natural Science Funds for Distinguished Young Scholar,Grant/Award Number:2308085J02State Key Laboratory of Intelligent Green Vehicle and Mobility,Grant/Award Number:KFY2417State Key Laboratory of Advanced Design and Manufacturing Technology for Vehicle,Grant/Award Number:32215010。
文摘A mixed adaptive dynamic programming(ADP)scheme based on zero-sum game theory is developed to address optimal control problems of autonomous underwater vehicle(AUV)systems subject to disturbances and safe constraints.By combining prior dynamic knowledge and actual sampled data,the proposed approach effectively mitigates the defect caused by the inaccurate dynamic model and significantly improves the training speed of the ADP algorithm.Initially,the dataset is enriched with sufficient reference data collected based on a nominal model without considering modelling bias.Also,the control object interacts with the real environment and continuously gathers adequate sampled data in the dataset.To comprehensively leverage the advantages of model-based and model-free methods during training,an adaptive tuning factor is introduced based on the dataset that possesses model-referenced information and conforms to the distribution of the real-world environment,which balances the influence of model-based control law and data-driven policy gradient on the direction of policy improvement.As a result,the proposed approach accelerates the learning speed compared to data-driven methods,concurrently also enhancing the tracking performance in comparison to model-based control methods.Moreover,the optimal control problem under disturbances is formulated as a zero-sum game,and the actor-critic-disturbance framework is introduced to approximate the optimal control input,cost function,and disturbance policy,respectively.Furthermore,the convergence property of the proposed algorithm based on the value iteration method is analysed.Finally,an example of AUV path following based on the improved line-of-sight guidance is presented to demonstrate the effectiveness of the proposed method.
文摘Objective:Mycophenolate mofetil(MMF)is frequently prescribed to pediatric patients with nephrotic syndrome(NS);however,information on the active metabolite mycophenolic acid(MPA)in this population is limited.Method:Using ultra-high performance liquid chromatography–tandem mass spectrometry(UHPLC–MS/MS),we validated a rapid and simple approach to measure MPA in accordance with the Bioanalytical Method Validation Guidance issued by the relevant regulatory authorities.Statistical analyses were performed on 69 pediatric patients with frequently relapsing/steroid-dependent nephrotic syndrome(FRNS/SDNS)who received corticosteroids plus MMF.Results:Forty-two patients achieved the endpoints and reported adverse events(AEs).The area under the concentration–time curve of MPA in the AE group was further distributed.Monitoring blood MPA concentrations is critical to prevent AEs during MMF administration in children with FRNS/SDNS.Conclusion:UHPLC–MS/MS offers a more accurate reference than immunoassays.
基金the Fundamental Research Foundation of CAF(CAFYBB2022QB001)National Nature Science Foundation of China(32222058)for financial support.
文摘A novel environmentally benign biphasic system composed of propylene carbonate(PC) and aqueous solution of p-toluenesulfonic acid(p-TsOH aq) was designed for the efficient valorization of lignocellulosic bamboo residues, resulting in more than 95.5% of hemicellulose and 97.2% of lignin digested under mild conditions of 130°C for 1 h. Meanwhile, 91.9% of cellulose was retained with loose structure, followed by 95.8% enzyme hydrolysis yield and 347.9 mg g-1of glucose yield. Notably, the synergistic effect between PC and p-TsOH on efficiency and selectivity was proposed by a control group experiment and subsequently verified, which is believed to be responsible for the simultaneous degradation and separation of lignin and hemicelluloses into oligomeric phenols and pentose, also facilitating subsequent valorization.Furthermore, the novel PC/p-TsOH aq biphasic system demonstrated excellent retrievability and adaptability to different feedstocks, offering a promising green strategy for the efficient valorization of lignocellulosic biomass in industrial biorefineries.
基金Supported by the China Ocean Mineral Resources R&D Association(No.DY135-S2-2)the Basic Scientific Fund for National Public Research Institutes of China(No.2021Q01)the National Natural Science Foundation of China(Nos.42106080,42006180,42276080)。
文摘The hydrothermal signatures of mid-ocean ridge sediments are crucial geochemical data providing insights into investigating hydrothermal anomalies and locating seafloor massive sulfide deposits.This paper outlines the geochemical features of 24 surface sediments and one sediment core(26 V-GC 01,294 cm)along the South Mid-Atlantic Ridge(SMAR)from 18°S to 22°S,an area where hydrothermal active fields have yet to be discovered.The surface sediments mainly consist of biogenic carbonates,aluminosilicates,and hydrothermal Fe-Mn(oxy)oxides.The core sediments primarily comprise organic matter,detrital materials,hydrothermal components,and substances scavenged from seawater.The rare Earth element(REE)patterns suggest the presence of hydrothermal contributions within the surface and core sediments.The enrichment factors for Fe,Mn,Cu,and Zn in surface sediments suggest these metals are concentrated at the 19°S,21°S,and 21.5°S segments,further indicating their potential as hydrothermal active fields.Downcore variations of Fe,Mn,P,Cu,Pb,V,and Co suggest at least six episodes of hydrothermal activity.The impact of hydrothermal processes on the sediments from SMAR 18°S to 22°S indicates that the study area has the potential to host a significant number of hydrothermal active fields.
基金funded by Tongzhou District Health Development Research Reserve Project Foundation(No.KJ2024CX024)Natural Science Foundation of Tianjin City(No.23JCQNJC01640)+1 种基金National Natural Science Foundation of China(Nos.82304393,22404122)Beijing Nova Program(No.Z211100002121127).
文摘Metal ions trigger Fenton/Fenton-like reactions,generating highly toxic hydroxyl radicals(•OH)for chemodynamic therapy(CDT),which is crucial in inducing lethal oxidative DNA damage and subsequent cell apoptosis.However,tumor cells can counteract this damage through repair pathways,particularly MutT homolog 1(MTH1)protein attenuation of oxidative DNA damage.Suppression of MTH1 can enhance CDT efficacy,therefore,orderly integrating Fenton/Fenton-like agents with an MTH1 inhibitor is expected to significantly augment CDT effectiveness.Carrier-free CuTH@CD,self-assembled through the supramolecular orchestration ofγ-cyclodextrin(γ-CD)with Cu^(2+)and the MTH1 inhibitor TH588,effectively overcoming tumor resistance by greatly amplifying oxidative damage capability.Without additional carriers and mediated by multiple supramolecular regulatory effects,CuTH@CD enables high drug loading content,stability,and uniform size distribution.Upon internalization by tumor cells,CuTH@CD invalidates repair pathways through Cu^(2+)-mediated glutathione(GSH)depletion and TH588-mediated MTH1 inhibition.Meanwhile,both generated Cu^(+)ions and existing ones within the nanoassembly initiate a Fentonlike reaction,leading to the accumulation of•OH.This strategy enhances CDT efficiency with minimal side effects,improving oxidative damage potency and advancing self-delivery nanoplatforms for developing effective chemodynamic tumor therapies.
基金supported by the National Natural Science Foundation of China(Nos.42077289,42277197,and 41877422).
文摘Microorganisms play a critical role in the biotransformation of arsenic and the form which it exists in the environment. In this study, a methyl parathion-degrading bacterium Caballeronia jiangsuensis, isolated from an abandoned pesticide manufacturing plant, was used to analyze arsenic accumulation and transformation. The accumulation of trivalent organoarsenic compounds in C. jiangsuensis occurred to a greater extent than that of their pentavalent counterparts. The chromosome of C. jiangsuensis contains an arsenic gene island whose GC content is significantly lower than that of the genome, suggesting that the island was acquired via horizontal gene transfer. There was approximately 90%-99% similarity between the proteins encoded by the gene island and the corresponding sequence of the plasmid pkk5 from Burkholderia sp. KK1. The biotransformation of different arsenic species by C. jiangsuensis was subsequently analyzed. The results revealed that monomethylarsenic acid(MAs(Ⅴ)) was rapidly demethylated to arsenate with very small amounts of intermediate monomethylarsonous acid(MAs(Ⅲ)), whereas MAs(Ⅲ) was largely oxidized to MAs(Ⅴ) despite the occurrence of the gene arsI probably responsible for aerobic demethylation of MAs(Ⅲ) in C. jiangsuensis. In addition, dimethylarsenic acid was partly demethylated to arsenate. Horizontal gene transfer of ars operon from a plasmid to other bacteria represents an adaptation to a specific environment. This study provides a new perspective for understanding arsenic biogeochemical cycling.
基金Jingmen science and technology research and development plan(2019yfzd024).
文摘Objective:To observe the clinical effect of modified Yu Rong San gel eye mask in the treatment of dark circles.Methods:96 cases of patients with dark circles were randomly divided into treatment group and control group.In the control group and the treatment group,the common eye mask and the modified Yu Rong San gel eye mask were applied to the black circle area respectively.After 15min,water was used to wash the face,the application of the mask for one time a day,four weeks,one course,and three courses were observed.Results:After three courses of treatment,the total effective rate of the treatment group was higher than that of the control group(P<0.05);the area of black eye circles in the treatment group was smaller than that before treatment(P<0.05);compared with the control group,the score of black eye circles was lower than that before treatment,the difference was statistically significant(P<0.05).Conclusions Addition and reduction of Yu Rong San gel eye mask is effective in the treatment of dark circles.
基金supported by the grants from the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.:2021-I2M-1-026)the Beijing Natural Science Foundation of China(Grant Nos.:7212155 and 7162135).
文摘Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.
基金financially supported by Beijing Nova Program(Nos.Z211100002121127 and 20220484219)Beijing Natural Science Foundation(No.L212059)+1 种基金Fundamental Research Funds for the Central Universities(No.3332021101)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2021-I2M-1-026 and 2021-I2M-1-028).
文摘Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.
基金supported by the National Nature Science Foundation of China (32222058, 32001274)the Youth Talent Support Program for Science & Technology Innovation of National Forestry and Grassland (2019132603) for financial support。
文摘Converting carbohydrates into 5-hydroxymethylfurfural(5-HMF) is an attractive and promising route for value-added utilization of agricultural and forestry biomass resource. As an important platform compound, 5-HMF possesses high active furan structure with hydroxymethyl and aldehyde group for production of various bio-chemicals and materials, meanwhile, which suffer from low stability and poor yield during the industrial biorefinery process. Hence, selective production of 5-HMF with high-yield and low-cost has attracted extensive attention from scientific and industrial researchers. This review sorted and described the latest advanced research on solvent and catalyst system, as well as energy field effect for production of 5-HMF with different feedstock in detail, emphatically discussing the solvent effect and its synergistic effect with other aspects. Besides, the future prospects and challenges for production of 5-HMF from carbohydrates were also presented, which provide a profound insight into industrial 5-HMF process with economic and environmental feature.
基金Supported by the Anhui Provincial Natural Science Foundation,No.2108085MH298the Scientific Research Project of the Second Affiliated Hospital of Anhui Medical University,No.2019GMFY02 and 2021lcxk027the Scientific Research Project of Colleges and Universities in Anhui Province,No.KJ2021A0323.
文摘BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.
基金funded by the National Natural Science Foundation of China(Grant Nos:62172131 and 81872135)the Outstanding Youth Foundation of Heilongjiang Province of China(Grant No.:YQ2021C026).
文摘Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high heterogeneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell proliferation,differentiation,and disease progression.Significant associations between tumor grade,prognosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.
基金financially supported by the National Natural Science Foundation(No.82304393,China)Beijing Nova Program(Nos.Z211100002121127 and 20220484219,China)+1 种基金Beijing Natural Science Foundation(No.L212059,China)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-028,China)。
文摘Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.
基金the National Natural Science Foundation of China(Grant No.:51803120).
文摘Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.
文摘BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.
基金Natural Science Foundation of Anhui Province,No.1608085MH164
文摘AIM To investigate whether serum interleukin(IL)-34 levels are correlated with hepatic inflammation and fibrosis in patients with chronic hepatitis B virus(HBV) infection. METHODS In this study, serum IL-34 levels were assessed by enzyme-linked immunosorbent assay in 19 healthy controls and 175 patients with chronic HBV infection undergoing biopsy. The frequently used serological markers of liver fibrosis were based on laboratory indexes measured at the Clinical Laboratory of the Second Affiliated Hospital of Anhui Medical University. Liver stiffness was detected by transient elastography with Fibro Touch. The relationships of non-invasive makers of liver fibrosis and IL-34 levels with inflammation and fibrosis were analyzed. The diagnostic value of IL-34 and other liver fibrosis makers wereevaluated using areas under the receiver operating characteristic curves, sensitivity and specificity.RESULTS Serum IL-34 levels were associated with inflammatory activity in the liver, and IL-34 levels differed among phases of chronic HBV infection(P = 0.001). By comparing serum IL-34 levels among patients with various stages of liver fibrosis determined by liver biopsy, we found that IL-34 levels ≥ 15.83 pg/m L had a high sensitivity of 86.6% and a specificity of 78.7% for identifying severe fibrosis(S3-S4). Furthermore, we showed that IL-34 is superior to the fibrosis-4 score, one of the serum makers of liver fibrosis, in identifying severe liver fibrosis and early cirrhosis in patients with HBV-related liver fibrosis in China.CONCLUSION Our results indicate that IL-34, a cytokine involved in the induction of activation of profibrogenic macrophages, can be an indicator of liver inflammation and fibrosis in patients with chronic HBV infection.
基金funded by the National Basic Research Program of China (2009CB825101)the National Natural Science Foundation of China (30960210)
文摘In arid and semi-arid regions, freshwater scarcity and high water salinity are serious and chronic problems for crop production and sustainable agriculture development. We conducted a field experiment to evaluate the effect of irrigation water salinity and nitrogen（N） application rate on soil salinity and cotton yield under drip irrigation during the 2011 and 2012 growing seasons. The experimental design was a 3×4 factorial with three irrigation water salinity levels（0.35, 4.61 and 8.04 dS/m） and four N application rates（0, 240, 360 and 480 kg N/hm2）. Results showed that soil water content increased as the salinity of the irrigation water increased, but decreased as the N application rate increased. Soil salinity increased as the salinity of the irrigation water increased. Specifically, soil salinity measured in 1：5 soil：water extracts was 218% higher in the 4.61 dS/m treatment and 347% higher in the 8.04 dS/m treatment than in the 0.35 dS/m treatment. Nitrogen fertilizer application had relatively little effect on soil salinity, increasing salinity by only 3%–9% compared with the unfertilized treatment. Cotton biomass, cotton yield and evapotranspiration（ET） decreased significantly in both years as the salinity of irrigation water increased, and increased as the N application rate increased regardless of irrigation water salinity; however, the positive effects of N application were reduced when the salinity of the irrigation water was 8.04 dS/m. Water use efficiency（WUE） was significantly higher by 11% in the 0.35 dS/m treatment than in the 8.04 dS/m treatment. There was no significant difference in WUE between the 0.35 dS/m treatment and the 4.61 dS/m treatment. The WUE was also significantly affected by the N application rate. The WUE was highest in the 480 kg N/hm2 treatment, being 31% higher than that in the 0 kg N/hm2 treatment and 12% higher than that in the 240 kg N/hm2 treatment. There was no significant difference between the 360 and 480 kg N/hm2 treatments. The N use efficiency（NUE） was significantly lower in the 8.04 dS/m treatment than in either the 4.61 dS/m or the 0.35 dS/m treatment. There was no significant difference in NUE between the latter two treatments. These results suggest that irrigation water with salinity 〈4.61 dS/m does not have an obvious negative effect on cotton production, WUE or NUE under the experimental conditions. Application of N fertilizer（0–360 kg N/hm2） could alleviate salt damage, promote cotton growth, and increase both cotton yield and water use efficiency.
基金supported by the Department of Education of Zhejiang Province(No. Y200804636)the Department of Science and Tech-nology of Zhejiang Province(Nos. 2008C23049,2007C23027,and2009C33081)the Natural Science Foundation of Zhejiang Province(No. Y206174),China
文摘Objective:To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.Methods:Cell counting and MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium,inner salt) method were used to monitor the effects of cordycepin on cell proliferation.Flow cytometry(FCM) was used to analyze the effects of cordycepin on the cell cycle progress.Annexin V-fluorescein isothiocyanate(FITC) analysis was used to detect apoptosis at a very early stage.Caspase-Glo was used to determine caspase activity and Western blot was used to measure protein expression levels of c-Jun N-terminal kinase(JNK),p38,and Bcl-2 pro-apoptosis family.Results:The numbers of viable SW480 and SW620 cells and the proliferation of these cells were significantly reduced with increases in cordycepin concentration(P<0.01).The cell cycle progression of SW480 and SW620 was arrested at the G0/G1 phase by the addition of cordycepin,and apoptosis rates of cordycepin treatments were increased compared with the control group.Cordycepin-treated cells showed phosphatidylserine valgus,suggesting the existence of early apoptosis.Caspase-3/7 and-9 activity significantly increased and the protein expression levels of JNK,p38,and Bax,Bid,Bim,and Puma from Bcl-2 pro-apoptosis molecules also increased after the treatment with cordycepin.Conclusions:Cordycepin can inhibit SW480 and SW620 cell proliferation and induce apoptosis.Apoptosis might be induced by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules.
