Simultaneous removing SO_2 and NO by a new system containing cobalt complex

Absorption and catalytic oxidation of nitric oxide can be achieved by using cobalt（Ⅲ） ethylenediamine （Co（en）3^3＋. When simultaneous absorbing SO2 and NO, the precipitation of Co2（SO3）3 will be yielded and the NO removal will be decreased. A new catalyst system using Co（en）3^3＋ coupled with urea has been developed to simultaneous remove NO and SO2 in the flue gas. NO is absorbed and catalytically oxidized to nitrite and nitrate by Co（en）3^3＋. The dissolved oxygen in scrubbing solution from the feed stream acts as oxidant. Urea restrains the precipitation of Co2（SO3）3 by oxidizing SO3^2-to SO4^2- as COSO4 is more soluble in water. The experimental results proved that nearly all SO3^2- can be oxidized to SO4^2- and the high NO and SO2 removal could be obtained with the new system. The NO removal is influenced by gas flow rate, the concentration of Co（en）3^3＋ and urea in the absorption solution, the temperature of the scrubbing solution and the content of oxygen in the flue gas. The low gas flow rate is favorable to increase the NO removal. The experiments proved that the NO removal could be maintained at more than 95% by the system of 0.02 mol/L Co（en）3^3＋ and 1% urea at 50℃ with 10% O2 in the flue gas.

Evaluation of the intracellular lipid-lowering effect of polyphenols extract from highland barley in HepG2 cells

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.

Sensory Phenotypic and Molecular Identification of Aromatic Rice Accessions Cultivated in Benin

Rice is one of the most widely cultivated cereals in the world, and its aroma is increasingly in demand. With the advancement of research, a major rice flavor gene has been identified on rice chromosome 8. It encodes non-functional betaine aldehyde dehydrogenase leading to the accumulation of 2-acetyl-1-pyrroline which is the major olfactory compound that confers the fragrant character to rice. The aroma of rice is considered a special trait of enormous economic importance that determines the prime price in world trade. To satisfy the needs of the population and reduce rice imports into Benin, we conducted this study to identify aromatic rice accessions grown in Benin. Seventy-two rice accessions collected across Benin were PCR amplified with three SSR markers RM 7049, Aro 7, and RM 223, linked to the fgr (fragrance of rice) aroma gene. Molecular analysis revealed that 12 of the 72 accessions, namely Bagou 19, Bagou 22, Tchaka 34, Foun 15, Tchaka 41, Nana 32, Kan 61, Kung 69, Kung 67, Bagou 20, Agbab 101 and Koum 55 possess the fgr gene and can be considered as aromatic rice accessions. A sensory phenotypic test using KOH was carried out on rice accessions carrying fgr gene. Of the twelve positives, only one had the smell of aromatic rice, like the Azucena control. These results show that Benin also has aromatic rice varieties that can be sold on national and international markets.

Leveraging Nanotechnology for Addressing COVID-19: Revealing Antiviral Approaches and Hurdles

The emergence of COVID-19 has caused extensive harm and is recognized as a significant threat to human life worldwide. Currently, the application of nanomedicine techniques in pre-clinical studies related to various infections, such as respiratory viruses, herpes viruses, human papillomavirus, and HIV, has demonstrated success. Nanoparticles, due to their specific attributes, have garnered considerable attention in combating COVID-19. Strategies employing nanomaterials for COVID-19 prevention encompass the development of rapid, precise diagnostic tools, the creation of effective disinfectants, the delivery of mRNA vaccines to the biological system, and the administration of antiretroviral medications within the body. This article focuses on recent research regarding the effectiveness of nano platforms as antiviral measures against coronaviruses. It delves into the molecular characteristics of coronaviruses and the affected target systems, highlighting challenges and limitations in combating SARS-CoV-2. Additionally, it explores potential nanotechnology-based treatments to confront current and future variants of coronaviruses associated with COVID-19 infections.

Identification and Validation of Novel Biomarkers Related to the Calcium Metabolism Pathway in Hypertension Patients Based on Comprehensive Bioinformatics Methods

Background: Hypertension is a universal risk factor for cardiovascular diseases and is thus the leading cause of death worldwide. The identification of novel prognostic and pathogenesis biomarkers plays a key role in disease management. Methods: The GSE145854 and GSE164494 datasets were downloaded from the Gene Expression Omnibus (GEO) database and used for screening and validating hypertension signature genes, respectively. Gene Ontology (GO) enrichment analysis was performed on the differentially expressed genes (DEGs) related to calcium ion metabolism in patients with hypertension. The core genes related to immune infiltration were analyzed and screened, and the activity of the signature genes and related pathways was quantified using gene set enrichment analysis (GSEA). The infiltration of immune cells in the blood samples was analyzed, and the DEGs that were abnormally expressed in the clinical blood samples of patients with hypertension were verified via RT-qPCR. Results: A total of 176 DEGs were screened. GO showed that DEGs was involved in the regulation of calcium ion metabolism in biological processes (BP), actin mediated cell contraction, negative regulation of cell movement, and calcium ion transmembrane transport, and in the regulation of protease activity in molecular functions (MF). KEGG analysis revealed that the DEGs were involved mainly in the cGMP-PKG signaling pathway, ubiquitin-protein transferase, tight junction-associated proteins, and the regulation of myocardial cells. MF analysis revealed the immune infiltration function of the cells. RT-qPCR revealed that the expression of Cacna1d, Serpine1, Slc8a3, and Trpc4 was up regulated in hypertension, the expression of Myoz2 and Slc25a23 was down regulated. Conclusion: Cacna1d, Serpine1, Slc8a3, Trpc4, Myoz2 and Slc25a23 may be involved in the regulation of calcium metabolism pathways and play key roles in hypertension. These differentially expressed calcium metabolism-related genes may serve as prognostic markers of hypertension.

Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC.Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups.Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.

Mitochondrial carrier homolog 2 increases malignant phenotype of human gastric epithelial cells and promotes proliferation,invasion,and migration of gastric cancer cells

BACKGROUND The precise role of mitochondrial carrier homolog 2(MTCH2)in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated.AIM To determine the role of MTCH2 in gastric cancer.METHODS We collected 65 samples of poorly differentiated gastric cancer tissue and adjacent tissues,constructed MTCH2-overexpressing and MTCH2-knockdown cell models,and evaluated the proliferation,migration,and invasion of human gastric epithelial cells(GES-1)and human gastric cancer cells(AGS)cells.The mito-chondrial membrane potential(MMP),mitochondrial permeability transformation pore(mPTP)and ATP fluorescence probe were used to detect mitochondrial function.Mitochondrial function and ATP synthase protein levels were detected via Western blotting.RESULTS The expression of MTCH2 and ATP2A2 in gastric cancer tissues was significantly greater than that in adjacent tissues.Overexpression of MTCH2 promoted colony formation,invasion,migration,MMP expression and ATP production in GES-1 and AGS cells while upregulating ATP2A2 expression and inhibiting cell apoptosis;knockdown of MTCH2 had the opposite effect,promoting overactivation of the mPTP and promoting apoptosis.CONCLUSION MTCH2 can increase the malignant phenotype of GES-1 cells and promote the proliferation,invasion,and migration of gastric cancer cells by regulating mitochondrial function,providing a basis for targeted therapy for gastric cancer cells.

Phospholipase A2 enzymes PLA2G2A and PLA2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma

BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.

Nrf2 and Her3 co-expression in cholangiocarcinoma:Possible biological pathways for potential therapeutic approach

To the Editor:Cholangiocarcinomas(CCAs)are heterogeneous group of malignancies,encompassing intrahepatic CCA(iCCA),and extrahepatic CCA(eCCA);they are also classified into common hepatic duct cholangiocarcinoma(CHDCCA),choledocus extrapancreatic cholangiocarcinoma(EPCCA)and choledocus intrapancreatic cholangiocarcinoma(IPCCA)and,finally,gallbladder carcinoma(GBCCA).CCAs are relatively uncommon but.

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.

Solar-driven CO_(2) conversion to methane and methanol using different nanostructured Cu_(2)O-based catalysts modified with Au nanoparticles

This work describes the use of TiO_(2)nanotubes-based electrodes(TNT)modified with Cu_(2)O nanostructures and gold nanoparticles for the photoelectroreduction of CO_(2)to produce value-added compounds.A thin layer of polydopamine was used as both an adherent agent and an electron transfer mediator,due to itsπ-conjugated electron system.The highest production yield was achieved using a TNT@PDA/Nc/Au40%electrode,with Faradaic efficiencies of 47.4%(110.5μM cm^(-2))and 27.8%(50.4μM cm^(-2))for methanol and methane,respectively.The performance of the photoelectrodes was shown to be Cu_(2)O facet-dependent,with cubic structures leading to greater conversion of CO_(2)to methanol(43%)and methane(27%),compared to the octahedral morphology,while a higher percentage of metallic gold on the nanostructured Cu_(2)O surface was mainly important for CH4production.Density functional theory(DFT)calculations supported these findings,attributing the superior photoelectrocatalytic performance of the TNT@PDA/Nc/Au40%electrode for CH4generation to the formation of an OCH3intermediate bonded to Au atoms.Studies using isotope-labeling and analysis by gas chromatograph-mass(GC-MS)demonstrated that13CO_(2)was the source for photoelectrocatalytic generation of13CH3OH and13CH313CH2OH.

Hypoglycemic mechanism of Tegillarca granosa polysaccharides on type 2 diabetic mice by altering gut microbiota and regulating the PI3K-akt signaling pathwaye

Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.

High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1βproduction in monocytes:the modulatory effects of EGCG

Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.

Galectin 2 regulates JAK/STAT3 signaling activity to modulate oral squamous cell carcinoma proliferation and migration in vitro

Background:Galectin 2(LGALS2)is a protein previously reported to serve as a mediator of disease progression in a range of cancers.The function of LGALS2 in oral squamous cell carcinoma(OSCC),however,has yet to be explored,prompting the present study to address this literature gap.Methods:Overall,144 paired malignant tumor tissues and paracancerous OSCC patient samples were harvested and the LGALS2 expression levels were examined through qPCR and western immunoblotting.The LGALS2 coding sequence was introduced into the pcDNA3.0 vector,to enable the overexpression of this gene,while an LGALS2-specific shRNA and corresponding controls were also obtained.The functionality of LGALS2 as a regulator of the ability of OSCC cells to grow and undergo apoptotic death in vitro was assessed through EdU uptake and CCK-8 assays,and flow cytometer,whereas a Transwell system was used to assess migratory activity and invasivity.An agonist of the Janus Kinase 2(JAK2)/Signal Transducer and Activator of Transcription 3(STAT3)pathway was also used to assess the role of this pathway in the context of LGALS2 signaling.Results:Here,we found that lower LGALS2 protein and mRNA expression were evident in OSCC tumor tissue samples,and these expression levels were associated with clinicopathological characteristics and patient survival outcomes.Silencing LGALS2 enhanced proliferation in OSCC cells while rendering these cells better able to resist apoptosis.The opposite was instead observed after LGALS2 was overexpressed.Mechanistically,the ability of LGALS2 to suppress the progression of OSCC was related to its ability to activate the JAK/STAT3 signaling axis.Conclusion:Those results suggest a role for LGALS2 as a suppressor of OSCC progression through its ability to modulate JAK/STAT3 signaling,supporting the potential utility of LGALS2 as a target for efforts aimed at treating OSCC patients.

Active Cancelation of Acoustic Noise in Waveguides by Standard Control Task Decision Usage

Cybernetic decision variants were analyzed in order to use for physical task of active noise cancelation. 10 dB mean active noise cancellation is demonstrated in two decades frequency band by usage of cybernetic decision for acoustical duct physical scale model. The used decision was found on minimization of acoustical field power transfer function from the beginning of waveguide to their end.

Automatic modulation recognition of radio fuzes using a DR2D-based adaptive denoising method and textural feature extraction

The identification of intercepted radio fuze modulation types is a prerequisite for decision-making in interference systems.However,the electromagnetic environment of modern battlefields is complex,and the signal-to-noise ratio(SNR)of such environments is usually low,which makes it difficult to implement accurate recognition of radio fuzes.To solve the above problem,a radio fuze automatic modulation recognition(AMR)method for low-SNR environments is proposed.First,an adaptive denoising algorithm based on data rearrangement and the two-dimensional(2D)fast Fourier transform(FFT)(DR2D)is used to reduce the noise of the intercepted radio fuze intermediate frequency(IF)signal.Then,the textural features of the denoised IF signal rearranged data matrix are extracted from the statistical indicator vectors of gray-level cooccurrence matrices(GLCMs),and support vector machines(SVMs)are used for classification.The DR2D-based adaptive denoising algorithm achieves an average correlation coefficient of more than 0.76 for ten fuze types under SNRs of-10 d B and above,which is higher than that of other typical algorithms.The trained SVM classification model achieves an average recognition accuracy of more than 96%on seven modulation types and recognition accuracies of more than 94%on each modulation type under SNRs of-12 d B and above,which represents a good AMR performance of radio fuzes under low SNRs.

Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P<0.05).At the 12-month follow-up,13 patients(1.9%)died and 96 patients(14.2%)experienced MACCEs.Patients with CLR(9.6%vs.11.7%vs.22.1%,P<0.05)or poor metabolizer(10.7%vs.16.4%vs.22.6%,P=0.026)experienced a higher rate of MACCEs.A MACCEs risk score between zero and two was calculated.The highest incidence of MACCEs significantly increased with the 2-positive results,and the area under the curve(AUC)was 0.712(95%CI:0.650-0.774,P<0.05).There was no significant difference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.