Hepatocellular carcinoma (HCC) is a malignancy with a high incidence and fatality rate worldwide. Hepatitis B virus (HBV) infection is one of the most important risk factors for its occurrence and ...development. Early detection of HBV-associated HCC (HBV-HCC) can improve clinical decision-making and patient outcomes. Biomarkers are extremely helpful, not only for early diagnosis, but also for the development of therapeutics. MicroRNAs (miRNAs), a subset of non-coding RNAs approximately 22 nucleotides in length, have increasingly attracted scientists’ attention due to their potential utility as biomarkers for cancer detection and therapy. HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis. In this review, we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC. From a molecular standpoint, we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC. In the near future, miRNA-based diagnostic, prognostic, and therapeutic applications will make their way into the clinical routine.
Incorrect use of neonicotinoid pesticides poses a serious threat to human and pollinator health, as these substances are commonly present in bee products and even drinking water. To combat this ...threat, the study developed a new method of degrading the pesticide imidacloprid using surface discharge cold plasma oxidation technology. The study showed that this method achieved a very high efficiency of imidacloprid degradation of 91.4%. The main reactive oxygen species (H2O2, O3, ·OH, O2-, 1O2) effectively participated in the decomposition reaction of imidacloprid. Reactive oxygen species were more sensitive to the structure of the nitroimine group. Density functional theory (DFT) further explored the sites of reactive oxygen species attack on imidacloprid and revealed the process of energy change of attacking imidacloprid. In addition, a degradation pathway for imidacloprid was proposed, mainly involving reactive oxygen species chemisorption, a ring-opening intermediate, and complete cleavage of the nitroimine group structure. Model predictions indicated that acute oral and developmental toxicity were significantly reduced after cold plasma treatment, as confirmed by insect experiments. Animal experiments have shown that plasma treatment reduces imidacloprid damage to mice hippocampal tissue structure and inhibits the reduction of brain-derived neurotrophic factor content, thus revealing the detoxification mechanism of the body.
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•A new energy-efficient method for discharge cold plasma degradation of imidacloprid is proposed.•91.4% of imidacloprid was removed in the cold plasma system within 40 min.•1O2, O2–and •OH generated in the cold plasma process contributed to imidacloprid decomposition.•The sensitive sites for ROS attack on imidacloprid molecules were predicted by DFT calculations.•Possible imidacloprid degradation pathways and toxicity assessment are proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Plants use a dual defense system to cope with microbial pathogens. The first involves pathogen-associated molecular pattern-triggered immunity which is conferred by membrane receptors, and the second ...involves effector-triggered immunity (ETI), which is conferred by disease-resistance proteins (nucleotide-binding leucine-rich repeat-containing proteins; NLRs). Calmodulin-Binding Protein 60 (CBP60) family transcription factors are crucial for pathogen defense: CBP60g and Systemic Acquired Resistance Deficient 1 (SARD1) positively regulate immunity, whereas CBP60a negatively regulates immunity. The roles of other Arabidopsis (Arabidopsis thaliana) CBP60s remain unclear. We report that CBP60b positively regulates immunity and is redundant with-yet distinct from-CBP60g and SARD1. By combining chromatin immunoprecipitation-PCRs and luciferase reporter assays, we demonstrate that CBP60b is a transcriptional activator of immunity genes. Surprisingly, CBP60b loss-of-function results in autoimmunity, exhibiting a phenotype similar to that of CBP60b gain-of-function. Mutations at the ENHANCED DISEASE SUSCEPTIBILITY 1-PHYTOALEXIN DEFICIENT 4-dependent ETI pathway fully suppressed the defects of CBP60b loss-of-function but not those of CBP60b gain-of-function, suggesting that CBP60b is monitored by NLRs. Functional loss of SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1, an R-gene, partially rescued the phenotype of cbp60b, further supporting that CBP60b is a protein targeted by pathogen effectors, that is, a guardee. Unlike CBP60g and SARD1, CBP60b is constitutively and highly expressed in unchallenged plants. Transcriptional and genetic studies further suggest that CBP60b plays a role redundant with CBP60g and SARD1 in pathogen-induced defense, whereas CBP60b has a distinct role in basal defense, partially via direct regulation of CBP60g and SARD1.
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•Seismic performance of RC and FRC beam-column joints are investigated.•Experimental tests on RC and FRC beam-column joints are performed.•Numerical study on beam-column joints with ...FRC is presented.•The seismic performance of beam-column joints can be improved by usage of FRC.
Fiber-reinforced concrete (FRC), as an advanced alternative to normal concrete, has been increasingly used to construct beam-column joints which is one of the most congested parts of reinforcements in reinforced concrete (RC) structures because of its potentially beneficial properties. The present work aims to investigate the seismic performance of FRC beam-column joints experimentally and numerically. A total of eight beam-column joints, including both FRC beam-column joints and RC beam-column joint, were conducted to explore its seismically important features under quasi-static reversed cyclic load, mainly including the failure modes, hysteretic response, energy dissipation, stiffness degradation. It was found that the application of FRC can effectively improve the seismic performance of beam-column joints because it leads to higher load-carrying capacity and a greater deformation capability prior to the formation of the major diagonal cracks in the joint core zone. A numerical study, using the Open System for Earthquake Engineering Simulation (OpenSEES), was also conducted to study the seismic performance of beam-column joints deeply after its applicability and accuracy being validated with test data. The prediction from the proposed numerical model shows a good agreement with test data. Furthermore, a parametric study was generated to address and evaluate the effects on the seismic performance of FRC beam-column joints from different parameters, including the axial load ratios, transverse reinforcement ratios and FRC compressive strength. The results indicate that the increment of axial load ratios and FRC compressive strength can enhance the load-carrying capacity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Ovarian cancer is the leading cause of death among gynecologic cancer patients. Although platinum-based chemotherapy as a frontline treatment for ovarian cancer has been widely used in clinical ...settings, its clinical efficacy is not satisfactory due to the resistance of ovarian cancer cells to apoptosis. Therefore, it is of great significance to induce non-apoptotic programed cell death patterns, such as paraptosis, in ovarian cancer. In this study, we aimed to explore the potential anticancer mechanisms of novel rhein derivative 4a, which was modified with rhein as a lead compound. The results showed that a wide range of vacuoles from the endoplasmic reticulum and mitochondria appeared in ovarian SKOV3, SKOV3-PM4, and A2780 cells treated with derivative 4a, and the cell death caused by derivative 4a is a type of non-apoptotic and non-autophagic death, which is caused by expansion and damage of the endoplasmic reticulum or mitochondria, showing the characteristics of para-apoptotic death. Furthermore, derivative 4a stimulated the unfolded protein reaction of ovarian cancer cells by upregulating the expression of Bip78 and activating the PERK-eIF2α-ATF4 pathways. Notably, rhein derivative 4a-induced cell death was positively correlated with activation of p38, ERK, and JNK, and negatively correlated with Alix, a known protein that inhibits paraptosis. In addition, derivative 4a treatment also induced G2/M phase arrest in ovarian cancer cells. Taken together, our study reveals that derivative 4a induces paraptosis, and this finding can serve as a basis in developing a new strategy for the treatment of antiapoptotic ovarian cancer.
•Ovarian cancer is the leading cause of death among gynecologic cancer patients.•Paraptosis is an alternative, non-apoptotic form of programed cell death.•Derivative 4a treatment can induce paraptosis death in ovarian cancer cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Herpes zoster (HZ) refers to the rash appearing on dermatomes due to varicella zoster virus (VZV) reactivation. The incidence of HZ is significantly higher in allogeneic hematopoietic stem cell ...transplantation (allo‐HSCT) recipients than in non‐HSCT recipients. Although acyclovir prophylaxis is routinely administered to every allo‐HSCT recipient for 1 year after transplantation, some individuals eventually develop late‐onset HZ after completing prophylaxis. Little information is known about the clinical features of HZ after prophylactic antiviral treatment discontinuation, and an effective predictive model of late‐onset HZ needs to be established. A total of 3366 patients who had received allo‐HSCT from 2012 to 2017 were included in our study, among whom 201 developed HZ after 1 year (late‐onset HZ). We designed a nested case–control study to identify potential predictors of late‐onset HZ. Finally, we established a predictive model using binary logistic regression analysis. Age (p < .001), use of immunosuppressants at +1 year (p < .001), CD4‐CD8 ratio at +1 year (p < .001), certain mental disorders (depression, anxiety, insomnia and adjustment disorder) (p < .001), engraftment time of neutrophils (p < .001), and CD8+ cell count at +30 days (p < .001) were independent predictors of late‐onset HZ. A risk grading system was established based on regression coefficients. Discrimination and calibration analysis indicated that the model had good performance. We also identified several predictive factors of the incidence of HZ‐related complications. This is the first scoring system for predicting the incidence of late‐onset HZ after allo‐HSCT. This model can be applied to identify individuals at high risk of late‐onset HZ in the early period after receiving allo‐HSCT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Selenium (Se) is essential for successful male reproduction. However, the association of Se status with human semen quality remains controversial and the underlying mechanisms are poorly understood. ...We measured seminal plasma Se concentrations, sperm mitochondrial DNA copy number (mtDNAcn), and sperm quality parameters among healthy Chinese men screened as potential sperm donors. Linear mixed-effects models were used to investigate the associations of within-subject pooled seminal plasma Se concentrations (n = 1159) with repeated sperm quality parameters (n = 5617); mediation analyses were applied to evaluate the mediating role of sperm mtDNAcn (n = 989). Seminal plasma Se concentrations were positively associated with sperm concentration and total count (both P for trend < 0.001). In adjusted models, men in the top vs. bottom quartiles of seminal plasma Se concentrations had 70.1 % (95 % CI: 53.3 %, 88.9 %) and 59.1 % (95 % CI: 40.5 %, 80.2 %) higher sperm concentration and total count, respectively. Meanwhile, we observed inverse associations between seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm motility, concentration, and total count (all P for trend < 0.05). Mediation analyses suggested that sperm mtDNAcn mediated 19.7 % (95 % CI: 15.9 %, 25.3 %) and 23.1 % (95 % CI: 17.4 %, 33.4 %) of the associations between seminal plasma Se concentrations and sperm concentration and total count, respectively. Our findings suggest that Se is essential for male spermatogenesis, potentially by affecting sperm mtDNAcn.
•We collected 5617 semen samples from 1159 healthy men.•Seminal plasma Se concentrations were inversely associated with sperm mtDNAcn.•Seminal plasma Se was positively related to sperm concentration and total count.•The association of Se with semen quality was partly mediated by sperm mtDNAcn.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cuproptosis seems to promote the progression of diverse diseases. Hence, we explored the cuproptosis regulators in human spermatogenic dysfunction (SD), analyzed the condition of immune cell ...infiltration, and constructed a predictive model.
Two microarray datasets (GSE4797 and GSE45885) related to male infertility (MI) patients with SD were downloaded from the Gene Expression Omnibus (GEO) database. We utilized the GSE4797 dataset to obtain differentially expressed cuproptosis-related genes (deCRGs) between SD and normal controls. The correlation between deCRGs and immune cell infiltration status was analyzed. We also explored the molecular clusters of CRGs and the status of immune cell infiltration. Notably, weighted gene co-expression network analysis (WGCNA) was used to identify the cluster-specific differentially expressed genes (DEGs). Moreso, gene set variation analysis (GSVA) was performed to annotate the enriched genes. Subsequently, we selected an optimal machine-learning model from four models. Finally, nomograms, calibration curves, decision curve analysis (DCA), and the GSE45885 dataset were utilized to verify the predictions' accuracy.
Among SD and normal controls, we confirmed that there are deCRGs and activated immune responses. Through the GSE4797 dataset, we obtained 11 deCRGs. ATP7A, ATP7B, SLC31A1, FDX1, PDHA1, PDHB, GLS, CDKN2A, DBT, and GCSH were highly expressed in testicular tissues with SD, whereas LIAS was lowly expressed. Additionally, two clusters were identified in SD. Immune-infiltration analysis showed the existing heterogeneity of immunity at these two clusters. Cuproptosis-related molecular Cluster2 was marked by enhanced expressions of ATP7A, SLC31A1, PDHA1, PDHB, CDKN2A, DBT, and higher proportions of resting memory CD4
T cells. Furthermore, an eXtreme Gradient Boosting (XGB) model based on 5-gene was built, which showed superior performance on the external validation dataset GSE45885 (AUC = 0.812). Therefore, the combined nomogram, calibration curve, and DCA results demonstrated the accuracy of predicting SD.
Our study preliminarily illustrates the relationship between SD and cuproptosis. Moreover, a bright predictive model was developed.
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