Bioinformatics Analysis of Hub Genes in Craniofacial Microsomia Combined With Congenital Heart Disease.

OBJECTIVE: The primary objective of this study was to investigate potential mechanisms and explore hub genes of craniofacial microsomia (CFM) patients associated with congenital heart defects (CHD). METHODS: Initially, the authors acquired target gene data related to CFM and congenital cardiac anomalies. Subsequently, the authors established a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were conducted using Metascape. Finally, the authors hub genes were screened by the cytoHubba plugin. RESULTS: A total of 43 CFM genes and 120 optimal CHD candidate genes were selected. The PPI networks for pathogenic genes contained 163 nodes and 1179 edges. Functional enrichment analysis largely focused on tissue formation and development. Five modules were identified from the PPI network, and 7 hub genes were screened out. The genes most relevant to CFM associated with congenital cardiac anomalies pathogenesis included fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein. CONCLUSIONS: This study identified some significant hub genes, pathways, and modules of CFM associated with CHD by bioinformatics analyses. Our findings indicate that gene subfamilies fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein may have had significant involvement in both CFM and CHD.

Mitochondrial DNA-Activated cGAS-STING Signaling in Environmental Dry Eye.

Purpose: The cGAS-STING pathway has been shown to be an important mediator of inflammation. There is emerging evidence of the importance of this signaling cascade in a variety of inflammatory diseases settings. Here, we present evidence that the mitochondrial DNA (mtDNA) damage-mediated cGAS-STING pathway plays an important role in the induction of inflammation in environmental dry eye (DE). Methods: RT-qPCR and Western blot were used to assess the induction of the cGAS-STING pathway and inflammatory cytokines in environmental DE mouse model, primary human corneal epithelial cells (pHCECs), and patients with DE. RNA sequencing was used to determine mRNA expression patterns of high osmotic pressure (HOP)-stimulated pHCECs. mtDNA was detected with electron microscopy, flow cytometry, and immunofluorescent staining. mtDNA was isolated and transfected into pHCECs for evaluating the activation of the cGAS-STING pathway. Results: The expression levels of cGAS, STING, TBK1, IRF3, and IFNß were significantly increased in an environmental DE model and HOP-stimulated pHCECs. The STING inhibitor decreased the expression of inflammatory factors in DE. An upregulation of STING-mediated immune responses and IRF3 expression mediated by TBK1 were observed in the HOP group. HOP stimulation induced mitochondrial oxidative damage and the leakage of mtDNA into the cytoplasm. Then, mtDNA activated the cGAS-STING pathway and induced intracytoplasmic STING translocated to the Golgi apparatus. Finally, we also found activated cGAS-STING signaling in the human conjunctival blot cell of patients with DE. Conclusions: Our findings suggest that the cGAS-STING pathway is activated by recognizing cytoplasmic mtDNA leading to STING translocation, further exacerbating the development of inflammation in environmental DE.

Efficacy and safety of Shenbai Granules for recurrent colorectal adenoma: A multicenter randomized controlled trial.

BACKGROUND: Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas. PURPOSE: To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China. METHODS: Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression. RESULTS: Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18). CONCLUSION: Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.

Perioperative Insulin Pump Therapy Decreases Readmission Risk and Improves Outcomes in Patients with Diabetes.

OBJECTIVE: To evaluate the impact of temporary insulin pump use during hospitalization on glycemia, postoperative complications, and cost/utilization in perioperative patients with diabetes. METHODS: Patients (n=159) with type 2 diabetes and hospitalized for elective surgery were recruited from three hospitals. Subjects were categorized into the insulin pump group and the multiple daily subcutaneous insulin injection group according to their treatment therapy. Data were collected at admission, discharge, and 3 months post-discharge. RESULTS: Subjects in the CSII group who were still on insulin therapy transitioned from CSII to MDII; however, their daily insulin dosages were lower than those in the MDII group (15.31±10.98 U/d vs. 23.48±17.02 U/d, P=0.015) after discharge. In terms of medical costs, the CSII group had significantly higher hospitalization costs than the MDII group (112.36±103.43 thousand RMB vs. 82.65±77.98 thousand RMB, P=0.043). After 3 months, the CSII group had significantly lower outpatient costs than the MDII group (3.17±0.94 thousand RMB vs. 3.98±1.76 thousand RMB, P ˂ 0.001). In the MDII group, 10 patients reported severe postoperative complications requiring re-hospitalization; there were no similar reports in the CSII group. CONCLUSION: Temporary use of insulin pump therapy for perioperative patients with diabetes results in a reduction in blood glucose and blood glucose fluctuation during hospitalization, HbA1c, and the risk of postoperative complication and readmission, thus significantly decreasing costs in this complex patient cohort. Further work is needed to better understand indications for utilizing pump therapy based on diabetes phenotype and the complexity of planned surgical intervention.

Synthesis of Carboranylated Dihydropyrrolo[1,2-a]quinoxalines and Dihydroindolo[1,2-a]quinoxalines by BF3·OEt2-Catalyzed Heterocyclization of C-Formyl-o-carboranes and Investigation of Their Oxidation Stability.

A BF3·OEt2-catalyzed synthesis of carboranylated dihydropyrrolo[1,2-a]quinoxalines and dihydroindolo[1,2-a]quinoxalines in 30-99% yields is presented through the heterocyclization of various C-modified C-formyl-o-carboranes with 1-(2-aminophenyl)-pyrroles/indoles. A systematic comparative investigation of their oxidation stability in air confirmed that 4-carboranyl-4,5-dihydropyrrolo[1,2-a]quinoxaline had better stability than the 4-phenyl analogue. A cage-deboronation reaction for N-acetyl-substituted carboranylated dihydropyrrolo[1,2-a]quinoxaline produced the corresponding 7,8-nido-carborane cesium salt. A kinetic resolution was also realized to obtain an optically pure carboranylated N-heterocycle scaffold bearing a carborane cage carbon-bonded chiral stereocenter.

CD46 inhibits the replication of swine influenza viruses by promoting the production of type I IFNs in PK-15 cells.

Swine flu caused by swine influenza A virus (swIAV) is an acute respiratory viral disease that is spreading in swine herds worldwide. Although the effect of some host factors on replication of swIAV has been identified, the role of CD46 in this process is unclear. Here, we report that CD46 inhibits the replication of swIAV by promoting the production of type I interferons (IFNs) in porcine kidney (PK-15) cells. CD46 knockout (CD46-KO) and stably expressing (CD46-overexpression) PK-15 cells were prepared using lentivirus-mediated CRISPR/Cas9 gene editing and seamless cloning technology. The results of virus infection in CD46-overexpression PK-15 cells showed that the replication of H1N1 and H3N2 swIAVs were inhibited, and the production of type I IFNs (IFN-α, IFN-ß), interferon regulatory factor (IRF) 3, and mitochondrial antiviral-signaling protein (MAVS) was enhanced. Virus infection in CD46-KO PK-15 cells showed the opposite results. Further results showed that CD46-KO PK-15 cells have a favorable ability to proliferate influenza viruses compared to Madin-Darby canine kidney (MDCK) and PK-15 cells. These findings indicate that CD46 acts as promising target regulating the replication of swIAV, and help to develop new agents against infection and replication of the virus.

Correlation Between the Variability of Different Obesity Indices and Diabetic Kidney Disease: A Retrospective Cohort Study Based on Populations in Taiwan.

Purpose: To investigate the association of five obesity indices and the variability of these indices with diabetic kidney disease (DKD) in patients with type 2 diabetes and compare the predictive validity of these markers for the risk of DKD in this large longitudinal cohort study. Patients and Methods: A total of 2659 patients with type 2 diabetes who did not have DKD were enrolled between 2006 and 2019 at Lee's United Clinic in Taiwan. Data were collected for each subject, including demographic data, personal medical history, clinical parameters and calculated Body mass index (BMI), visceral adiposity index (VAI), lipid accumulation product (LAP), body roundness index (BRI) and variability of five obesity indices. Cox regression analysis was performed to determine the relationship between different obesity indicators and DKD risk. Cox's proportional hazards model was evaluated the predictive effect of obesity indices on DKD. Results: The risk of developing DKD increased with an increase in the BRI, LAP, VAI, WC and BMI (all P trend<0.05), and the variability of VAI was significantly associated with DKD [HR=1.132, 95% CI (1.001, 1.281)] after adjusting for corresponding variables. BRI had the strongest predictive effect on DKD. BRI had the best predictive performance, with AUC of 0.807, 0.663 and 0.673 at 1, 3 and 5 years, respectively. Cox regression analysis of risk factors for DKD in patients stratified by BRI quartiles showed that patients in the Q4 group had the highest risk of developing DKD [HR=1.356, 95% CI (1.131, 1.626)]. Conclusion: BMI, WC, VAI, LAP, BRI and VAI variability were associated with a significant increase in the risk of DKD events, and BRI was superior and alternative obesity index for predicting DKD.

Online Multi-Label Streaming Feature Selection Based on Label Group Correlation and Feature Interaction.

Multi-label streaming feature selection has received widespread attention in recent years because the dynamic acquisition of features is more in line with the needs of practical application scenarios. Most previous methods either assume that the labels are independent of each other, or, although label correlation is explored, the relationship between related labels and features is difficult to understand or specify. In real applications, both situations may occur where the labels are correlated and the features may belong specifically to some labels. Moreover, these methods treat features individually without considering the interaction between features. Based on this, we present a novel online streaming feature selection method based on label group correlation and feature interaction (OSLGC). In our design, we first divide labels into multiple groups with the help of graph theory. Then, we integrate label weight and mutual information to accurately quantify the relationships between features under different label groups. Subsequently, a novel feature selection framework using sliding windows is designed, including online feature relevance analysis and online feature interaction analysis. Experiments on ten datasets show that the proposed method outperforms some mature MFS algorithms in terms of predictive performance, statistical analysis, stability analysis, and ablation experiments.

Recombinant Orf virus induced antibody production against capsid protein of porcine circovirus type 3 in mice.

The emerging worldwide distributed porcine circovirus type 3 (PCV3) infection poses a serious threat to swine herds. An important means of preventing and controlling PCV3 infection is the development of the vaccine, while, the inability to cultivate in vitro has become the biggest obstacle. Orf virus (ORFV), the prototypic member of the Parapoxviridae, has been proven to be a novel valid vaccine vector for preparing various candidate vaccines. Here, recombinant ORFV expressing capsid protein (Cap) of PCV3 was obtained and proved its favorable immunogenicity inducing antibody against Cap in BALB/c mice. Based on the enhanced green fluorescent protein (EGFP) as a selectable marker, the recombinant rORFVΔ132-PCV3Cap-EGFP was generated. Then, recombinant ORFV expressing Cap only, rORFVΔ132-PCV3Cap, was obtained based on rORFVΔ132-PCV3Cap-EGFP using a double homologous recombination method by screening single non-fluorescent virus plaque. Results of the western blot showed that the Cap can be detected in rORFVΔ132-PCV3Cap infected OFTu cells. The results of immune experiments in BALB/c mice indicated that a specific antibody against Cap of PCV3 in serum was induced by rORFVΔ132-PCV3Cap infection. The results presented here provide a candidate vaccine against PCV3 and a feasible technical platform for vaccine development based on ORFV.

The effect of benevolent leadership on safety behavior: A moderated mediation model.

INTRODUCTION: While high quality leadership is of great importance for enhancing safety behavior in the workplace, there has been a lack of research on how benevolent leadership influences such behavior. Subordinates' moqi (i.e., their unspoken understanding of the work expectations, intentions, and requirements of their superiors) and safety climate were introduced to examine this relationship. METHOD: Based on implicit followership theory, this study explores the relationship between benevolent (well meaning, kindly) leadership and employees' safety behavior, as well as the mediating role of subordinates' moqi and the moderating role of safety climate. 608 employees of a petroleum company in China were randomly selected as participants, and the data were collected in two stages. RESULTS: The results showed that: (1) Benevolent leadership is positively correlated with employees' safety behavior. (2) Subordinates' moqi mediates between benevolent leadership and employees' safety behavior. (3) Safety climate moderates the mediating role of subordinates' moqi between benevolent leadership and employees' safety behavior. (4) The positive effect of subordinates' moqi on employees' safety behavior is enhanced under a positive safety climate. CONCLUSIONS: Benevolent leadership is an effective leadership style that enhances employees' safety behaviors by promoting a moqi state between supervisors and subordinates. The invisible environmental climate, in particular, the safety climate, should be a key focus in the promotion of safety behaviors. PRACTICAL APPLICATIONS: This study further broadens the research perspective of employee safety behavior from the perspective of implicit followership theory. It also provides practical guidance for improving employee safety behavior, namely selecting and cultivating benevolent leaders, enhancing subordinates' moqi, and actively fostering a positive organizational safety climate.

Senecavirus A-induced glycolysis facilitates virus replication by promoting lactate production that attenuates the interaction between MAVS and RIG-I.

Senecavirus A (SVA)-induced porcine idiopathic vesicular disease has caused huge economic losses worldwide. Glucose metabolism in the host cell is essential for SVA proliferation; however, the impact of the virus on glucose metabolism in host cells and the subsequent effects are still unknown. Here, glycolysis induced by SVA is shown to facilitate virus replication by promoting lactate production, which then attenuates the interaction between the mitochondrial antiviral-signaling protein (MAVS) and retinoic acid-inducible gene I (RIG-I). SVA induces glycolysis in PK-15 cells, as indicated by significantly increased expression of hexokinase 2 (HK2), 6-phosphofructokinase (PFKM), pyruvate kinase M (PKM), phosphoglycerate kinase 1 (PGK1), hypoxia-inducible factor-1 alpha (HIF-1α), and superoxide dismutase-2 (SOD2) in a dose-and replication-dependent manner, and enhanced lactate production, while reducing ATP generation. Overexpression of PKM, PGK1, HIF-1α, and PDK3 in PK-15 cells and high glucose concentrations promote SVA replication, while glycolytic inhibitors decrease it. Inhibition of RLR signaling allowed better replication of SVA by promoting lactate production to attenuate the interaction between MAVS and RIG-I, and regulatory effect of glycolysis on replication of SVA was mainly via RIG-I signaling. SVA infection in mice increased expression of PKM and PGK1 in tissues and serum yields of lactate. Mice treated with high glucose and administered sodium lactate showed elevated lactate levels and better SVA replication, as well as suppressed induction of RIG-I, interferon beta (IFNß), IFNα, interferon-stimulated gene 15 (ISG15), and interleukin 6 (IL-6). The inhibitory effect on interferons was lower in mice administered sodium oxamate and low glucose compared to the high glucose, indicating that RLR signaling was inhibited by SVA infection through lactate in vitro and in vivo. These results provide a new perspective on the relationship between metabolism and innate immunity of the host in SVA infection, suggesting that glycolysis or lactate may be new targets against the virus.

Role of cuproptosis in understanding diseases.

Cell death is involved in a wide range of physiological and pathological processes. Recently, the term "cuproptosis" was coined to describe a novel type of cell death. This type of cell death, characterized by copper accumulation and proteotoxic stress, is a copper-dependent manner of death. Despite the progress achieved toward a better understanding of cuproptosis, mechanisms and related signaling pathways in physiology and pathology across various diseases remain to be proved. This mini review summarizes current research on cuproptosis and diseases, providing insights into prospective clinical therapies via targeting cuproptosis.

Metabolic profiles in the xylem sap of Brassica juncea exposed to cadmium.

Metabolic profiles in xylem sap are considered a fundamental mechanism for Cadmium (Cd) detoxification in plants. However, the metabolic mechanism of Brassica juncea xylem sap in response to Cd is still unclear. Here, we investigated the effects on the metabolomics of B. juncea xylem sap treated with Cd at different times by utilizing a nontargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics method for further elucidating the response mechanism of Cd exposure. The findings indicated that 48 h and 7 days Cd exposure caused significant differences in metabolic profiles of the B. juncea xylem sap. Those differential metabolites are primarily involved in amino acids, organic acids, lipids, and carbohydrates, and most of them were downregulated, which played essential roles in response to Cd stress. Furthermore, B. juncea xylem sap resisted 48-h Cd exposure via regulation of glycerophospholipid metabolism, carbon metabolism, aminoacyl-tRNA biosynthesis, glyoxylate and dicarboxylate metabolism, linoleic acid metabolism, C5-branched dibasic acid metabolism, alpha-linolenic acid metabolism, cyanoamino acid metabolism, ABC transporters, biosynthesis of amino acids, and pyrimidine metabolism; whereas alpha-linolenic acid metabolism, glycerophospholipid metabolism, photosynthesis, and oxidative phosphorylation were regulated for resisting 7-day Cd exposure.

Study on the Association between LRRC8B Gene InDel and Sheep Body Conformation Traits.

Marker-assisted selection is an important method for livestock breeding. In recent years, this technology has been gradually applied to livestock breeding to improve the body conformation traits. In this study, the LRRC8B (Leucine Rich Repeat Containing 8 VRAC Subunit B) gene was selected to evaluate the association between its genetic variations and the body conformation traits in two native sheep breeds in China. Four body conformation traits, including withers height, body length, chest circumference, and body weight, were collected from 269 Chaka sheep. We also collected the body length, chest width, withers height, chest depth, chest circumference, cannon bone circumference, and height at hip cross of 149 Small-Tailed Han sheep. Two different genotypes, ID and DD, were detected in all sheep. Our data showed that the polymorphism of the LRRC8B gene was significantly associated with chest depth (p < 0.05) in Small-Tailed Han sheep, and it is greater in sheep with DD than those with ID. In conclusion, our data suggested that the LRRC8B gene could serve as a candidate gene for marker-assisted selection in Small-Tailed Han sheep.

A case report of invasive infantile primary hyperoxaluria type 1 and literature review.

Infantile primary hyperoxaluria type 1 (PH1) is the most devastating primary hyperoxaluria (PH) subtype as it leads to early end-stage kidney disease (ESKD) associated with high mortality. We report a case of a three-month-old female Chinese infant who was diagnosed with PH1 by renal biopsy and genetic studies. She carried two heterozygous mutations in the alanine-glyoxylate and serine pyruvate aminotransferase (AGXT) gene, one of which has never been previously reported. The patient had multiple organ failures caused by kidney failure, which was improved by extracorporeal membrane oxygenation and continuous renal replacement therapy. However, her primary disease responded poorly to conservative treatment. Fortunately, after waiting for four months, the patient underwent a successful combined liver-kidney transplantation and has progressed well so far. This case highlights the importance of suspecting PH in infant patients with ESKD of uncertain etiology, as early initiation of therapy prevents poor outcomes.

External validation of the risk prediction model for early diabetic kidney disease in Taiwan population: a retrospective cohort study.

OBJECTIVES: This study aims to independently and externally validate the Risk Prediction Model for Diabetic Kidney Disease (RPM-DKD) in patients with type 2 diabetes mellitus (T2DM). DESIGN: This is a retrospective cohort study. SETTING: Outpatient clinics at Lee's United Clinics, Taiwan, China. PARTICIPANTS: A total of 2504 patients (average age 55.44 years, SD, 7.49 years) and 4455 patients (average age 57.88 years, SD, 8.80 years) were included for analysis in the DKD prediction and progression prediction cohorts, respectively. EXPOSURE: The predicted risk for DKD and DKD progression for each patient were all calculated using the RPM-DKD. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was overall incidence of DKD. Secondary outcomes included DKD progression. The discrimination, calibration and precision of the RPM-DKD score were assessed. RESULTS: The DKD prediction cohort and progression prediction cohort consisted of patients with 2504 and 4455 T2DM, respectively. The RPM-DKD examined in this study showed moderately discriminative ability with area under the curve ranged from 0.636 to 0.681 for the occurrence of DKD and 0.620 to 0.654 for the progression of DKD. The Hosmer-Lemeshow χ2 test indicted the RPM-DKD was not well calibrated for predicting the occurrence of DKD and overestimated the progression of DKD. The precision for predicting the occurrence and progression of DKD were 43.2% and 42.2%, respectively. CONCLUSIONS: On external validation, the RPM-DKD cannot accurately predict the risk of DKD occurrence and progression in patients with T2DM.

Role of USP13 in physiology and diseases.

Ubiquitin specific protease (USP)-13 is a deubiquitinase that removes ubiquitin from substrates to prevent protein degradation by the proteasome. Currently, the roles of USP13 in physiology and pathology have been reported. In physiology, USP13 is highly associated with cell cycle regulation, DNA damage repair, myoblast differentiation, quality control of the endoplasmic reticulum, and autophagy. In pathology, it has been reported that USP13 is important in the pathogenesis of infection, inflammation, idiopathic pulmonary fibrosis (IPF), neurodegenerative diseases, and cancers. This mini-review summarizes the most recent advances in USP13 studies involving its pathophysiological roles in different conditions and provides new insights into the prevention and treatment of relevant diseases, as well as further research on USP13.

Acetaminophen-induced reduction of NIMA-related kinase 7 expression exacerbates acute liver injury.

Background & Aims: Acetaminophen (APAP)-induced acute liver injury (ALI) is a global health issue characterised by an incomplete understanding of its pathogenesis and unsatisfactory therapies. NEK7 plays critical roles in both cell cycle regulation and inflammation. In the present study, we investigated the role and mechanism of NEK7 in APAP-induced ALI. Methods: In mice with NEK7 overexpression (hydrodynamic tail vein injection of NEK7 plasmids), hepatocyte-specific NEK7 knockout (cKO), and inducible NEK7 knockout (iKO), an overdose of APAP was administered to induce ALI. Liver injury was determined by an analysis of serum liver enzymes, pathological changes, inflammatory cytokines, and metabonomic profiles. In vitro, hepatocyte damage was evaluated by an analysis of cell viability, the reactive oxygen species levels, and mitochondrial function in different cell lines. Hepatocyte proliferation and the cell cycle status were determined by Ki-67 staining, EdU staining, and the cyclin levels. Results: NEK7 was markedly downregulated in APAP-induced injured liver and damaged hepatocytes. NEK7 overexpression in the liver significantly alleviated APAP-induced liver injury, as shown by the restored liver function, reduced pathological injury, and decreased inflammation and oxidative stress, which was confirmed in a hepatocyte cell line. Moreover, both NEK7 cKO and iKO mice exhibited exacerbation of APAP-induced ALI. Finally, we determined that cyclin B1-mediated cell cycle progression could mediate the protective effect of NEK7 against APAP-induced ALI. Conclusions: Reduced NEK7 contributes to APAP-induced ALI, possibly by dysregulating cyclins and disturbing cell cycle progression. Lay summary: Acetaminophen-induced acute liver injury is one of the major global health issues, owing to its high incidence, potential severity, and limited therapeutic options. Our current understanding of its pathogenesis is incomplete. Herein, we have shown that reduced NEK7 (a protein with a key role in the cell cycle) exacerbates acetaminophen-induced acute liver injury. Hence, NEK7 could be a possible therapeutic target for the prevention or treatment of this condition.

Role of nuclear receptor PXR in immune cells and inflammatory diseases.

Pregnane X receptor (PXR, NR1I2), a prototypical member of the nuclear receptor superfamily, has been implicated in various processes including metabolism, immune response, and inflammation. The immune system is made up of many interdependent parts, including lymphoid organs, cells, and cytokines, which play important roles in identifying, repelling, and eliminating pathogens and other foreign chemicals. An impaired immune system could contribute to various physical dysfunction, including severe infections, allergic diseases, autoimmune disorders, and other inflammatory diseases. Recent studies revealed the involvement of PXR in the pathogenesis of immune disorders and inflammatory responses. Thus, the aim of this work is to review and discuss the advances in research associated with PXR on immunity and inflammatory diseases and to provide insights into the development of therapeutic interventions of immune disorders and inflammatory diseases by targeting PXR.

Effect of Rosuvastatin on Myocardial Apoptosis in HypertensiveRats Through SIRT1/NF-κB Signaling Pathway.

The study aimed to observe the effect of rosuvastatin on myocardial apoptosis in hypertensive rats through the silent information regulator 1 (SIRT1)/nuclear factor-κB (NF-κB) signaling pathway. The spontaneously hypertensive rat (SHR) model was established, and the rats were randomly divided into the SHR group, Rosuvastatin group and Control group. The blood pressure, creatine kinase (CK) and other myocardial indexes in each group were detected, the cardiac function indexes of rats were determined using magnetic resonance imaging (MRI) and echocardiography (ECG), and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in myocardial tissues were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the apoptosis level of myocardial tissues was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Finally, the expression levels of the SIRT1/NF-κB signaling pathway and apoptosis genes and proteins in myocardial tissues in each group were detected via quantitative polymerase chain reaction (qPCR) and Western blotting. In the SHR group, the blood pressure, the levels of serum creatinine (CR) and CK were increased (p<0.05). In the SHR group, both fractional shortening (FS%) and ejection fraction (EF%) were obviously lower than those in the control group (p<0.05), while both left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) were higher than those in the control group (p<0.05), and the levels of TNF-α, IL-6 and myeloperoxidase (MPO) were increased (p<0.05). The number of apoptotic cells in myocardial tissues in the SHR group was larger than that in the other two groups (p<0.05). In the SHR group, the expression levels of Caspase3 and NF-κB were remarkably higher than those in the Rosuvastatin group (p<0.05), while the expression levels of Bcl-2 and SIRT1 were remarkably lower than those in the Rosuvastatin group (p<0.05). Rosuvastatin can inhibit myocardial apoptosis in hypertensive rats through up-regulating SIRT1 and down-regulating NF-κB.