Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling.

Background: Xuelian injection (XI), a classic preparation extracted from Saussureae Involucratae Herba, has been clinically used to manage rheumatoid arthritis (RA) for nearly twenty years in China. However, the underlying anti-RA mechanism of XI remains unclear. In this study, complete Freund's adjuvant (CFA)-induced acute arthritic model was used to examine the anti-RA effects of XI in vivo. The molecular mechanisms of this action were further investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: XI and XI freeze dried powder were characterized by UPLC analysis. CD68 and TLR4 expression in the ankle joints was measured by immunohistochemistry. The secretion of inflammatory mediators was detected by ELISA. The expression levels of TLR4 involved components were measured by Western blotting. The localization of transcription factors was measured by immunofluorescence assay. Results: XI treatment ameliorated arthritic symptoms induced by CFA in the ankle joints of rats. The serum levels of inflammatory mediators, including TNF-α, MCP-1, and Rantes were decreased by XI treatment. The elevation of CD68 and TLR4 levels in ankle joints caused by CFA was suppressed by XI treatment. Moreover, XI treatment inhibited the secretion of nitric oxide and prostaglandin E2 in LPS-treated RAW264.7 macrophages. The expression of their enzymes iNOS and COX-2 was also decreased after XI treatment. The production of inflammatory mediators, including TNF-α, IL-6, IL-1ß, MCP-1, MIP-1α, and Rantes was reduced by XI treatment in LPS-stimulated RAW264.7 cells. The phosphorylation of p38, JNK, ERK, TBK1, IKKα/ß, IκB, p65, c-Jun, and IRF3 was reduced after XI treatment. Additionally, the expression levels of nuclear proteins of p65, c-Jun, and IRF3 were inhibited by XI treatment. Conclusions: Taken together, XI possesses potential anti-RA effect and the underlying mechanism may be closely associated with the inhibition of TLR4 signaling. Our findings provide further pharmacological justifications for the clinical use of XI in RA treatment.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

A novel risk model of three SUMOylation genes based on RNA expression for potential prognosis and treatment sensitivity prediction in kidney cancer.

Introduction: Kidney cancer is one of the most common and lethal urological malignancies. Discovering a biomarker that can predict prognosis and potential drug treatment sensitivity is necessary for managing patients with kidney cancer. SUMOylation is a type of posttranslational modification that could impact many tumor-related pathways through the mediation of SUMOylation substrates. In addition, enzymes that participate in the process of SUMOylation can also influence tumorigenesis and development. Methods: We analyzed the clinical and molecular data which were obtanied from three databases, The Cancer Genome Atlas (TCGA), the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC), and ArrayExpress. Results: Through analysis of differentially expressed RNA based on the total TCGA-KIRC cohort, it was found that 29 SUMOylation genes were abnormally expressed, of which 17 genes were upregulated and 12 genes were downregulated in kidney cancer tissues. A SUMOylation risk model was built based on the discovery TCGA cohort and then validated successfully in the validation TCGA cohort, total TCGA cohort, CPTAC cohort, and E-TMAB-1980 cohort. Furthermore, the SUMOylation risk score was analyzed as an independent risk factor in all five cohorts, and a nomogram was constructed. Tumor tissues in different SUMOylation risk groups showed different immune statuses and varying sensitivity to the targeted drug treatment. Discussion: In conclusion, we examined the RNA expression status of SUMOylation genes in kidney cancer tissues and developed and validated a prognostic model for predicting kidney cancer outcomes using three databases and five cohorts. Furthermore, the SUMOylation model can serve as a biomarker for selecting appropriate therapeutic drugs for kidney cancer patients based on their RNA expression.

Telomere-related gene risk model for prognosis and drug treatment efficiency prediction in kidney cancer.

Kidney cancer is one of the most common urological cancers worldwide, and kidney renal clear cell cancer (KIRC) is the major histologic subtype. Our previous study found that von-Hippel Lindau (VHL) gene mutation, the dominant reason for sporadic KIRC and hereditary kidney cancer-VHL syndrome, could affect VHL disease-related cancers development by inducing telomere shortening. However, the prognosis role of telomere-related genes in kidney cancer has not been well discussed. In this study, we obtained the telomere-related genes (TRGs) from TelNet. We obtained the clinical information and TRGs expression status of kidney cancer patients in The Cancer Genome Atlas (TCGA) database, The International Cancer Genome Consortium (ICGC) database, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Totally 353 TRGs were differential between tumor and normal tissues in the TCGA-KIRC dataset. The total TCGA cohort was divided into discovery and validation TCGA cohorts and then using univariate cox regression, lasso regression, and multivariate cox regression method to conduct data analysis sequentially, ten TRGs (ISG15, RFC2, TRIM15, NEK6, PRKCQ, ATP1A1, ELOVL3, TUBB2B, PLCL1, NR1H3) risk model had been constructed finally. The kidney patients in the high TRGs risk group represented a worse outcome in the discovery TCGA cohort (p<0.001), and the result was validated by these four cohorts (validation TCGA cohort, total TCGA cohort, ICGC cohort, and CPTAC cohort). In addition, the TRGs risk score is an independent risk factor for kidney cancer in all these five cohorts. And the high TRGs risk group correlated with worse immune subtypes and higher tumor mutation burden in cancer tissues. In addition, the high TRGs risk group might benefit from receiving immune checkpoint inhibitors and targeted therapy agents. Moreover, the proteins NEK6, RF2, and ISG15 were upregulated in tumors both at the RNA and protein levels, while PLCL1 and PRKCQ were downregulated. The other five genes may display the contrary expression status at the RNA and protein levels. In conclusion, we have constructed a telomere-related genes risk model for predicting the outcomes of kidney cancer patients, and the model may be helpful in selecting treatment agents for kidney cancer patients.

Correlation analysis between the expression of cannabinoid 2 receptor and the related indicators of pyroptosis in sepsis / 中华急诊医学杂志

Objective:To explore the correlation between cannabinoid 2 receptor (CB2R) and pyroptosis-related indicators in mice with septic lung injury.Methods:Mice were randomly (ramdon number) divided into four groups ( n=6 per group): sham operation group (sham), mild sepsis group (ALIMi), moderate sepsis group (ALIMo) and severe sepsis group (ALIS). The model of septic lung injury was established by cecal ligation and puncture. The wet-dry weight ratio of lung tissues and lung injury scores were measured 12 hours after operation. The expression of CB2R protein was measured by western blot, and the expression of mRNA of CB2R, NLRP3, caspase-1/11, GSDMD were detected by RT-PCR. Meanwhile ELISA was used to measure the level of inflammatory factor IL-6 and TNF-α. SPSS 22.0 software was used for data analysis. Multiple comparison was analyzed by one-way analysis of variance (one-way ANOVA) and comparison between two groups was performed by LSD test or Games-Howell test. Then, the correlation between the expression of CB2R mRNA and the level of inflammatory cytokines as well as the expression of the pyroptosis-related indicators mRNA was analyzed by pearson correlation analysis, respectively. Results:The statistical value F was obtained by one-way ANOVA and comparison between two groups was performed. Compared to sham group, all above indicators increased with the aggravation of inflammation in the sepsis groups ( P<0.05). Compared to ALIMi group, the concentrations of IL-6 [(277.31±41.07) vs.(140.09±27.56), P<0.05] and TNF-α [(501.09±73.91) vs. (261.36±40.73), P<0.05] in lung tissue homogenate increased in ALIMo group. And the level of CB2mRNA [(2.99±0.28) vs. (2.02±0.19), P<0.05], the expression of CB2 protein [(0.44±0.08) vs.(0.23±0.05), P<0.05] and the level of NLRP3 [(2.53±0.26) vs.(1.61±0.15), P<0.05], caspase-1 [(6.02±0.35) vs.(3.60±0.38), P<0.05], caspase-11 [(11.43±0.83) vs.(6.30±0.65), P<0.05] and GSDMD [(10.46±0.62) vs. (5.67±0.54), P<0.05] mRNA also increased. Compared to ALIMo group, the concentrations of IL-6 [(475.90±67.65) vs. (277.31±41.07), P<0.05] and TNF-α [(713.93±58.85) vs. (501.09±73.91), P<0.05] in lung tissue homogenate increased in ALIS group. And the level of CB2mRNA [(4.00±0.19) vs.(2.99±0.28), P<0.05], the expression of CB2 protein [(0.61±0.05) vs.(0.44±0.08), P<0.05] and the level of NLRP3 [(4.75±0.40) vs.(2.53±0.26), P<0.05], caspase-1 [(8.76±0.72) vs.(6.02±0.35), P<0.05], caspase-11 [(16.31±1.13) vs.(11.43±0.83), P<0.05] and GSDMD [(16.46±1.22) vs. (10.46±0.62), P<0.05] mRNA also increased. Furthermore, correlation analysis showed that there was a highly positive correlation between the expression of CB2R mRNA and the expression of mRNA of NLRP3, caspase-1/11, and GSDMD respectively ( r>0.9, P<0.01). Conclusion:The correlation between the aggravation of inflammation, the indicators of pyroptosis and CB2R mRNA was highly positive in different degrees of septic lung injury. Consequently, CB2R may play a role in the regulatory process of inflammation.

Chinese Herbal Medicine Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating Endoplasmic Reticulum Stress.

Myocardial ischemia/reperfusion injury is the main cause of increased mortality and disability in cardiovascular diseases. The injury involves many pathological processes, such as oxidative stress, calcium homeostasis imbalance, inflammation, and energy metabolism disorders, and these pathological stimuli can activate endoplasmic reticulum stress. In the early stage of ischemia, endoplasmic reticulum stress alleviates the injury as an adaptive survival response, but the long-term stress on endoplasmic reticulum amplifies oxidative stress, inflammation, and calcium overload to accelerate cell damage and apoptosis. Therefore, regulation of endoplasmic reticulum stress may be a mechanism to improve ischemia/reperfusion injury. Chinese herbal medicine has a long history of clinical application and unique advantages in the treatment of ischemic heart diseases. This review focuses on the effect of Chinese herbal medicine on myocardial ischemia/reperfusion injury from the perspective of regulation of endoplasmic reticulum stress.

How to appropriately assess the oxygen reduction reaction activity of platinum group metal catalysts with rotating disk electrode.

The sluggish oxygen reduction reaction (ORR) has becoming the bottleneck of largescale implementation of proton exchange membrane fuel cells. However, when it comes to the ORR activity assessing of platinum group metals (PGMs) with rotating disk electrode, the corresponding potential conversion vs. reversible hydrogen electrode, test protocols, and activity calculation processes are still in chaos in many published literatures. In this work, two standard calculation processes for PGM ORR activities are demonstrated, followed by a specification for the usage of reference electrodes. Then a 4-fold discrepancy in ORR activities obtained via different test protocols is found for the same Pt/C, and an average adsorption model and the "coverage effects" are proposed to illustrate the hysteresis loop between negative and positive-going ORR polarization plots. Finally, four motions over appropriate assessment of PGM ORR activity are emphasized, hoping to bring a fair communication platform for researchers from different groups.

Identification of a Hypoxia-Related Gene Model for Predicting the Prognosis and Formulating the Treatment Strategies in Kidney Renal Clear Cell Carcinoma.

PURPOSE: The present study aimed to establish a hypoxia related genes model to predict the prognosis of kidney clear cell carcinoma (KIRC) patients using data accessed from The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database. METHODS: Patients' data were downloaded from the TCGA and ICGC databases, and hypoxia related genes were accessed from the Molecular Signatures Database. The differentially expressed genes were evaluated and then the differential expressions hypoxia genes were screened. The TCGA cohort was randomly divided into a discovery TCGA cohort and a validation TCGA cohort. The discovery TCGA cohort was used for constructing the hypoxia genes risk model through Lasso regression, univariate and multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves were used to assess the reliability and sensitivity of our model. Then, we established a nomogram to predict the probable one-, three-, and five-year overall survival rates. Lastly, the Tumor Immune Dysfunction and Exclusion (TIDE) score of patients was calculated. RESULTS: We established a six hypoxia-related gene prognostic model of KIRC patients in the TCGA database and validated in the ICGC database. The patients with high riskscore present poorer prognosis than those with low riskscore in the three TCGA cohorts and ICGC cohort. ROC curves show our six-gene model with a robust predictive capability in these four cohorts. In addition, we constructed a nomogram for KIRC patients in the TCGA database. Finally, the high risk-group had a high TIDE score than the patients with low riskscore. CONCLUSIONS: We established a six hypoxia-related gene risk model for independent prediction of the prognosis of KIRC patients was established and constructed a robust nomogram. The different riskscores might be a biomarker for immunotherapy strategy.

Relationship between over-expression of endocannabinoid receptor 2 and macrophage pyroptosis in mice / 中华麻醉学杂志

Objective:To evaluate the relationship between the over-expression of endocannabinoid receptor 2 (CB2R) and macrophage pyroptosis in mice.Methods:Bone marrow-derived macrophages of mice were transfected by lentivirus vector and successfully screened out two stable cell lines: lentivirus LV5 negative control cells (LV5-NC) and lentivirus LV5CB2R overexpressing cells (OE). Two cell lines were respectively divided into 3 groups ( n=18 each) using a random number table method: control group (LV5-NC-C group, OE-C group), LPS/ATP group (LV5-NC-LPS/ATP group, OE-LPS/ATP group) and CB2R specific agonist HU308 group (LV5-NC-HU308 group, OE-HU308 group). Cells in group C were commonly cultured.In LPS/ATP group, cells were incubated with LPS at a final concentration of 0.5 μg/ml for 5 h, and then incubated with ATP at the final concentration of 5 mmol/L for 1 h. In group LPS/ATP+ HU308, cells were incubated for 5 h with LPS at the final concentration of 0.5 μg/ml and HU308 at the final concentration of 10 μmol/L and then with ATP at the final concentration of 5 mmol/L for 1 h. The expression of CB2R, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), caspase-1, and gasdermin D (GSDMD) mRNA was detected by real-time polymerase chain reaction, the expression of caspase-1 was detected by Western blot, and the concentrations of interleukin-18 (IL-18) and IL-1β in the culture medium were determined by enzyme-linked immunosorbent assay. Results:In each cell line, compared with group C, the expression of NLRP3, caspase-1 and GSDMD was significantly up-regulated, and the concentrations of IL-18 and IL-1β were increased in group LPS/ATP ( P<0.05). Compared with group LPS/ATP, the expression of NLRP3, caspase-1 and GSDMD was significantly down-regulated, the concentrations of IL-18 and IL-lβ were decreased in group HU308 ( P<0.05). There was no significant differences in the indicators mentioned above between group V5-NC-C and group OE-C, between group LV5-NC-LPS/ATP and group OE-LPS/ATP, and between group LV5-NC-HU308 and OE-HU308 ( P>0.05). Conclusion:Over-expression of CB2R gene cannot effectively inhibit the occurrence of macrophage pyroptosis, and only activation of CB2R can inhibit it in mice.

Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

BACKGROUND AND AIM: In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China. METHODS: Treatment-naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate-treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred-treatment group, DTG). The primary efficacy end-point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end-point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN-5172-067). RESULTS: A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug-related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug-related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient-reported outcomes indicate improved quality of life at follow-up week 4 in participants receiving EBR/GZR compared to placebo. CONCLUSION: EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection.

A Three Protein-Coding Gene Prognostic Model Predicts Overall Survival in Bladder Cancer Patients.

Bladder cancer (BLCA) is the most common urinary tract tumor and is the 11th most malignant cancer worldwide. With the development of in-depth multisystem sequencing, an increasing number of prognostic molecular markers have been identified. In this study, we focused on the role of protein-coding gene methylation in the prognosis of BLCA. We downloaded BLCA clinical and methylation data from The Cancer Genome Atlas (TCGA) database and used this information to identify differentially methylated genes and construct a survival model using lasso regression. We assessed 365 cases, with complete information regarding survival status, survival time longer than 30 days, age, gender, and tumor characteristics (grade, stage, T, M, N), in our study. We identified 353 differentially methylated genes, including 50 hypomethylated genes and 303 hypermethylated genes. After annotation, a total of 227 genes were differentially expressed. Of these, 165 were protein-coding genes. Three genes (zinc finger protein 382 (ZNF382), galanin receptor 1 (GALR1), and structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1)) were selected for the final risk model. Patients with higher-risk scores represent poorer survival than patients with lower-risk scores in the training set (HR = 2.37, 95% CI 1.43-3.94, p = 0.001), in the testing group (HR = 1.85, 95% CI 1.16-2.94, p = 0.01), and in the total cohort (HR = 2.06, 95% CI 1.46-2.90, p < 0.001). Further univariate and multivariate analyses using the Cox regression method were conducted in these three groups, respectively. All the results indicated that risk score was an independent risk factor for BLCA. Our study screened the different methylation protein-coding genes in the BLCA tissues and constructed a robust risk model for predicting the outcome of BLCA patients. Moreover, these three genes may function in the mechanism of development and progression of BLCA, which should be fully clarified in the future.

Identification and Analysis of NBS-LRR Genes in Actinidia chinensis Genome.

Nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes represent the most important disease resistance genes in plants. The genome sequence of kiwifruit (Actinidia chinensis) provides resources for the characterization of NBS-LRR genes and identification of new R-genes in kiwifruit. In the present study, we identified 100 NBS-LRR genes in the kiwifruit genome and they were grouped into six distinct classes based on their domain architecture. Of the 100 genes, 79 are truncated non-regular NBS-LRR genes. Except for 37 NBS-LRR genes with no location information, the remaining 63 genes are distributed unevenly across 18 kiwifruit chromosomes and 38.01% of them are present in clusters. Seventeen families of cis-acting elements were identified in the promoters of the NBS-LRR genes, including AP2, NAC, ERF and MYB. Pseudomonas syringae pv. actinidiae (pathogen of the kiwifruit bacterial canker) infection induced differential expressions of 16 detected NBS-LRR genes and three of them are involved in plant immunity responses. Our study provides insight of the NBS-LRR genes in kiwifruit and a resource for the identification of new R-genes in the fruit.

Photosystem Disorder Could be the Key Cause for the Formation of Albino Leaf Phenotype in Pecan.

Pecan is one of the most famous nut species in the world. The phenotype of mutants with albino leaves was found in the process of seeding pecan, providing ideal material for the study of the molecular mechanisms leading to the chlorina phenotype in plants. Both chlorophyll a and chlorophyll b contents in albino leaves (ALs) were significantly lower than those in green leaves (GLs). A total of 5171 differentially expression genes (DEGs) were identified in the comparison of ALs vs. GLs using high-throughput transcriptome sequencing; 2216 DEGs (42.85%) were upregulated and 2955 DEGs (57.15%) were downregulated. The expressions of genes related to chlorophyll biosynthesis (HEMA1, encoding glutamyl-tRNA reductase; ChlH, encoding Mg-protoporphyrin IX chelatase (Mg-chelatase) H subunit; CRD, encoding Mg-protoporphyrin IX monomethylester cyclase; POR, encoding protochlorophyllide reductase) in ALs were significantly lower than those in GLs. However, the expressions of genes related to chlorophyll degradation (PAO, encoding pheophorbide a oxygenase) in ALs were significantly higher than those in GLs, indicating that disturbance of chlorophyll a biosynthesis and intensification of chlorophyll degradation lead to the absence of chlorophyll in ALs of pecan. A total of 72 DEGs associated with photosynthesis pathway were identified in ALs compared to GLs, including photosystem I (15), photosystem II (19), cytochrome b6-f complex (3), photosynthetic electron transport (6), F-type ATPase (7), and photosynthesis-antenna proteins (22). Moreover, almost all the genes (68) mapped in the photosynthesis pathway showed decreased expression in ALs compared to GLs, declaring that the photosynthetic system embedded within the thylakoid membrane of chloroplast was disturbed in ALs of pecan. This study provides a theoretical basis for elucidating the molecular mechanism underlying the phenotype of chlorina seedlings of pecan.

Role of cannabinoid receptor 2 in macrophage pyroptosis induced by lipopolysaccharide in mice / 中华麻醉学杂志

Objective:To evaluate the role of cannabinoid receptor 2 (CB2R) in macrophage pyroptosis induced by lipopolysaccharide (LPS) in mice.Methods:Macrophage line RAW264.7 cells of mice were routinely cultured and divided into 3 groups ( n=18 each) using a random number table method: control group (group C), LPS group and LPS plus CB2R agonist HU308 group (group HU308). Group C received no mediation, LPS at the final concentration of 1 μg/ml was added in the other groups.After incubation for 15 min, HU308 with the final concentration of 10 μmol/L was added in group LPS+ HU308.All groups were then incubated for 6 h. The expression of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), caspase-1, caspase-11 and gasdermin D (GSDMD) mRNA was measured by real-time polymerase chain reaction, the expression of NLRP3, caspase-1, caspase-11, GSDMD and C-terminal domain of human GSDMD (GSDMD-C) was detected by Western blot, and the concentrations of interleukin-18 (IL-18) and IL-1β in the supernatant were determined by enzyme-linked immunosorbent assay.GSDMD-C/GSDMD ratio was calculated. Results:Compared with group C, the expression of NLRP3, caspase-1, caspase-11, GSDMD and GSDMD-C was significantly up-regulated, GSDMD-C/GSDMD ratio was increased, and the concentrations of IL-18 and IL-1β in the supernatant were increased in group LPS ( P<0.05). Compared with group LPS, the expression of NLRP3, caspase-1, caspase-11, GSDMD and GSDMD-C was significantly down-regulated, GSDMD-C/GSDMD ratio was decreased, and the concentrations of IL-18 and IL-1β were decreased in group HU308 ( P<0.05). Conclusion:CB2R is involved in macrophage pyroptosis induced by LPS in mice.

Organ-associated pseudosarcomatous myofibroblastic proliferation with ossification in the lower pole of the kidney mimicking renal pelvic carcinoma: A case report.

BACKGROUND: Organ-associated pseudosarcomatous myofibroblastic proliferation (PMP) is a very rare disorder. In the urogenital tract, PMP preferentially involves the urinary bladder; kidney involvement is rare. Here, we report a rare case of PMP with ossification in the lower pole of the kidney, which mimics urothelial carcinoma or an osteogenic tumor. CASE SUMMARY: A Chinese man was admitted to our hospital due to intermittent hematuria for more than 1 mo. Enhanced renal computed tomography revealed a mass in the left renal pelvis and upper ureter. The preoperative clinical diagnosis was renal pelvic carcinoma, determined by imaging examination and biopsy. After a standard preparation for surgery, the patient underwent retroperitoneoscopic radical nephroureterectomy. The operative findings were an extensive renal tumor (6 cm × 4.5 cm × 4.5 cm) invading the lower pole of the kidney and upper ureter. The final pathological diagnosis was organ-associated PMP with ossification. After 6-mo follow-up, no recurrence or metastasis was found. CONCLUSION: This case of PMP was unusual for its mimicking renal pelvic carcinoma in imaging examinations, making biopsy necessary.

AdRAP2.3, a Novel Ethylene Response Factor VII from Actinidia deliciosa, Enhances Waterlogging Resistance in Transgenic Tobacco through Improving Expression Levels of PDC and ADH Genes.

APETALA2/ethylene-responsive factor superfamily (AP2/ERF) is a transcription factor involved in abiotic stresses, for instance, cold, drought, and low oxygen. In this study, a novel ethylene-responsive transcription factor named AdRAP2.3 was isolated from Actinidia deliciosa 'Jinkui'. AdRAP2.3 transcription levels in other reproductive organs except for the pistil were higher than those in the vegetative organs (root, stem, and leaf) in kiwi fruit. Plant hormones (Salicylic acid (SA), Methyl-jasmonate acid (MeJA), 1-Aminocyclopropanecarboxylic Acid (ACC), Abscisic acid (ABA)), abiotic stresses (waterlogging, heat, 4 °C and NaCl) and biotic stress (Pseudomonas Syringae pv. Actinidiae, Psa) could induce the expression of AdRAP2.3 gene in kiwi fruit. Overexpression of the AdRAP2.3 gene conferred waterlogging stress tolerance in transgenic tobacco plants. When completely submerged, the survival rate, fresh weight, and dry weight of transgenic tobacco lines were significantly higher than those of wile type (WT). Upon the roots being submerged, transgenic tobacco lines grew aerial roots earlier. Overexpression of AdRAP2.3 in transgenic tobacco improved the pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) enzyme activities, and improved the expression levels of waterlogging mark genes NtPDC, NtADH, NtHB1, NtHB2, NtPCO1, and NtPCO2 in roots under waterlogging treatment. Overall, these results demonstrated that AdRAP2.3 might play an important role in resistance to waterlogging through regulation of PDC and ADH genes in kiwi fruit.

[Clinical characterization of testicular yolk sac tumor in children and adults].

OBJECTIVE: To compare the clinical characteristics of simple testicular yolk sac tumor (YST) in children with those in adults so as to improve the diagnosis and treatment of the malignance. METHODS: This study included 75 cases of simple testicular YST pathologically confirmed between May 2008 and July 2018, which were divided into groups A (aged <18 years, n = 64) and B (aged ≥18 years, n = 11). We analyzed the clinical data on all the cases and compared the clinical manifestations, laboratory results, pathological findings, clinical stages, treatment methods and prognostic outcomes between the two groups of patients. RESULTS: The patients of group A ranged in age from 6 months to 5 years (ï¼»1.38 ± 0.89ï¼½ yr), with the tumor diameter of 0.9－6.0 (2.48 ± 1.12) cm, while those of group B from 25 to 49 years (median 34 years), with the tumor diameter of 3.5－6.3 (5.16 ± 1.32) cm, most presenting with a painless scrotal mass, 4 (6.2%) in group A and 5 (45.5%) in group B with testis pain. There were statistically significant differences between the two groups in the tumor diameter and initial manifestations (P < 0.05). All the patients were treated by radical high-level spermatectomy and orchiectomy and, in addition, 1 in group A and 3 in group B by retroperitoneal lymph node dissection (RPLND), 24 in the former and 5 in the latter group followed by chemotherapy. Elevated levels of serum alpha-fetoprotein (AFP) were observed in all the cases. Sixty-five of the patients were followed up for 10－78 (52.00 ± 23.78) months, during which 2 cases of simple metastasis, 3 cases of simple relapse, 3 cases of relapse with metastasis and 5 cases of death were found in group A, and 5 cases of simple metastasis, 1 case of simple relapse, 1 case of relapse with metastasis and 4 cases of death in group B. CONCLUSIONS: There are significant differences in the clinical manifestation, biological behavior, treatment and prognosis of testicular YST between children and adults. In children, most of the testicular YST cases are at clinical stage I and preferably treated by radical high-level spermatectomy and orchiectomy with favorable prognosis. In adults, however, the tumor is highly malignant, with high incidences of recurrence and metastasis and poor prognosis, for the treatment of which the first choice is radical high-level spermatectomy and orchiectomy combined with RPLND and chemotherapy.

Role of activated cannabinoid receptor 2 in lipopolysaccharide-induced secretion of RAW264.7 macrophage inflammatory cytokines and its possible mechanism / 中华急诊医学杂志

Objective To investigate the role of activated cannabinoid receptor 2 (CB2R) in lipopolysaccharide (LPS)-induced secretion of RAW264.7 macrophage inflammatory cytokines and its possible mechanism. Methods Macrophages were seeded in 6-well plates (2 mL/well) at the density of 1×105 cells/mL and randomly divided into four groups (n=6 each group): control group (group C), LPS group (group LPS), LPS plus CB2R agonist HU308 group (group LPS+HU308), and LPS plus HU308 plus 3-Methyladenine group (group LPS+HU308+3-MA). LPS with the final concentration of 1 μg/mL were added in group LPS, group LPS+HU308 and group LPS+HU308+3-MA. After incubation for 15 min, 3-MA with a final concentration of 10 mmol/L was added into group LPS+HU308+3-MA . HU308 with the final concentration of 10 μmol/L was added in group LPS+HU308 and group LPS+HU308+3-MA at 15 min after 3-MA intervention, and the cells were then incubated for 24 h. The concentrations of TNF-α, IL-18 and IL-1β in supernatant serum of each group were determined by ELISA. The expressions of ICAM-1 and NLRP3 mRNA were detected by RT-PCR. The expressions of LC3 and Beclin1 were detected by Western blot, and the ratio of LC3-Ⅱ/LC3-Ⅰ was calculated. LSD-t test was used for sample pairwise comparison, and one way ANOVA for inter-group comparison. A P<0.05 was considered statistically significant. Results Compared with group C, the concentrations of TNF-α [(228.86±10.20) pg/mL vs (140.05±5.54) pg/mL], IL-1β [(363.62±8.14) pg/mL vs (244.82±9.11) pg/mL], and IL-18 [(293.28±13.57) pg/mL vs (202.84±9.54) pg/mL] in supernatant serum were increased (all P<0.05), the expressions of ICAM-1 [(5.88±0.32) vs (1.00±0.03)] and NLRP3 [(8.07±0.93) vs (1.01±0.05)] mRNA were increased (all P<0.05), the expressions of LC3-Ⅱ/LC3-Ⅰ ratio [(0.50±0.03) vs (0.40±0.06)] and Beclin1 [(0.51±0.04) vs (0.16±0.03)] were up-regulated in group LPS (all P<0.05). Compared with group LPS, the concentrations of TNF-α [(165.44±7.07) pg/mL], IL-1β [(272.09±3.35) pg/mL] and IL-18 [(220.41±6.01) pg/mL] in supernatant serum were significantly decreased (all P<0.05), the expressions of ICAM-1 [(3.21±0.35)] and NLRP3 [(1.54±0.30)] mRNA were decreased (all P<0.05), the expressions of LC3-Ⅱ/LC3-Ⅰ ratio [(0.71±0.03)] and Beclin1 [(0.71±0.02)] were up-regulated in group LPS+HU308 (all P<0.05). Compared with group LPS+HU308, the concentrations of TNF-α [(197.06±5.59) pg/mL], IL-1β [(318.98±11.54) pg/mL] and IL-18 [(243.33±8.71) pg/mL] in supernatant serum were significantly increased (all P<0.05), the expressions of ICAM-1 [(4.04±0.21)] and NLRP3 [(5.87±0.77)] mRNA were increased (all P<0.05), the expressions of LC3-Ⅱ/LC3-Ⅰ ratio [(0.44±0.08)] and Beclin1 [(0.32±0.03)] were down-regulated in group LPS+HU308+3-MA (all P<0.05). Conclusions Activation of cannabinoid receptor 2 can alleviate LPS-induced the secretion of RAW264.7 macrophage inflammatory cytokines, and its mechanism may be related to enhanced autophagy.

Cobalt and Nitrogen Codoped Carbon Nanosheets Templated from NaCl as Efficient Oxygen Reduction Electrocatalysts.

The oxygen reduction reaction (ORR) in a cathode is an essential component of many electrochemical energy storage and conversion systems. Two-dimensional materials are beneficial for electron conduction and mass transport with high density, showing prominent electrochemical catalytic performance towards the ORR. Herein, a simple NaCl-assisted method to synthesize cobalt-nitrogen-doped carbon materials (CoNC), which present prominent performance towards the ORR in alkaline media, is described. The utilization of the NaCl template endows the product with a large specific surface area of 556.4 m2 g-1 , as well as good dispersion of cobalt nanoparticles. CoNC-800@NaCl (800 indicates the calcination temperature in °C) displays an excellent onset potential of 0.94 V (vs. a reversible hydrogen electrode), which is close to that of commercial Pt/C. Additionally, CoNC-800@NaCl also exhibits better long-term durability and methanol tolerance than that of Pt/C. The high-performance CoNC-800@NaCl catalyst provides a hopeful alternative to noble-metal catalysts for the ORR in practical applications.

Genome-Wide Bioinformatics Analysis of MAPK Gene Family in Kiwifruit (Actinidia Chinensis).

Mitogen activated protein kinase (MAPK) cascades are universal signal transduction modules that play crucial roles in various biotic and abiotic stresses, hormones, cell division, and developmental processes in plants. Mitogen activated protein kinase (MAPK/MPK), being a part of this cascade, performs an important function for further appropriate cellular responses. Although MAPKs have been investigated in several model plants, no systematic analysis has been conducted in kiwifruit (Actinidia chinensis). In the present study, we identified 18 putative MAPKs in the kiwifruit genome. This gene family was analyzed bioinformatically in terms of their chromosome locations, sequence alignment, gene structures, and phylogenetic and conserved motifs. All members possess fully canonical motif structures of MAPK. Phylogenetic analysis indicated that AcMAPKs could be classified into five subfamilies, and these gene motifs in the same group showed high similarity. Gene structure analysis demonstrated that the number of exons in AcMAPK genes ranged from 2 to 29, suggesting large variation among kiwifruit MAPK genes. The expression profiles of these AcMAPK genes were further investigated using quantitative real-time polymerase chain reaction (qRT-PCR), which demonstrated that AcMAPKs were induced or repressed by various biotic and abiotic stresses and hormone treatments, suggesting their potential roles in the biotic and abiotic stress response and various hormone signal transduction pathways in kiwifruit. The results of this study provide valuable insight into the putative physiological and biochemical functions of MAPK genes in kiwifruit.