A novel tree shrew model of lipopolysaccharide-induced acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure, with substantial attributable morbidity and mortality. The small animal models that are currently used for ARDS do not fully manifest all of the pathological hallmarks of human patients, which hampers both the studies of disease mechanism and drug development. OBJECTIVES: To examine whether the phenotypic changes of primate-like tree shrews in response to a one-hit lipopolysaccharides (LPS) injury resemble human ARDS features. METHODS: LPS was administered to tree shrews through intratracheal instillation; then, the animals underwent CT or PET/CT imaging to examine the changes in the structure and function of the whole lung. The lung histology was analyzed by H&E staining and immunohistochemical staining of inflammatory cells. RESULTS: Results demonstrated that tree shrews exhibited an average survival time of 3-5 days after LPS insult, as well as an obvious symptom of dyspnea before death. The ratios of PaO2 to FiO2 (P/F ratio) were close to those of moderate ARDS in humans. CT imaging showed that the scope of the lung injury in tree shrews after LPS treatment were extensive. PET/CT imaging with 18F-FDG displayed an obvious inflammatory infiltration. Histological analysis detected the formation of a hyaline membrane, which is usually present in human ARDS. CONCLUSION: This study established a lung injury model with a primate-like small animal model and confirmed that they have similar features to human ARDS, which might provide a valuable tool for translational research.

Validation of an ICD-Based Algorithm to Identify Sepsis: A Retrospective Study.

Background: Sepsis surveillance was important for resources allocation, prevention, and development of health policy. Objective: The aim of the study was to validate a modified International Classification of Diseases (ICD)-10 based algorithm for identifying hospitalized patients with sepsis. Methods: We retrospectively analyzed a prospective, single-center cohort of adult patients who were consecutively admitted to one medical ICU ward and ten non-ICU wards with suspected or confirmed infections during a 6-month period. A modified ICD-10 based algorithm was validated against a reference standard of Sequential Organ Failure Assessment (SOFA) score based on Sepsis-3. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and areas under the receiver operating characteristic curves (AUROCs) were calculated for modified ICD-10 criteria, eSOFA criteria, Martin's criteria, and Angus's criteria. Results: Of the 547 patients in the cohort, 332 (61%) patients met Sepsis-3 criteria and 274 (50%) met modified ICD-10 criteria. In the ICU setting, modified ICD-10 criteria had SE (84.47%), SP (88.57%), PPV (95.60), and NPV (65.96). In non-ICU settings, modified ICD-10 had SE (64.19%), SP (80.00%), PPV (80.33), and NPV (63.72). In the whole cohort, the AUROCs of modified ICD-10 criteria, eSOFA, Angus's criteria, and Martin's criteria were 0.76, 0.75, 0.62, and 0.62, respectively. Conclusion: This study demonstrated that modified ICD-10 criteria had higher validity compared with Angus's criteria and Martin's criteria. Validity of the modified ICD-10 criteria was similar to eSOFA criteria. Modified ICD-10 algorithm can be used to provide an accurate estimate of population-based sepsis burden of China.

Mechanism of baixiangdan capsules on anti-neuroinflammation: combining dry and wet experiments.

Neuroinflammation plays an important role in the pathogenesis of neurological disorders, and despite intensive research, treatment of neuroinflammation remains limited. BaiXiangDan capsule (BXD) is widely used in clinical practice. However, systematic studies on the direct role and mechanisms of BXD in neuroinflammation are still lacking. We systematically evaluated the potential pharmacological mechanisms of BXD on neuroinflammation using network pharmacological analysis combined with experimental validation. Multiple databases are used to mine potential targets for bioactive ingredients, drug targets and neuroinflammation. GO and KEGG pathway analysis was also performed. Interactions between active ingredients and pivotal targets were confirmed by molecular docking. An experimental model of neuroinflammation was used to evaluate possible therapeutic mechanisms for BXD. Network pharmacological analysis revealed that Chrysoeriol, Kaempferol and Luteolin in BXD exerted their anti-neuroinflammatory effects mainly by acting on targets such as NCOA2, PIK3CA and PTGS2. Molecular docking results showed that their average affinity was less than -5 kcal/mol, with an average affinity of -8.286 kcal/mol. Pathways in cancer was found to be a potentially important pathway, with involvement of PI3K/AKT signaling pathways. In addition, in vivo experiments showed that BXD treatment ameliorated neural damage and reduced neuronal cell death. Western blotting, RT-qPCR and ELISA analysis showed that BXD inhibited not only the expression of IL-1ß, TNF-α and NO, but also NF-κB, MMP9 and PI3K/AKT signaling pathways. This study applied network pharmacology and in vivo experiments to explore the possible mechanisms of BXD against neuroinflammation, providing insight into the treatment of neuroinflammation.

Ethnic-racial socialization, family climate, and anxiety among African American and Latinx emerging adults.

Ethnic-racial socialization (ERS) is an essential strategy that families of color utilize to discuss race, racism, and promote ethnic-racial pride. These strategies are necessary to help youth navigate a racialized world, particularly in emerging adulthood as youth transition away from home. There are mixed findings about the psychological benefits of messages focused on racial barriers, which raise questions about whether certain ERS messages may elicit anxiety symptoms and if there are conditions (e.g., family climate) under which ERS messages are most beneficial. Further, the interplay between ERS and family climate may vary across ethnic-racial groups. Thus, the present study examined the associations between ERS (i.e., cultural socialization, preparation for bias, promotion of mistrust) and anxiety symptoms, and whether the moderating effects of family climate (i.e., cohesion, conflict) varied for 142 African American (AA; 83% women) and 275 Latinx (LX; 70.5% women) college students (M = 18.89, SD = 1.06). Cultural socialization and family cohesion were negatively associated with anxiety symptoms, while promotion of mistrust and family conflict were positively associated with anxiety symptoms. Preparation for bias was not associated with anxiety symptoms. For both AA and LX youth who reported high family cohesion, cultural socialization was associated with lower anxiety symptoms. Additionally, among AA youth who reported high levels of family conflict, cultural socialization was associated with lower levels of anxiety symptoms. The findings have important implications for understanding the unique and interactive effects of ERS and family climate on anxiety symptoms for AA and LX emerging adults. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cancer-derived exosomal miR-375 targets DIP2C and promotes osteoblastic metastasis and prostate cancer progression by regulating the Wnt signaling pathway.

Bone metastasis is the most common complication responsible for most deaths in the advanced stages of prostate cancer (PCa). However, the exact mechanism of bone metastasis in PCa remains unelucidated. Herein, we explored the function and potential underlying mechanism of exosomal miR-375 in bone metastasis and tumor progression in PCa. This study revealed that miR-375 expression was markedly upregulated in advanced PCa with bone metastasis and metastatic PCa cell lines. Moreover, miR-375 showed high expression in PCa-derived exosomes and could be delivered to human mesenchymal stem cells (hMSCs) via exosomes. Mechanistically, miR-375 directly targeted DIP2C and upregulated the Wnt signaling pathway, thereby promoting osteoblastic differentiation in hMSCs. Furthermore, miR-375 promoted the proliferation, invasion, and migration of PCa cells in vitro and enhanced tumor progression and osteoblastic metastasis in vivo. Notably, the expression of miR-375, TCF-1, LEF-1, and ß-catenin in was higher in PCa tissues with bone metastasis than in PCa tissues without bone metastasis and showed a continuous increase, whereas DIP2C, cyclin D1, and Axin2 showed an opposite expression pattern. In conclusion, our study suggests that cancer-derived exosomal miR-375 targets DIP2C, activates the Wnt signaling pathway, and promotes osteoblastic metastasis and PCa progression.

Sphingomyelin synthase 2 is a positive regulator of the CSF1R-STAT3 pathway in pancreatic cancer-associated macrophage.

Background: Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the pancreatic cancer stroma and are related to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC) patients. Therefore, targeting tumor-associated macrophages is a possible strategy for the treatment of pancreatic cancer. Purpose: We would like to investigate the role of sphingomyelin synthase 2 (SMS2) and the effect of the synthase 2 selective inhibitor YE2 in TAMs and the pancreatic tumor microenvironment. In addition, we also would like to investigate the mechanism by which YE2 attenuates macrophage M2 polarization. Methods: YE2 was utilized to treat macrophages (in vitro) and mice (in vivo). Western blotting and real-time PCR were used to detect the protein levels and mRNA levels of macrophage M2 polarization markers and their downstream signaling pathways. Sphingomyelin synthase 2 gene knockout (KO) mice and their controls were used to establish a PANC-02 orthotopic pancreatic cancer model, and immune cell infiltration in the tumor tissue was analyzed by immunohistochemistry (IHC). Results: We found that sphingomyelin synthase 2 mRNA expression is positively correlated with tumor-associated macrophages, the immunosuppressive microenvironment, and poor prognosis in pancreatic ductal adenocarcinoma patients. Sphingomyelin synthase 2 deficiency was confirmed to have an inhibitory effect on the growth of orthotopic PANC-02 tumors in vivo. The deficiency not only reduced the infiltration of tumor-associated macrophages but also regulated other immune components in the tumor microenvironment. In tissue culture, YE2 inhibited M2 polarization in both bone marrow-derived macrophages (BMDMs) and THP-1 macrophages and eliminated the protumor effect of M2 macrophages. In the mouse model, YE2 treatment reduced the infiltration of TAMs and regulated other immune components in the tumor microenvironment, slowing the progression of PANC-02 tumors. In terms of mechanism, we found that the inhibition of sphingomyelin synthase 2 could downregulate the expression of IL4Rα and CSF1R, thereby attenuating M2 polarization. Conclusion: The sphingomyelin synthase 2 inhibitor YE2 or sphingomyelin synthase 2 deficiency can prevent macrophage M2 polarization in pancreatic cancer, and sphingomyelin synthase 2 could be a new potential target for the treatment of pancreatic cancer.

Divergent Regioselective Csp2-H Difluoromethylation of Aromatic Amines Enabled by Nickel Catalysis.

Herein, the first catalytic protocol for nickel-catalyzed ortho or para position difluoromethylation of various aromatic amines has been developed with the assistance of a bidentate phosphine ligand, offering an invaluable synthesis means to construct extensive p-difluoromethylated products and difluorooxindole derivatives with significant functional fragments. Furthermore, the gram-scale reaction, broad substrate scope, excellent functional-group compatibility, late-stage difluoromethylation of pesticides, and even formal synthesis of HDAC6 inhibitors further demonstrate the usefulness of this method.

Clinical and Biological Significance of DNA Methylation-Driven Differentially Expressed Genes in Biochemical Recurrence After Radical Prostatectomy.

Background: Biochemical recurrence (BCR) after radical prostatectomy indicates poor prognosis in patients with prostate cancer (PCA). DNA methylation (DNAm) is a critical factor in tumorigenesis and has attracted attention as a biomarker for the diagnosis, treatment, and prognosis of PCA. However, the predictive value of DNAm-derived differentially expressed genes (DMGs) in PCA with BCR remains elusive. Methods: We filtered the methylated genes and the differentially expressed genes (DGEs) for more than 1,000 clinical samples from the TCGA cohort using the chAMP and DESeq2 packages of R language, respectively. Next, we integrated the DNAm beta value and gene expression data with the Mithymix package of R language to obtain the DMGs. Then, 1,000 times Cox LASSO regression with 10-fold cross validation was performed to screen signature DMGs and establish a predictive classifier. Univariate and multivariate cox regressive analyses were used to identify the prognostic factors to build a predictive model, and its performance was measured by receiver operating characteristic, calibration curves, and Harrell's concordance index (C-index). Additionally, a GEO dataset was used to validate the prognostic classifier. Results: One hundred DMGs were mined using the chAMP and Methymix packages of R language. Of these, seven DMGs (CCK, CD38, CYP27A1, EID3, HABP2, LRRC4, and LY6G6D) were identified to build the prognostic classifier (Classifier) through LASSO analysis. Moreover, univariate and multivariate Cox regression analysis determined that the Classifier and pathological T stage (pathological_T) were independent predictors of BCR (hazard ratio (HR 2.2), (95% CI 1.4-3.5), p < 0.0012, and (HR 1.8), (95% CI 1.0-3.2), p < 0.046). A nomogram based on the Classifier was constructed, with high prediction accuracy for BCR-free survival in TCGA and GEO datasets. GSEA enrichment analysis showed that the DMGs were mainly enriched in the metabolism pathways. Conclusion: We identified and validated the nomogram of BCR-free survival for PCA patients, which has the potential to guide treatment decisions for patients at differing risks of BCR. Our study deepens the understanding of DMGs in the pathogenesis of PCA.

Screening and identification of NOTCH1, CDKN2A, and NOS3 as differentially expressed autophagy-related genes in erectile dysfunction.

BACKGROUND: Loss of function of key autophagy genes are associated with a variety of diseases. However specific role of autophagy-related genes in erectile dysfunction ED remains unclear. This study explores the autophagy-related differentially expressed genes (ARGs) profiles and related molecular mechanisms in Corpus Cavernosum endothelial dysfunction, which is a leading cause of ED. METHODS: The Gene Expression Omnibus (GEO) database was used to identify the key genes and pathways. Differentially expressed genes (DEGs) were mined using the limma package in R language. Next, ARGs were obtained by matching DEGs and autophagy-related genes from GeneCard using Venn diagrams. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of ARGs were described using clusterProfiler and org.Hs.eg.db in R. Moreover, hub ARGs were screened out through protein-protein interaction (PPI), gene-microRNAs, and gene-transcription factors (TFs) networks then visualized using Cytoscape. Of note, the rat model of diabetic ED was established to validate some hub ARGs with qRT-PCR and Western blots. RESULTS: Twenty ARGs were identified from four ED samples and eight non-ED samples. GO analysis revealed that molecular functions (MF) of upregulated ARGs were mainly enriched in nuclear receptor activity. Also, MF of downregulated ARGs were mainly enriched in oxidoreductase activity, acting on NAD(P)H and heme proteins as acceptors. Moreover, six hub ARGs were identified by setting high degrees in the network. Additionally, hsa-mir-24-3p and hsa-mir-335-5p might play a central role in several ARGs regulation, and the transcription factors-hub genes network was centered with 13 ARGs. The experimental results further showed that the expression of Notch1, NOS3, and CDKN2A in the diabetic ED group was downregulated compared to the control. CONCLUSIONS: Our study deepens the autophagy-related mechanistic understanding of endothelial dysfunction of ED. NOTCH1, CDKN2A, and NOS3 are involved in the regulation of endothelial dysfunction and may be potential therapeutic targets for ED by modulating autophagy.

Research on preparation and in vitro evaluation of the dendrimer-peptide nuclear acid conjugate for amplification pretargeting.

Amplification pretargeting has the potential to increase the tracer's accumulation in the tumor. This study aimed to develop a three-step amplification pretargeting strategy in nuclear medicine with a polymer conjugated with multiple copies of peptide nuclear acid (PNA). In this study, the tracer 18 F-labeled complementary PNA (18 F-cPNA) was prepared by click-chemistry with high radiochemical purity (>99%) and great stability in vitro. The PAMMA dendrimer generation 4 (G4) was conjugated with multiple copies of PNAs. The average number of PNA groups in the G4-PNA conjugate was determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and the accessibility to the 18 F-cPNA was identified by size-exclusion high-performance liquid chromatography (SE-HPLC). There were approximately 11.7 of 64 carboxyl groups modified with PNAs, of which more than 99% were accessible to 18 F-cPNA. 18 F-cPNA was added to a mixture of CC49-cPNA and G4-PNA, and the complex exhibited a single peak on high-performance liquid chromatography (HPLC) as evidence of complete hybridization between 18 F-cPNA and CC49-cPNA/G4-PNA. The LS174T tumor cells were incubated with CC49-cPNA followed by G4-PNA as an amplification platform before 18 F-cPNA was added to hybridize with CC49-cPNA/G4-PNA. Compared with conventional pretargeting without G4-PNA, the radioactivity signal was amplified about four times, which demonstrated that the dendrimer-PNA conjugate plays a crucial role in signal amplification.

A bibliometric analysis of international publication trends in premature ejaculation research (2008-2018).

The incidence of premature ejaculation (PE) has been on the rise over the years. Thus, significant research efforts have been directed toward understanding the pathogenesis and hence treatment of PE. Here, we performed a comprehensive analysis of the worldwide trends in research outputs in the field of PE. This study investigated the universal findings of previous PE studies and the trending issues surrounding the condition. We employed the Web of Science Core Collection for data collection. The Excel (2016) and CiteSpace IV were used for information analysis. The information was categorized using journal names, institutions, research frontiers, citation reports, regions/countries, and authors. A sum of 886 publications concerning PE between 2008 and 2018 were identified as of July 6, 2019. The highest number of publications was identified in the Journal of Sexual Medicine published. The United States of America (USA) had the highest number of publications and H-index value. The highest co-citations were from Waldinger MD. The most common keyword was 'drug treatment'. A steady pattern was observed for PE publications done between the period of 2008-2018. Thus, the USA is at the forefront of research on PE research. The interesting advanced research frontiers were drug treatment, circumcision, and sertraline.

Sphingomyelin synthase 2 facilitates M2-like macrophage polarization and tumor progression in a mouse model of triple-negative breast cancer.

High infiltration of M2-polarized macrophages in the primary tumor indicates unfavorable prognosis and poor overall survival in the patients with triple-negative breast cancer (TNBC). Thus, reversing M2-polarized tumor-associated macrophages in the tumors has been considered as a potential therapeutic strategy for TNBC. Sphingomyelin synthase 2 (SMS2) is the key enzyme for sphingomyelin production, which plays an important role in plasma membrane integrity and function. In this study we investigated whether SMS2 inhibitor or SMS2 gene knockout could reduce macrophages M2 polarization and tumor progression in a mouse model of TNBC. We showed that SMS2 mRNA expression was linked to immunosuppressive tumor microenvironment and poor prognosis in TNBC patients. The knockout of SMS2 or application of 15w (a specific SMS2 inhibitor) markedly decreased the generation of M2-type macrophages in vitro, and reduced the tumor weight and lung metastatic niche formation in a 4T1-TNBC mouse model. We further demonstrated that the in vivo antitumor efficacy of 15w was accompanied by a multifaceted remodeling of tumor immune environment reflecting not only the suppression of M2-type macrophages but also diminished levels of regulatory T cells and myeloid-derived suppressor cells leading to a dramatically improved infiltration of antitumor CD8+ T lymphocytes. Collectively, our results reveal a novel and important role of SMS2 in the protumorigenic function and may offer a new strategy for macrophage-targeted anticancer therapy.

Effects of "metabolic memory" on erectile function in diabetic men: A retrospective case-control study.

OBJECTIVE: This study was performed to explore the effects of metabolic memory on diabetic erectile dysfunction (ED), especially the severity and response to treatment. METHODS: Through medical records and follow-up by telephone, 67 patients meeting the criteria with a clinical diagnosis of ED and a diabetic history of more than 5 years were enrolled for erectile function analysis. They were divided into a glycemic control group, a glycemic non-control group and a metabolic memory group according to glycemic levels and treatments for diabetes in the past 5 years, and they were treated with phosphodiesterase type 5 (PDE5) inhibitors for 4 weeks. Erectile function and efficacy were assessed by the International Index for Erectile Function (IIEF), the Erection Hardness Score (EHS), and the Sexual Encounter Profile (SEP). RESULTS: The patients in the glycemic control group performed better in erectile function than those in the other groups. The patients in the glycemic control group received a significantly greater score on both the EHS and the five domains of the IIEF than did the patients in the glycemic non-control group and the metabolic memory group (all P < .001). There were also statistically significant differences favoring the glycemic control group (P < .05) in SEP2 and SEP3 success rates. However, there were no significant differences between the metabolic memory group and the glycemic non-control group in these erectile function assessments (P > .05). Significant negative correlations were seen between HbA1c levels at the time of consultation and the scores on the IIEF-EF and the EHS (Pearson r-values of -0.338 with P = .005 and -0.273 with P = .025, respectively). HbA1c levels at the first diagnosis of diabetes mellitus (DM) were also significantly negatively correlated with scores on the IIEF-EF and the EHS with greater Pearson correlation coefficients (Pearson r-values of -0.478 with P < .001 and -0.392 with P = .001, respectively). Significant improvements on each of the erectile function assessments were observed among diabetic patients with ED, but no significant difference in efficacy was observed between each group. CONCLUSIONS: The phenomenon of metabolic memory did have a significant influence on ED in men with diabetes, associated with the severity of ED but not the response to medical treatment. Early hyperglycemia exposure would have long-term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. PATIENTS SUMMARY: In this report, we looked at the erectile functions of 67 patients with a clinical diagnosis of ED and a diabetic history of more than 5 years. We found that early hyperglycemia exposure would have long-term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. We further found that the effects were associated with the severity of ED but not the response to medical treatment in men with diabetes.

Corrigendum to "Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia".

[This corrects the article DOI: 10.1155/2020/7286958.].

High-Yield Production of Lignin-Derived Functional Carbon Nanosheet for Dye Adsorption.

In this article, we report the preparation of lignin-derived carbon nanosheet (L-CNS) by direct thermal treatment of lignin without activation operation and the functions of the L-CNS as an adsorbent for rhodamine dye. The L-CNSs are fabricated by freeze-drying (FD) methods of lignin followed by high-temperature carbonization. It is found that lower frozen temperature in FD or lower concentration of lignin aqueous solution renders L-CNSs' more porous morphology and higher specific surface area (SSA), allowing a promising application of the L-CNSs as an efficient adsorbent for organic pollutants. In particular, the alkaline hydroxide catalyst helps to increase the SSA of carbon products, leading to a further improved adsorption capacity. On the other hand, p-toluenesulfonic acid (TsOH) catalyzed pyrolysis, which dramatically increased the L-CNS product yield, and provided a high-yield approach for the production of pollutant absorbent.

Screening and identification of critical biomarkers in erectile dysfunction: evidence from bioinformatic analysis.

PURPOSE: Erectile dysfunction (ED) is one of the most common male-disease globally. Despite efforts to explain its pathogenesis, the molecular mechanisms of ED are still not well understood. METHODS: The microarray dataset GSE10804 was downloaded from the Gene Expression Omnibus (GEO) to find candidate genes in ED progression. After differentially expressed genes (DEGs) were identified, functional enrichment analysis was performed. In addition, a protein-protein interaction network (PPI) was established and module analysis was performed through the STRING and Cytoscape. RESULTS AND CONCLUSIONS: A total of 618 DEGs were identified in all, containing 430 downregulated genes and 188 upregulated genes. The enriched functions and pathways of the DEGs include transcription from RNA polymerase II promoter, cell adhesion, calcium ion binding, receptor binding, Akt signaling pathway, receptor interaction, protein digestion, and absorption. We picked out twenty-five hub genes, with biological process (BP) analyses revealing that the genes were principally associated with cellular responses to amino acid stimuli, extracellular matrix structural constituent, collagen trimer, protein digestion and absorption, ECM-receptor interaction and PI3K-Akt signaling pathway. To sum up, DEGs and hub genes distinguished in this study not only help us understand the molecular mechanisms behind the carcinogenesis and progression of ED, but also play a part in the diagnosis and treatment of ED by providing candidate targets.

Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia.

Hyperlipidemia is considered one of the most important risk factors for erectile dysfunction (ED). To determine the effect of sodium tanshinone IIA sulfonate (STS) as an antioxidant agent on ED in high-fat diet- (HFD-) induced hyperlipidemia in rats and to investigate if STS administration could improve erectile function via hydrogen sulfide (H2S) production by inhibition of oxidative stress. Hyperlipidemia was induced in Sprague-Dawley rats by feeding HFD for 16 weeks. The rats were randomly divided into 3 groups: control, HFD, and HFD treated with STS (10 mg/kg/day for 12 weeks, intraperitoneal injection). Erectile function including intracavernosal pressure (ICP), H2S production, and antioxidant capacity was assessed. In addition, cavernosal smooth muscle cells (CSMC) isolated from SD rats were pretreated with STS in vitro and exposed to H2O2. Expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), activity of antioxidant enzymes, and H2S-generating enzymes within CSMC were examined. ICP was significantly decreased in HFD rats compared with control. In addition, decreased H2S production and expression of cystathionine É£-lyase (CSE) and cystathionine ß-synthase (CBS) associated with increased oxidative stress were observed in the penile tissue of HFD rats. However, all these changes were reversed by 16 weeks after STS administration. STS also increased antioxidant defense as evidenced by increased expression of Nrf2/HO-1 in the penile tissue of HFD rats. In CSMC, pretreatment with STS attenuated the decreased expression of CSE and CBS and H2S production by H2O2. STS exerted similar protective antioxidative effect as shown in the in vivo hyperlipidemia model. The present study demonstrated the redox effect of STS treatment on ED via increased H2S production in HFD-induced hyperlipidemia rat model by increased antioxidant capacity via activation of the Nrf2/HO-1 pathway, which provides STS potential clinical application in the treatment of hyperlipidemia-related ED.

Cobalt-Catalyzed C-H Acetoxylation of Phenols with Removable Monodentate Directing Groups: Access to Pyrocatechol Derivatives.

An efficient cobalt-catalyzed C-H acetoxylation of phenols has been developed by using PIDA (phenyliodine diacetate) as a sole acetoxy source to synthesize pyrocatechol derivatives for the first time. The key feature of this method is the use of earth-abundant metal cobalt as the green and inexpensive catalyst for the acetoxylation of C(sp2)-H bonds under neutral reaction conditions. Furthermore, the gram-scale reaction and late-stage functionalization demonstrated the usefulness of this method.

Improving dermal delivery of hyaluronic acid by ionic liquids for attenuating skin dehydration.

The aim of this study is to evaluate the enhanced ability of various choline based ionic liquids (ILs) for dermal delivery of hyaluronic acid (HA). Eight ILs were synthesized via neutralization reactions, which were characterized using Fourier transform infrared spectrometer and proton nuclear magnetic resonance. The enhanced capacity of ILs varied with organic acids. The IL formed by choline and citric acid ([Ch][Cit]) exerted the strongest ability to promote HA penetrating deep into the skin among all ILs. The enhanced ability of [Ch][Cit] were still maintained and even improved after diluted by water although it could be disassociated partially according to electricity. The moisture and transepidermal water loss (TEWL) were employed to evaluate the effect of attenuating skin dehydration. As expected, the IL of choline and malic acid ([Ch][Mala]) and [Ch][Cit] increased moisture and decreased TEWL significantly by improving the penetration of HA into skin. Meanwhile, no irritation was observed on skin of nude mice after treatment by the three ILs which showed optimal enhanced effect. In conclusion, ILs could be high potential biocompatible carriers for facilitating HA dermal delivery to resist skin dehydration for medical or cosmetic uses.