A novel heterozygous frameshift mutation in the KRT6A gene responsible for an uncommon phenotype of pachyonychia congenita: One case report and review of literature.

Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. And fissured tongue is rarely reported in patients with pachyonychia congenita. The disease is primarily associated with mutations in five keratin genes, namely KRT6A, KRT6B, KRT6C, KRT16 or KRT17. Herein we report a 9-year-old Chinese girl who has thickened nails, keratinized plaques, and fissured tongue since birth. To investigate the underlying genetic cause, whole-exome sequencing and Sanger sequencing were performed in this patient and her family members. We identified a candidate variant c.1460-2_1460del (p.S487Lfs*21) in the KRT6A gene (NM_005554.4) by whole-exome sequencing. Sanger sequencing revealed the absence of the mutation in both parents, indicating that it is a de novo variant. Thus, the novel heterozygous frameshift mutation c.1460-2_1460del (p.S487Lfs*21) within exon 9 of KRT6A was identified as the genetic cause of the patient. Our study identified a rare de novo heterozygous frameshift mutation in the KRT6A gene in a patient with pachyonychia congenita presenting fissured tongue. Our findings expand the KRT6A gene mutation spectrum of Pachyonychia congenita, and will contribute to the future genetic counseling and gene therapy for this disease.

Successful treatment of eyebrow intradermal nevi by shearing combined with electrocautery and curettage: Two case reports.

BACKGROUND: An intradermal nevus is a common skin tumour, and the classical method of removal has a risk of recurrence and scarring. It is a challenge for dermatologists to treat eyebrow intradermal nevi quickly and efficiently. This study focused on investigating the efficacy and safety of shearing combined with electrocautery and curettage in the treatment of eyebrow intradermal nevi. CASE SUMMARY: We describe two adult patients with eyebrow intradermal nevi treated by shearing combined with electrocautery and curettage. Both patients were followed up regularly after surgery. At follow-up, no recurrence of eyebrow intradermal nevus and no obvious scars or hypopigmentation were found in either patient. The results indicated that shearing combined with electrocautery and curettage could remove eyebrow intradermal nevus without side effects and confirmed the efficacy and safety of this modality for treating these skin lesions. CONCLUSION: Shearing combined with electrocautery and curettage has superior merits, including simple operation, good cosmetic effects, and high patient satisfaction, presenting great application potential for treating intracutaneous nevus.

Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders.

Pachymic acid (Pac), a major bioactive constituent of Poria cocos, is an antioxidant that inhibits triglyceride (TG) accumulation. To the best of our knowledge, the present study investigated for the first time whether Pac activated sirtuin 6 (SIRT6) signaling to alleviate oleic acid (OA)-palmitic acid (PA)-induced lipid metabolism disorders in mouse primary hepatocytes (MPHs). In the present study, MPHs challenged with Pac were used to test the effects of Pac on intracellular lipid metabolism. Molecular docking studies were performed to explore the potential targets of Pac in defending against lipid deposition. MPHs isolated from liver-specific SIRT6-deficient mice were subjected to OA + PA incubation and treated with Pac to determine the function and detailed mechanism. It was revealed that Pac activated SIRT6 by increasing its expression and deacetylase activity. Pa prevented OA + PA-induced lipid deposition in MPHs in a dose-dependent manner. Pac (50 µM) administration significantly reduced TG accumulation and increased fatty acid oxidation rate in OA + PA-incubated MPHs. Meanwhile, as per the results of molecular docking and relative mRNA levels, Pac activated SIRT6 and increased SIRT6 deacetylation levels. Furthermore, SIRT6 deletions in MPHs abolished the protective effects of Pac against OA + PA-induced hepatocyte lipid metabolism disorders. The present study demonstrated that Pac alleviates OA + PA-induced hepatocyte lipid metabolism disorders by activating SIRT6 signaling. Overall, SIRT6 signaling increases oxidative stress burden and promotes hepatocyte lipolysis.

Shorter TR combined with finer atlas positively modulate topological organization of brain network: A resting state fMRI study.

BACKGROUND: The use of shorter TR and finer atlases in rs-fMRI can provide greater detail on brain function and anatomy. However, there is limited understanding of the effect of this combination on brain network properties. METHODS: A study was conducted with 20 healthy young volunteers who underwent rs-fMRI scans with both shorter (0.5s) and long (2s) TR. Two atlases with different degrees of granularity (90 vs 200 regions) were used to extract rs-fMRI signals. Several network metrics, including small-worldness, Cp, Lp, Eloc, and Eg, were calculated. Two-factor ANOVA and two-sample t-tests were conducted for both the single spectrum and five sub-frequency bands. RESULTS: The network constructed using the combination of shorter TR and finer atlas showed significant enhancements in Cp, Eloc, and Eg, as well as reductions in Lp and γ in both the single spectrum and subspectrum (p < 0.05, Bonferroni correction). Network properties in the 0.082-0.1 Hz frequency range were weaker than those in the 0.01-0.082 Hz range. CONCLUSION: Our findings suggest that the use of shorter TR and finer atlas can positively affect the topological characteristics of brain networks. These insights can inform the development of brain network construction methods.

Diminished AdipoR1/APPL1 Interaction Mediates Reduced Cardioprotective Actions of Adiponectin against Myocardial Ischemia/Reperfusion Injury in Type-2 Diabetic Mice.

Background: Obesity-related diseases have important implications for the occurrence, severity, and outcome of ischemic heart disease. Patients with obesity, hyperlipidemia, and diabetes mellitus (metabolic syndrome) are at increased risk of heart attack with decreased plasma lipocalin levels, and lipocalin is negatively correlated with heart attack incidence. APPL1 is a signaling protein with multiple functional structural domains and plays an important role in the APN signaling pathway. There are two known subtypes of lipocalin membrane receptors, AdipoR1 and AdipoR2. AdioR1 is mainly distributed in skeletal muscle while AdipoR2 is mainly distributed in the liver. Objective: To clarify whether the AdipoR1-APPL1 signaling pathway mediates the effect of lipocalin in reducing myocardial ischemia/reperfusion injury and its mechanism will provide us with a new approach to treat myocardial ischemia/reperfusion injury using lipocalin as an intervention and therapeutic target. Methods: (1) Induction of hypoxia/reoxygenation in SD mammary rat cardiomyocytes to simulate myocardial ischemia/reperfusion; (2) downregulation of APPL1 expression in cardiomyocytes to observe the effect of lipocalin on myocardial ischemia/reperfusion and its mechanism of action. Results: (1) Primary mammary rat cardiomyocytes were isolated and cultured and induced to simulate MI/R by hypoxia/reoxygenation; (2) lipocalin inhibited H/R-induced apoptosis in cardiomyocytes; and (3) APN attenuated MI/R injury through AdipoR1-APPL1 and the possible mechanism. Conclusion: This study demonstrates for the first time that lipocalin can attenuate myocardial ischemia/reperfusion injury through the AdipoR1-APPL1 signaling pathway and that the reduction of AdipoR1/APPL1 interaction plays an important role in cardiac APN resistance to MI/R injury in diabetic mice.

First Report of Enterobacter roggenkampii and E. cloacae complex sp. Caused Tomato Pith Necrosis in Guangdong Province, China.

Tomato (Solanum lycopersicum L.) is an important greenhouse and field-grown vegetable. During 2019 to 2021, a new bacterial pith necrosis broke out in tomato producing areas in China. The disease incidence rate in the field was approximately 10% to 30% in a few tomato planting areas of Guangdong province, and even 100% in Dianbai distinct, Maoming city. Diseased plants showed yellowing of the lower leaves, brown vascular tissues, and wilting along with brown necrotic spots and a large number of adventitious roots on the stem. Diseased plants were collected, and short fragments of the diseased stems were sterilized with 75% alcohol for 2 minutes, washed with sterile water twice, and stripped the cortex (Fang 1998). Dilutions of xylem specimen soaking solution were plated onto the TTC medium (peptone 10.0 g, acid hydrolyzed casein 1.0 g, glucose 5.0 g, agar 15.0 g, distilled water 1000 mL, 0.5% 2, 3, 5-triphenyltetrazolium chloride, pH7.0), and cultured at 28℃ for 24 h. Three pink single colonies (A2 from Guangzhou (113°21' E, 23°9' N), Guangdong, and K6, and K7 from Maoming (110°55' E, 21°25' N), Guangdong) were selected and purified. Strains A2, K6, and K7 were Gram-negative, motile, and showed white fluidal colonies with pink center on TTC medium, and white, round, and smooth-surface colonies on NA medium (peptone 10 g, beef extract 3 g, sodium chloride 5 g, agar 15 g, distilled water 1000 mL, pH7.0) at 28℃ for 24 h. Three strains could utilize citrate, sorbitol, lactose and arginine, and were negative for methylred reaction test, determination of phenylalanine amino acid deaminase, lysine decarboxylase, urease, soluble starch decomposition and gelatin liquefaction, whereas were positive for Voges-Proskauer test, which conformed to the characteristics of genus Enterobacter (Davin-Regli et al. 2019). To determine the species of the Enterobacter isolates, partial sequences 16S rDNA, gyrB, and rpoB of strain A2, K6, and K7 were amplified. The PCR products were purified, sequenced, and deposited to GenBank. The BLASTN analysis of 16S rDNA, rpoB and gyrB sequences showed strain A2 (MW785888, OL364948, OL364943) was 99.20%, 99.17% and 98.57% identity with E. roggenkampii DSM16690, respectively, strain K6 (MW785890, OL364950, OL364945) was 99.73%, 99.63%, 99.63% identity with E. cloacae complex sp. N13-01531, and strain K7 (MW785893, OL364951, OL364946) was 99.8%, 98.81%, 98.99% identity with the E. roggenkampii Ed-982 and Ek140. Nucleotide sequences of 3 strains were aligned using ClustalW program, and neighbor-joining method (NJ) was used in the construction of a phylogenetic tree using MEGA7 program. Phylogenetic trees based on gyrB sequence, rpoB sequence, and the concatenated sequence of 16S rDNA-rpoB-gyrB and rpoB-gyrB showed strain A2 and K7 were clustered to E. roggenkampii, strain K6 was clustered to E. cloacae complex sp. The roots of tomato material 'Moneymaker' at stage of 4-5 true leaves were cut and irrigated 10 mL bacterial suspension (OD600=0.6) of strains A2, K6, and K7, respectively. As a control, the tomato roots were treated with 10 mL sterile water. All plants were incubated at 30°C. The experiments were conducted with 20 tomato seedlings for each tested strain and control, and repeated twice. All plants inoculated showed yellowing in the lower leaves 6-7 days after inoculation (DAI), subsequently the stems of some plants were rotten, along with bacterial pus in the internodes. The plants wilted, and stems were hollow 20 DAI, which is similar to the field symptoms. No symptoms were observed in control plants. Strains were successfully reisolated from wilting plants, and identified as A2, K6, and K7, respectively, based on gyrB sequence analysis, fulfilling Koch's postulates. Zhou et al. (2021) reported that E. roggenkampii caused bacterial wilt of mulberry in Guangxi, China. Chen et al. (2021) reported E. asburiae caused tomatoes pith necrosis in Fujian and Zhejiang, China. To our knowledge, this is the first report of E. roggenkampii and E. cloacae complex sp. causing bacterial pith necrosis of tomato. Further research would focus on exploring the pathogenic mechanism of the pathogen, and providing reference of controlling the disease.

Disruption of RBMS3 suppresses PD-L1 and enhances antitumor immune activities and therapeutic effects of auranofin against triple-negative breast cancer.

Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction exerts a vital role in tumor-associated immune evasion. While strategies disrupting PD-1/PD-L1 axis have shown clinical benefits in various cancers, the limited response rate prompts us to investigate the complex mechanisms underlying the molecular regulation of PD-L1. Here, we identify the RNA binding protein RBMS3 as a crucial PD-L1 regulator in triple-negative breast cancer (TNBC). Correlation analysis shows that Rbms3 significantly correlates with immunosuppressive CD274, Rbms1, NT5E and ENTPD1. RBMS3 protein binds to CD274 mRNA specifically in TNBC cells to increase PD-L1 levels. Mechanistically, RBMS3 stabilizes CD274 mRNA by interacting with its 3'UTR, which represents as an intrinsic cancer cell mechanism for driving PL-D1 upregulation in TNBC. RBMS3 depletion not only destabilizes the mRNA stability and protein expression of PD-L1, but also suppresses the migratory abilities of TNBC MDA-MB-231 cells. Importantly, combination of RBMS3 ablation with auranofin (AUF), an FDA-approved thioredoxin reductase inhibitor, facilitates anti-tumor T-cell immunity in vivo and improves AUF-mediated anti-cancer effect. Taken together, our findings reveal RBMS3 as a key post-transcriptional regulator of PD-L1 and how they contribute to immune escape in TNBC, which could lead to novel combinatorial therapeutic strategies to enhance the efficacy of cancer immunotherapy.

An efficient five-lncRNA signature for lung adenocarcinoma prognosis, with AL606489.1 showing sexual dimorphism.

Background: Lung adenocarcinoma (LUAD) is a sex-biased and easily metastatic malignant disease. A signature based on 5 long non-coding RNAs (lncRNAs) has been established to promote the overall survival (OS) prediction effect on LUAD. Methods: The RNA expression profiles of LUAD patients were obtained from The Cancer Genome Atlas. OS-associated lncRNAs were identified based on the differential expression analysis between LUAD and normal samples followed by survival analysis, univariate and multivariate Cox proportional hazards regression analyses. OS-associated lncRNA with sex dimorphism was determined based on the analysis of expression between males and females. Functional enrichment analysis of the Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to explore the possible mechanisms of 5-lncRNA signatures. Results: A 5-lncRNA signature (composed of AC068228.1, SATB2-AS1, LINC01843, AC026355.1, and AL606489.1) was found to be effective in predicting high-risk LUAD patients as well as applicable to female and male subgroups and <65-year and ≥65-year age subgroups. The forecasted effect of the 5-lncRNA signature was more efficient and stable than the TNM stage and other clinical risk factors (such as sex and age). Functional enrichment analysis revealed that the mRNA co-expressed with these five OS-related lncRNAs was associated with RNA regulation within the nucleus. AL606489.1 demonstrated a sexual dimorphism that may be associated with microtubule activity. Conclusion: Our 5-lncRNA signature could efficaciously predict the OS of LUAD patients. AL606489.1 demonstrated gender dimorphism, which provides a new direction for mechanistic studies on sexual dimorphism.

Sex difference in response to non-small cell lung cancer immunotherapy: an updated meta-analysis.

BACKGROUND: Studying sex differences in the efficacy of immunotherapy may contribute to the practice of the precision medicine, especially in non-small cell lung cancer (NSCLC), a kind of cancer with sexual bimorphism. METHODS: Published randomized controlled trials (RCTs), published by PubMed, Medline, Embase, and Scopus, before 15 June 2022, testing immunotherapy (CTLA-4 or PD-1/L1 inhibitor alone, combination or with chemotherapy) versus non-immunotherapy (receiving chemotherapy or placebo only) were included to assess different efficacy between males and females. The primary endpoint was overall survival (OS). This meta-analysis was registered with PROSPERO (CRD42022298439). RESULTS: Sixteen RCTs, involving 10,155 patients with advanced NSCLC, was collected in this meta-analysis. The pooled HR comparing immunotherapy vs non-immunotherapy were 0.76 (95%CI 0.71-0.81) for males and 0.74 (95%CI 0.63-0.87) for females. The pooled HRs comparing immune-checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy were 0.79 (95%CI 0.70-0.89) for males and 0.63 (95%CI 0.42-0.92) for females. The pooled HRs comparing ICIs versus chemotherapy were 0.74 (95%CI 0.67-0.81) for males and 0.83 (95%CI 0.73-0.95) for females. In squamous NSCLC, the pooled HRs comparing immunotherapy vs non-immunotherapy were 0.73 (95%CI 0.58-0.91) for males and 0.74 (95%CI 0.37-1.48) for females. In non-squamous NSCLC, the pooled HRs comparing immunotherapy versus non-immunotherapy were 0.62 (95%CI 0.71-0.94) for males and 0.59 (95%CI 0.39-0.89) for females. CONCLUSION: Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. Meanwhile, there are sex differences in the efficacy of immunotherapy.KEY MESSAGECompared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC.The most interesting thing in this study is that immunotherapy showed significant sex differences in the treatment of squamous NSCLC.

Comparison of hybrid coronary revascularization versus coronary artery bypass grafting in patients with multivessel coronary artery disease: a meta-analysis.

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are widely used in the treatment of coronary heart disease, but the best revascularization method for multivessel coronary artery disease (MVD) patients is still controversial. Hybrid coronary revascularization (HCR), together with CABG and PCI, have been proved to be feasible methods, but the long-term effect of HCR is not as clear as CABG. METHOD: By October 2020, we retrieved articles from PubMed, Web of science, EMBASE and Cochrane library databases. The main results are based on major adverse cardiovascular and cerebral events (MACCE). RESULT: A total of 18 articles (3 randomized controlled trials (RCTs) and 15 observational studies) were included in this meta-analysis. The outcomes of MACCE in the HCR group at perioperative, short-term (30 days to 1 year), medium-term (1 year to 5 years) and long-term (5 years and above) follow-up period were similar to those in the CABG group. The mortality rates of patients in perioperative, short-term and medium-term follow-up were similar to those in the CABG group, but lower than that in the CABG group at long-term follow-up (OR = 0.35, 95% CI 0.18-0.69, p = 0.002). The revascularization rate was higher in the HCR group during the perioperative period (OR = 3.50, 95% CI 2.07-5.94, p < 0.001), short-term (OR = 3.28, 95% CI 1.62-6.64, p < 0.001) and mid-term follow-up (OR = 2.84, 95% CI 1.64-4.92, p < 0.001). CONCLUSION: Our results reveal that HCR is a safe and therapeutically effective alternative in treatments for MVD patients. It has not only less short-term adverse effect, but also better long-term effect, especially in death.

PD-1/L1 With or Without CTLA-4 Inhibitors Versus Chemotherapy in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: With the use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination vs chemotherapy in patients with advanced or metastatic NSCLC. METHODS: This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). This meta-analysis's Prospero registration number is CRD42022323570. RESULTS: The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both OS [HR = .75, 95% CI (.70-.80), P < .001] and PFS [HR = .83, 95% CI (.73-.95), P < .001]. Besides, ICIs were associated with fewer AEs compared to chemotherapy. CONCLUSION: PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in advanced or metastatic NSCLC.

Group Visits Improve Health in Patients With COPD in Post-Discharge Transition Period.

OBJECTIVE: Continuous care during the post-discharge transition period is necessary for convalescence in patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the effect of group visits on the health of patients with COPD during the post-discharge transition period. METHODS: In this prospective randomized study, a total of 116 patients with COPD post-discharge were randomly assigned to either the control group (n = 57) or the group visit intervention group (GV; n = 59). A healthy lifestyle, quality of life, self-efficacy and lung function before and after the intervention and acute COPD exacerbation(s) during the intervention were recorded and analyzed. RESULTS: Healthy lifestyle and self-efficacy scores were higher in the GV group after compared with before the intervention and the control group. Lung function was improved in both groups, with greater improvement in the GV group. In addition, the frequency of outpatient emergency services and hospitalizations due to acute COPD exacerbations was lower in the GV group compared with the control group. CONCLUSION: Group visits are efficient administration models in patients with COPD. Through health education and companion support, group visits increase patients' self-efficacy, promote patients' transition to a healthy lifestyle, improve their quality of life, reduce acute exacerbations and lower medical costs during the post-discharge transition period.

Increased intrinsic default-mode network activity as a compensatory mechanism in aMCI: a resting-state functional connectivity MRI study.

Numerous studies have investigated the differences in the mean functional connectivity (FC) strength between amnestic mild cognitive impairment (aMCI) patients and normal subjects using resting-state functional magnetic resonance imaging. However, whether the mean FC is increased, decreased or unchanged in aMCI patients compared to normal controls remains unclear. Two factors might lead to inconsistent results: the determination of regions of interest and the reliability of the FC.We explored differences in FC and the degree centrality (Dc) constructed by the bootstrap method, between and within networks (default-mode network (DN), frontoparietal control network (CN), dorsal attention network (AN)), and resulting from a hierarchical-clustering algorithm.The mean FC within the DN and CN was significantly increased (P < 0.05, uncorrected) in patients. Significant increases (P < 0.05, uncorrected) in the mean FC were found in patients between DN and CN and between DN and AN. Five pairs of FC (false discovery rate corrected) and the Dc of six regions (Bonferroni corrected) displayed a significant increase in patients. Lower cognitive ability was significantly associated with a greater increase in the Dc of the left superior temporal sulcus.Our results demonstrate that the early dysfunctions in aMCI disease are mainly compensatory impairments.

Patchouli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota.

Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients' intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1ß, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.

Superoxide-Triggered Luminol Electrochemiluminescence for Detection of Oxygen Vacancy in Oxides.

Oxygen vacancy is known to act as a reactive center in oxides to produce radicals. Currently, X-ray photoelectron spectra (XPS) become a unique spectral tool for analyzing oxygen vacancy based on the differences in atomic number ratios between metal ions and lattice oxygen. In this work, it was found that the superoxide radical (O2•-)-luminol electrochemiluminescence (ECL) intensity linearly increases with increasing the oxygen vacancy concentrations of TiO2 samples coated on the electrodes. An experimental study of the mechanism demonstrates that an increase in oxygen vacancy concentrations could lead to an increase in the generation of O2•-, resulting in an increase in the O2•--related luminol ECL signals. Accordingly, we have developed a rapid and simple O2•--luminol ECL platform to detect oxygen vacancy in TiO2 samples, based on the relationship between O2•- generation and oxygen vacancy. The proposed ECL platform exhibits good reproducibility and stability through the parallel ECL measurements. Moreover, the feasibility is verified by analyzing the oxygen vacancy concentrations in different TiO2 samples with varying the Co, Cr, Fe, and N doping concentrations. The oxygen vacancy concentrations obtained by the proposed ECL method could match well with those obtained by conventional XPS measurements. Our successful construction of the ECL platform will significantly promote the development of the oxygen vacancy detection in oxides and deepen the understanding of the relationship between oxygen vacancy and radicals.

Rapid screening of the hydrogen bonding strength of radicals by electrochemiluminescent probes.

In this study, we discovered that a clear decrease in the electrochemiluminescence (ECL) intensities of luminol occurred upon increasing the electron donating capacity of amides. Therefore, herein, a novel ECL probe was used for the first time to screen the strength of the hydrogen bonds formed between HOO˙ radicals and amides. This proposed hydrogen bonding strength-sensitive ECL probe has a significant prospect in distinguishing the hydrogen bonding strength of different radicals.

Therapeutic effect of Brucea javanica oil emulsion on experimental Crohn's disease in rats: Involvement of TLR4/ NF-κB signaling pathway.

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.

Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3-Crnde negative feedback in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM)-ventricular dysfunction in the absence of underlying heart disease-is a common complication of diabetes and a leading cause of mortality associated with the disease. In DCM, cardiac fibrosis is the main cause of heart failure. Although it is well-established that the transforming growth factor-beta signaling pathway plays a part in inducing cardiac fibrosis in DCM, details of the molecular mechanism involved remain elusive. Therefore, it is crucial to study the gene reg;ulation of key signaling effectors in DCM-associated cardiac fibrosis. A recently emerged hotspot in the field of gene regulation is the role of long noncoding RNAs (lncRNAs). Recent evidence indicates that lncRNAs play a critical role in cardiac fibrosis; however, in DCM, the function of these regulatory RNAs have not been studied in depth. In this study, we identified a conserved cardiac-specific lncRNA named colorectal neoplasia differentially expressed (Crnde). By analyzing 376 human heart tissues, it was found that Crnde expression is negatively correlated with that of cardiac fibrosis marker genes. Moreover, Crnde expression was shown to be enriched in cardiac fibroblasts (CFs). Overexpression of Crnde attenuated cardiac fibrosis and enhanced cardiac function in mice with DCM. Further, in vitro experiments showed that Crnde negatively regulates the myofibroblast differentiation of CFs. The expression of Crnde was activated by SMAD family member 3 (Smad3), shedding light on the underlying molecular mechanism. Interestingly, Crnde also inhibited the transcriptional activation of Smad3 on target genes, thereby inhibiting the expression of myofibroblastic marker genes in CFs. Overall, our data provide valuable insights into the development of potential anti-cardiac fibrosis strategies centered on lncRNAs, for the treatment of DCM.

Ameliorative effect of supercritical fluid extract of Chrysanthemum indicum Linnén against D-galactose induced brain and liver injury in senescent mice via suppression of oxidative stress, inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum Linne (C. indicum), a healthy food and folk medicine in China for thousands of years, has been reported to exert heat-clearing and detoxifying effects and extensively applied to treat various symptoms such as inflammation diseases, hepatitis and headache. AIM OF THIS STUDY: The purpose of the present study was to investigate the protective effect of the supercritical carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) on D-galactose-induced brain and liver damage during aging process and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with CISCFE (100, 150 and 300 mg/kg) after injection with D-galactose. 24 h after the last administration, the blood samples, whole brain and liver tissues were collected for biochemical analysis, histological examination and western blot analysis. The body weight, spleen and thymus indexes, alanine transaminase (ALT), aspartate transaminase (AST), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) in brain and liver, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and necrosis factor-α (TNF-α) were detected. Besides, the expressions of Bax, Bcl-2 and cleaved caspase-3 were determined by western blot assay. RESULTS: The results indicated that CISCFE effectively increased the suppressed body weight, attenuated the decline of thymus and spleen indexes, and reduced the elevated levels of ALT and AST induced by D-gal. Furthermore, CISCFE might notably alleviate D-gal-induced abnormal alterations in structure and function of brain and liver dose-dependently via renewing normal antioxidant enzymes activities (SOD, CAT, GSH-Px), reducing MDA accumulation, decreasing inflammatory cytokines productions (IL-1ß, IL-6, TNF-α), as well as attenuating the increase of Bax/Bcl-2 ratio and cleaved caspase-3 activation in the liver and brain. CONCLUSIONS: Taken together, our present results suggested that CISCFE treatment could effectively mitigate the D-gal-induced hepatic and cerebral injury, and the underlying mechanism might be tightly related to the decreased oxidative stress, inflammation and apoptosis, indicating CISCFE might be an alternative and promising agent for the treatment of aging and age-associated brain and liver diseases.