Acetylation of xenogeneic silencer H-NS regulates biofilm development through the nitrogen homeostasis regulator in Shewanella.

Adjusting intracellular metabolic pathways and adopting suitable live state such as biofilms, are crucial for bacteria to survive environmental changes. Although substantial progress has been made in understanding how the histone-like nucleoid-structuring (H-NS) protein modulates the expression of the genes involved in biofilm formation, the precise modification that the H-NS protein undergoes to alter its DNA binding activity is still largely uncharacterized. This study revealed that acetylation of H-NS at Lys19 inhibits biofilm development in Shewanella oneidensis MR-1 by downregulating the expression of glutamine synthetase, a critical enzyme in glutamine synthesis. We further found that nitrogen starvation, a likely condition in biofilm development, induces deacetylation of H-NS and the trimerization of nitrogen assimilation regulator GlnB. The acetylated H-NS strain exhibits significantly lower cellular glutamine concentration, emphasizing the requirement of H-NS deacetylation in Shewanella biofilm development. Moreover, we discovered in vivo that the activation of glutamine biosynthesis pathway and the concurrent suppression of the arginine synthesis pathway during both pellicle and attached biofilms development, further suggesting the importance of fine tune nitrogen assimilation by H-NS acetylation in Shewanella. In summary, posttranslational modification of H-NS endows Shewanella with the ability to respond to environmental needs by adjusting the intracellular metabolism pathways.

Carvacrol inhibits the progression of oral submucous fibrosis via downregulation of PVT1/miR-20a-5p-mediated pyroptosis.

Oral submucous fibrosis (OSF) is a precancerous condition in the oral cavity, which is closely related to the myofibroblast conversion of buccal mucosal fibroblasts (BMFs) after chronic consumption of areca nut. Emerging evidence suggests pyroptosis, a form of programmed cell death that is mediated by inflammasome, is implicated in persistent myofibroblast activation and fibrosis. Besides, numerous studies have demonstrated the effects of non-coding RNAs on pyroptosis and myofibroblast activities. Herein, we aimed to target key long non-coding RNA PVT1 with natural compound, carvacrol, to alleviate pyroptosis and myofibroblast activation in OSF. We first identified PVT1 was downregulated in the carvacrol-treated fBMFs and then demonstrated that myofibroblast features and expression of pyroptosis makers were all reduced in response to carvacrol treatment. Subsequently, we analysed the expression of PVT1 and found that PVT1 was aberrantly upregulated in OSF specimens and positively correlated with several fibrosis markers. After revealing the suppressive effects of carvacrol on myofibroblast characterisitcs and pyroptosis were mediated by repression of PVT1, we then explored the potential mechanisms. Our data showed that PVT1 may serve as a sponge of microRNA(miR)-20a to mitigate the myofibroblast activation and pyroptosis. Altogether, these findings indicated that the anti-fibrosis effects of carvacrol merit consideration and may be due to the attenuation of pyroptosis and myofibroblast activation by targeting the PVT1/miR-20a axis.

Er:YAG Laser Alleviates Inflammaging in Diabetes-Associated Periodontitis via Activation CTBP1-AS2/miR-155/SIRT1 Axis.

Periodontitis is a significant health concern for individuals with diabetes mellitus (DM), characterized by inflammation and periodontium loss. Hyperglycaemia in DM exacerbates susceptibility to periodontitis by inducing inflammaging in the host immune system. The use of erbium-doped yttrium-aluminum-garnet laser (ErL) in periodontitis treatment has gained attention, but its impact on diabetic-associated periodontitis (DP) and underlying mechanisms remain unclear. In this study, we simulated DP by exposing human periodontal ligament fibroblasts (PDLFs) to advanced glycation end products (AGEs) and lipopolysaccharides from P. gingivalis (Pg-LPS). Subsequently, we evaluated the impact of ErL on the cells' wound healing and assessed their inflammaging markers. ErL treatment promoted wound healing and suppressed inflammaging activities, including cell senescence, IL-6 secretion, and p65 phosphorylation. Moreover, the laser-targeted cells were observed to have upregulated expression of CTBP1-AS2, which, when overexpressed, enhanced wound healing ability and repressed inflammaging. Moreover, bioinformatic analysis revealed that CTBP1-AS2 acted as a sponge for miR155 and upregulated SIRT1. In conclusion, ErL demonstrated the ability to improve wound healing and mitigate inflammaging in diabetic periodontal tissue through the CTBP1-AS2/miR-155/SIRT1 axis. Targeting this axis could represent a promising therapeutic approach for preventing periodontitis in individuals with DM.

Engineering Robust Triazine Crosslinked and Pyridine Capped Anion Exchange Membrane for Advanced Water Electrolysis.

Exploring high-performance anion exchange membranes (AEM) for water electrolyzers (AEMWEs) is significant for green hydrogen production. However, the current AEMWEs are restricted by the poor mechanical strength and low OH- conductivity of AEMs, leading to the low working stability and low current density. Here, we develop a robust AEM with polybiphenylpiperidium network by combining the crosslinking with triazine and the capping with pyridine for advanced AEMWEs. The AEM exhibits an excellent mechanical strength (79.4 MPa), low swelling ratio (19.2 %), persistent alkali stability (¼ 5,000 hours) and high OH- conductivity (247.2 mS cm-1) which achieves the state-of-the-art AEMs. Importantly, when applied in AEMWEs, the corresponding electrolyzer equipped with commercial nickel iron and nickel molybdenum catalysts obtained a current density of up to 3.0 A cm-2 at 2 V and could be stably operated ~430 h at a high current density of 1.6 A cm-2, which exceeds the most of AEMWEs. Our results suggest that triazine crosslinking and pyridine capping can effectively improve the overall performance of the AEMWEs.

Dissemination of Neisseria gonorrhoeae with decreased susceptibility to extended-spectrum cephalosporins in Southern China, 2021: a genome-wide surveillance from 20 cities.

BACKGROUND: Antimicrobial resistance (AMR) of untreatable gonococcal infection is an emerging threat, especially in Guangdong, a prosperous province in Southern China. METHODS: N.gonorrhoeae was isolated from 20 cities in Guangdong and determined antimicrobial susceptibility. Through whole-genome sequencing (WGS), multilocus sequence typing (MLST), N.gonorrhoeae multiantigen sequence typing (NG-MAST), and N.gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were obtained based on the PubMLST database ( https://pubmlst.org/ ). Phylogenetic analysis was used for dissemination and tracking analysis. RESULTS: Antimicrobial susceptibility was performed on 347 isolates, and 50 isolates were identified as decreased susceptibility (DS) to cephalosporins. Of which 16.0% (8/50) were ceftriaxone DS, 38.0% (19/50) were cefixime DS, and 46.0% (23/50) were both ceftriaxone and cefixime DS. In all, the dual-resistant rate of the cephalosporin-DS isolates was 96.0% for penicillin and 98.0% for tetracycline-resistant, and 10.0% (5/50) were resistant to azithromycin. All cephalosporin-DS isolates were resistant to ciprofloxacin but sensitive to spectinomycin. The predominant MLSTs were ST7363 (16%, 8/50), ST1903 (14%, 7/50), ST1901 (12%, 6/50), and ST7365 (10%, 5/50). Besides some isolates that failed genotyping (NA), NG-STAR ST1143 (n = 6) and NG-MAST ST17748 (n = 4) were the most prevalent. Twelve isolates with mosaic penA-60.001 allele retained the most elevated cephalosporin MIC (Minimum Inhibitory Concentration). Phylogenetic analysis revealed that epidemic penA-60.001 clones, either domestic or foreign, had spread to nine cities in Guangdong, and 9/12 clones were from the Pearl River Delta region. CONCLUSIONS: N. gonorrhoeae with cephalosporins-DS was extensively disseminated in Guangdong, Southern China, requiring strict surveillance.

Nanoemulsion-Coated Ni-Fe Hydroxide Self-Supported Electrode as an Air-Breathing Cathode for High-Performance Zinc-Air Batteries.

To improve the energy conversion efficiency and durability of zinc-air batteries (ZABs) for large-scale implementations, here we propose an "air-breathing" strategy to significantly enlarge triple-interfaces with intensified mass transfer. By dip-coating the aerophilic perfluorochemical compounds (PFC) and amphiphilic ionomers into the self-supported electrodes, (1) the high solubility of O2 in the PFC nanoemulsions greatly increases triple-phase boundaries and facilitates the efficient supply/removal of O2 from the electrolyte; (2) the ionomers with hydrophobic and hydrophilic functionalities enable fast gas, water, and ion transport to the triple-phase boundaries; and (3) the self-supported electrode without binder ensures fast electron transfer while the firm integration prevents catalyst shedding. By applying this strategy, the ZABs show a high power density of 115 mW cm-2 and a narrow discharge/charge gap of 0.64 V at 10 mA cm-2 and a long-cycling durability (over 1000 h). This work provides a universal approach to promote gas-evolving reactions for electrochemical applications.

MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) has been recognized as a potentially malignant disorder and is characterized by inflammation and the deposition of collagen. Among various regulators of fibrogenesis, microRNAs (miR) have received great attention but the detailed mechanisms underlying the miR-mediated modulations remain largely unknown. Here, we showed that miR-424 was aberrantly overexpressed in OSF tissues, and then we assessed its functional role in the maintenance of myofibroblast characteristics. Our results demonstrated that the suppression of miR-424 markedly reduced various myofibroblast activities (such as collagen contractility and migration ability) and downregulated the expression of fibrosis markers. Moreover, we showed that miR-424 exerted this pro-fibrosis property via direct binding to TGIF2, an endogenous repressor of the TGF-ß signaling. In addition, our findings indicated that overexpression of miR-424 activated the TGF-ß/Smad pathway, leading to enhanced myofibroblast activities. Altogether, our data revealed how miR-424 contributed to myofibroblast transdifferentiation, and targeting the miR-424/TGIF2 axis may be a viable direction for achieving satisfactory results from OSF treatment.

A Risk Model to Predict Statin Non-Adherence Following an Acute Coronary Syndrome.

BACKGROUND: Patients at risk of statin non-adherence are often not identified during hospital admission with an acute coronary syndrome (ACS). METHODS: In 19,942 patients hospitalised for ACS, statin dispensing was determined from the national pharmaceutical dispensing database. A risk score for non-adherence was developed from a multivariable Poisson regression model of associations between risk factors and the statin Medication Possession Ratio (MPR) <0.8 6-18 months after hospital discharge. RESULTS: Statin MPR was <0.8 in 4,736 (24%) patients. MPR <0.8 was more likely in patients with a history of cardiovascular disease (CVD) (RR 3.79, CI 95% 3.42-4.20) and those without known CVD (RR 2.25, 95% CI 2.04-2.48) who were not taking a statin on ACS admission, compared to patients with low density lipoprotein (LDL) cholesterol <2 mmol/L who were on a statin. For patients taking a statin on admission, higher LDL was associated with MPR <0.8 (≥3 versus <2 mmol/L, RR 1.96, 95%CI 1.72-2.24). Other independent risk factors for MPR <0.8 were age <45 years, female, disadvantaged ethnic groups, and no coronary revascularisation during the ACS admission. The risk score, which included nine variables, had a C-statistic of 0.67. MPR was <0.8 in 12% of 5,348 patients with a score ≤5 (lowest quartile) and 45% of 5,858 patients with a score ≥11 (highest quartile). CONCLUSION: A risk score generated from routinely collected data predicts statin non-adherence in patients hospitalised with ACS. This may be used to target inpatient and outpatient interventions to improve medication adherence.

Markedly Increasing Antibiotic Resistance and Dual Treatment of Neisseria gonorrhoeae Isolates in Guangdong, China, from 2013 to 2020.

The emergence of multidrug resistance in Neisseria gonorrhoeae is concerning, especially the cooccurrence of azithromycin resistance and decreased susceptibility to extended-spectrum cephalosporin. This study aimed to confirm the antibiotic resistance trends and provide a solution for N. gonorrhoeae treatment in Guangdong, China. A total of 5,808 strains were collected for assessment of antibiotic MICs. High resistance to penicillin (53.80 to 82%), tetracycline (88.30 to 100%), ciprofloxacin (96 to 99.8%), cefixime (6.81 to 46%), and azithromycin (8.60 to 20.03%) was observed. Remarkably, spectinomycin and ceftriaxone seemed to be the effective choices, with resistance rates of 0 to 7.63% and 2.00 to 16.18%, respectively. Moreover, the rates of azithromycin resistance combined with decreased susceptibility to ceftriaxone and cefixime reached 9.28% and 8.64%, respectively. Furthermore, genotyping identified NG-STAR-ST501, NG-MAST-ST2268, and MLST-ST7363 as the sequence types among representative multidrug-resistant isolates. Evolutionary analysis showed that FC428-related clones have spread to Guangdong, China, which might be a cause of the rapid increase in extended-spectrum cephalosporin resistance currently. Among these strains, the prevalence of N. gonorrhoeae was extremely high, and single-dose ceftriaxone treatment might be a challenge in the future. To partially relieve the treatment pressure, a susceptibility test for susceptibility to azithromycin plus extended-spectrum cephalosporin dual therapy was performed. The results showed that all the representative isolates could be effectively killed with the coadministration of less than 1 mg/liter azithromycin and 0.125 mg/liter extended-spectrum cephalosporin, with a synergistic effect according to a fractional inhibitory concentration (FIC) of <0.5. In conclusion, dual therapy might be a powerful measure to treat refractory N. gonorrhoeae in the context of increasing antibiotic resistance in Guangdong, China.

Development and application of Cas13a-based diagnostic assay for Neisseria gonorrhoeae detection and azithromycin resistance identification.

BACKGROUND: Gonorrhoea, caused by Neisseria gonorrhoeae, has spread worldwide. Strains resistant to most antibiotics, including ceftriaxone and azithromycin, have emerged to an alarming level. Rapid testing for N. gonorrhoeae and its antimicrobial resistance will therefore contribute to clinical decision making for early diagnosis and rational drug use. METHODS: A Cas13a-based assay (specific high-sensitivity enzymatic reporter unlocking; SHERLOCK) was developed for N. gonorrhoeae detection (porA gene) and azithromycin resistance identification (A2059G, C2611T). Assays were evaluated for sensitivity with purified dsDNA and specificity with 17 non-gonococcal strains. Performance of SHERLOCK (porA) was compared with Roche Cobas 4800 using 43 urine samples. Identification of azithromycin resistance mutations (A2059G, C2611T) was evaluated using a total of 84 clinical isolates and 18 urine samples. Lateral flow was tested for this assay as a readout tool. Moreover, we directly assayed 27 urethral swabs from patients with urethritis to evaluate their status in terms of N. gonorrhoeae infection and azithromycin resistance. RESULTS: The SHERLOCK assay was successfully developed with a sensitivity of 10 copies/reaction, except 100 copies/reaction for A2059G, and no cross-reaction with other species. Comparison of the SHERLOCK assay with the Cobas 4800 revealed 100% concordance within 18 positive and 25 negative urine samples. Of the 84 isolates, 21 strains with azithromycin resistance mutations were distinguished and further verified by sequencing and MIC determination. In addition, 62.96% (17/27) strains from swab samples were detected with no mutant strains confirmed by sequencing. CONCLUSIONS: The SHERLOCK assay for rapid N. gonorrhoeae detection combined with azithromycin resistance testing is a promising method for application in clinical practice.

Galectin-7 promotes proliferation and wound healing capacities in periodontal ligament fibroblasts by activating ERK signaling.

Periodontitis is a progressive inflammation condition and a primary cause of tooth loss in adults. As one of the abundant cell types in the periodontium, periodontal ligament fibroblasts (PDLFs) play an integral role in the maintenance and regeneration of periodontal tissue. Our previous work has shown that the application of Er:YAG laser increased the cell proliferation and migratory capacity of PDLFs via induction of galectin-7. In the present study, we aimed to evaluate if the forced expression of galectin-7 directly affected the cellular phenotypes of PDLFs. Our results showed that the cell proliferation, transwell migration, invasion, and wound healing capacities were all upregulated in PDLFs with the ectopic expression of galectin-7. These results suggest that therapeutic approaches to enhance the expression of galectin-7 in periodontium may accelerate tissue regeneration by recruiting more PDLFs to the injured site.

Depletion of miR-155 hinders the myofibroblast activities and reactive oxygen species generation in oral submucous fibrosis.

BACKGROUND/PURPOSE: Emerging evidence suggests the significance of microRNA-155 (miR-155) in fibrogenesis and oxidative stress accumulation, but its function in oral submucous fibrosis (OSF) has not been investigated. In this study, we assessed the expression of miR-155 and its effects on the maintenance of myofibroblast activation. METHODS: qRT-PCR was conducted to assess the expression of miR-155 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF samples. Collagen gel contraction, migration, and invasion capabilities were examined in fBMFs. DCFDA ROS assay was used to examine ROS generation. A luciferase reporter assay was carried out to verify the relationship between miR-155 and its potential target RPTOR. RESULTS: We showed that the expression of miR-155 was aberrantly upregulated in OSF specimens and fBMFs. Inhibition of miR-155 ameliorated various myofibroblast activities, including collagen gel contraction, migration, and invasion abilities as well as ROS production. Results from the luciferase reporter assay demonstrated that miR-155 directly interacted with its target RPTOR. CONCLUSION: Taken together, these findings indicate that miR-155 is implicated in the pathogenesis of oxidative stress-associated OSF, possibly through the regulation of RPTOR.

Fenofibrate diminishes the self-renewal and metastasis potentials of oral carcinoma stem cells through NF-κB signaling.

BACKGROUND/PURPOSE: NF-κB family of transcription factors are the major contributors to malignant tumor progression, maintenance of cancer stemness, and enhancement of chemoresistance. Fenofibrate, a lipid-lowering drug, has been considered as a candidate for repurposing in the treatment of cancer through various pathways involved in apoptosis, cell cycle, migration, and invasion, including NF-κB. Nevertheless, whether fenofibrate possesses the potential to inhibit cancer stemness remained to be examined. METHODS: Cytotoxicity of fenofibrate was estimated by MTT assay. The cells expressing stemness marker were detected by flow cytometry using ALDEFLUOR™ Kit. The secondary sphere formation assay was used to assess the self-renewal ability. Transwell system was used to evaluate migration and invasion capacities. NF-κB expression was measured by the immunoblotting system. RESULTS: In the present study, we demonstrated that fenofibrate inhibited cell viability, expression of stemness marker, self-renewal, migration, and invasion capacities in a dose-dependent manner. Of note, fenofibrate targeted cancer stem cells of oral squamous cell carcinoma (OSCC-CSCs) and had minimal effects on normal cells. Moreover, administration of fenofibrate at a lower concentration was sufficient to diminish the expression of NF-κB p50 and p65. CONCLUSION: This study demonstrated that the inhibitory effects of fenofibrate on OSCC-CSCs properties may be associated with downregulation of NF-κB. These results indicated that administration of fenofibrate may serve as an alternative strategy for OSCC therapy.

Down-regulation of miR-29c promotes the progression of oral submucous fibrosis through targeting tropomyosin-1.

BACKGROUND/PURPOSE: Various microRNAs (miRs) have been found to be associated with the development of the precancerous condition of the oral cavity, oral submucous fibrosis (OSF). The expression of miR-29c is dysregulated in oral cancer, but its role in OSF has not been investigated. The purpose of the study is to investigate the functional role of miR-29c and its target in OSF. METHODS: The expression levels of miR-29c in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were assessed using next-generation sequencing and real-time Polymerase Chain Reaction (PCR) analysis. MiR-29c mimic and inhibitors were employed to examine its functional role of myofibroblast transdifferentiation. In addition, several myofibroblast phenotypes, such as collagen gel contraction and migration were tested, and a luciferase reporter assay was conducted to confirm the relationship between miR-29c and its predicted target, tropomyosin-1 (TPM1). RESULTS: We observed that miR-29c expression was downregulated in fBMFs. fBMFs transfected with miR-29c mimics exhibited reduced migration ability and collagen gel contractility, whereas inhibition of miR-29c in normal BMFs induced the myofibroblast phenotypes. Results from the luciferase reporter assay showed that TPM1 was a direct target of miR-29c and the expression of TPM1 was suppressed in the fBMFs transfected with miR-29c mimics. Besides, we confirmed that the expression of miR-29c was indeed downregulated in OSF specimens. CONCLUSION: MiR-29c seems to exert an inhibitory effect on myofibroblast activation, such as collagen gel contractility and migration ability, via suppressing TPM1. These results suggested that approaches to upregulate miR-29c may be able to ameliorate the progression of OSF.

Paeonol inhibits profibrotic signaling and HOTAIR expression in fibrotic buccal mucosal fibroblasts.

BACKGROUND/PURPOSE: Betel nut chewing is the major risk factor of oral submucous fibrosis (OSF). Various studies have sought to discover alternative strategies to alleviate oral fibrogenesis. In the present study, we aimed to evaluate the anti-fibrosis effect of paeonol, a phenolic component derived from Paeonia Suffruticosa. METHODS: The cytotoxicity of paeonol was tested using normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues. Collagen gel contraction, Transwell migration, invasion, and wound healing capacities were examined. Besides, the activation of TGF-ß/Smad2 signaling and expression levels of type I collagen, α-SMA, and long non-coding RNA HOTAIR were measured as well. RESULTS: Paeonol exerted a higher cytotoxic effect on fBMFs compared to normal BMFs. The arecoline-induced myofibroblast activities, including collagen gel contractility, cell motility, and wound healing ability were all suppressed by paeonol treatment. In addition, the activation of the TGF-ß/Smad2 pathway was inhibited along with a lower expression of α-SMA and type I collagen in paeonol-treated cells. Also, the administration of paeonol decreased the mRNA expression of HOTAIR in fBMFs. CONCLUSION: Our results indicate that paeonol may be a promising compound to attenuate the progression of oral fibrogenesis in OSF patients.

Magnolol inhibits cancer stemness and IL-6/Stat3 signaling in oral carcinomas.

BACKGROUND/PURPOSE: Cancer stem cells (CSCs) have been known to be implicated in tumorigenesis, metastasis, and drug resistance in oral squamous cell carcinomas (OSCC). In this study, we aimed to investigate whether magnolol, a polyphenolic component derived from Magnolia officinalis, exhibited the anti-CSCs properties. METHODS: The cytotoxicity of magnolol was tested using normal gingival epithelioid SG cells and sphere-forming OSCC-CSCs isolated from SAS, OECM1, and GNM cells. Secondary sphere-forming ability, the proportion of ALDH1 positive cells, Transwell migration, and invasion capacities were examined as well. The chemosensitive effects of magnolol were investigated using MTT, secondary sphere-forming, and invasion assays. RESULTS: Magnolol exerted a higher cytotoxicity of OSCC-CSCs and cancer stemness features, including self-renewal ability, the expression CSC marker, migration, and invasion capacities were all downregulated in magnolol-treated OSCC-CSCs. Moreover, administration of magnolol potentiated the effect of cisplatin, including a decrease in cell viability, self-renewal, and invasion activities. In addition, we observed that the secretion of IL-6 and phosphorylation of Stat3 were decreased in OSCC-CSCs treated with magnolol. CONCLUSION: Our data suggest that magnolol is able to target CSCs and suppress the cancer stemness properties, at least in part, via IL-6/Stat3 signaling. Besides, a dietary supplement of magnolol may function as an adjunct to cisplatin treatment.

Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas.

Oral cancer is one of the most common cancers worldwide, especially in South Central Asia. It has been suggested that cancer stem cells (CSC) play crucial roles in tumor relapse and metastasis, and approaches to target CSC may lead to promising results. Here, aldehyde dehydrogenase 1 (ALDH1) and CD44 were utilized to isolate CSCs of oral cancer. Butylidenephthalide, a bioactive phthalide compound from Angelica sinensis, was tested for its anti-CSC effects. MTT assay showed that a lower concentration of butylidenephthalide was sufficient to inhibit the proliferation of patient-derived ALDH1+/CD44+ cells without affecting normal cells. Administration of butylidenephthalide not only reduced ALDH1 activity and CD44 expression, it also suppressed the migration, invasion, and colony formation abilities of ALDH1+/CD44+ cells using a transwell system and clonogenic assay. A patient-derived xenograft mouse model supported our in vitro findings that butylidenephthalide possessed the capacity to retard tumor development. We found that butylidenephthalide dose-dependently downregulated the gene and protein expression of Sox2 and Snail. Our results demonstrated that overexpression of Snail in ALDH1-/CD44- (non-CSCs) cells induced the CSC phenotypes, whereas butylidenephthalide treatment successfully diminished the enhanced self-renewal and propagating properties. In summary, this study showed that butylidenephthalide may serve as an adjunctive for oral cancer therapy.

Meta-Analysis of Mitral Valve Repair Versus Replacement for Rheumatic Mitral Valve Disease.

BACKGROUND: Rheumatic heart disease remains one of the leading causes of heart valve disease worldwide despite being a preventable condition. Mitral valve repair is superior to replacement in severe degenerative mitral valve disease, however its role in rheumatic valve disease remains controversial. This meta-analysis compared mitral valve repair and replacement in rheumatic heart disease. METHODS: Medline, EMBASE, Cochrane and Scopus were searched from January 1980 to June 2016 for original studies reporting outcomes of both mitral valve repair and replacement in rheumatic heart disease in adults, children or both. Two (2) authors independently assessed studies for inclusion, followed by data extraction and analysis. RESULTS: The search yielded 930 articles, with 98 full-texts reviewed after initial screening and 13 studies subsequently included for analysis, totalling 2,410 mitral valve repairs and 3,598 replacements. Pooled rates and odds ratio (95% confidence interval) for operative mortality of repair versus replacement was 3.2% versus 4.3%, 0.68 (0.50-0.92; p=0.01). Pooled odds ratios (95% confidence interval) were for long-term mortality 0.41 (0.30-0.56; p<0.001); reoperation 3.02 (1.72-5.31; p<0.001); and bleeding 0.26 (0.11-0.63; p=0.003). There was a trend towards lower thrombo-embolism 0.42 (0.17-1.03; p=0.06), and no significant difference in endocarditis (p=0.76), during follow-up. CONCLUSION: Mitral valve repair is associated with reduction in operative and long-term mortality and bleeding, so is recommended in rheumatic mitral valve disease where feasible, but it does entail a higher rate of reoperation during follow-up.

Performance of Sexually Transmitted Disease Laboratories for Chlamydia trachomatis Detection in Guangdong, China.

BACKGROUND: Chlamydia trachomatis detection plays a crucial role in early diagnosis and treatment of C. trachomatis infection. In the current study, the capability of sexually transmitted disease (STD) laboratories to detect C. trachomatis was investigated in Guangdong, China. METHODS: An external quality assessment panel, including 5 positive samples with different C. trachomatis loads and 2 negative samples was distributed to 654 participating laboratories in October 2019, and the test results were analyzed by Guangdong Central STD Laboratory. The use of various C. trachomatis detection methods in Guangdong from 2015 to 2019 was also retrospectively investigated. RESULTS: Of the 654 participating STD laboratories, 559 (85.47%) used immune chromatographic-rapid diagnostic tests (IC-RDTs) to detect C. trachomatis in 2019, and 95 (14.53%) used nucleic acid amplification tests (NAATs). The rate of NAATs use increased approximately 4-fold from 2015 to 2019. The sensitivity of IC-RDTs decreased markedly from 97.32% to 30.89% with decreasing C. trachomatis load, whereas that of NAATs was 97.62% to 100% in all positive samples. With respect to negative samples the specificity of IC-RDTs was 97.13% to 97.30% and that of NAATs was 98.95% to 100%. Laboratories using IC-RDTs were less likely to detect C. trachomatis than those using NAATs in samples with C. trachomatis loads of 20000 copies/mL or less (P < 0.0001). Further analysis indicated no significant difference (P > 0.05) in detection rate among the 4 IC-RDT assays commonly used by the participating laboratories. CONCLUSIONS: Immune chromatographic-rapid diagnostic tests are commonly used for C. trachomatis detection by many laboratories in Guangdong, but their low sensitivity may lead to missed diagnoses. Nucleic acid amplification tests exhibit high sensitivity and specificity and should be recommended for C. trachomatis detection in STD laboratories.

LncRNA MEG3 inhibits self-renewal and invasion abilities of oral cancer stem cells by sponging miR-421.

BACKGROUND/PURPOSE: Oral cancer stem cells (CSCs) have been considered as the key cells that are implicated in tumor recurrence and metastasis. In recent years, great attention has been paid to the significance of various non-coding RNAs due to their regulatory roles in oral CSCs. Although the function of long non-coding RNA MEG3 in various cancers has been investigated, its effects on the features of oral CSCs remained to be determined. METHODS: The expression levels of MEG3 in tongue squamous cell carcinomas and prognostic effect have been evaluated. We assessed the expression of MEG3 in sphere cells (oral CSCs) using qRT-PCR. Secondary sphere formation and invasion assays were conducted to evaluate the self-renewal and metastatic abilities, respectively. Bioinformatics software and luciferase reporter assay were used to predict and verify the relationship between MEG3 and miR-421. RESULTS: MEG3 was downregulated in the tissues of oral cancer and associated with a poor prognosis. In oral CSCs, the expression of MEG3 was repressed and overexpression of MEG3 resulted in suppression of self-renewal and invasion abilities. Luciferase reporter assay showed that miR-421 directly interacted with MEG3, and our subsequent experiment demonstrated that elevation of miR-421 reversed the MEG3-inhibited characteristics of oral CSCs. CONCLUSION: Our findings suggest that MEG3 can serve as a tumor suppressor in oral CSCs by impeding the action of miR-421. Moreover, targeting MEG3-miR-421 axis has the potential to mitigate the tumor recurrence and metastasis.