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.

Targeting MetaLnc9/miR-143/FSCN1 axis inhibits oxidative stress and myofibroblast transdifferentiation in oral submucous fibrosis.

Background/purpose: Persistent activation of myofibroblasts is attributed to various dysregulated biological events conferring multiple types of fibrosis diseases, including oral submucous fibrosis (OSF). Although the significance of non-coding RNAs (ncRNAs) in the occurrence of fibrosis has been appreciated, the detailed mechanisms still have not been fully elucidated. The aim of this study was to identify key dysregulated ncRNAs and elucidate their pro-fibrotic mechanisms in promoting myofibroblast activation and the pathological development of OSF. Materials and methods: Expression of non-coding RNAs and mRNAs in OSF cohort was determined using RNA sequencing and qRT-PCR. The molecular axis of pro-fibrotic ncRNAs were exploited via luciferase reporter activity assay and RNA expression rescue experiments. Functional assays, including collagen gel contraction, wound healing ability, cell migration, and reactive oxygen species (ROS) production, were conducted to assess the changes in the myofibroblastic phenotypes of primary human buccal mucosal fibroblasts. Results: Herein, we found that long non-coding RNA MetaLnc9 was upregulated in OSF specimens and positively associated with several fibrosis markers. Silencing of MetaLnc9 diminished the features of activated myofibroblasts and the production of ROS. We not only showed that MetaLnc9 functioned as a competitive endogenous RNA of microRNA (miR)-143, but also demonstrated that the pro-fibrosis effect of MetaLnc9 on myofibroblast activities was mediated by suppression of miR-143. Moreover, our data showed that fascin actin-bundling protein 1 (FSCN1) was a direct target of miR-143 and positively related to MetaLnc9. Conclusion: Upregulation of MetaLnc9 may enhance the activation of myofibroblasts by sponging miR-143 and titrating its inhibitory property on FSCN1.

Gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) promotes oral cancer stemness by acting as a molecular sponge of miR331-3p.

Background/purpose: Accumulating evidence has suggested that treatment failure of cancer therapy can be attributed to cancer stem cells (CSCs). Among numerous regulators of cancer stemness, non-coding RNAs (ncRNAs) have gained significant attention recently. In this study, we examined the role of gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) in oral CSCs (OCSCs). Materials and methods: RNA Sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the expression of GAPLINC. Flow cytometry and sphere-forming assay were exploited to isolate OCSCs. Measurement of aldehyde dehydrogenase 1 (ALDH1) activity, CD44 expressing cells, and various phenotypic assays, such as self-renewal, migration, invasion, and colony-forming abilities, were conducted in CSCs of two types of oral cancer cells (SAS and GNM) following the knockdown of GAPLINC. A luciferase reporter was also carried out to validate the direct interaction between GAPLINC and microRNA (miR)-331-3p. Results: Our results showed that GAPLINC was overexpressed in OCSCs from patient-derived and oral cancer cell lines. We demonstrated that silencing of GAPLINC in OCSCs downregulated various CSC hallmarks, such as ALDH1 activity, percentage of CD44-expressing cells, self-renewal capacity, and colony-forming ability. Moreover, our results revealed that the effect of GAPLINC on cancer stemness was mediated by direct repression of miR-331-3p. Conclusion: These data have potential clinical implications in that we unraveled the aberrant upregulation of GAPLINC and demonstrated that suppression of GAPLINC may reduce cancer stemness via sequestering miR-331-3p.

Ganoderma Microsporum Immunomodulatory Protein Alleviates Inflammaging and Oxidative Stress in Diabetes-Associated Periodontitis via Nrf2 Signaling Activation: An In Vitro Study.

Periodontitis, characterized by inflammation and loss of periodontal tissue, is a significant health complication for individuals with diabetes mellitus (DM). Buildup of advanced glycation end-products (AGEs) in DM poses an increased risk of periodontitis via inflammaging. Ganoderma immunomodulatory protein (GMI) shows promise in suppressing inflammaging by mitigating oxidative stress and inflammation via Nrf2 modulation. However, its specific protective effects are not fully understood. Thus, this study aimed to investigate GMI's anti-inflammaging properties and its underlying mechanism in diabetic-associated periodontitis (DP). We first simulated DP by culturing human gingival fibroblasts (HGFs) with AGEs and lipopolysaccharides from P. gingivalis (LPS). We then evaluated the impact of GMI on cell proliferation, migration and wound healing. Additionally, we assessed GMI's effects on the components of inflammaging such as reactive oxygen species (ROS) formation, cellular senescence expression, IL-6 and IL-8 secretions, and NF-κB phosphorylation. Next, we explored whether GMI's anti-inflammaging effects are mediated through the Nrf2 pathway by evaluating Nrf2 and HO-1, followed by the assessment of IL-6 and IL-8 post-Nrf2 knockdown. Our findings revealed that GMI treatment suppressed ROS production, cell senescence, IL-6 and IL-8 and NF-κB phosphorylation. Furthermore, GMI upregulated Nrf2/HO-1 expression and its protective effects were reversed when Nrf2 was knocked down. In conclusion, GMI exerts its anti-inflammaging effect via the modulation of the Nrf2/NF-κB signaling axis in DP in vitro, highlighting its potential as an effective adjunct treatment for diabetes-related periodontitis.

Ginseng extract improves pancreatic islet injury and promotes ß-cell regeneration in T2DM mice.

Introduction: Panax ginseng C. A. Mey. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting ß-cell regeneration. Methods: The T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H & E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet ß-cell regeneration was evaluated through insulin & PCNA double immunofluorescence staining. Furthermore, the mechanism behind ß-cells regeneration was explored through insulin & glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses. Results and Discussion: The present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1ß decreased. Ginseng extract preserved normal islet morphology, increased nascent ß-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing ß-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to ß-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance ß-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.

Deep Learning-Based Surgical Treatment Recommendation and Nonsurgical Prognosis Status Classification for Scaphoid Fractures by Automated X-ray Image Recognition.

Biomedical information retrieval for diagnosis, treatment and prognosis has been studied for a long time. In particular, image recognition using deep learning has been shown to be very effective for cancers and diseases. In these fields, scaphoid fracture recognition is a hot topic because the appearance of scaphoid fractures is not easy to detect. Although there have been a number of recent studies on this topic, no studies focused their attention on surgical treatment recommendations and nonsurgical prognosis status classification. Indeed, a successful treatment recommendation will assist the doctor in selecting an effective treatment, and the prognosis status classification will help a radiologist recognize the image more efficiently. For these purposes, in this paper, we propose potential solutions through a comprehensive empirical study assessing the effectiveness of recent deep learning techniques on surgical treatment recommendation and nonsurgical prognosis status classification. In the proposed system, the scaphoid is firstly segmented from an unknown X-ray image. Next, for surgical treatment recommendation, the fractures are further filtered and recognized. According to the recognition result, the surgical treatment recommendation is generated. Finally, even without sufficient fracture information, the doctor can still make an effective decision to opt for surgery or not. Moreover, for nonsurgical patients, the current prognosis status of avascular necrosis, non-union and union can be classified. The related experimental results made using a real dataset reveal that the surgical treatment recommendation reached 80% and 86% in accuracy and AUC (Area Under the Curve), respectively, while the nonsurgical prognosis status classification reached 91% and 96%, respectively. Further, the methods using transfer learning and data augmentation can bring out obvious improvements, which, on average, reached 21.9%, 28.9% and 5.6%, 7.8% for surgical treatment recommendations and nonsurgical prognosis image classification, respectively. Based on the experimental results, the recommended methods in this paper are DenseNet169 and ResNet50 for surgical treatment recommendation and nonsurgical prognosis status classification, respectively. We believe that this paper can provide an important reference for future research on surgical treatment recommendation and nonsurgical prognosis classification for scaphoid fractures.

Rapid Detection of Bacterial Pathogens Causing Lower Respiratory Tract Infections via Microfluidic-Chip-Based Loop-Mediated Isothermal Amplification.

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.

Resveratrol inhibits arecoline-induced fibrotic properties of buccal mucosal fibroblasts via miR-200a activation.

Background/purpose: Oral submucous fibrosis (OSF) is a precancerous lesion in the oral cavity, commonly results from the Areca nut chewing habit. Arecoline, the main component of Areca nut, is known to stimulate the activation of myofibroblasts, which can lead to abnormal collagen I deposition. Meanwhile, Resveratrol is a non-flavonoid phenolic substance that can be naturally obtained from various berries and foods. Given that resveratrol has significant anti-fibrosis traits in other organs, but little is known about its effect on OSF, this study aimed to investigate the therapeutic impact of resveratrol on OSF and its underlying mechanism. Materials and methods: The cytotoxicity of resveratrol was tested using normal buccal mucosal fibroblasts (BMFs). Myofibroblast phenotypes such as collagen contractile, enhanced migration, and wound healing capacities in dose-dependently resveratrol-treated fBMFs were examined. Results: Current results showed that arecoline induced cell migration and contractile activity in BMFs as well as upregulated the expressions of α-SMA, type I collagen, and ZEB1 markers. Resveratrol intervention, on the other hand, was shown to inhibit arecoline-induced myofibroblast activation and reduce myofibroblast hallmarks and EMT markers. Additionally, resveratrol was also demonstrated to restore the downregulated miR-200a in the arecoline-stimulated cells. Conclusion: In a nutshell, these findings implicate that resveratrol may have an inhibitory influence on arecoline-induced fibrosis via the regulation of miR-200a. Hence, resveratrol may be used as a therapeutic strategy for OSF intervention.

Er:YAG laser suppresses pro-inflammatory cytokines expression and inflammasome in human periodontal ligament fibroblasts with Porphyromonas gingivalis-lipopolysaccharide stimulation.

Background/purpose: Periodontitis is an inflammatory condition of the tooth-supporting structures triggered by the host's immune response towards the bacterial deposits around the teeth. It is well acknowledged that pro-inflammatory interleukin (IL)-6, IL-8, MCP-1 as well as the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, are the key modulators in the activation of this response. Erbium-doped yttrium-aluminium-garnet (Er:YAG) laser, a solid-state crystal laser have been commonly used in the treatment of periodontal diseases. However, little is understood about the molecular mechanism of the Er:YAG laser, especially in targeting the host immune response brought on by periodontal pathogens. Hence, the current study focused on the protective effects of Er:YAG laser on periodontitis in-vitro in terms of pro-inflammatory cytokines, chemokines and NLRP3 inflammasome expressions. Materials and methods: Human periodontal ligament fibroblast (PDLFs) were first stimulated with lipopolysaccharides (LPS) from P. gingivalis (Pg-LPS) to simulate periodontitis. Cells were then irradiated with Er:YAG laser of ascending energy densities (3.6-6.3 J/cm2), followed by cell proliferation and wound healing assay. Next, the effects of Er:YAG laser on the expressions of IL-6, IL-8, MCP-1, NLRP3, and cleaved GSDMD were examined. Results: Pg-LPS was found to reduce cell's proliferation rate and wound healing ability in PDLFs and these were rescued by Er:YAG laser irradiation. In addition, LPS stimuli resulted in a marked upregulation in the secretion of IL-6, IL-8 and MCP-1 as well as the mRNA and protein expression of NLRP3 and cleaved-GSDMD protein whereas Er:YAG laser suppressed the elicited phenomena. Conclusion: To our knowledge, this is the first study to look into the laser's implication on the NLRP3 inflammasome in periodontitis models. Our study reveals a crucial role of Er:YAG laser in ameliorating periodontitis in-vitro through the modulation of IL-6, IL-8, MCP-1 and the NLRP3 inflammasome and highlights that the control of the NLRP3 inflammasome may become a potential approach for periodontitis.

Aberrantly downregulated FENDRR by arecoline elevates ROS and myofibroblast activation via mitigating the miR-214/MFN2 axis.

Long non-coding RNA FENDRR possesses both anti-fibrotic and anti-cancer properties, but its significance in the development of premalignant oral submucous fibrosis (OSF) remains unclear. Here, we showed that FENDRR was downregulated in OSF specimens and fibrotic buccal mucosal fibroblasts (fBMFs), and overexpression of FENDRR mitigated various myofibroblasts hallmarks, and vice versa. In the course of investigating the mechanism underlying the implication of FENDRR in myofibroblast transdifferentiation, we found that FENDRR can directly bind to miR-214 and exhibit its suppressive effect on myofibroblast activation via titrating miR-214. Moreover, we showed that mitofusin 2 (MFN2), a protein that is crucial to the fusion of mitochondria, was a direct target of miR-214. Our data suggested that FENDRR was positively correlated with MFN2 and MFN2 was required for the inhibitory property of FENDRR pertaining to myofibroblast phenotypes. Additionally, our results showed that the FENDRR/miR-214 axis participated in the arecoline-induced reactive oxygen species (ROS) accumulation and myofibroblast transdifferentiation. Building on these results, we concluded that the aberrant downregulation of FENDRR in OSF may be associated with chronic exposure to arecoline, leading to upregulation of ROS and myofibroblast activation via the miR-214-mediated suppression of MFN2.

Resveratrol attenuates advanced glycation end product-induced senescence and inflammation in human gingival fibroblasts.

Background/purpose: The accumulation of advanced glycation end products (AGEs) lead to a series of immune responses such as: increased oxidative stress and inflammation which contribute to the development of diabetic complications and periodontal disease. Resveratrol is a natural compound that has anti-oxidant and anti-inflammatory effects. Studies have found that diabetes-induced periodontitis is mainly caused by oxidative stress, aging and increased inflammation. In view of resveratrol has been proposed to have the ability in anti-oxidant and anti-inflammation in a variety of tissues. However, the role of resveratrol in diabetic periodontitis remains to be investigated. In this study, we aimed to investigate the role of resveratrol in preventing and treating diabetic periodontitis. Materials and methods: First, cell proliferation was measured in AGEs-treated human gingival fibroblast with or without resveratrol. We examined the reactive oxygen species (ROS) generation, senescence-associated beta-galactosidase (SA-ß-gal) and senescence marker p16 in human gingival fibroblasts (HGFs) stimulated with AGEs with or without the treatment of resveratrol. To determine whether resveratrol has the potential to regulate inflammaging which is mediated via the NF-κB signaling pathway and, the expression of p65 and p-IκB were also investigated. Furthermore, the concentration of interleukin (IL)-6 and IL-8 were also measured in AGEs-stimulated HGFs treated with or without resveratrol. Results: ROS generation, cell senescence, and the secretion of IL-6 and IL-8 were significantly upregulated following the treatment of AGEs. However, the administration of resveratrol suppresses the generation of IL-6 and IL-8 and cell senescence via inhibiting NF-κB signaling pathway. Our results revealed that resveratrol inhibits inflammaging by downregulating NF-κB signaling pathway. Conclusion: According to our findings, AGEs increase senescence and the production of proinflammatory cytokines in the gingiva, while the administration of resveratrol impedes inflammaging via suppressing NF-κB signaling pathway.

Targeting histone deacetylase 9 represses fibrogenic phenotypes in buccal mucosal fibroblasts with arecoline stimulation.

Background/purpose: Oral submucosal fibrosis (OSF) is a premalignant disorder positively associated with betel nut chewing. Recent studies supported the promising benefits of histone deacetylase (HDAC) inhibitors for fibrosis treatment. Here we aim to clarify the pro-fibrogenic role of HDAC9 in regulating OSF. Materials and methods: Healthy and OSF specimens were collected to investigate the clinical significance of HDAC9. Chronic arecoline treatment process was used to induce arecoline-mediated myofibroblasts-related activation of primary buccal mucosa fibroblasts (BMFs). Functional analysis of collagen gel contraction, transwell migration, and wound-healing assays were performed to assess the change in pro-fibrogenic properties of BMFs and fibrotic BMFs (fBMFs). Lentiviral-mediated HDAC9 knockdown was used to verify the role of HDAC9 in the pro-fibrogenic process. Results: We found that arecoline significantly increased the mRNA and protein expression of HDAC9 of BMFs in a dose-dependent manner. Knockdown of HDAC9 in BMFs reversed the strengthened effects of arecoline on collagen gel contraction, cell migration, and wound-healing ability. We further demonstrated that knockdown of HDAC9 in fBMFs significantly attenuated its inherent pro-fibrogenic properties. Furthermore, we confirmed a significantly increased expression of HDAC9 mRNA in OSF compared to normal tissues, which suggested a positive correlation between the up-regulation of HDAC9 and OSF. Conclusion: We demonstrated that silencing of HDAC9 inhibited arecoline-induced activation and inherent pro-fibrogenic properties, suggesting potential therapeutics by targeting HDAC9 in the OSF treatment.

Quercetin ameliorates advanced glycation end product-induced wound healing impairment and inflammaging in human gingival fibroblasts.

Background/purpose: Diabetes mellitus (DM) and periodontal disease are both prevalent and chronic inflammatory disorders that have significant health impact. Many studies have pointed out that advanced glycation end-products (AGEs) in DM induces inflammaging, which is a pre-aging and hyperinflammatory condition, and it has been linked to a greater likelihood in developing periodontitis. Inflammaging in DM has been shown to be driven by AGEs-induced cell senescence, inflammatory cytokines, and oxidative stress, resulting in the degradation of periodontium. Quercetin has shown abilities to decrease inflammation and oxidative stress in a variety of tissues, however, the effect in diabetic periodontitis remains uncertain. Thus, the aim of this study was to investigate its impacts on inflammaging in diabetic periodontitis. Materials and methods: We examined cell proliferation in human gingival fibroblasts (HGF), wound healing, IL-6 and IL-8 secretions, cellular senescence expression, and the formation of reactive oxygen species (ROS) in response to AGE stimulation with and without Quercetin intervention. Following that, we looked into NF-κß activity to see if Quercetin mediate its effects via this pro-inflammatory signaling. Results: Quercetin at 20 µM and below did not have any impact on HGFs' cell proliferation rate. Quercetin intervention improved the AGEs-impaired wound healing, in addition to the attenuation of AGEs-induced ROS in a dose-dependent pattern. Moreover, Quercetin therapy dose-dependently inhibited AGEs-induced cell senescence activity along with its senescence associated secretion phenotype (SASP) secretions such as IL-6 and IL-8. Western blot analysis indicated that Quercetin was able to reverse the phosphorylation of p65 and Iκß in AGEs-stimulated HGFs, demonstrating it can modulate NF-κß pathway. Conclusion: Accumulation of AGEs can elicit inflammaging in HGFs, as seen by increased pro-inflammatory cytokines, cell senescence expression and oxidative stress. The results proposed that Quercetin is able to ameliorate inflammaging in diabetic periodontitis and improve wound healing via the suppression of NF-κß pathway and hence, may be a promising approach for treatment of diabetes-associated periodontitis.

Overexpression of a Ramie (Boehmaeria nivea L. Gaud) Group I WRKY Gene, BnWRKY49, Increases Drought Resistance in Arabidopsis thaliana.

Plants face multiple stresses in their natural habitats. WRKY transcription factors (TFs) play an important regulatory role in plant stress signaling, regulating the expression of multiple stress-related genes to improve plant stress resistance. In this study, we analyzed the expression profiles of 25 BnWRKY genes in three stages of ramie growth (the seedling stage, the rapid-growth stage, and the fiber maturity stage) and response to abiotic stress through qRT-PCR. The results indicated that 25 BnWRKY genes play a role in different growth stages of ramie and were induced by salt and drought stress in the root and leaf. We selected BnWRKY49 as a candidate gene for overexpression in Arabidopsis. BnWRKY49 was localized in the nucleus. Overexpression of BnWRKY49 affected root elongation under drought and salt stress at the Arabidopsis seedling stage and exhibited increased tolerance to drought stress. Further research found that BnWRKY49-overexpressing lines showed decreased stomatal size and increased cuticular wax deposition under drought compared with wild type (WT). Antioxidant enzyme activities of SOD, POD, and CAT were higher in the BnWRKY49-overexpressing lines than the WT. These findings suggested that the BnWRKY49 gene played an important role in drought stress tolerance in Arabidopsis and laid the foundation for further research on the functional analysis of the BnWRKYs in ramie.

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.

penA profile of Neisseria gonorrhoeae in Guangdong, China: Novel penA alleles are related to decreased susceptibility to ceftriaxone or cefixime.

BACKGROUND: Resistance to extended-spectrum cephalosporins (ESCs) has become a public health concern with the spread of Neisseria gonorrhoeae and increasing antimicrobial resistance. Mutation of penA, encoding penicillin-binding protein 2, represents a mechanism of ESC resistance. This study sought to assess penA alleles and mutations associated with decreased susceptibility (DS) to ESCs in N. gonorrhoeae. MATERIALS AND METHODS: In 2021, 347 gonococci were collected in Guangdong, China. Minimum inhibitory concentations (MICs) of ceftriaxone and cefixime were determined, and whole-genome sequencing and phylogenetic analysis were performed. Multi-locus sequence typing (MLST) and conventional resistance determinants such as penA, mtrR, PonA and PorB were analysed. penA was genotyped and sequence-aligned using PubMLST. RESULTS: Genome-wide phylogenetic analysis revealed that the prevalence of DS to ESCs was highest in Clade 11.1 (100.0%), Clade 2 (66.7%) and Clade 0 (55.7%), and the leading cause was strains with penA-60.001 or new penA alleles in clades. The penA phylogenetic tree is divided into two branches: non-mosaic penA and mosaic penA. The latter contained penA-60.001, penA-10 and penA-34. penA profile analysis indicated that A311V and T483S are closely related to DS to ESCs in mosaic penA. The new alleles NEIS1753_2840 and NEIS1753_2837 are closely related to penA-60.001, with DS to ceftriaxone and cefixime of 100%. NEIS1753_2660, a derivative of penA-10 (A486V), has increased DS to ceftriaxone. NEIS1753_2846, a derivative of penA-34.007 (G546S), has increased DS to cefixime. CONCLUSION: This study identified critical penA alleles related to elevated MICs, and trends of gonococcus-evolved mutated penA associated with DS to ESCs in Guangdong.

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.

Effective Invasiveness Recognition of Imbalanced Data by Semi-Automated Segmentations of Lung Nodules.

Over the past few decades, recognition of early lung cancers was researched for effective treatments. In early lung cancers, the invasiveness is an important factor for expected survival rates. Hence, how to effectively identify the invasiveness by computed tomography (CT) images became a hot topic in the field of biomedical science. Although a number of previous works were shown to be effective on this topic, there remain some problems unsettled still. First, it needs a large amount of marked data for a better prediction, but the manual cost is high. Second, the accuracy is always limited in imbalance data. To alleviate these problems, in this paper, we propose an effective CT invasiveness recognizer by semi-automated segmentation. In terms of semi-automated segmentation, it is easy for doctors to mark the nodules. Just based on one clicked pixel, a nodule object in a CT image can be marked by fusing two proposed segmentation methods, including thresholding-based morphology and deep learning-based mask region-based convolutional neural network (Mask-RCNN). For thresholding-based morphology, an initial segmentation is derived by adaptive pixel connections. Then, a mathematical morphology is performed to achieve a better segmentation. For deep learning-based mask-RCNN, the anchor is fixed by the clicked pixel to reduce the computational complexity. To incorporate advantages of both, the segmentation is switched between these two sub-methods. After segmenting the nodules, a boosting ensemble classification model with feature selection is executed to identify the invasiveness by equalized down-sampling. The extensive experimental results on a real dataset reveal that the proposed segmentation method performs better than the traditional segmentation ones, which can reach an average dice improvement of 392.3%. Additionally, the proposed ensemble classification model infers better performances than the compared method, which can reach an area under curve (AUC) improvement of 5.3% and a specificity improvement of 14.3%. Moreover, in comparison with the models with imbalance data, the improvements of AUC and specificity can reach 10.4% and 33.3%, respectively.

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.

Downregulation of histone deacetylase 8 (HDAC8) alleviated the progression of oral submucous fibrosis.

Background/purpose: Oral submucous fibrosis (OSF) is a premalignant disorder that is associated with betel nut chewing. The purpose of the study was to establish the role of histone deacetylase (HDAC) 8, one of histone deacetylases, in the regulation of fibrotic conditions to provide a therapeutic potential for OSF. Materials and methods: First, we examined the expression of HDAC8 in fibrotic buccal mucosal fibroblasts (fBMFs) and OSF tissues. Markers of myofibroblasts and TGF-ß signaling were conducted in fBMFs with HDAC8 knockdown were examined. Furthermore, epithelial-mesenchymal transition (EMT) markers, collagen gel contraction and migration ability were also examined in fBMFs transfected with sh-HDAC8. HDAC8 inhibitor was used to analyze the collagen gel contraction and wound healing ability in fBMFs. Results: We observed the mRNA expression of HDAC8 was significantly increased in fBMFs. Compared to normal tissues, the protein level of HDAC8 was upregulated in OSF. Next, mRNA and protein expression of HDAC8 was significantly decreased, accompanying downregulation of α-SMA and COL1A1 in fBMFs infected with sh-HDAC8. To determine the critical role of HDAC8 in OSF fibrogenesis, results revealed that TGF-ß secretion and the expression of EMT transcription factor SNAIL and p-Smad were significantly decreased in HDAC8-knockdown fBMFs. We further demonstrated that collagen gel contraction and migration ability were significantly decreased in fBMFs transfected with sh-HDAC8. Last, results revealed that significantly reduced collagen gel contraction and wound healing ability in fBMFs with HDAC8 inhibitor treatment. Conclusion: We concluded that downregulation of HDAC8 alleviated the activities of myofibroblasts and TGF-ß/Smad signaling pathway in OSF.