The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening.

A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.

Enhancing contrast distribution with the far lateral approach in lumbar transforaminal epidural steroid injections: A retrospective analysis.

BACKGROUND: Herniated intervertebral disc (HIVD) with radiculopathy is a common degenerative spine disorder. Transforaminal epidural steroid injection (TFESI) is one of the pain relief treatments for lumbar radiculopathy recommended by evidence-based guidelines. Adequate contrast distribution is correlated with better pain control, but the best approach has not been confirmed yet. AIM: To confirm the distribution of contrast medium injected with a new approach of TFESI, that is, far lateral lateral recess approach (FLLR-TFESI). METHODS: Patients receiving TFESI due to HIVD with radiculopathy between 2010 January and 2020 August were retrospectively enrolled. While the FLLR-TFESI was taken as the experimental group, the conventional approach was viewed as the control group. The baseline characteristics, the pattern of contrast enhancement under fluoroscopic guidance, and the complications of these patients were collected and analyzed. RESULTS: A total of 380 patients were analyzed (143 in control group and 237 in experimental group). The two groups were balanced in most baseline characteristics, except disc extrusion (p = 0.01) and scoliosis (p = 0.04). The FLLR-TFESI have a better contrast distribution (p < 0.01), even after adjustment (p < 0.001). No intrathecal injection was noted, but higher rate of intra-disc injection was noted in FLLR-TFESI group (10% vs. 3%, p = 0.008). CONCLUSION: The FLLR-TFESI has a superior contrast enhancement and distribution in comparison to conventional approach. Prospective study to confirm the study result as well as the clinical benefits is suggested in the future.

Trop2-targeted therapies in solid tumors: advances and future directions.

Trophoblast cell surface antigen 2 (Trop2) is overexpressed in a range of solid tumors and participants in multiple oncogenic signaling pathways, making it an attractive therapeutic target. In the past decade, the rapid development of various Trop2-targeted therapies, notably marked by the advent of the antibody-drug conjugate (ADC), revolutionized the outcome for patients facing Trop2-positive tumors with limited treatment opinions, such as triple-negative breast cancer (TNBC). This review provides a comprehensive summary of advances in Trop2-targeted therapies, including ADCs, antibodies, multispecific agents, immunotherapy, cancer vaccines, and small molecular inhibitors, along with in-depth discussions on their designs, mechanisms of action (MOAs), and limitations. Additionally, we emphasize the clinical research progress of these emerging Trop2-targeted agents, focusing on their clinical application and therapeutic efficacy against tumors. Furthermore, we propose directions for future research, such as enhancing our understanding of Trop2's structure and biology, exploring the best combination strategies, and tailoring precision treatment based on Trop2 testing methodologies.

Effect of endoscopic sphincterotomy and endoscopic papillary balloon dilation endoscopic retrograde cholangiopancreatographies on the sphincter of Oddi.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP), with its clinical ad-vantages of less trauma and faster recovery, has become the primary treatment for choledocholithiasis. AIM: To investigate the effects of different ERCP procedures on the sphincter of Oddi. METHODS: The clinical data of 91 patients who underwent ERCP at Yixing Hospital of Traditional Chinese Medicine between February 2018 and February 2021 were analyzed retrospectively. The patients were divided into endoscopic sphincterotomy (EST, n = 24) and endoscopic papillary balloon dilation (EPBD, n = 67) groups. The duration of operation, pancreatic development, pancreatic sphincterotomy, intubation difficulties, stone recurrence, and incidence of reflux cholangitis and cholecystitis were statistically analyzed in patients with a history of choledocholithiasis, pancreatitis, and Oddi sphincter dysfunction in the EST and EPBD groups. RESULTS: Differences in hypertension, diabetes, increased bilirubin, small diameter of the common bile duct, or ampullary diverticulum between the two groups were not significant. Statistically significant differences were observed between the two groups concerning sex and age (< 60 years). Patients with a history of choledocholithiasis, pancreatitis, and Oddi sphincter dysfunction were higher in the EST group than in the EPBD group. The number of cases of pancreatic development, pancreatic duct sphincterotomy, and difficult intubation were higher in the EST group than in the EPBD group. The number of Oddi's sphincter manometries, ERCP surgical outcomes, and guidewires entering the pancreatic duct several times in EST group were lower than those in the EPBD group. The numbers of stone recurrences, reflux cholangitis, and cholecystitis were higher in the EST group than in the EPBD group. CONCLUSION: In summary, common bile duct stones, pancreatitis history, and multiple guided wire introductions into the pancreatic duct are independent risk factors for EST and EPBD. Based on this evidence, this study can provide actionable insights for clinicians and researchers.

Promoting the transformation of green rust for As immobilization with Acidovorax sp. strain BoFeN1.

Microbially mediated Fe(II) oxidation has a great potential for attenuating arsenic (As) mobility in an anoxic groundwaters. Green rust (GR), a common Fe(II)-bearing phase in such environments, could be easily oxidized into Fe (oxyhydr)oxides through microbial activity. This study focused on Acidovorax sp. strain BoFeN1, an anaerobic nitrate-reducing Fe(II)-oxidizing (NRFO) bacterium, to promote the transformation of GR. In biotic GR transformation experiments, magnetite formation occurred at [As]ini = 5 mg/L while lepidocrocite and goethite were formed at [As]ini = 10 mg/L. In the absence of bacterium, the GR persisted throughout the 120-h experiment. Meanwhile, with the addition of strain BoFeN1, the final aqueous As concentration significantly decreased from 0.237 to 0.004 mg/L (C0 = 5 mg/L) and from 1.457 to 0.096 mg/L (C0 = 10 mg/L) at 120 h. It was indicated that strain BoFeN1 played a crucial role in promoting the GR transformation and enhancing As immobilization. Further investigations revealed that the role of strain BoFeN1 extended beyond Fe-oxidation. With nitrite (the intermediate of nitrate bioreduction) as oxidizer, lepidocrocite/goethite were formed in the chemical-oxidation system, excluding magnetite. In the Bio - [As]ini = 5 mg/L, the occurrence of lepidocrocite via the bio-oxidation of Fe(II) in GR at 24 h, along with the metabolism of strain BoFeN1 reducing nitrate accompanied with H+ consumption, it should be reasonably deduced that the alkaline micro-environment of periplasm induced by strain BoFeN1 were vital for the transformation of lepidocrocite to magnetite triggered by trace Fe(II). However, in the Bio - [As]ini = 10 mg/L, more As adsorbed on GR inhibiting the adsorption of bacterium, so the alkaline micro-environment had no obvious effect on such transformation. This study helps to understand the interdependence between GR and anaerobic NRFO bacterium, and provides a new perspective for more effective As remediation strategies in anoxic groundwaters.

Adsorption behaviors of perfluorooctanoic acid on aged microplastics.

The presence of perfluoroalkyl substances (PFAS) in the environment poses a significant threat to ecological safety and environmental health. Widespread microplastics (MPs) have been recognized as vectors for emerging contaminants due to human activities. However, the adsorption behaviors of PFAS on MPs, especially on aged MPs, have not been extensively investigated. This study aimed to investigate the adsorption behaviors of perfluorooctanoic acid (PFOA) on aged MPs (polystyrene, polyethylene, and polyethylene terephthalate) treated with UV irradiation and persulfate oxidation under salinity and dissolve organic matter (DOM) condition. Carbonyl index values of MPs increased after the aged treatment, indicating the production of oxygen-containing groups. The PFOA adsorption on aged MPs was impacted by the co-existence of Na+ ions and DOM. As PFOA adsorption onto aged MPs was mainly controlled by hydrophobic interaction, the electrostatic interaction also made a contribution, but there was no significant change in PFOA adsorption behavior between the pristine and aged MPs. While these findings provide insight into PFAS adsorption on aged MPs, further research is necessary to account for the complexity of the real environment. PRACTITIONER POINTS: Adsorption behaviors of perfluorooctanoic acid (PFOA) on aged microplastics were investigated. Hydrophobic interaction mainly controlled PFOA adsorption on aged microplastics (MPs). Co-existence dissolve organic matter and salinity influenced PFOA adsorption behaviors on aged MPs.

Preoperative electroacupuncture versus sham electroacupuncture for the treatment of postoperative ileus after laparoscopic surgery for colorectal cancer in China: a study protocol for a multicentre, randomised, sham-controlled trial.

INTRODUCTION: Postoperative ileus (POI) is a postoperative complication that can cause lingering recovery after colorectal resection and a heavy healthcare system burden. Acupuncture aims to prevent postoperative complications, reduce the duration of POI, help recovery and shorten hospital stays. We hypothesise that preoperative electroacupuncture (EA) can promote POI recovery under the enhanced recovery after surgery protocol after laparoscopic surgery in patients with POI. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 80 patients will be enrolled and randomly assigned to the EA or sham electroacupuncture (SA) group. The eligible patients will receive EA or SA for one session per day with treatment frequency starting on preoperative day 1 for four consecutive days. The primary outcome is the time to first defecation. The secondary outcomes include the time to first flatus, length of postoperative hospital stay, time to tolerability of semiliquid and solid food, postoperative nausea, vomiting, pain and extent of abdominal distention, time to first ambulation, preoperative anxiety, 30-day readmission rate, the usage of anaesthetics and analgesics during operation, length of postanaesthesia care unit stay. A mechanistic study by single-cell RNA sequencing in which postintervention normal intestinal tissue samples will be collected. The results of this study will provide evidence of the effects of acupuncture on POI and promote good clinical decision to millions of patients globally every year. ETHICS AND DISSEMINATION: This study has been approved by the ethical application of Beijing University of Chinese Medicine (2022BZYLL0401), Beijing Friendship Hospital Affiliated to Capital Medical University(2022-P2-368-02), Cancer Hospital Chinese Academy of Medical Science (23/175-3917), Huanxing Cancer Hospital (2023-002-02). The results will be published in a medical journal. In addition, we plan to present them at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077633.

Prominent response to savolitinib monotherapy in high-grade fetal adenocarcinoma with MET amplification and concurrent brain metastasis: a case report.

Background: Mesenchymal-epithelial transition (MET) represents a potential therapeutic target in various cancers, with amplification of the MET gene identified in a subset of patients with pulmonary adenocarcinomas. However, MET gene amplification is rarely observed in high-grade fetal adenocarcinoma (H-FLAC). Case Description: Here we present a novel case of a patient diagnosed with stage IV H-FLAC harboring MET amplifications and treated with savolitinib. The 69-year-old male patient, who presented with a primary complaint of cough and white sputum, had a history of hypertension for over 10 years and a 45-year smoking history. The patient received savolitinib monotherapy treatment due to brain metastases. Despite the omission of radiotherapy for asymptomatic brain metastases, a notable response to savolitinib therapy was observed, with a partial response (PR) achieved after 4 weeks and a reduction in the brain tumor. At the time of the submission of this report, the patient received over 24 weeks of savolitinib treatment, and was maintained PR. The patient was still undergoing treatment. This highlights the potential clinical benefits of targeted therapy against MET amplification in H-FLAC. Conclusions: H-FLAC harboring MET amplification and brain metastasis is rare. Treatment with savolitinib monotherapy resulted in a PR, providing preliminary insights to the efficacy of savolitinib for H-FLAC with MET amplification.

Superparamagnetic photonic crystals with DNA probes for rapid visual detection of mercury.

A novel superparamagnetic photonic crystal DNA probe (Fe3O4@SiO2@amino@DNA SPC) was developed to enable rapid visual detection of Hg2+. This unique photonic crystal (PC) was synthesized by combining superparamagnetic nanospheres with DNA probes. The DNA probe, rich in thymine (T), detects mercury ions through base mismatch, resulting in the formation of T-Hg2+-T loop hairpin structures. With the binding of Hg2+ to the probe attached to superparamagnetic nanospheres, the PC structure assembled by these nanospheres, formed by the magnetic field, was changed. This change enhanced the reflection intensity; it could be quantified using a fiber optic spectrometer and was visible to the naked eye. The Fe3O4@SiO2@amino@DNA SPC, specific to Hg2+, exhibited a reflection peak at 679 nm, which intensified with increasing Hg2+ concentration. The reflection intensity increased by 132.58 a.u., and the PC color shifted from red to yellow as the Hg2+ concentration increased from 0.1 µg/L to 1 mg/L.

Poly-L-lactic acid fillers for nasal alar retraction: safety and effectiveness in 13 cases.

OBJECTIVE: To assess the effectiveness and safety of poly-L-lactic acid (PLLA) fillers in treating nasal alar retraction. We conducted a series of case reports on 13 patients treated for nasal alar retraction at the Chengdu Ningyue FRESKIN Medicine Cosmology Clinic from September 2022 to July 2023. Patients ranged from 23 to 49 years, comprising 12 females and 1 male. Of these, 5 had no prior medical history, 7 had previously undergone rhinoplasty, and 1 had a history of nasal trauma. Treatment outcomes and adverse reactions were monitored following PLLA filler injections. The mean pre-treatment severity score was 1.62±0.65, improving to 0.54±0.66 post-treatment (t=4.19, df=23, P<0.001). All participants reported satisfaction with their results without adverse effects. PLLA facial fillers are a safe and effective treatment for nasal alar retraction, presenting no embolism risk. This treatment merits consideration for broader clinical application.

Exercise-Induced Central Fatigue: Biomarkers, and Non-Medicinal Interventions.

Fatigue, commonly experienced in daily life, is a feeling of extreme tiredness, shortage or lack of energy, exhaustion, and difficulty in performing voluntary tasks. Central fatigue, defined as a progressive failure to voluntarily activate the muscle, is typically linked to moderate- or light-intensity exercise. However, in some instances, high-intensity exercise can also trigger the onset of central fatigue. Exercise-induced central fatigue often precedes the decline in physical performance in well-trained athletes. This leads to a reduction in nerve impulses, decreased neuronal excitability, and an imbalance in brain homeostasis, all of which can adversely impact an athlete's performance and the longevity of their sports career. Therefore, implementing strategies to delay the onset of exercise-induced central fatigue is vital for enhancing athletic performance and safeguarding athletes from the debilitating effects of fatigue. In this review, we discuss the structural basis, measurement methods, and biomarkers of exercise-induced central fatigue. Furthermore, we propose non-pharmacological interventions to mitigate its effects, which can potentially foster improvements in athletes' performances in a healthful and sustainable manner.

Prediction and analysis of components and functions of Ixeris chinensis based on network pharmacology and molecular docking.

Background: It is reported that the Ixeris chinensis has high medicinal value, but there are few reports about its potential molecular mechanism. We used a network pharmacology approach to predict the active ingredients, targets of action and possible interventions in diseases of Ixeris chinensis. Methods: We employed various databases and software to predict the active ingredients, target genes, protein interactions, signaling pathways, network diagrams, and molecular docking of Ixeris chinensis. Simultaneously, we searched multiple Chinese and English databases and conducted meta-analyses of five randomized controlled trials. Results: The analysis results revealed 12 effective components, including apigenin ß-sitosterol, baicalin, baicalein, and luteolin; and selected 40 key targets, including AKT1, TNF, EGFR, ESR1, SRC, among others. GO analysis generated 225 biological processes, 39 cellular components, and 65 molecular functions; KEGG analysis revealed 103 signaling pathways. Molecular docking results indicated that the main active components of Ixeris chinensis can bind well with key targets. Five randomized controlled trials were included. Meta-analysis showed that Ixeris extract can effectively reduce animal blood lipid levels. Conclusion: This study revealed the main active ingredients and key targets of Ixeris chinensis, analyzed the signaling pathways of potential targets, conducted disease prediction, and performed molecular docking prediction, providing a basis for research on the pathways of Ixeris treatment for related diseases and subsequent new drug development.

Deep migration learning-based recognition of diseases and insect pests in Yunnan tea under complex environments.

BACKGROUND: The occurrence, development, and outbreak of tea diseases and pests pose a significant challenge to the quality and yield of tea, necessitating prompt identification and control measures. Given the vast array of tea diseases and pests, coupled with the intricacies of the tea planting environment, accurate and rapid diagnosis remains elusive. In addressing this issue, the present study investigates the utilization of transfer learning convolution neural networks for the identification of tea diseases and pests. Our objective is to facilitate the accurate and expeditious detection of diseases and pests affecting the Yunnan Big leaf kind of tea within its complex ecological niche. RESULTS: Initially, we gathered 1878 image data encompassing 10 prevalent types of tea diseases and pests from complex environments within tea plantations, compiling a comprehensive dataset. Additionally, we employed data augmentation techniques to enrich the sample diversity. Leveraging the ImageNet pre-trained model, we conducted a comprehensive evaluation and identified the Xception architecture as the most effective model. Notably, the integration of an attention mechanism within the Xeption model did not yield improvements in recognition performance. Subsequently, through transfer learning and the freezing core strategy, we achieved a test accuracy rate of 98.58% and a verification accuracy rate of 98.2310%. CONCLUSIONS: These outcomes signify a significant stride towards accurate and timely detection, holding promise for enhancing the sustainability and productivity of Yunnan tea. Our findings provide a theoretical foundation and technical guidance for the development of online detection technologies for tea diseases and pests in Yunnan.

Temporal variations in absorption and translocation of heavy metal(loid)s in pak choi (Brassica rapa L.) under open-field and greenhouse cultivation.

Elucidating the absorption and translocation of heavy metal(loid)s by common vegetables across different growth environments and stages is crucial for conducting accurate environmental risk assessments and for associated control. This study investigated temporal variations in the absorption and translocation capacities of pak choi (Brassica rapa L.) for As, Cd, Cr, Cu, Pb, and Zn in polluted soils during the plant growth cycle under greenhouse and open-field cultivation modes. Results showed high root metal(loid) bioconcentration factors and root-to-shoot translocation factors for Cd (0.25 and 1.44, respectively) and Zn (0.26 and 1.01), but low values for As (0.06 and 0.88) and Pb (0.06 and 0.87). The Cd concentration in the aerial edible parts peaked during the early slow growth period, whereas other heavy metal(loid)s peaked during the later stable maturity period. Root bioconcentration and root-to-shoot translocation factors did not significantly differ between cultivation modes. However, greenhouse cultivation exhibited lower average Cd and Zn concentrations in the edible parts and cumulative uptake amounts of most metal(loid)s than open-field cultivation during the typical harvest period spanning days 60 and 90. Short-term transitioning from open-field to greenhouse cultivation may reduce health risks associated with heavy metal(loid) intake via pak choi consumption. These findings facilitate sustainable agricultural practices and food safety management.

Chiral Inversion of Au40(SR)24 Nanocluster Driven by Rotation of Gold Tetrahedra in the Kekulé-like Core.

Studying the chiral characteristics and chiral inversion mechanisms of gold nanoclusters is important to promote their applications in the field of chiral catalysis and chiral recognition. Herein, we investigated the chiral inversion process of the Au40(SR)24 nanocluster and its derivatives using density functional theory calculations. The results showed that the chiral inversion process can be achieved by rotation of tetrahedra units in the gold core without breaking the Au-S bond. This work found that Au40 nanoclusters protected by different ligands have different chiral inversion mechanisms, and the difference is mainly attributable to the steric effects of the ligands. Moreover, the chiral inversion of the derivative clusters (Au34, Au28, and Au22) of the Au40 nanocluster can also be accomplished by the rotation of the Au4 tetrahedra units in the gold core. The energy barrier in the chiral inversion process of gold nanoclusters increases with the decrease of Au4 tetrahedra units in the gold core. This work identifies a chiral inversion mechanism with lower reaction energy barriers and provided a theoretical basis for the study of gold nanocluster chirality.

Network pharmacology combined with experimental validation reveals the mechanism of action of erpixing granules on functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Functional dyspepsia (FD) is a prevalent gastrointestinal disorder characterised by high incidence and recurrence rates, posing significant health risks. Erpixing Granules (EPX), approved by the National Food and Drug Administration in 2002, are known for their spleen and stomach invigorating properties, effectively treating FD. However, its mechanism of action remains unclear. AIM OF THE STUDY: This study aims to elucidate EPX's mechanism of treating FD through network pharmacology, and experimental validation using FD animal models. METHODS: In this study, the chemical composition of EPX in positive and negative ion modes was analyzed by UHPLC-Q-TOF MS. The mass spectral data were processed and analyzed using MS-DIAL software to automatically match compound fragment information and identify the known components with the compound database to obtain the active components of EPX. SwissTargetPrediction was used to obtain EPX targets, while FD-related targets were sourced from GeneCards, OMIM and DisGeNET databases. A protein-protein interaction (PPI) network was constructed using the STRING platform, and potential signalling pathways of EPX were determined through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, an FD model was established in rates by administering a 0.1% iodoacetamide sucrose solution, followed by tail clamp stimulation to experimentally validate the network pharmacology findings. RESULTS: Our results revealed 139 effective ingredients in EPX, targeting 60 core FD-related genes. PPI network analysis identified EGFR, CTNNB1 and NFκB1 as core target genes. The KEGG pathway analysis indicated that EPX can modulate FD progression through the PI3K/AKT signalling pathway. Animal experiments demonstrated EPX's capacity to increase body mass, food intake and food utilisation efficiency in FD rats, alongside increased gastric juice secretion, pepsin activity, trypsin activity, cholesterol, bile acid and bilirubin activity. HE examination revealed that EPX improved the inflammatory infiltration of gastric mucosal cells in rats. Furthermore, EPX also promoted gastric emptying and intestinal propulsion in mice. These results suggest that EPX improves spleen and stomach function, enhances the protective effect on the spleen and stomach and promotes food digestion and absorption. Immunofluorescence studies revealed upregulated expression of PI3K, AKT and ANO1 proteins in gastric tissue following EPX administration, while Western blotting indicated increased expression of SCF and C-kit proteins. CONCLUSION: Suggesting EPX's anti-FD effect may involve the regulation of the SCF/C-kit signalling pathway and activation of downstream PI3K/AKT signalling pathway, thereby promoting gastrointestinal motility and improving FD symptoms.

Innovative approaches for coronary heart disease management: integrating biomedical sensors, deep learning, and stellate ganglion modulation.

Coronary heart disease (CHD) is a significant global health concern, necessitating continuous advancements in treatment modalities to improve patient outcomes. Traditional Chinese medicine (TCM) offers alternative therapeutic approaches, but integration with modern biomedical technologies remains relatively unexplored. This study aimed to assess the efficacy of a combined treatment approach for CHD, integrating traditional Chinese medicinal interventions with modern biomedical sensors and stellate ganglion modulation. The objective was to evaluate the impact of this combined treatment on symptom relief, clinical outcomes, hemorheological indicators, and inflammatory biomarkers. A randomized controlled trial was conducted on 117 CHD patients with phlegm-turbidity congestion and excessiveness type. Patients were divided into a combined treatment group (CTG) and a traditional Chinese medicinal group (CMG). The CTG group received a combination of herbal decoctions, thread-embedding therapy, and stellate ganglion modulation, while the CMG group only received traditional herbal decoctions. The CTG demonstrated superior outcomes compared to the CMG across multiple parameters. Significant reductions in TCM symptom scores, improved clinical effects, reduced angina manifestation, favorable changes in hemorheological indicators, and decreased serum inflammatory biomarkers were observed in the CTG post-intervention. The combination of traditional Chinese medicinal interventions with modern biomedical sensors and stellate ganglion modulation has shown promising results in improving symptoms, clinical outcomes, and inflammatory markers in CHD patients. This holistic approach enhances treatment efficacy and patient outcomes. Further research and advancements in sensor technology are needed to optimize this approach.

Antibacterial and oral tissue effectiveness of a mouthwash with a novel active system of amine + zinc lactate + fluoride.

OBJECTIVES: Reflecting the need for an effective support for the daily oral hygiene routine of patients experiencing (symptoms of) gum inflammation, a new mouthwash has been developed containing an amine + zinc lactate + fluoride system. The in vitro efficacy of this product was assessed using traditional laboratory methods, as well as novel experimentation. MATERIALS AND METHODS: This mouthwash has been evaluated in a series of laboratory tests including two short interval kill tests (SIKTs), a 12-h (longer term) biofilm regrowth assay, a plaque glycolysis assay, and an aerobic, repeated exposure biofilm model, as well as tests for soft tissue uptake and LPS neutralization. RESULTS: Several laboratory studies demonstrate that a mouthwash containing an amine + zinc lactate + fluoride system provides short-term and long-term antibacterial activity. While the immediate efficacy of this formula has been shown to be driven by the presence of the amine, zinc lactate provides a long-term antibacterial effect, as well as is able to inhibit bacterial metabolism. CONCLUSIONS: This research provides the basis for understanding the mode of action of this new mouthwash formulation and explains the previously observed clinical efficacy of this formula against plaque and gingivitis.

DNA methylation of miR-181a-5p mediated by DNMT3b drives renal interstitial fibrosis developed from acute kidney injury.

Aim: To explore the role of miR-181a-5p in the progression of acute kidney injury (AKI) to renal interstitial fibrosis (RIF) from the perspective of DNA methylation. Materials & methods: The role of miR-181a-5p was confirmed by collecting clinical samples, injecting miR-181a-5p agomir into tail vein, and transfecting miR-181a-5p mimic in vitro. The mechanism of miR-181a-5p's influence on AKI induced RIF was investigated by methylation-specific PCR, bioinformatic analysis, transcriptome sequencing and so on. Results: MiR-181a-5p plays an important role in AKI induced RIF. DNMT3b-mediated miR-181a-5p promoter hypermethylation is the main reason for the downregulation of miR-181a-5p. HDAC9 and SNAI2 are direct targets of miR-181a-5p. Conclusion: Hypermethylation of miR-181a-5p promoter mediated by DNMT3b promotes AKI induced RIF by targeting HDAC9 and SNAI2.

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