DLK1 regulates periodontal inflammation by inhibiting NF-κB p65 and JNK signaling pathways.

The roles and molecular mechanisms of Delta-like 1 (DLK1) in periodontitis remain largely unknown. Here, we investigated the expression of DLK1 and NF-κB p65 in Porphyromonas gingivalis (Pg.)-induced periodontitis in vivo. Periodontal inflammation and alveolar bone resorption were analyzed using western blotting, micro-computed tomography, TRAP staining, immunohistochemistry, and immunofluorescence. Raw246.7 cells were stimulated with 1 µg/ml Porphyromonas gingivalis lipopolysaccharide (Pg.LPS) to assess DLK1 expression in vitro. DLK1 overexpression was achieved, and transfection efficiency was confirmed using western blotting and immunofluorescence. The NF-κB and MAPK pathways were activated by treating cells with 1 µg/ml Pg.LPS to explore related mechanisms. Compared with normal tissues, both DLK1 and NF-κB p65 expression increased in periodontitis gingival tissues. DLK1-positive expression was observed in inflammatory infiltrating cells and osteoclasts in the marginal lacunae of the alveolar bone. DLK1 expression in CD68-positive macrophages was detected by immunofluorescence. However, DLK1 expression in Raw246.7 cells decreased after Pg.LPS stimulation and during osteoclast differentiation. DLK1 levels negatively correlated with TNF-α, IL-1ß, and NFATC1. Increased DLK1 in Raw246.7 cells further inhibited COX2 and iNOS expressions. Mechanistically, DLK1 overexpression down-regulated NF-κB p65 and JNK levels. In summary, these findings suggest that DLK1 overexpression inhibits periodontal inflammation through the NF-κB p65 and JNK pathways. Interventions targeting increased DLK1 levels may have therapeutic implications for periodontitis.

Examining High-Risk Factors for Sleep Disorders in Depressed Patients: Evaluating the Impact of Psychological Interventions on Sleep Quality and Mental Well-Being.

Objective: This study aims to analyze the risk factors associated with sleep disorders in patients suffering from depression and investigate the efficacy of psychological interventions in improving these conditions. Methods: A comparative observational study was conducted and a cohort of 162 patients aged 18 to 68, admitted to outpatient or inpatient departments between October 2022 and August 2023, were included in the study. All patients were diagnosed with depression according to the ICD-10 criteria. The patients were divided into two groups: experimental group 1 received cognitive-behavioral therapy (CBT) psychological intervention, while experimental group 2 received conventional psychological treatment. Various parameters, including Hamilton Depression Rating Scale (Ham-D), Hamilton Anxiety Rating Scale (Ham-A), Social Support Rating Scale (SSRS), marital status, and occupation, were assessed and compared between the groups. Multivariate logistic regression was employed to identify risk factors for sleep disorders in depressed patients. The Pittsburgh Sleep Quality Index (PSQI) was utilized to evaluate sleep quality. Results: Logistic regression analysis revealed that depression severity, anxiety levels, subjective social support, and occupational status were significant risk factors for sleep disorders in depressed patients (P < .05). Following intervention, both groups exhibited a significant decrease in PSQI, SAS, and SDS scores, with experimental group 1 demonstrating significantly lower PSQI scores compared to experimental group 2 (P < .05). Moreover, experimental group 1 displayed significantly lower SAS and SDS scores compared to experimental group 2 (P < .05). Conclusions: The severity of depression, anxiety levels, subjective social support, and occupational status contribute to the risk of sleep disorders in depressed patients. Implementing psychological interventions for depressed patients with sleep disorders can effectively improve sleep quality, alleviate anxiety, and enhance overall psychological well-being. These interventions represent a valuable approach to manage depression and comorbid sleep disorders.

Infliximab inhibits TNF-α-dependent activation of the NLRP3/IL-1ß pathway in acne inversa.

Background: Acne inversa (AI) is a refractory inflammatory skin disease, and TNF-α plays an important role in the pathogenesis of AI. By blocking TNF-α, infliximab (IFX) has been proven to be a promising method. Objectives: To explore the underlying mechanisms of IFX treatment in AI patients. Methods: In this research, we integrated transcriptome sequencing data from the samples of our patients with AI and the GEO database. Ex vivo skin culture of AI patients was conducted to evaluate the efficacy of IFX treatment. Animal studies and cell experiments were used to explore the therapeutic effect and mechanism of IFX treatment. Results: Both TNF-α and NLRP3 inflammasome-related pathways were enriched in skin lesions of AI patients and murine AI models. After IFX treatment, the NLRP3 inflammasome-related pathway was effectively blocked, and the IL-1ß level was normalized in ex vivo AI skin explants and murine AI models. Mechanistically, IFX suppressed the NF-κB signaling pathway to lower the expression of NLRP3 and IL-1ß in keratinocytes. Conclusions: IFX treatment alleviated skin lesions in murine AI models and downregulated NLRP3 and IL-1ß expression levels by inhibiting the NF-κB signaling pathway, which was helpful for understanding the mechanism of IFX therapy.

Mixed uncertainty analysis on pumping by peristaltic hearts using Dempster-Shafer theory.

In this paper, we introduce the numerical strategy for mixed uncertainty propagation based on probability and Dempster-Shafer theories, and apply it to the computational model of peristalsis in a heart-pumping system. Specifically, the stochastic uncertainty in the system is represented with random variables while epistemic uncertainty is represented using non-probabilistic uncertain variables with belief functions. The mixed uncertainty is propagated through the system, resulting in the uncertainty in the chosen quantities of interest (QoI, such as flow volume, cost of transport and work). With the introduced numerical method, the uncertainty in the statistics of QoIs will be represented using belief functions. With three representative probability distributions consistent with the belief structure, global sensitivity analysis has also been implemented to identify important uncertain factors and the results have been compared between different peristalsis models. To reduce the computational cost, physics constrained generalized polynomial chaos method is adopted to construct cheaper surrogates as approximations for the full simulation.

The effect of white grub (Maladera Verticalis) larvae feeding on rhizosphere microbial characterization of aerobic rice (Oryza sativa L.) in Puer City, Yunnan Province, China.

BACKGROUND: Rhizosphere microorganisms are vital in plants' growth and development and these beneficial microbes are recruited to the root-zone soil when experiencing various environmental stresses. However, the effect of white grub (Maladera verticalis) larvae feeding on the structure and function of rhizosphere microbial communities of aerobic rice (Oryza sativa L.) is unclear. RESULTS: In this study, we compared physicochemical properties, enzyme activities, and microbial communities using 18 samples under healthy and M. verticalis larvae-feeding aerobic rice rhizosphere soils at the Yunnan of China. 16 S rRNA and ITS amplicons were sequenced using Illumina high throughput sequencing. M. verticalis larvae feeding on aerobic rice can influence rhizosphere soil physicochemical properties and enzyme activities, which also change rhizosphere microbial communities. The healthy and M. verticalis larvae-feeding aerobic rice rhizosphere soil microorganisms had distinct genus signatures, such as possible_genus_04 and Knoellia genera in healthy aerobic rice rhizosphere soils and norank_f__SC - I-84 and norank_f__Roseiflexaceae genera in M. verticalis larvae-feeding aerobic rice rhizosphere soils. The pathway of the metabolism of terpenoids and polyketides and carbohydrate metabolism in rhizosphere bacteria were significantly decreased after M. verticalis larvae feeding. Fungal parasite-wood saprotroph and fungal parasites were significantly decreased after M. verticalis larvae feeding, and plant pathogen-wood saprotroph and animal pathogen-undefined saprotroph were increased after larvae feeding. Additionally, the relative abundance of Bradyrhizobium and Talaromyces genera gradually increased with the elevation of the larvae density. Bacterial and fungal communities significantly correlated with soil physicochemical properties and enzyme activities, respectively. CONCLUSIONS: Based on the results we provide new insight for understanding the adaptation of aerobic rice to M. verticalis larvae feeding via regulating the rhizosphere environment, which would allow us to facilitate translation to more effective measures.

Association between statin use and acute pulmonary embolism in intensive care unit patients with sepsis: a retrospective cohort study.

Introduction: Acute pulmonary embolism (APE) is a life-threatening medical condition that is frequently encountered and associated with significant incidence and mortality rates, posing a substantial threat to patients' well-being and quality of life. Sepsis is prominent independent risk factor for the development of APE. Despite recent investigations indicating a reduced APE risk through statin therapy, its impact on patients with sepsis and APE remains unresolved. Methods: The Medical Information Mart for Intensive Care (MIMIC)-IV database was utilized to identify patients diagnosed with sepsis and APE, irrespective of statin treatment status, as part of this study. The primary study aim was to assess the risk of APE, which was analyzed using multivariate logistic regression models. Results: The study encompassed a total of 16,633 participants, with an average age of 64.8 ± 16.2 years. Multivariate logistic regression revealed that septic patients receiving statin therapy in the intensive care unit (ICU) exhibited a 33% reduction in the risk of developing APE (OR = 0.67, 95% CI: 0.52-0.86, p < 0.001). The findings of further analyses, including stratification based on statin usage, dosage, and propensity score matching, consistently reinforced the hypothesis that administering statins to patients with sepsis effectively mitigates their potential APE risk. Discussion: The results of the study provide compelling evidence in favor of administering statins to septic patients as a prophylactic measure against APE, given that statins may reduce the risk of developing APE, and their anti-APE effect appears to be dose-dependent. Nonetheless, future randomized controlled trials are needed to validate these results.

Preparation of biocompatibility coating on magnesium alloy surface by sodium alginate and carboxymethyl chitosan hydrogel.

Magnesium alloy is an excellent material for biodegradable cerebrovascular stents. However, the rapid degradation rate of magnesium alloy will make stent unstable. To improve the biocompatibility of magnesium alloy, in this study, biodegradable sodium alginate and carboxymethyl chitosan (SA/CMCS) was used to coat onto hydrothermally treated the surface of magnesium alloy by a dipping coating method. The results show that the SA/CMCS coating facilitates the growth, proliferation, and migration of endothelial cells and promotes neovascularization. Moreover, the SA/CMCS coating suppresses macrophage activation while promoting their transformation into M2 type macrophages. Overall, the SA/CMCS coating demonstrates positive effects on the safety and biocompatibility of magnesium alloy after implantation, and provide a promising therapy for the treatment of intracranial atherosclerotic stenosis in the future.

4-Octyl itaconate promotes alveolar ridge preservation following tooth extraction.

The search for medications that can effectively reduce alveolar bone loss following tooth extraction is of great interest. This study aimed to observe the roles of 4-octyl itaconate (4-OI) in RANKL-induced osteoclastogenesis of bone marrow macrophages (BMMs) in vitro. Mandibular second molars were extracted to evaluate whether 4-OI could alleviate alveolar bone loss. 4-OI inhibited RANKL-induced osteoclastogenesis and promoted Nrf2 expression in bone marrow macrophages in vitro. Positive Nrf2 expressions were observed in inflammatory cells and osteoclasts in vivo. Treatment with 4-octyl itaconate increased Nrf2 expression, resulting in reduced inflammatory infiltration and osteoclastic activity after tooth extraction. Furthermore, increased expression of OCN and enhanced-alveolar bone healing of extraction socket were observed in the 4-OI group compared to the control group. Our results suggested that 4-OI could serve as a promising pharmacologic candidate for alveolar ridge preservation by alleviating alveolar bone loss following tooth extraction in rats.

Combined MRI-TRUS fusion targeted and systematic biopsy versus systematic biopsy alone for the detection of prostate cancer: protocol for a prospective single-centre trial.

INTRODUCTION: The classic way of diagnosing prostate cancer (PCa) is by conducting the 12-core systematic biopsy (SB). However, it has a low detection rate for clinically significant PCa (csPCa) and can lead to the detection of clinically insignificant PCa (cisPCa). Although MRI-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TB) can effectively improve the detection rate of csPCa, it may still miss some cases. Therefore, we propose using a combination of TB and SB methods to enhance the detection rate of csPCa while minimising the detection rate of cisPCa. METHODS AND ANALYSIS: This study is a prospective, single-centre investigation that aims to assess and compare the detection rate of csPCa using MRI-TRUS fusion TB combined with SB versus TRUS 12-core SB alone. Biopsy-naïve men with suspected PCa will be subjected to multiparametric MRI. Patients with Prostate Imaging Reporting and Data System (V.2.1) score ≥3 will be enrolled in the TB-SB combination group. The sample size is established as 660 participants, considering a 10% drop-out rate. The primary outcome is the detection rate of csPCa in men without prior biopsy using MRI-TRUS fusion TB combined with the standard TRUS-guided 12-core SB method. CsPCa will be defined as International Society of Urological Pathology Grade ≥2. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee at the Shanghai Tenth People's Hospital, an affiliated hospital of Tongji University School of Medicine. The research results will be published in a peer-reviewed international journal. TRIAL REGISTRATION NUMBER: ChiCTR2000036089.

A novel cerebrovascular drug-coated balloon catheter for treating symptomatic intracranial atherosclerotic stenosis lesions: Study protocol for a prospective, multicenter, single-arm, target-value clinical trial.

Background: Previous single-center studies have demonstrated that drug-coated balloons (DCBs) may reduce restenosis rates, which is an important factor affecting the prognosis for intracranial interventional therapy. However, currently available cardiac DCBs are not always suitable for the treatment of intracranial atherosclerotic stenosis (ICAS). This study aimed to evaluate the safety and efficacy of a novel DCB catheter designed for patients with severely symptomatic ICAS. Methods: This prospective, multicenter, single-arm, target-value clinical trial was conducted in 9 Chinese stroke centers to evaluate the safety and efficacy of a novel DCB catheter for treating symptomatic severe ICAS. Primary metrics and other indicators were collected and analyzed using SAS version 9.4 (SAS Institute, Cary, NC, USA). Results: A total of 155 patients were enrolled in this study. The preliminary collection of follow-up data has been completed, while data quality control is ongoing. Conclusion: Results of this study demonstrated the patency rate, safety, and effectiveness of a novel on-label paclitaxel DCB designed for the treatment of ICAS. Trial registration: ChiCTR, ChiCTR2100047223. Registered June 11, 2021-Prospective registration, https://www.chictr.org.cn/ChiCTR2100047223.

Genomic and transcriptomic analysis of genes involved in exopolysaccharide biosynthesis by Streptococcus thermophilus IMAU20561 grown on different sources of nitrogen.

Exopolysaccharides (EPSs), which are produced by lactic acid bacteria, have been found to improve the texture and functionality of fermented dairy products. In a previous study, four nitrogen sources were identified as affecting the yield, molecular weight and structure of EPSs produced by Streptococcus thermophilus IMAU20561 in M17 medium. In this genomic and transcriptomics study, a novel eps gene cluster responsible for assembly of repeating units of EPS is reported. This eps cluster (22.3 kb), consisting of 24 open reading frames, is located in the chromosomal DNA. To explore the biosynthetic mechanisms in EPS, we completed RNA-seq analysis of S. thermophilus IMAU20561 grown in four different nitrogen sources for 5 h (log phase) or 10 h (stationary phase). GO functional annotation showed that there was a significant enrichment of differentially expressed genes (DEGs) involved in: amino acid biosynthesis and metabolism; ribonucleotide biosynthesis and metabolism; IMP biosynthesis and metabolism; and phosphorus metabolism. KEGG functional annotation also indicated enrichment of DEGs involved in amino acid biosynthesis, glycolysis, phosphotransferase system, fructose, and mannose metabolism. Our findings provide a better understanding the genetic traits of S. thermophilus, the biosynthetic pathways needed for the production of EPS, and a theoretical basis for screening dairy starter cultures.