Factors associated with implant marginal bone resorption after implant restoration in elderly patients with severe periodontitis

Objective To analyze the factors related to implant marginal bone resorption after implant restoration in elderly patients with severe periodontitis. Methods One hundred and ninety-five elderly patients with severe periodontitis who underwent implant restoration in Hospital of Stomatology of Jilin University from January 2017 to June 2021 were selected， and the implant marginal bone resorption was recorded after 12 months of follow-up. Patients with alveolar ridge resorption height >0.5 mm were included in the resorption group， and the rest were included in the non-resorption group. The general data of the non-resorption group and the resorption group were compared. The influencing factors of implant marginal bone resorption were analyzed by Logistic regression model. Results After 12 months of follow-up， 40.80% of the patients had implant marginal bone resorption. Logistic regression analysis showed that smoking （OR=3.080， 95% CI 1.494-6.349）， diabetes （OR=2.542， 95% CI 1.355-4.769）， missing teeth in the upper jaw （OR=3.951， 95% CI 1.800-8.671）， the angle between the long axis of the implant and the long axis of the crown （OR=2.000， 95% CI 1.066-3.752）， and poor peri-implant hygiene （OR=2.573， 95% CI 1.435-4.614） were risk factors for adverse marginal bone resorption around implants. In contrast， the thickness of the bone quality at the implantation site （OR=0.214， 95% CI 0.086-0.533） was a protective factor， with all P < 0.05. Conclusion Smoking， diabetes， missing teeth in the upper jaw， the angle between the long axis of the implant and the crown， poor peri-implant hygiene， and the bone quality at the implantation site affected the marginal bone resorption around implants in elderly patients

Effective Utilization of Waste Glass as Cementitious Powder and Construction Sand in Mortar

The purpose of this study is to investigate the availability of waste glass as alternative materials in sustainable constructions. Collected waste glass was ground into waste glass powder (WGP) with similar particle size distribution as Portland cement (PC) and waste glass sand (WGS) with similar grade as sand. The compressive strength was investigated through the Taguchi test to evaluate the effect of different parameters on WGP-blended mortar, which include WG-replacement rate (G/B, 0, 10%, 20%, 30%), water/binder ratio (w/b, 0.35. 0.40, 0.50, 0.60), cementitious material dosage (Cpaste, 420, 450, 480, 500 kg/m3), and color of powder (green (G) and colorless (C)). The alkali–silica reaction (ASR) expansion risk of WGS-blended mortar was assessed. The experimental results indicated that WGP after 0.5 h grinding could be used as substituted cement in mortar and help to release potential ASR expansion. The replacement rate played a dominant role on strength at both the early or long-term age. The water/binder ratio of 0.35 was beneficial to the compressive strength at three days and 0.50 was better for strength at 60 and 90 days. An optimal value of cementitious material dosage (450 Kg/m3) exited in view of its strength, while the effect of the color of WG was minor. WGS could be graded as standard construction sand and no ASR expansion risk was found even for 100% replacement of regular sand in mortar. Through the comprehensive reuse of waste glass, this study could provide basic knowledge and a concept for the sustainable development of building materials

MolCRAFT: Structure-Based Drug Design in Continuous Parameter Space

Generative models for structure-based drug design (SBDD) have shown promising results in recent years. Existing works mainly focus on how to generate molecules with higher binding affinity, ignoring the feasibility prerequisites for generated 3D poses and resulting in false positives. We conduct thorough studies on key factors of ill-conformational problems when applying autoregressive methods and diffusion to SBDD, including mode collapse and hybrid continuous-discrete space. In this paper, we introduce MolCRAFT, the first SBDD model that operates in the continuous parameter space, together with a novel noise reduced sampling strategy. Empirical results show that our model consistently achieves superior performance in binding affinity with more stable 3D structure, demonstrating our ability to accurately model interatomic interactions. To our best knowledge, MolCRAFT is the first to achieve reference-level Vina Scores (-6.59 kcal/mol) with comparable molecular size, outperforming other strong baselines by a wide margin (-0.84 kcal/mol). Code is available at https://github.com/AlgoMole/MolCRAFT.Comment: Accepted to ICML 202

Water absorption and chloride diffusivity of concrete under the coupling effect of uniaxial compressive load and freeze-thaw cycles

In cold coastal area, the destruction mechanism of reinforced concrete structures is mainly governed by a combination of factors such as self-loading, freeze-thaw and chloride erosion. In this study, ordinary cube concretes (C30 and C50, while w/c = 0.53 and 0.35 respectively) underwent a coupling effect of pressure load with stress ratio of 0, 0.3 and 0.5 and freeze-thaw cycles, following by capillary water absorption test and chloride penetration test. Concrete samples with 0.3fc showed the best water and chloride penetration resistance under the coupling effect, followed by samples with 0.5fc and 0fc, which is consistent with the conclusion that under load only. Water and chloride ions penetration increased sharply when freeze-thaw cycles was over 100 times, which is different with samples without load. Outside part of concrete showed higher permeability and chloride content than inside part. MIP results confirmed that stress played an important role in the water absorption and chloride penetration of concrete under the coupling effect. These results provide important new insights into the permeability of concrete under a coupling effect. The applied load performed a more important role on the service life prediction of concrete structure

Cardiomyocyte-Derived Small Extracellular Vesicle: a New Mechanism Driving Diabetic Cardiac Fibrosis and Cardiomyopathy

Rationale: Diabetic cardiomyopathy is one of the major diabetic cardiovascular complications in which fibrosis plays a critical pathogenetic role. However, the precise mechanisms by which diabetes triggers cardiac fibrosis in the heart remain elusive. Small extracellular vesicles (sEVs) play an important role in the cellular communication. Nevertheless, whether and how diabetes may adversely alter sEVs-mediated cardiomyocyte-fibroblast communication, promoting diabetic cardiac fibrosis and contributing to diabetic cardiomyopathy, has not been previously investigated. Methods and results: High-fat diet (HFD)-induced and genetic (db/db) type 2 diabetic models were utilized. Cardiomyocyte sEVs (Myo-sEVs) were isolated by ultracentrifugation. Normal cardiomyocyte-derived Myo-sEVs attenuated diabetic cardiac fibrosis in vitro and in vivo and improved cardiac diastolic function. In contrast, diabetic cardiomyocyte-derived Myo-sEVs significantly exacerbated diabetic cardiac fibrosis and worsened diastolic function. Unbiased miRNA screening analysis revealed that miR-194-3p was significantly reduced in diabetic Myo-sEVs. Additional in vitro and in vivo experiments demonstrated that miR-194-3p is a novel upstream molecule inhibiting TGFβR2 expression and blocking fibroblast-myofibroblast conversion. Administration of miR-194-3p mimic or agomiR-194-3p significantly reduced diabetic cardiac fibrosis in vitro and in vivo, and attenuated diabetic cardiomyopathy. Conclusion: Our study demonstrates for the first time that cardiomyocyte-derived miR194-3p inhibits TGFβ-mediated fibroblast-to-myofibroblast conversion, acting as an internal break against cardiac fibrosis. Diabetic downregulation of sEV-mediated miR-194-3p delivery from cardiomyocytes to fibroblasts contributes to diabetic cardiac fibrosis and diabetic cardiomyopathy. Pharmacological or genetic restoration of this system may be a novel therapy against diabetic cardiomyopathy. © The author(s)

Transcription and Post-translational Mechanisms: Dual Regulation of Adiponectin-Mediated Occludin Expression in Diabetes

BACKGROUND: Occludin, a crucial component of tight junctions, has emerged as a promising biomarker for the diagnosis of acute ischemic disease, highlighting its significant potential in clinical applications. In the diabetes, Occludin serves as a downstream target gene intricately regulated by the adiponectin (APN) signaling pathway. However, the specific mechanism by which adiponectin regulates Occludin expression remains unclear. METHODS AND RESULTS: Endothelial-specific Ocln knockdown reduced APN-mediated blood flow recovery after femoral artery ligation and nullified APN\u27s protection against high-fat diet (HFD)-triggered apoptosis and angiogenesis inhibition in vivo. Mechanically, we have meticulously elucidated APN\u27s regulatory role in Occludin expression through a comprehensive analysis spanning transcriptional and post-translational dimensions. Foxo1 has been elucidated as a crucial transcriptional regulator of Occludin that is modulated by the APN/APPL1 signaling axis, as evidenced by validation through ChIP-qPCR assays and Western blot analysis. APN hindered Occludin degradation via the ubiquitin-proteasome pathway. Mass spectrometry analysis has recently uncovered a novel phosphorylation site, Tyr467, on Occludin. This site responds to APN, playing a crucial role in inhibiting Occludin ubiquitination by APN. The anti-apoptotic and pro-angiogenic effects of APN were attenuated in vitro and in vivo following Foxo1 knockdown or expression of a non-phosphorylatable mutant, OccludinY467A. Clinically, elevated plasma concentrations of Occludin were observed in patients with diabetes. A significant negative correlation was found between Occludin levels and APN concentrations. CONCLUSION: Our study proposes that APN modulates Occludin expression through mechanisms involving both transcriptional and post-translational interactions, thereby conferring a protective effect on endothelial integrity within diabetic vasculature

Identification and investigation of depression-related molecular subtypes in inflammatory bowel disease and the anti-inflammatory mechanisms of paroxetine

BackgroundUp to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental biological pathways driving depression in IBD remain unknown.MethodsWe identified 33 core genes that drive depression in IBD patients and performed consensus molecular subtyping with the NMF algorithm in IBD. The CIBERSORT were employed to quantify the immune cells. Metabolic signature was characterized using the “IOBR” R package. The scoring system (D. score) based on PCA. Pre-clinical models are constructed using DSS.ResultsUsing transcriptome data from the GEO database of 630 IBD patients, we performed a thorough analysis of the correlation between IBD and depression in this research. Firstly, the samples were separated into two different molecular subtypes (D. cluster1 and D. cluster2) based on their biological signatures. Moreover, the immunological and metabolic differences between them were evaluated, and we discovered that D. cluster2 most closely resembled IBD patients concomitant with depression. We also developed a scoring system to assess the IBD-related depression and predict clinical response to anti-TNF- therapy, with a higher D. score suggesting more inflammation and worse reaction to biological therapies. Ultimately, we also identified through animal experiments an antidepressant, paroxetine, has the added benefit of lowering intestinal inflammation by controlling microorganisms in the digestive tract.ConclusionsThis study highlights that IBD patients with or without depression show significant variations and antidepressant paroxetine may help reduce intestinal inflammation

Adiponectin-Mediated Promotion of CD44 Suppresses Diabetic Vascular Inflammatory Effects

While adiponectin (APN) was known to significantly abolish the diabetic endothelial inflammatory response, the specific mechanisms have yet to be elucidated. Aortic vascular tissues from mice fed normal and high-fat diets (HFD) were analyzed by transcriptome analysis. GO functional annotation showed that APN inhibited vascular endothelial inflammation in an APPL1-dependent manner. We confirmed that activation of the Wnt/β-catenin signaling plays a key role in APN-mediated anti-inflammation. Mechanistically, APN promoted APPL1/reptin complex formation and β-catenin nuclear translocation. Simultaneously, we identified APN promoted the expression of CD44 by activating TCF/LEF in an APPL1-mediated manner. Clinically, the serum levels of APN and CD44 were decreased in diabetes; the levels of these two proteins were positively correlated. Functionally, treatment with CD44 C-terminal polypeptides protected diabetes-induced vascular endothelial inflammation in vivo. Collectively, we provided a roadmap for APN-inhibited vascular inflammatory effects and CD44 might represent potential targets against the diabetic endothelial inflammatory effect