The Impact of the Restoration of Invisible Orthodontic Titanium Alloy Implant Without Bracket on Individuals Afflicted with Dental Malocclusion and Arch Deficiency Accompanied by Periodontitis and a Local Periodontal Inflammation.

Objective: To investigate the impact of the restoration of non-bracket invisible orthodontic titanium alloy implant on individuals with dental malocclusion and arch deficiency accompanied by periodontitis and local periodontal Inflammation.

Method: A cohort of 120 patients presenting with dental malocclusion and defects compounded by periodontitis, were treated at our institution between January 2021 and January 2022; these patients were enrolled in a randomized controlled trial..

[Imaging measurement and analysis of related indexes of variation of femoral head rotation center].

Objective: To provide guidance for hip replacement by analyzing the variation of femoral head rotation center in different hip diseases.

Methods: A total of 5 459 patients were collected from March 2016 to June 2021, who took positive and proportional plain films of both hips for various reasons. The relative position between the rotation center of the femoral head and the apex of the greater trochanter was measured.

Accelerated Discovery of Macrocyclic CDK2 Inhibitor QR-6401 by Generative Models and Structure-Based Drug Design.

Selective CDK2 inhibitors have the potential to provide effective therapeutics for CDK2-dependent cancers and for combating drug resistance due to high cyclin E1 (CCNE1) expression intrinsically or CCNE1 amplification induced by treatment of CDK4/6 inhibitors. Generative models that take advantage of deep learning are being increasingly integrated into early drug discovery for hit identification and lead optimization. Here we report the discovery of a highly potent and selective macrocyclic CDK2 inhibitor QR-6401 () accelerated by the application of generative models and structure-based drug design (SBDD).

Treatment effects and periodontal status of chronic periodontitis after routine Er:YAG laser-assisted therapy.

Background: Routine preclinical interventions for patients with chronic periodontitis such as supragingival cleaning and subgingival curettage, establishing a balanced occlusal relationship, and irrigation with 3% hydrogen peroxide can relieve the symptoms to some extent. However, there is room for improvement in the overall effect. For example, Er:YAG lasers can quickly increase the temperature of the irradiated tissue, effectively eliminate dental plaque and calculus, reduce periodontal pockets, adjust periodontal microecology, and reduce the gingival sulcus.

Esterase-Sensitive Prodrugs of a Potent Bisubstrate Inhibitor of Nicotinamide -Methyltransferase (NNMT) Display Cellular Activity.

A recently discovered bisubstrate inhibitor of Nicotinamide -methyltransferase (NNMT) was found to be highly potent in biochemical assays with a single digit nanomolar IC value but lacking in cellular activity. We, here, report a prodrug strategy designed to translate the observed potent biochemical inhibitory activity of this inhibitor into strong cellular activity. This prodrug strategy relies on the temporary protection of the amine and carboxylic acid moieties of the highly polar amino acid side chain present in the bisubstrate inhibitor.

Potent Inhibition of Nicotinamide -Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics.

Nicotinamide -methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the -adenosyl-l-methionine (SAM) cofactor.

Nicotinamide N-methyl transferase (NNMT): An emerging therapeutic target.

Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (NA) to generate 1-methyl nicotinamide. Since its discovery 70 years ago, the appreciation of the role of NNMT in human health has evolved from serving only metabolic functions to also being a driving force in diseases, including a variety of cancers. Despite the increasing evidence indicating NNMT as a viable therapeutic target, the development of cell-active inhibitors against this enzyme is lacking.

Bisubstrate Inhibitors of Nicotinamide -Methyltransferase (NNMT) with Enhanced Activity.

Nicotinamide -methyltransferase (NNMT) catalyzes the methylation of nicotinamide to form -methylnicotinamide. Overexpression of NNMT is associated with a variety of diseases, including a number of cancers and metabolic disorders, suggesting a role for NNMT as a potential therapeutic target. By structural modification of a lead NNMT inhibitor previously developed in our group, we prepared a diverse library of inhibitors to probe the different regions of the enzyme's active site.