Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5.

Two-thirds of signaling hormones and one-third of approved drugs exert their effects by binding and modulating the G protein-coupled receptors (GPCRs) activation. While the activation mechanism for monomeric GPCRs has been well-established, little is known about GPCRs in dimeric form. Here, by combining transition pathway generation, extensive atomistic simulation-based Markov state models, and experimental signaling assays, we reveal an asymmetric, stepwise millisecond allosteric activation mechanism for the metabotropic glutamate receptor subtype 5 receptor (mGlu5), an obligate dimeric class C GPCR.

Exploring optimal pathways for enterprise procurement management systems based on fast neural modeling and semantic segmentation.

Corporate procurement management assumes a pivotal role within the contemporary business landscape, yet confronts an array of challenges as markets continue to evolve and globalize. Conventional procurement management systems frequently grapple with issues of inefficiency, resource depletion, and noncompliance, necessitating the exploration of innovative avenues for optimization. This paper delves into the realm of risk mitigation associated with collusion behavior in the administration of intelligent procurement systems, presenting a novel procurement collusion identification model founded on a convolutional neural network (CNN) with reinforcement learning techniques.

Mechanistic Elucidation of Activation/Deactivation Signal Transduction within Neurotensin Receptor 1 Triggered by 'Driver Chemical Groups' of Modulators: A Comparative Molecular Dynamics Simulation.

Small-molecule modulators of neurotensin receptor 1 (NTSR1), a class A G-protein-coupled receptor (GPCR), has emerged as promising therapeutic agent for psychiatric disorders and cancer. Interestingly, a chemical group substitution in NTSR1 modulators can launch different types of downstream regulation, highlighting the significance of deciphering the internal fine-tuning mechanism. Here, we conducted a synergistic application of a Gaussian accelerated molecular dynamics simulation, a conventional molecular dynamics simulation, and Markov state models (MSM) to investigate the underlying mechanism of 'driver chemical groups' of modulators triggering inverse signaling.

Using NanoB to gain insights into ligand pharmacology.

In this issue of , van den Bor et al. report a novel assay called NanoB, which harnesses the use of nanobodies to broaden the applications of NanoBRET approaches for investigating ligand pharmacology. They demonstrate the generalizability of NanoB on a range of membrane proteins.

Delineating the activation mechanism and conformational landscape of a class B G protein-coupled receptor glucagon receptor.

Class B G protein-coupled receptors (GPCRs) are important targets in the treatment of metabolic syndrome and diabetes. Although multiple structures of class B GPCRs-G protein complexes have been elucidated, the detailed activation mechanism of the receptors remains unclear. Here, we combine Gaussian accelerated molecular dynamics simulations and Markov state models (MSM) to investigate the activation mechanism of a canonical class B GPCR, human glucagon receptor-GCGR, including the negative allosteric modulator-bound inactive state, the agonist glucagon-bound active state, and both glucagon- and Gs-bound fully active state.

Therapeutic effects of low-frequency phonophoresis with a Chinese herbal medicine versus sodium diclofenac for treatment of knee osteoarthritis: a double-blind, randomized, placebo-controlled clinical trial.

Objective: To evaluate the therapeutic effects of low-frequency phonophoresis with a Chinese herbal medicine (CHM) compared with sodium diclofenac (SD) for knee osteoarthritis (KOA).

Methods: In this double-blind, randomized, placebo-controlled trial, 100 KOA patients were assigned randomly to a placebo group, a CHM group, or SD group. Low-frequency phonophoresis was used to improve the efficiency of drug delivery.

[Analysis and comparison about musculoskeletal ultrasonoLranhv and x-rav of knee osteoarthritis].

Objective: To analyze and compare the characteristics of musculoskeletal ultrasonography and X-ray of knee osteoarthritis, and to investigate the advantages of them.

Methods: According to the inclusion and exclusion criteria, 57 cases (66 knees) were collected from February 2015 to May 2015. Among them, there were 48 females and 9 males with an average age of (58.

[Study about Traditional Chinese Medicine syndrome of adolescent neck pain].

Objective: To preliminarily research the formular about the Traditional Chinese Medicine (TCM) syndrome of adolescent neck pain.

Methods: An observation table of adolescent neck pain syndromes was formulated,and 1 397 patients with adolescent neck pain were investigated to establish a database of adolescent neck pain. The Descriptive Statistical Analysis and Hierarchical Cluster Analysis were performed by statistical software.