MTRSRP: Joint Design of Multi-Triangular Ring and Self-Routing Protocol for BLE Networks.

This paper presents the multi-triangular ring and self-routing protocol (MTRSRP), which is a new decentralized strategy designed to boost throughput and network efficiency in multiring scatternets. MTRSRP comprises two primary phases: leader election and scatternet formation, which collaborate to establish an effective multi-triangular ring topology. In the leader election phase, nodes exchange broadcast messages to gather neighbor information and elect coordinators through a competitive process.

Chinese Tuina ameliorates muscle damage by regulating endoplasmic reticulum stress and autophagy in a rat model of skeletal muscle contusion.

Chinese Tuina has been used to treat skeletal muscle contusion (SMC) for a long time in China, yet its efficacy and mechanisms remain unclear. Previous studies have shown the vital roles of endoplasmic reticulum (ER) stress and autophagy during injured skeletal muscle recovery, we postulated that Chinese Tuina could expedite the healing of SMC by fine-tuning these processes. In this study, we established a rat model of SMC through weight-dropping and divided the rats into three groups: SMC, SMC+Tuina, and SMC+Tuina+ 3-methyladenine (3-MA) groups, while using untreated normal SD rats as a control.

Discovery of novel dual-target inhibitors of LSD1/EGFR for non-small cell lung cancer therapy.

Histone lysine-specific demethylase 1 (LSD1) is overexpressed in various solid and hematological tumors, suggesting its potential as a therapeutic target, but there are currently no LSD1 inhibitors available on the market. In this study we employed a computer-guided approach to identify novel LSD1/EGFR dual inhibitors as a potential therapeutic agent for non-small cell lung cancer. Through a multi-stage virtual screening approach, we found L-1 and L-6, two compounds with unique scaffolds that effectively inhibit LSD1 with IC values of 6.

Large-scale comparison of machine learning algorithms for target prediction of natural products.

Natural products (NPs) and their derivatives are important resources for drug discovery. There are many in silico target prediction methods that have been reported, however, very few of them distinguish NPs from synthetic molecules. Considering the fact that NPs and synthetic molecules are very different in many characteristics, it is necessary to build specific target prediction models of NPs.

Long noncoding RNA HCP5 promotes osteosarcoma cell proliferation, invasion, and migration via the miR-29b-3p-LOXL2 axis.

Osteosarcoma (OS) is the second most common primary malignant bone tumors in adolescents that causes cancer-related deaths. Previous studies have confirmed the promoting role of lncRNA HCP5 in the development of OS, but the specific mechanism is still not well understood. MiRNA levels were measured via RT-qPCR and protein expression was detected via western blotting.

Metal-free hypervalent iodine-promoted tandem carbonyl migration and unactivated C(Ph)-C(Alkyl) bond cleavage for quinolone scaffold synthesis.

An unexpected iodine()-mediated C(sp)-C(sp) bond cleavage of 3-(methylamino)-2-(2-substitutedbenzoyl)acrylates for efficient synthesis of privileged scaffold 4-quinolones was described. Notably, a wide range of alkyl groups ( methyl, -butyl or alkyl chain) can be conveniently cleaved in this system. The detailed mechanism studies revealed that the transformation proceeded through cascade ipso-cyclization and 1,2-carbonyl migration, the smaller bond energy determined C-C bond cleavage rather than C-H bond cleavage, an enamine radical intermediate.

Recent progress in strategies for steroid production in yeasts.

As essential structural molecules of fungal cell membrane, ergosterol is not only an important component of fungal growth and stress-resistance but also a key precursor for manufacturing steroid drugs of pharmaceutical or agricultural significance. So far, ergosterol biosynthesis in yeast has been elucidated elaborately, and efforts have been made to increase ergosterol production through regulation of ergosterol metabolism and storage. Furthermore, the same intermediates shared by yeasts and animals or plants make the construction of heterologous sterol pathways in yeast a promising approach to synthesize valuable steroids, such as phytosteroids and animal steroid hormones.

Combined Biosynthetic Pathway Engineering and Storage Pool Expansion for High-Level Production of Ergosterol in Industrial .

Ergosterol, a terpenoid compound produced by fungi, is an economically important metabolite serving as the direct precursor of steroid drugs. Herein, ergsosterol biosynthetic pathway modification combined with storage capacity enhancement was proposed to synergistically improve the production of ergosterol in . strain S1 accumulated the highest amount of ergosterol [7.

Advancement of multi-target drug discoveries and promising applications in the field of Alzheimer's disease.

Complex diseases (e.g., Alzheimer's disease) or infectious diseases are usually caused by complicated and varied factors, including environmental and genetic factors.

Enhanced Performance of Rhizopus oryzae Lipase by Reasonable Immobilization on Magnetic Nanoparticles and Its Application in Synthesis 1,3-Diacyglycerol.

Nano-sized FeO was synthesized by chemical co-precipitation and subsequently modified with 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde to introduce aldehyde group on its surface. With the help of "interface activation" by adding sucrose esters-11 as surfactant, lipase from Rhizopus oryzae was successfully immobilized onto the carrier with great enhancement of activity. The hydrolysis activity of immobilized enzyme were 9.

Enhancing the thermostability of lipase by combined mutation of hot-spots and engineering a disulfide bond.

lipase (ROL) is important because of its extreme -1,3-regioselectivity, but it shows poor thermostability, which severely restricts its application. In this work, the thermostability of ROL was greatly enhanced by rational design. First, several sites that may affect the thermostability of ROL were identified by multiple-sequence alignment.

Using virtual reality for drug discovery: a promising new outlet for novel leads.

: Virtual reality (VR) environments are increasingly being used by researchers in various fields in addition to being increasingly integrated into various areas of human life, ranging from videogames to different industrial uses. VR can be used to create interactive and multimodal sensory stimuli and thus offers unique advantages over other computer-based approaches for scientific research and molecular-level applications. Consequently, VR is starting to be used in novel drug development, such as in drug discovery, and rational drug design.

Increased productivity of L-2-aminobutyric acid and total turnover number of NAD/NADH in a one-pot system through enhanced thermostability of L-threonine deaminase.

Objective: To strengthen NADH regeneration in the biosynthesis of L-2-aminobutyric acid (L-ABA).

Results: L-Threonine deaminase (L-TD) from Escherichia coli K12 was modified by directed evolution and rational design to improve its endurance to heat treatment. The half-life of mutant G323D/F510L/T344A at 42 °C increased from 10 to 210 min, a 20-fold increase compared to the wild-type L-TD, and the temperature at which the activity of the enzyme decreased by 50% in 15 min increased from 39 to 53 °C.

The advancement of multidimensional QSAR for novel drug discovery - where are we headed?

The Multidimensional quantitative structure-activity relationship (multidimensional-QSAR) method is one of the most popular computational methods employed to predict interesting biochemical properties of existing or hypothetical molecules. With continuous progress, the QSAR method has made remarkable success in various fields, such as medicinal chemistry, material science and predictive toxicology. Areas covered: In this review, the authors cover the basic elements of multidimensional -QSAR including model construction, validation and application.

A non-canonical binding interface in the crystal structure of HIV-1 gp120 core in complex with CD4.

Numerous crystal structures of HIV gp120 have been reported, alone or with receptor CD4 and cognate antibodies; however, no sole gp120/CD4 complex without stabilization by an antibody is available. Here, we report a crystal structure of the gp120/CD4 complex without the aid of an antibody from HIV-1 CRF07_BC, a strain circulating in China. Interestingly, in addition to the canonical binding surface, a second interacting interface was identified.

Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway.

Pterostilbene has been reported as a potential drug to inhibit oxidative stress and inflammation. However, the effect of pterostilbene on chondrocytes and osteoarthritis remains to be elucidated. We sought to investigate whether pterostilbene could protect chondrocytes from inflammation and ROS production through factor erythroid 2-related factor 2 (Nrf2) activation.

Serum N-terminal telopeptide of type I collagen as an early marker of fracture nonunion in rabbits.

The aim of the present study was to establish an experimental animal model of fracture nonunion, and to investigate the changes in serum biomarker concentrations in fracture nonunion. A total of 20 purebred New Zealand rabbits were divided into two group: A bone defect group and a bone fracture group. In the bone defect group, a 15-mm section of bone (including the periosteum) was removed from the mid-radius, and the medullary cavities were closed with bone wax.

N-terminal telopeptides of type I collagen and bone mineral density for early diagnosis of nonunion: An experimental study in rabbits.

Background: The diagnosis and treatment of bone nonunion have been studied extensively. Diagnosis and treatment of nonunion are mainly performed based on the interpretation of clinico-radiographic findings, which depend on the clinician's experience and the degree of bone callus formation during the fracture-healing process. However, resolution may be compromised when the bone mineral content is <25%.

Mefloquine inhibits chondrocytic proliferation by arresting cell cycle in G2/M phase.

Mefloquine (MQ), an analog of chloroquine, exhibits a promising cytotoxic activity against carcinoma cell lines and for the treatment of glioblastoma patients. The present study demonstrates the effect of mefloquine on proliferation and cell cycle in chondrocytes. MTT assay and propidium iodide staining were used for the analysis of proliferation and cell cycle distribution, respectively.

Protective effects of paeoniflorin against FasL-induced apoptosis of intervertebral disc annulus fibrosus cells via Fas-FasL signalling pathway.

In the present study, we demonstrate that the degeneration of intervertebral discs is caused by ageing and apoptosis of matrix cells. Apoptosis is as essential as the function of proteoglycan synthesis in assessing the possible degeneration of intervertebral discs; paeoniflorin (PF) induces cytoprotective effects on various types of cells. In this study, the function of PF in inhibiting Fas ligand (FasL)-induced apoptosis in annulus fibrosus cells was assessed, and the correlation between apoptosis and the Fas-FasL pathway was determined.

Quantitative structure-activity relationship: promising advances in drug discovery platforms.

Introduction: Quantitative structure-activity relationship (QSAR) modeling is one of the most popular computer-aided tools employed in medicinal chemistry for drug discovery and lead optimization. It is especially powerful in the absence of 3D structures of specific drug targets. QSAR methods have been shown to draw public attention since they were first introduced.

Advances in Computational Structure-Based Drug Design and Application in Drug Discovery.

Compared with the increasing and widespread bacterial resistance to clinical medicines and the urgent need for cures of intractable diseases, there is a dramatic decline in the numbers of drugs reaching the market or clinical trials. Accordingly, it has become imperative to discover more rational and efficient strategies to design and develop novel drugs. Structure-based drug design/discovery (SBDD) is one of the computer-aided methods, by which novel drugs are designed or discovered based on the knowledge of 3D structures of the relevant specific targets.

Direct synthesis of 2-aryl-4-quinolones via transition-metal-free intramolecular oxidative C(sp(3))-H/C(sp(3))-H coupling.

A novel, metal-free oxidative intramolecular Mannich reaction was developed between secondary amines and unmodified ketones, affording a simple and direct access to a broad range of 2-arylquinolin-4(1H)-ones through C(sp(3))-H activation/C(sp(3))-C(sp(3)) bond formation from readily available N-arylmethyl-2-aminophenylketones, using TEMPO as the oxidant and KO(t)Bu as the base.

Fragment-based drug discovery and molecular docking in drug design.

Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD.

Solvent/oxidant-switchable synthesis of multisubstituted quinazolines and benzimidazoles via metal-free selective oxidative annulation of arylamidines.

A fast and simple divergent synthesis of multisubstituted quinazolines and benzimidazoles was developed from readily available amidines, via iodine(III)-promoted oxidative C(sp(3))-C(sp(2)) and C(sp(2))-N bond formation in nonpolar and polar solvents, respectively. Further selective synthesis of quinazolines in polar solvent was realized by TEMPO-catalyzed sp(3)C-H/sp(2)C-H direct coupling of the amidine with K2S2O8 as the oxidant. No metal, base, or other additives were needed.