Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system.

Chemokine receptors constitute an important subfamily of G protein-coupled receptors (GPCRs), and they are critically involved in a broad range of immune response mechanisms. Ligand promiscuity among these receptors makes them an interesting target to explore multiple aspects of biased agonism. Here, we comprehensively characterize two chemokine receptors namely, CXCR4 and CXCR7, in terms of their transducer-coupling and downstream signaling upon their stimulation by a common chemokine agonist, CXCL12, and a small molecule agonist, VUF11207.

Paeoniflorin mitigates high glucose-induced lifespan reduction by inhibiting insulin signaling in .

In organisms, high glucose can cause several aspects of toxicity, including the lifespan reduction. Paeoniflorin is the major component of Paeoniaceae plants. Nevertheless, the possible effect of paeoniflorin to suppress high glucose toxicity in reducing lifespan and underlying mechanism are largely unclear.

Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review.

The morbidity and mortality of diabetes have increased dramatically in recent decades. Novel strategies for treating diabetes and its complications with minimal side effects are in urgent need. New monomeric molecules extracted from herbal medicine, which is a form of alternative medicine, are being sought as drug candidates for the treatment of diabetes and its complications.

Two novel strategies to overcome the resistance to ALK tyrosine kinase inhibitor drugs: Macrocyclic inhibitors and proteolysis-targeting chimeras.

Lung cancer is the most malignant tumor in the worldwide. About 3%-5% non-small cell lung cancer (NSCLC) patients carry anaplastic lymphoma kinase (ALK) gene fusions and receive great benefits from ALK-targeted therapy. However, drug resistance inevitably occurs even with the most potent inhibitor drug lorlatinib.

An ionic lock and a hydrophobic zipper mediate the coupling between an insect pheromone receptor BmOR3 and downstream effectors.

Pheromone receptors (PRs) recognize specific pheromone compounds to guide the behavioral outputs of insects, which are the most diverse group of animals on earth. The activation of PRs is known to couple to the calcium permeability of their coreceptor (Orco) or putatively with G proteins; however, the underlying mechanisms of this process are not yet fully understood. Moreover, whether this transverse seven transmembrane domain (7TM)-containing receptor is able to couple to arrestin, a common effector for many conventional 7TM receptors, is unknown.

3D bioprinting of conductive hydrogel for enhanced myogenic differentiation.

Recently, hydrogels have gained enormous interest in three-dimensional (3D) bioprinting toward developing functional substitutes for tissue remolding. However, it is highly challenging to transmit electrical signals to cells due to the limited electrical conductivity of the bioprinted hydrogels. Herein, we demonstrate the 3D bioprinting-assisted fabrication of a conductive hydrogel scaffold based on poly-3,4-ethylene dioxythiophene (PEDOT) nanoparticles (NPs) deposited in gelatin methacryloyl (GelMA) for enhanced myogenic differentiation of mouse myoblasts (C2C12 cells).

Discovery of a Brigatinib Degrader SIAIS164018 with Destroying Metastasis-Related Oncoproteins and a Reshuffling Kinome Profile.

Proteolysis-targeting chimera (PROTAC) is an attractive technology in drug discovery. Canonically, targets act as a basic starting point in the most previous PROTAC design. Here, we designed degraders considering from the view of clinical benefits.

Effective degradation of EGFR mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems.

Targeted therapy of treating patients with specific tyrosine kinase inhibitors (TKIs) is currently the standard care for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer. However, the inevitably developed drug resistance in patients to EGFR TKIs is the biggest obstacle for cancer targeted therapy. About 60% of drug resistance to the 1st generation of EGFR TKIs was resulted from an acquired T790M mutation in the kinase domain of EGFR protein.

Isolation and identification of a novel erythromycin-degrading fungus, Curvularia sp. RJJ-5, and its degradation pathway.

Erythromycin pollution is an important risk to the ecosystem and human health worldwide. Thus, it is urgent to develop effective approaches to decontaminate erythromycin. In this study, we successfully isolated a novel erythromycin-degrading fungus from an erythromycin-contaminated site.

Biodegradation of erythromycin by Delftia lacustris RJJ-61 and characterization of its erythromycin esterase.

The residual erythromycin in fermentation waste can pollute the environment and threaten human health. However, there are no effective approaches to remedy this issue. In this study, an erythromycin-degrading bacterium named RJJ-61 was isolated and identified as a strain of Delftia lacustris based on morphological and phylogenetic analyses.

DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl H-NMR probe.

Characterization of the dynamic conformational changes in membrane protein signaling complexes by nuclear magnetic resonance (NMR) spectroscopy remains challenging. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion. Crystallographic analysis revealed structural changes that reshaped the TMSiPhe-specific amino-acyl tRNA synthetase active site to selectively accommodate the trimethylsilyl (TMSi) group.

Biodegradation of acephate by Bacillus paramycoides NDZ and its degradation pathway.

Acephate is widely used in agriculture, but its poisonous metabolites and poor sorption characteristics make it a serious environmental pollutant and toxicant to human health. To screen novel bacteria for biodegradation of acephate and uncover its degradation pathway, a strain called NDZ that is capable of utilizing acephate as a sole carbon and energy source was isolated from severely contaminated cultivated land. The bacterium was identified as Bacillus paramycoides based on 16S rDNA sequence analyses.

Regulation of intracellular ATP supply and its application in industrial biotechnology.

Efficient cell factories are the core of industrial biotechnology. In recent years, synthetic biology develops rapidly, and more and more modified microbial cell factories are employed in industrial biotechnology. ATP plays vital roles in biosynthesis, metabolism regulation, and cellular maintenance.

Enzyme-responsive turn-on nanoprobes for fluorescence imaging and localized photothermal treatment of multidrug-resistant bacterial infections.

Sensitive diagnosis and elimination of multidrug-resistant bacterial infections at an early stage remain paramount challenges. Herein, we present a gelatinase-responsive turn-on nanoprobe for in situ near-infrared (NIR) fluorescence imaging and localized photothermal treatment (PTT) of in vivo methicillin-resistant Staphylococcus aureus (MRSA) infections. The designed nanoprobe (named AuNS-Apt-Cy) is based on gold nanostars functionalized with MRSA-identifiable aptamer and gelatinase-responsive heptapeptide linker (CPLGVRG)-cypate complexes.

An Effective Hybrid Strategy for Conversion of Biomass into Furfurylamine by Tandem Pretreatment and Biotransamination.

In this work, an effective hybrid strategy was developed for tandem conversion of biomass to furfurylamine with tin-based solid acid Sn-Maifanitum stone and recombinant Escherichia coli whole cells harboring ω-transaminase. 90.3 mM furfural was obtained from corncob (75 g/L) at 170 °C for 0.

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot -allylation and intramolecular Heck reactions.

Two kinds of [3 + 2] cycloaddition intermediates generated from the three-component reactions of 2-bromobenzaldehydes and maleimides with amino esters or amino acids were used for a one-pot -allylation and intramolecular Heck reactions to form pyrrolidinedione-fused hexahydropyrrolo[2,1-]isoquinolines. The multicomponent reaction was combined with one-pot reactions to make a synthetic method with good pot, atom and step economy. MeCN was used as a preferable green solvent for the reactions.

Chemoenzymatic conversion of Sorghum durra stalk into furoic acid by a sequential microwave-assisted solid acid conversion and immobilized whole-cells biocatalysis.

In this study, chemoenzymatic conversion of Sorghum durra stalk (SDS) into furoic acid was developed by a sequential microwave-assisted solid acid conversion and immobilized whole-cells biocatalysis method. Dry dewaxed SDS (75 g/L) was catalyzed into furfural at 57.8% yield with heterogeneous Sn-argil (2.

Electrospun Icariin-Loaded Core-Shell Collagen, Polycaprolactone, Hydroxyapatite Composite Scaffolds for the Repair of Rabbit Tibia Bone Defects.

Background: Electrospinning is a widely used technology that can produce scaffolds with high porosity and surface area for bone regeneration. However, the small pore sizes in electrospun scaffolds constrain cell growth and tissue-ingrowth. In this study, novel drug-loading core-shell scaffolds were fabricated via electrospinning and freeze drying to facilitate the repair of tibia bone defects in rabbit models.

Effect of Aldosterone on Senescence and Proliferation Inhibition of Endothelial Progenitor Cells Induced by Sirtuin 1 (SIRT1) in Pulmonary Arterial Hypertension.

BACKGROUND Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary circulatory resistance. Pulmonary vascular endothelial dysfunction is one of the main causes of primary PAH. Endothelial progenitor cells (EPCs) can proliferate and differentiate into vascular endothelial cells and play an important role in maintaining normal endothelial function.

Isolation and characterization of the novel oil-degrading strain Kosakonia cowanii IUMR B67 and expression of the degradation enzyme.

Oils in food waste can pollute the environment and negatively affect human health. Biodegradation is a promising method for disposing of waste edible oils. In this study, an oil-degrading bacterium was isolated from kitchen waste for efficient degradation of edible oils.

Safeguarding intestine cells against enteropathogenic by intracellular protein reaction, a preventive antibacterial mechanism.

A critical problem in the fight against bacterial infection is the rising rates of resistance and the lack of new antibiotics. The discovery of new targets or new antibacterial mechanisms is a potential solution but is becoming more difficult. Here we report an antibacterial mechanism that safeguards intestine cells from enteropathogenic (EPEC) by shutting down an infection-responsive signal of the host intestine cell.

Multienzyme detection and in-situ monitoring of enzyme activity by bending CE using quantum dots-based polypeptide substrate.

Multienzyme detection and monitoring enzyme activity in situ are significant for the disease to diagnose. This study aims to develop a quantum dots (QDs)-based nanoprobe Cyanine5-DDDLEVLFQFPGLVPRGSGGHHHHHH-QDs (Cy5-LEVLVP-QD), which is able to detect two enzymes inside a bent capillary using CE. Cy5-LEVLVP and QDs were allowed to bind with each other through metal affinity interaction and then injected the Cy5-LEVLVP-QD complex into a capillary with different bends, followed by related enzyme that can cleave the Cy5-LEVLVP peptide.

Cell active and functionally-relevant small-molecule agonists of calcitonin receptor.

The natural calcitonin (CT) receptor and its peptide agonists are considered validated targets for drug discovery. A small molecule agonist, SUN-B8155, has previously been shown to efficiently activate cellular CTR. Herein, we report the synthesis of a series of compounds (S8155 1-9) derived from SUN-B8155, and investigate the structural-functional relationship, bias properties and their cellular activity profile.

Aldosterone Contributed to Pulmonary Arterial Hypertension Development via Stimulating Aquaporin Expression and Pulmonary Arterial Smooth Muscle Cells Proliferation.

Introduction And Objective: The regulatory network of aquaporin (AQP) 1 and renin-angiotensin-aldosterone (ALDO) system are not quite clear in pulmonary arterial hypertension (PAH). Thus, we explored the role of AQP1, ALDO and spirolactone (SP) in the PAH animal model and pulmonary arterial smooth muscle cells (PASMCs).

Method: PAH rat model was established by monocrotaline (MCT) via intraperitoneal in SD rat.

Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5.

The voltage-gated potassium channel Kv1.5, which mediates the cardiac ultra-rapid delayed-rectifier (I) current in human cells, has a crucial role in atrial fibrillation. Therefore, the design of selective Kv1.