Intracellular organelle cross-talk is a new and important research area. Under stress conditions, the coordinated action of autophagy endosomal systems in tumor cells essential for maintaining cellular homeostasis survival. The activation IκB kinase (IKK) complex also involved regulation cells. Here, we try to explore effects constitutively active IKKβ subunits (CA-IKKβ) on system interactions. We confirm that CA-IKKβ induces accumulation autophagosomes their fusion with MVBs form amphisomes...

β2AR is an important drug target protein involving many diseases. Biased drugs induce specific signaling and provide additional clinical utility to optimize β2AR-based therapies. However, the biased mechanism has not been elucidated. Motivated by issue, we chose four agonists with divergent bias (balanced agonist, G-protein-biased β-arrestin-biased agonists) utilized Gaussian accelerated molecular dynamics simulation coupled a dynamic network probe mechanisms of distinct activation induced...

Using aMD simulations with an interpretable deep learning model, the biased activation of μOR two distinct agonists is revealed.

Prostate cancer (PRAD) is a major cause of cancer-related deaths. Current monotherapies show limited efficacy due to often rapidly emerging resistance. Combination therapies could provide an alternative solution address this problem with enhanced therapeutic effect, reduced cytotoxicity, and delayed the appearance drug However, it prohibitively cost labor-intensive for experimental approaches pick out synergistic combinations from millions possibilities. Thus, highly desired explore other...

The photothermal-chemical combination therapy is a promising approach for cancer treatment, however, chemotherapy often causes severe toxic and side effects on normal tissues. Herein, tumor-specific FeOOH@PNE-Art nanoparticles were fabricated via coating poly(norepinephrine) (PNE) FeOOH nanoparticles, followed by loading of artemisinin (Art). as-prepared exhibited excellent biocompatibility, strong near-infrared (NIR) absorbance pH-responsive synchronous release Art iron ions. released ions...

Metabotropic glutamate receptors of class C GPCRs exist as constitutive dimers, which play important roles in activating excitatory synapses the central nervous system. However, activation mechanism induced by agonists has not been clarified experiments. To address problem, we used microsecond all-atom molecular dynamics (MD) simulation couple with protein structure network (PSN) to explore glutamate-induced for mGluR1 homodimer. The results indicate that binding stabilizes only closure...

In this work, we combined accelerated molecular dynamics (aMD) and conventional (cMD) simulations coupled with the potential of mean force (PMF), correlation analysis, principal component analysis (PCA), protein structure network (PSN) to study effects dimerization mutations I52V V150A on CCR5 homodimer, in order elucidate mechanism regarding cooperativity ligand binding between two protomers address controversy about mutation-induced dimer-separation. The results reveal that dimer interface...

In this work, accelerated molecular dynamics (aMD) simulations were used to study different effects of G286F and R126 mutations on the activity CCR5. Potential Mean Force (PMF) results indicate that there are stable inactive-like states active-like ones existing in conformation space wild type (WT), confirming CCR5 could possess some extent constitutive activity. But R126N mutation constrain inactive state through influencing TXP motif limiting movements TM5 TM6. contrast, promotes receptor...

G protein-coupled receptors (GPCRs) as the most important class of pharmacological targets regulate G-protein and β-arrestin-mediated signaling through allosteric interplay, which are responsible for different biochemical physiological actions like therapeutic efficacy side effects. However, mechanism underlying preferentially recruiting one transducer versus other has been poorly understood, limiting drug design. Motivated by this issue, we utilize accelerated molecular dynamics simulation...

The residue located at 15 positions before the most conserved in TM7 (7.35 of Ballesteros–Weinstein number) plays important roles ligand binding and receptor activity for class A GPCRs. Nevertheless, its regulation mechanism has not been clearly clarified experiments, some controversies also exist impact on μ-opioid receptors (μOR) bound by agonists. Thus, we chose GPCRs as a representative utilized microsecond accelerated molecular dynamics simulation (aMD) coupled with protein structure...

Caprine/ovine enterovirus (CEV/OEV) infection is an emerging disease and remains largely unknown for its distribution, epidemic pattern, the underlying contribution factors. Here, we report investigation on CEV/OEV pattern factors by employing a sandwich ELISA kit detection of antigen. Epidemiological revealed wide range rates from 19.80%−39.00% goat/sheep farms in major goat/sheep-raising provinces as such Henan, Shandong, Ningxia, Jilin, Inner Mongolia autonomous region, Xinjiang region...

Abstract Objective Vaginal microbiota evaluation is a methodology widely used in China to diagnose various vaginal inflammatory diseases. Although has many advantages, it time-consuming and requires highly skilled experienced operators. Here, we investigated six-index functional test that analyzed pH, hydrogen peroxide (H 2 O ), leukocyte esterase (LEU), sialidase (SNA), β-glucuronidase (GUS), acetylglucossidase (NAG), determined its diagnostic value by comparing with morphological tests of...

Glucagon-like peptide-1 receptor (GLP-1R), as a member of the class B G protein-coupled receptors (GPCRs), plays crucial role in regulating blood glucose level signal recognition through its activation. The conformation changes during activation pathway are particular importance for function. To investigate mechanism GLP-1R, crystal structures active and inactive forms chosen to perform total 2 μs accelerated molecular dynamics (aMD) simulations 400ns conventional (cMD) simulations. With aid...

As a nutrient in body functions, folic acid (FA) plays very important role for human health, and thus developing highly sensitive method its determination is of great significance. In the present work, carbon hollow nanospheres decorated with molybdenum disulfide nanosheets (CHN@MoS2) nanomaterials were produced through simple adopted to modify glassy electrode assembling electrochemical sensor FA. After characterizing prepared using scanning-/transmission-electron microscopy Raman spectra,...

Introduction: Klebsiella pneumoniae is classified as a critical pathogen in both animals and humans infections can be fatal chickens resulting substantial economic losses. However, the misuse of antibiotics also lead to drug resistance potential transmission chain between humans. Three K. strains with different susceptibility phenotypes were chosen study pharmacokinetic/pharmacodynamic (PK/PD) integration enrofloxacin (ENR) cefquinome (CEQ) alone combination. Results: Checkerboard assay...

Background The impact of anticancer therapy and related clinical factors on the severity COVID-19 in cancer patients during Omicron pandemic has not been established. recent outbreak China caused predominantly by BA.5.2 BF.7 strains provided us with opportunity to observe objectively this strain oncology patients. We initiated two–center retrospective study determine anti-cancer treatment, other factors, characteristics infected coronavirus SARS-CoV-2 variant China. Methods retrospectively...

Enterovirus, like the majority of RNA viruses, evolves to survive changeable environments by a variety strategies. Here, we showed that HY12 virus evolved alter its characteristics and pathogenicity employing non-synonymous mutation. Analyses 5'UTR, VP1 VP2 gene sequences revealed existence in an array mutants defined as quasispecies. The determination diversity complexity mutation rate quasispecies increased, while proportion consensus (master) decreased with increasing passages. Synonymous...