Chemoreactive-Inspired Discovery of Influenza A Virus Dual Inhibitor to Block Hemagglutinin-Mediated Adsorption and Membrane Fusion.

Owing to the emergence of drug resistance and high morbidity and mortality, the need for novel anti-influenza A virus (IAV) drugs with divergent targets is highly sought after. Herein, we reveal the discovery of an anti-IAV agent as a dual inhibitor to block hemagglutinin-mediated adsorption and membrane fusion using a chemoreactive -quinone methide (-QM) equivalent. Based on the -QM equivalent nonenzymatically multipotent behavior, we created a series of clavatol-derived pseudo-natural products and found that penindolone (PND), a new diclavatol indole adduct, exhibited potent and broad-spectrum anti-IAV activities with low risk of inducing drug resistance.

Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes.

Dynamic trafficking of G protein-coupled receptors (GPCRs) out of cilia is mediated by the BBSome. In concert with its membrane recruitment factor, the small GTPase ARL6/BBS3, the BBSome ferries GPCRs across the transition zone, a diffusion barrier at the base of cilia. Here, we present the near-atomic structures of the BBSome by itself and in complex with ARL6, and we describe the changes in BBSome conformation induced by ARL6 binding.

Study on Electrical Explosion Properties of Cu/Ni Multilayer Exploding Foil Prepared by Magnetron Sputtering and Electroplating.

The purpose of this study was to investigate the effects of the microstructure and properties of Cu/Ni multilayer films prepared by magnetron sputtering and electroplating on the electrical explosion performance of the films. In this study, Cu/Ni multilayer films of the same thickness were prepared by electroplating (EP) and magnetron sputtering (MS), and their morphology and crystal structure were characterized by scanning electron microscope (SEM) and transmission electron microscope (TEM). XRD was used to observe the crystal structure and size of the samples.

Fabrication of Poly(ethylene glycol) Capsules via Emulsion Templating Method for Targeted Drug Delivery.

To reduce nonspecific interactions and circumvent biological barriers, low-fouling material of poly(ethylene glycol) (PEG) is most used for the modification of drug nanocarriers. Herein, we report the fabrication of PEG capsules via the free-radical polymerization of linear PEG or 8-arm-PEG using an emulsion templating method for targeted drug delivery. Doxorubicin (DOX) could be loaded in capsules via electrostatic interactions.

Quality control and immunological activity of lentinan samples produced in China.

Lentinan is widely used as a therapeutic agent for treatment of malignant tumors in clinical practice. The chemical structure of lentinan is highly associated with its biological activity. In this study, the correlation between the structure of lentinan and its immune activity was investigated to assess the function of key parameters that can influence quality control of lentinan.

The Cocultured and , , and the Plant Host Bidirectionally Regulate the Production of Phytotoxins by Anti-phytopathogenic Metabolites.

The distinctive nature of the endophyte , host plant, and the phytopathogen resulted in both negative and positive regulation of the production of phytotoxins from . The coculture of nonhomologous and resulted in a greater number of anti-phytopathogenic metabolites from the dominant endophyte than the coculture of homologous and The coculture of the phytopathogen and either the nonhomologous (isolation of and from the different plants) or homologous (isolation of and from the same plant) endophyte from different sources indicated that the nonhomologous grew faster than the homologous , and the production of phytotoxic azaphilone from the phytopathogenic decreased due to the inhibition resulting from being cocultured with nonhomologous . On the other hand, the production of phytotoxic azaphilone was promoted by the coculture of two phytopathogens, and .

Determining In-Plane Carrier Diffusion in Two-Dimensional Perovskite Using Local Time-Resolved Photoluminescence.

The diffusion length of photogenerated carriers is a crucial parameter in semiconductors for optoelectronic applications. However, it is a challenging task to determine the diffusion length in layered nanoplatelets due to their anisotropic diffusion of photogenerated carriers and nanometer-thin thickness. Here, we demonstrate a novel method to determine the in-plane diffusion length of photogenerated carriers in layered nanoplatelets using local time-resolved photoluminescence.

Benign ferroelastic twin boundaries in halide perovskites for charge carrier transport and recombination.

Grain boundaries have been established to impact charge transport, recombination and thus the power conversion efficiency of metal halide perovskite thin film solar cells. As a special category of grain boundaries, ferroelastic twin boundaries have been recently discovered to exist in both CHNHPbI thin films and single crystals. However, their impact on the carrier transport and recombination in perovskites remains unexplored.

Glycomics studies using sialic acid derivatization and mass spectrometry.

Proteins can undergo glycosylation during and/or after translation to afford glycoconjugates, which are often secreted by a cell or populate cell surfaces. Changes in the glycan portion can have a strong influence on a glycoconjugate and are associated with a multitude of human pathologies. Of particular interest are sialylated glycoconjugates, which exist as constitutional isomers that differ in their linkages (α2,3, α2,6, α2,8 or α2,9) between sialic acids and their neighbouring monosaccharides.

Exploration of suitable pharmacodynamic parameters for acarbose bioequivalence evaluation: A series of clinical trials with branded acarbose.

Aims: To determine deficiencies in the Food and Drug Administration (FDA)'s guidance for assessing acarbose bioequivalence (BE) and to explore optimal pharmacodynamic (PD) metrics for better evaluation of acarbose BE.

Methods: Three clinical trials with branded acarbose were conducted in healthy subjects, including a pilot study (Study I, n = 11, 50 and 100 mg), a 2×2 crossover BE study (Study II, n = 36, 100 mg) and a 4×4 Williams study (Study III, n = 16, 50/100/150 mg). Serum glucose concentrations were measured by the glucose oxidase method.

Dynamics of the Transcriptome and Accessible Chromatin Landscapes During Early Goose Ovarian Development.

In contrast to the situation in mammals, very little is known about the molecular mechanisms regulating early avian ovarian development. This study aimed to investigate the dynamic changes in the histomorphology as well as the genome-wide transcriptome and chromatin accessibility landscapes of the goose ovary during late embryonic and early post-hatching stages. Results from hematoxylin-eosin, periodic acid-Schiff, and anti-CVH immunohistochemical stainings demonstrated that programmed oocyte loss, oocyte nest breakdown and primordial follicle formation, and the primordial-to-secondary follicle transition occur during the periods from embryonic day 15 (E15) to post-hatching day 0 (P0), from P0 to P4, and from P4 to P28, respectively.

WIP1 promotes cancer stem cell properties by inhibiting p38 MAPK in NSCLC.

Cancer stem cells (CSCs) are a small population of stem cell-like cancer cells that can initiate tumors in vivo, and are the major source of cancer initiation, relapse, and drug resistance. We previously reported that the p38 MAPK, through its downstream effectors MK2 and HSP27, suppressed CSC properties by downregulating the expression of transcription factors that mediate stemness in non-small-cell lung cancer (NSCLC) cells, and that despite unaltered total expression of total p38 proteins, the levels of activated p38 were reduced in NSCLC tissues. However, the mechanism underlying the reduced levels of activated p38 in NSCLC is unknown.

CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism.

Tumor metastasis is the most common cause of cancer-related deaths, yet it remains poorly understood. The transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) is involved in the epithelial-to-mesenchymal transition (EMT) and plays a pivotal role in tumor metastasis. However, the underlying mechanisms of the posttranslational modification of ZEB1 remain largely unknown.

The response regulator ArcA enhances biofilm formation in the vpsT manner under the anaerobic condition in Vibrio cholerae.

Vibrio cholerae, the agent of severe diarrheal disease cholera, is known to form biofilm to persist in the environmental and the hosts intestines. The bacteria execute a complex regulatory pathway producing virulence factors that allow colonization and cause disease in response to environmental signals in the intestine, including low oxygen-limited condition. VpsR and VpsT are primary regulators of the biofilm formation-regulatory network.

The size and affinity effect of counterions on self-assembly of charged block copolymers.

The effect of counterions' size and affinity on the microphase separated morphologies of neutral-charged diblock copolymers is investigated systematically using a random phase approximation (RPA) and self-consistent field theory (SCFT). The phase diagrams as a function of χ and f at different counterion sizes and different affinities to neutral blocks are constructed, respectively. Stability limits calculated using the RPA are in good agreement with the disorder-body-centered cubic phase boundaries from SCFT calculations.

1,25(OH) D alleviates DSS-induced ulcerative colitis via inhibiting NLRP3 inflammasome activation.

1,25-dihydroxyvitamin D3 (1,25(OH) D3, VitD3) is the major active ingredient of vitamin D and has anti-inflammatory activity; however, the mechanism for this remains poorly understood. In this study, we found that VitD3 was able to abolish NOD-like receptor protein 3 (NLRP3) inflammasome activation and subsequently inhibit caspase-1 activation and IL-1β secretion via the vitamin D receptor (VDR). Furthermore, VitD3 specifically prevented NLRP3-mediated apoptosis-associated speck-like protein with a caspase-recruitment domain (ASC) oligomerization.

QL0902, a proposed etanercept biosimilar: pharmacokinetic and immunogenicity profile to its reference product in healthy Chinese male subjects.

: To study the pharmacokinetics, safety and immunogenicity of Recombinant Human Tumor Necrosis Factor-α Receptor II: IgG Fc Fusion Protein for Injection (QL0902) and evaluate the pharmacokinetic similarity between QL0902 and reference Etanercept in healthy male subjects. : A randomized, double-blinded, single-dose, two-period, two-sequence and crossover study was conducted in healthy males. Sixty-eight subjects were randomized at 1:1 ratio to receive a single 50-mg subcutaneous injection of QL0902 or reference Etanercept.

Factors predicting the severity of acute pancreatitis in elderly patients.

Background: Moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) are associated with organ failure (OF), which can be lethal.

Aims: This study determined the factors that predict the severity of AP at admission in elderly patients.

Methods: In this retrospective study, the data from elderly patients (> 60 years of age) admitted within 72 h of onset of symptoms without OF were collected.

Inducing Intermediates in Biotransformation of Natural Polyacetylene and A Novel Spiro-γ-Lactone from Red Ginseng by Solid Co-Culture of Two Gut and The Potential Bioactivity Modification by Oxidative Metabolism.

The ω-hydroxyl-panaxytriol () and ω-hydroxyl-dihydropanaxytriol ()-are rare examples of polyacetylene metabolism by microbial transformation, and these new metabolites (, ) from fermented red ginseng (FRG) by solid co-culture induction of two should be the intermediates of biotransformation of panaxylactone (metabolite ). The metabolic pathway of panaxylactone was also exhibited. The ingredients of red ginseng (RG) also induced the production of rare 6/5/5 tricyclic ring spiro-γ-lactone skeleton ().

Catalytic Annulation of Alkynyl 1,2-Diketone Leading to Hydroxy Spirocyclopenteneindenedione: An Organic Dye with Strong Crystallization-Induced Emission and Data Storage Application.

An unprecedented cascade annulation between alkynyl 1,2-diketones and indene-1,3-diones is achieved for the first time, leading to a series of propeller-like large conjugated compounds in ≤99% yield. The products show strong crystallization-induced emission, with the colors changing from green to red. The fluorescence of the dye can be switched on and off by external acid/alkali stimuli, which can be utilized to develop a practical technology for rewritable information storage and security ink.

Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway.

Senescence of renal tubular epithelial cells plays an important role in diabetic nephropathy, but the mechanism is unknown. Metformin may alleviate diabetic nephropathy by reducing this senescence. This study is aimed at clarifying the effects and mechanism of metformin on the senescence of renal tubular epithelial cells in diabetic nephropathy.

Biological and Clinical Significance of GATA3 Detected from TCGA Database and FFPE Sample in Bladder Cancer Patients.

Purpose: The purpose of the present study was to investigate the biological and clinical significance of GATA binding protein 3 (GATA3) in bladder cancer patients.

Patients And Methods: For the detection of the correlation between GATA3 expression and bladder cancer, we downloaded the mRNA expression data from the Cancer Genome Atlas (TCGA) database and conducted immunohistochemistry staining on formalin-fixed paraffin-embedded (FFPE) sample tissues. Then, bladder cancer cell lines were utilized to investigate the potential functions of GATA3 by cell apoptosis, proliferation and cycle assays.