Increased expression of the membrane-bound CD40 ligand on peripheral CD4 T cells in the acute phase of AQP4-IgG-seropositive neuromyelitis optica spectrum disorders.

Currently, no data are available regarding the expression levels of CD40L on CD4 T cells in patients with neuromyelitis optica spectrum disorders (NMOSD). The percentage of circulating CD40LCD4 T cells was measured by flow cytometry in 23 NMOSD patients and 10 healthy controls. The ratio of CD40LCD4 to CD4 T cells in patients at acute phase (18.

Mannan-binding lectin deficiency exacerbates sterile liver injury in mice through enhancing hepatic neutrophil recruitment.

Noninfectious liver injury, including the effects of drugs and diet, is a major cause of liver diseases worldwide. The innate inflammatory response to hepatocyte death plays a crucial role in the outcome of liver injury. Mannan-binding lectin (MBL) is a pattern recognition molecule of the innate immune system, which is primarily produced by liver.

Altered expression of CD39 on memory regulatory T cells in type 1 diabetes patients.

Background: Type 1 diabetes (T1D) is an autoimmune disease resulting from an attack by autoreactive T lymphocytes against pancreatic islet β- cells. In recent studies, regulatory T cells (Tregs) have been implicated in the process of T1D. Furthermore, cluster of differentiation 39 (CD39), which is involved in the suppression of inflammation, has been shown to be expressed on Tregs.

Cyclin-dependent kinase 5-mediated phosphorylation of chloride intracellular channel 4 promotes oxidative stress-induced neuronal death.

Oxidative stress can cause apoptosis in neurons and may result in neurodegenerative diseases. However, the signaling mechanisms leading to oxidative stress-induced neuronal apoptosis are not fully understood. Oxidative stress stimulates aberrant activation of cyclin-dependent kinase 5 (CDK5), thought to promote neuronal apoptosis by phosphorylating many cell death-related substrates.

TaZIM-A1 negatively regulates flowering time in common wheat (Triticum aestivum L.).

Flowering time is a critical determinant of regional adaptation for crops and has strong effects on crop yields. Here, we report that TaZIM-A1, an atypical GATA-like transcription factor, is a negative regulator of flowering in wheat. TaZIM-A1 possessed weak transcriptional repression activity, with its CCT domain functioning as the major inhibitory region.

Adoptive transfer of xenoantigen‑stimulated T cell receptor Vβ‑restricted human regulatory T cells prevents porcine islet xenograft rejection in humanized mice.

Polyclonal expansion of human regulatory T cells (Tregs) prevents xenogeneic rejection by suppressing effector T cell responses in vitro and in vivo. However, a major limitation to using polyclonally expanded Tregs is that they may cause pan‑immunosuppressive effects. The present study was conducted to compare the ability of ex vivo expanded human xenoantigen‑stimulated Tregs (Xeno‑Treg) and polyclonal Tregs (Poly‑Treg) to protect islet xenografts from rejection in NOD‑SCID interleukin (IL)‑2 receptor (IL2r)γ‑/‑ mice.

Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation.

Astrocyte dysfunction and inflammation are associated with the pathogenesis of major depressive disorder (MDD). However, the mechanisms underlying these effects remain largely unknown. Here, we found that multiple endocrine neoplasia type 1 (Men1; protein: menin) expression is attenuated in the brain of mice exposed to CUMS (chronic unpredictable mild stress) or lipopolysaccharide.

Small molecule-induced degradation of the full length and V7 truncated variant forms of human androgen receptor.

The androgen receptor (AR) is a hormone-activated transcription factor that regulates the development and progression of prostate cancer (PCa) and represents one of the most well-established drug targets. Currently clinically approved small molecule inhibitors of AR, such as enzalutamide, are built upon a common chemical scaffold that interacts with the AR by the same mechanism of action. These inhibitors eventually fail due to the emergence of drug-resistance in the form of AR mutations and expression of truncated AR splice variants (e.

Complement 3 glomerulonephritis in rheumatoid arthritis: A case report and follow-up.

Glomerulonephritis (GN) caused by rheumatoid arthritis may manifest as various pathological types; however, to the best of our knowledge, rheumatoid arthritis-associated complement 3 (C3)-GN has not been reported by any previous studies. C3GN is caused by dysregulation of the alternative pathway of complements, which is completely different from activation of the classic pathway of a typical autoimmune disease to cause renal damage. The present study describes a patient with a history of rheumatoid arthritis for 18 years, who presented with edema, proteinuria, hematuria, hypoproteinemia and a hypocomplementemic state.

Selectively targeting the dimerization interface of human androgen receptor with small-molecules to treat castration-resistant prostate cancer.

Prostate cancer (PCa) is a leading cause of death for men in North America. The androgen receptor (AR) - a hormone inducible transcription factor - drives expression of tumor promoting genes and represents an important therapeutic target in PCa. The AR is activated by steroid recruitment to its ligand binding domain (LBD), followed by receptor nuclear translocation and dimerization via the DNA binding domain (DBD).

CD21 and FCRL5 form a receptor complex with robust B-cell activating capacity.

The B-cell response to antigen is critically regulated by co-receptors. CD21 (complement receptor 2) amplifies the response to antigen linked to its ligands, specific C3 fragments. In contrast, human Fc receptor-like 5 (FCRL5), a novel IgG receptor, was reported to inhibit B-cell receptor (BCR) signaling.

Fatigue Crack Growth Behavior of the MIG Welded Joint of 06Cr19Ni10 Stainless Steel.

In this paper, the fatigue crack growth behavior of the base metal (BM), the weld metal (WM) and the heat-affected zone (HAZ) in the metal-inert gas (MIG) welded joints of the 06Cr19Ni10 stainless steel are analyzed and studied. Results of the fatigue crack propagation tests show that a new fatigue crack initiates at the crack tip of a pre-existing crack, then propagates perpendicular to the direction of cyclic fatigue loads. This observation indicates that the original mixed-mode crack transforms into the mode I crack.

eIF2α kinases PERK and GCN2 act on FOXO to potentiate FOXO activity.

PERK and GCN2 are eIF2α kinases known to mediate the effects of ER stress and respond to an array of diverse stress stimuli. Previously, we reported that ER stress potentiates insulin resistance through PERK-mediated FOXO phosphorylation. Inhibition of PERK improves cellular insulin responsiveness at the level of FOXO activity.

Neuron-Specific Menin Deletion Leads to Synaptic Dysfunction and Cognitive Impairment by Modulating p35 Expression.

Menin (MEN1) is a critical modulator of tissue development and maintenance. As such, MEN1 mutations are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. Although menin is abundantly expressed in the nervous system, little is known with regard to its function in the adult brain.

Study on evaluation of toxicology and quality control of Yimusake tablet.

Ethnopharmacological Relevance: The Yimusake tablet (YMSK-T) is a type of Xinjiang Uygur Medicine, which affects curing diseases of impotence and premature ejaculation. It has remarkable pharmacological effects that mainly involve improving the number and shape of smooth muscle cells in the corpus cavernosum and enhancing the relaxation and contraction function of corpus cavernosum smooth muscle.

Aim Of The Study: The YMSK-T prescription, which consists of 11 traditional herbs, has significant pharmacological effects, however the evaluation of toxicology and quality control of the preparation has not yet been reported.

Fault Diagnosis of Tennessee-Eastman Process Using Orthogonal Incremental Extreme Learning Machine Based on Driving Amount.

Fault diagnosis is important to the industrial process. This paper proposes an orthogonal incremental extreme learning machine based on driving amount (DAOI-ELM) for recognizing the faults of the Tennessee-Eastman process (TEP). The basic idea of DAOI-ELM is to incorporate the Gram-Schmidt orthogonalization method and driving amount into an incremental extreme learning machine (I-ELM).

Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers.

Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulations were carried out to unravel changes in the MERS CoV heptad repeat domains (HRs) and factors affecting fusion state HR stability. Results indicated that HR trimer is more rapidly stabilized, having stable system energy and lower root mean square deviations (RMSDs).

Whole-genome resequencing reveals signatures of selection and timing of duck domestication.

Background: The genetic basis of animal domestication remains poorly understood, and systems with substantial phenotypic differences between wild and domestic populations are useful for elucidating the genetic basis of adaptation to new environments as well as the genetic basis of rapid phenotypic change. Here, we sequenced the whole genome of 78 individual ducks, from two wild and seven domesticated populations, with an average sequencing depth of 6.42X per individual.

Synthesis of Sub-10 nm Two-Dimensional Covalent Organic Thin Film with Sharp Molecular Sieving Nanofiltration.

We demonstrated here a novel and facile synthesis of two-dimensional (2D) covalent organic thin film with pore size around 1.5 nm using a planar, amphiphilic and substituted heptacyclic truxene based triamine and a simple dialdehyde as building blocks by dynamic imine bond formation at the air/water interface using Langmuir-Blodgett (LB) method. Optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM), all unanimously showed the formation of large, molecularly thin and free-standing membrane that can be easily transferred on different substrate surfaces.

Endogenous molecules released by haemocytes receiving Sargassum oligocystum extract lead to downstream activation and synergize innate immunity in white shrimp Litopenaeus vannamei.

White shrimp Litopenaeus vannamei haemocytes receiving immunostimulating Sargassum oligocystum extract (SE) caused necrosis in haemocyte cells, which released endogenous EM-SE molecules. This study examined the immune response of white shrimp L. vannamei receiving SE and EM-SE in vitro and in vivo.

Stabilization of golden cages by encapsulation of a single transition metal atom.

Golden cage-doped nanoclusters have attracted great attention in the past decade due to their remarkable electronic, optical and catalytic properties. However, the structures of large golden cage doped with Mo and Tc are still not well known because of the challenges in global structural searches. Here, we report anionic and neutral golden cage doped with a transition metal atom MAu (M = Mo and Tc) using Saunders 'Kick' stochastic automation search method associated with density-functional theory (DFT) calculation (SK-DFT).

Isolation, characterization and genome sequencing of the novel phage SL25 from the Yellow Sea, China.

Outnumbering all other biological entities on earth, bacteriophages play critical roles in structuring microbial communities. However, only a small number of phages have so far been reported. In this study, a novel Pseudoalteromonas phage, SL25, was isolated from the yellow sea, China.

Local Electronic Structure of a Single-Layer Porphyrin-Containing Covalent Organic Framework.

We have characterized the local electronic structure of a porphyrin-containing single-layer covalent organic framework (COF) exhibiting a square lattice. The COF monolayer was obtained by the deposition of 2,5-dimethoxybenzene-1,4-dicarboxaldehyde (DMA) and 5,10,15,20-tetrakis(4-aminophenyl) porphyrin (TAPP) onto a Au(111) surface in ultrahigh vacuum followed by annealing to facilitate Schiff-base condensations between monomers. Scanning tunneling spectroscopy (STS) experiments conducted on isolated TAPP precursor molecules and the covalently linked COF networks yield similar transport (HOMO-LUMO) gaps of 1.

Multiple timescale analysis of the urban heat island effect based on the Community Land Model: a case study of the city of Xi'an, China.

Urban heat islands (UHIs) are the phenomenon of urban regions usually being warmer than rural regions, which significantly impacts both the regional ecosystem and societal activities. Numerical simulation can provide spatially and temporally continuous datasets for UHI analysis. In this study, a spatially and temporally continuous ground temperature dataset of Xi'an, China was obtained through numerical simulation based on the Community Land Model version 4.

Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors.

The c-Met kinase has emerged as an attractive target for developing antitumor agents because of its close relationship with the development of many human cancers, poor clinical outcomes and even drug resistance. A series of novel c-Met kinase inhibitors have been identified with multiple workflow in this work, including virtual screening, X-ray crystallography, biological evaluation and structural optimization. The experimentally determined crystal structure of the best hit compound HL-11 in c-Met kinase domain was highly consistent with the computational prediction.