The cannabinoid CB receptor positive allosteric modulator EC21a exhibits complicated pharmacology .

Schizophrenia is a complex disease involving the dysregulation of numerous brain circuits and patients exhibit positive symptoms (hallucinations, delusions), negative symptoms (anhedonia), and cognitive impairments. We have shown that the antipsychotic efficacy of positive allosteric modulators (PAMs) of both the M muscarinic receptor and metabotropic glutamate receptor 1 (mGlu) involve the retrograde activation of the presynaptic cannabinoid type-2 (CB) receptor, indicating that CB activation or potentiation could result in a novel therapeutic strategy for schizophrenia. We used two complementary assays, receptor-mediated phosphoinositide hydrolysis and GIRK channel activation, to characterize a CB PAM scaffold, represented by the compound EC21a, to explore its potential as a starting point to optimize therapeutics for schizophrenia.

Phagocytic Plasma Cells in Teleost Fish Provide Insights into the Origin and Evolution of B Cells in Vertebrates.

Teleost IgM+ B cells can phagocytose, like mammalian B1 cells, and secrete Ag-specific IgM, like mammalian B2 cells. Therefore, teleost IgM+ B cells may have the functions of both mammalian B1 and B2 cells. To support this view, we initially found that grass carp (Ctenopharyngodon idella) IgM+ plasma cells (PCs) exhibit robust phagocytic ability, akin to IgM+ naive B cells.

Identification and functional analyses of CD4-1 cells in grass carp (Ctenopharyngodon idella).

In mammals, CD4 is found to be expressed on T cells and innate immune cells, however, teleost cells bearing CD4 have not been well identified and characterized. In this study, we identified two different CD4-1 cell subsets in grass carp (Ctenopharyngodon idella): CD4-1 lymphocytes (Lym) and CD4-1 myeloid cells (Mye), both of which had the highest proportions in the head kidney. The mRNA expression analysis showed that CD4-1, CD4-2, TCRβ, CD3γ/δ, and LCK1 are highly expressed in CD4-1 Lym and also expressed in CD4-1 Mye.

Antimicrobial Protein LECT2-b Helps Maintain Gut Microbiota Homeostasis via Selectively Targeting Certain Pathogenic Bacteria.

Antimicrobial peptides/proteins (AMPs) constitute a critical component of gut immunity in animals, protecting the gut from pathogenic bacteria. However, the interactions between AMPs and gut microbiota remain elusive. In this study, we show that leukocyte-derived chemotaxin-2 (LECT2)-b, a recently discovered AMP, helps maintain gut homeostasis in grass carp (Ctenopharyngodon idella), one of the major farmed fish species globally, by directly regulating the gut microbiota.

Tuning 3D refractive indices via constrained uniaxial stretch in cellulose triacetate films plasticized with triethyl citrate.

Tuning 3D refractive indices of polymers is urgently needed for optical films, but it is quite challenging. Here, we proposed a simple constrained uniaxial stretch method that successfully tuned the 3D refractive indices in cellulose triacetate (TAC) films plasticized with triethyl citrate (TEC). Our results suggest that, under constrained uniaxial stretch, the main chains and side groups prefer to orientate in the stretch direction and the constrained direction, respectively.

A versatile biaxial stretching device for in situ synchrotron radiation small- and wide-angle x-ray scattering measurements of polymer films.

A biaxial stretching device is designed and developed for the real-time structural measurements of polymer films. This device adopts a vertical layout to perform real-time x-ray scattering measurements. It has a maximum stretching ratio of 8 × 8 in two perpendicular directions.

Regulation of orientation birefringence for cellulose acetate film: The role of crystallization and orientation.

Cellulose acetate (CA) based films are widely used in liquid crystal displays due to their outstanding transparency, and a certain orientation birefringence of CA films is required when they are used as retardation films. The regulation of orientation birefringence is usually from the perspective of stretch-induced orientation, while the effects of crystallization behaviors of CA films remain obscure. In this study, the roles of crystallization and orientation on the orientation birefringence of CA films were elucidated.

Oral SARS-CoV-2 Spike Protein Recombinant Yeast Candidate Prompts Specific Antibody and Gut Microbiota Reconstruction in Mice.

A recent study showed that patients with coronavirus disease 2019 (COVID-19) have gastrointestinal symptoms and intestinal flora dysbiosis. Yeast probiotics shape the gut microbiome and improve immune homeostasis. In this study, an oral candidate of yeast-derived spike protein receptor-binding domain (RBD) and fusion peptide displayed on the surface of the yeast cell wall was generated.

Single-Nucleotide Polymorphisms Promote Dysregulation Activation by Essential Gene Mediated Bio-Molecular Interaction in Breast Cancer.

Background: Breast cancer (BRCA) is a malignant tumor with a high mortality rate and poor prognosis in patients. However, understanding the molecular mechanism of breast cancer is still a challenge.

Materials And Methods: In this study, we constructed co-expression networks by weighted gene co-expression network analysis (WGCNA).

and Four Species With Veterinary and Public Health Significance Identified in Tibetan Sheep () and Yaks () in Qinghai, China.

Tick-borne diseases (TBDs) can cause serious economic losses and are very important to animal and public health. To date, research on TBDs has been limited in Qinghai-Tibet Plateau, China. This epidemiological investigation was conducted to evaluate the distribution and risk factors of spp.

Effect of Etoricoxib on miR-214 and inflammatory reaction in knee osteoarthritis patients.

Purpose: To explore the effect of Etoricoxib on serum miR-214 expression level and inflammatory reaction in patients with knee osteoarthritis.

Methods: 96 patients with knee osteoarthritis admitted to our hospital (January 2019 to January 2020) were selected. 48 patients in the control group received Celecoxib and 48 patients in the observation group received Etoricoxib.

Selenium Deficiency Leads to Changes in Renal Fibrosis Marker Proteins and Wnt/β-Catenin Signaling Pathway Components.

Renal fibrosis is the final result of the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Earlier studies confirmed that selenium (Se) displays a close association with kidney diseases. However, the correlation between Se and fibrosis has rarely been explored.

Multiplex Real-Time PCR Method for Simultaneous Detection and Differentiation of Goat pox Virus, Sheeppox Virus, and Lumpy Skin Disease Virus.

Background: The diseases caused by the Capripoxvirus species have very similar symptoms and are difficult to distinguish clinically. According to a recent report, Capripoxvirus are not strictly host specific.

Objective: This study aimed to identify the viruses from ovine (include sheep and goat) or bovine, which will assist in selecting the appropriate vaccine and correct measures to control diseases.

Vector-Borne Pathogens with Veterinary and Public Health Significance in (Sheep Ked) from the Qinghai-Tibet Plateau.

(sheep ked) is a hematophagous ectoparasite that mainly parasitizes sheep. In addition to causing inflammation, wool loss, and skin damage to the animal hosts, also serves as a vector for a variety of pathogens and is highly likely to participate in the life and transmission cycle of pathogenic organisms. Herein, we investigated the presence and molecular characterization of vector-borne pathogens in from Qinghai-Tibet Plateau, China.

A quantum dot fluorescent microsphere based immunochromatographic strip for detection of brucellosis.

Background: Brucellosis is a serious zoonosis disease that frequently causes significant economic loss in animal husbandry and threatens human health. Therefore, we established a rapid, accurate, simple and sensitive fluorescent immunochromatographic strip test (ICST) based on quantum dots (QDs) for detection the antibodies of Brucella infection animals serum.

Results: The test strips were successfully prepared by quantum dot fluorescent microspheres (QDFM) as tracers, which were covalently coupled to an outer membrane protein of Brucella OMP22.

A practical synthesis of amino limonin/deoxylimonin derivatives as effective mitigators against inflammation and nociception.

A practical synthetic route, consisting of 5 steps, has been developed and applied successfully for converting limonin/deoxylimonin into the corresponding amino derivatives - and - . Deoxylimonin analogs and bearing an open A ring structure underwent ring closure reaction by employing the Mitsunobu procedure to afford and . All of the 12 newly synthesized compounds were subjected to preliminary screening for evaluating their inflammation and nociception inhibition efficacy.

Discovery of deoxylimonin δ-lactam derivative with favorable anti-inflammation and antinociception efficacy from chemical modified limonin/deoxylimonin analogs.

Chemical modifications on the A ring of limonin (1) and deoxylimonin (2) afforded 28 structural characterized derivatives, which were firstly subjected to preliminary in vivo analgesic and anti-inflammatory screen by mice model. The most promising candidate, deoxylimonin analog II-B-2 (70 mg/kg) with 3,4-dimethoxyphenylethyl moiety substitued δ-lactam in the A ring, exhibited better analgesic activity than aspirin (200 mg/kg) and stronger anti-inflammatory efficacy than naproxen (150 mg/kg). Further in vivo evaluation confirmed its advantage over limonin and showed dose-response dependent manner, and follow-up research suggested that the anti-inflammatory effect of compound II-B-2 may be attributed to the downregulation of cyclooxygenase 2 expression and the suppression of prostaglandin E formation.

Phenotype, Virulence and Immunogenicity of Cyclic AMP Receptor Protein (Crp) Mutants in Catfish Host.

, a facultative aerobic pathogen belonging to the Enterobacteriaceae family, is the etiological agent of edwardsiellosis that causes significant economic loses in the aquaculture industry. cAMP receptor protein (CRP) is one of the most important transcriptional regulators, which can regulate large quantities of operons in different bacteria. Here we characterize the gene and report the effect of a deletion in .

Identification and Molecular Analysis of Ixodid Ticks (Acari: Ixodidae) Infesting Domestic Animals and Tick-Borne Pathogens at the Tarim Basin of Southern Xinjiang, China.

Livestock husbandry is vital to economy of the Tarim Basin, Xinjiang Autonomous Region, China. However, there have been few surveys of the distribution of ixodid ticks (Acari: Ixodidae) and tick-borne pathogens affecting domestic animals at these locations. In this study, 3,916 adult ixodid ticks infesting domestic animals were collected from 23 sampling sites during 2012-2016.

Molecular characterization, expression and functional analysis of IRAK1 and IRAK4 in Nile tilapia (Oreochromis niloticus).

Interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 are critical signalling mediators and play pivotal roles in the innate immune and inflammatory responses mediated by TLR/IL-1R. In the present study, two IRAK family members, OnIRAK1 and OnIRAK4, were identified in the Nile tilapia Oreochromis niloticus with a conserved N-terminal death domain and a protein kinase domain, similar to those of other fishes and mammals. The gene structures of OnIRAK1 and OnIRAK4 are organized into fifteen exons split by fourteen introns and ten exons split by nine introns.

Identification and characterisation of tumour necrosis factor receptor (TNFR) associated factor 3 from Nile tilapia, Oreochromis niloticus.

In this study, we cloned the complementary (c)DNA sequences of tumour necrosis factor receptor (TNFR)-associated factor 3 (traf3) in Nile tilapia, Oreochromis niloticus. The expression patterns of the traf3 gene were investigated and preliminary functional analyses were performed. In healthy fish, traf3 transcript was broadly expressed in all examined tissues, with the highest expression level in the blood and the lowest in the liver.

Bacillus velezensis LF01: in vitro antimicrobial activity against fish pathogens, growth performance enhancement, and disease resistance against streptococcosis in Nile tilapia (Oreochromis niloticus).

Streptococcus agalactiae is a major pathogen causing streptococcosis. To prevent and control this bacterial disease, antagonistic bacteria have become a new research hotspot. This study evaluated the probiotic potential of Bacillus velezensis LF01 strain, which is antagonistic to S.

Establishment and optimization of a liquid bead array for the simultaneous detection of ten insect-borne pathogens.

Background: Insect-borne diseases could induce severe symptoms in human and clinical signs in animals, such as febrility, erythra, arthralgia and hemorrhagic fever, and cause significant economic losses and pose public health threat all over the world. The significant advantages of Luminex xMAP technology are high-throughput, high parallel and automation. This study aimed to establish a liquid bead array based on Luminex xMAP technology that was able to simultaneously detect multiple insect-borne pathogens.

NF90 is a novel influenza A virus NS1-interacting protein that antagonizes the inhibitory role of NS1 on PKR phosphorylation.

NF90 is a novel host antiviral factor that regulates PKR activation and stress granule formation in influenza A virus (IAV)-infected cells, but the precise mechanisms by which it operates remain unclear. We identified NF90 as a novel interacting protein of IAV nonstructural protein 1 (NS1). The interaction was dependent on the RNA-binding properties of NS1.