MiR-574-5p Activates Human TLR8 to Promote Autoimmune Signaling and Lupus

Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis

Phenotypic expansion in DDX3X - a common cause of intellectual disability in females

De novo variants in DDX3X account for 1-3% of unexplained intellectual disability (ID) cases and are amongst the most common causes of ID especially in females. Forty-seven patients (44 females, 3 males) have been described. We identified 31 additional individuals carrying 29 unique DDX3X variants, including 30 postnatal individuals with complex clinical presentations of developmental delay or ID, and one fetus with abnormal ultrasound findings. Rare or novel phenotypes observed include respiratory problems, congenital heart disease, skeletal muscle mitochondrial DNA depletion, and late-onset neurologic decline. Our findings expand the spectrum of DNA variants and phenotypes associated with DDX3X disorders

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Studies on pollen morphology of selected species of Annonaceae from Thailand

The pollen morphology of 49 species and one variety, representing 18 genera of the family Annonaceae from Thailand, is described and illustrated based on observations using scanning electron microscopy (SEM). The pollen grains of Anaxagorea show double-spheres as a result of the intine extrusion. The palynological evidence confirms the close relationship of Dasymaschalon, Desmos and Asian Friesodielsia. Decussate tetrads in Goniothalamus and coexisting tetragonal, rhomboidal, T-shaped, tetrahedral and decussate tetrads in Mitrephora are reported. Pollen morphology is consistent within Huberantha, Marsypopetalum and Monoon, but is more diverse in Polyalthia sensu stricto Pollen unit, shape, size, ornamentation and aperture number reaffirm the great diversity among and within genera in Annonaceae

A novel RGO-MoS2_2-CdS nanocomposite film for application in the ultrasensitive NO2_2 detection

In this work, we studied the synthesis and sensing performance of RGO-MoS$_2$-CdS nanocomposite films serving as the sensing layer. By a facile solvothermal treatment, CdS nanocones could be grown on the 2D layered RGO-MoS$_2$ substrate to form a new heterostructure. Importantly, the gas sensor based on RGO-MoS$_2$-CdS films, with the higher specific surface area, more adsorption sites and lots of heterojunctions, showed a largely enhanced sensor response of 27.4% toward 0.2 ppm NO$_2$, about 7 times higher than the value of RGO-MoS$_2$ based gas sensor. Moreover, the gas sensor presented an outstanding selectivity toward NO$_2$ gas against the other gases, which was of great significance in both environmental protection and human health

Evaluating Targeted Intervention on Coal Miners’ Unsafe Behavior

Miners’ unsafe behavior is the main cause of roof accidents in coal mines, and behavior intervention plays a significant role in reducing the occurrence of miners’ unsafe behavior. However, traditional behavior intervention methods lack pertinence. In order to improve the intervention effect and reduce the occurrence of coal mine roof accidents more effectively, this study proposed a targeted intervention method for unsafe behavior. The process of targeted intervention node locating was constructed, and based on the analysis of 331 coal mine roof accidents in China, three kinds of targeted intervention nodes were located. The effectiveness of targeted intervention nodes was evaluated by using structural equation model (SEM) through randomly distributing questionnaires to miners of Pingdingshan coal. The results show that, in preventing roof accidents of coal mines, the targeted intervention nodes have a significant positive impact on the intervention effect. The method can also be applied to the safety management of other industries by adjusting the node location and evaluation process

Polyacrylamide-Based Block Copolymer Bearing Pyridine Groups Shows Unexpected Salt-Induced LCST Behavior

Thermal-responsive block copolymers are a special type of macromolecule that exhibit a wide range of applications in various fields. In this contribution, we report a new type of polyacrylamide-based block copolymer bearing pyridine groups of polyethylene glycol-block-poly(N-(2-methylpyridine)-acrylamide; Px) that display distinct salt-induced lower critical solution temperature (LCST) behavior. Unexpectedly, the phase-transition mechanism of the salt-induced LCST behavior of Px block copolymers is different from that of the reported LCST-featured analogues. Moreover, their thermo-responsive behavior can be significantly regulated by several parameters such as salt species and concentration, urea, polymerization degree, polymer concentration and pH values. This unique thermal behavior of pyridine-containing block copolymers provides a new avenue for the fabrication of smart polymer materials with potential applications in biomedicine

Climate change regionalization in China (1961–2010)

Since climatic condition is the important foundation for human subsistence and development and the key factor in sustainable development of economy and society, climate change has been a global issue attracting great attentions of politicians, scientists, governments, and the public alike throughout the world. Existing climate regionalization in China aims to characterize the regional differences in climate based on years of the mean value of different climate indexes. However, with the accelerating climate change nowadays, existing climate regionalization cannot represent the regional difference of climate change, nor can it reflect the disasters and environmental risks incurred from climate changes. This paper utilizes the tendency value and fluctuation value of temperature and precipitation from 1961 to 2010 to identify the climate change quantitatively, and completes the climate change regionalization in China (1961–2010) with county administrative regionalization as the unit in combination with China’s terrain feature. Level-I regionalization divides China’s climate change (1961–2010) into five tendency zones based on the tendency of temperature and precipitation, which are respectively Northeast China-North China warm-dry trend zone, East China-Central China wet-warm trend zone, Southwest China-South China dry-warm trend zone, Southeast Tibet-Southwest China wet-warm trend zone, and Northwest China-Qinghai-Tibet Plateau warm-wet trend zone; level-II regionalization refers to fourteen fluctuation regions based on level-I regionalization according to the fluctuation of temperature and precipitation

Evaluation of humoral and cellular immune responses induced by a cocktail of recombinant African swine fever virus antigens fused with OprI in domestic pigs

Abstract Background African swine fever (ASF) is a highly fatal disease in domestic pigs caused by ASF virus (ASFV), for which there is currently no commercial vaccine available. The genome of ASFV encodes more than 150 proteins, some of which have been included in subunit vaccines but only induce limited protection against ASFV challenge. Methods To enhance immune responses induced by ASFV proteins, we expressed and purified three fusion proteins with each consisting of bacterial lipoprotein OprI, 2 different ASFV proteins/epitopes and a universal CD4+ T cell epitope, namely OprI-p30-modified p54-TT, OprI-p72 epitopes-truncated pE248R-TT, and OprI-truncated CD2v-truncated pEP153R-TT. The immunostimulatory activity of these recombinant proteins was first assessed on dendritic cells. Then, humoral and cellular immunity induced by these three OprI-fused proteins cocktail formulated with ISA206 adjuvant (O-Ags-T formulation) were assessed in pigs. Results The OprI-fused proteins activated dendritic cells with elevated secretion of proinflammatory cytokines. Furthermore, the O-Ags-T formulation elicited a high level of antigen-specific IgG responses and interferon-γ-secreting CD4+ and CD8+ T cells after stimulation in vitro. Importantly, the sera and peripheral blood mononuclear cells from pigs vaccinated with the O-Ags-T formulation respectively reduced ASFV infection in vitro by 82.8% and 92.6%. Conclusions Our results suggest that the OprI-fused proteins cocktail formulated with ISA206 adjuvant induces robust ASFV-specific humoral and cellular immune responses in pigs. Our study provides valuable information for the further development of subunit vaccines against ASF