Making Pb Adsorption-Saturated Attapulgite with Excellent Photocatalysis Properties through a Vulcanization Reaction and Its Application for MB Wastewater Degradation.

Attapulgite (AT) is a clay mineral with rich reserves in China, and it has good adsorption activity for Pb-containing wastewater. However, as a hazardous waste, the treatment of Pb adsorption-saturated attapulgite was quite difficult. In this work, through a simple vulcanization reaction, the waste Pb adsorption-saturated attapulgite (AT@Pb) was transformed into composite materials (AT@PbS) with good photocatalytic performance. After comprehensive material characterization (including XRD, TEM, XPS, and UV-Vis), the photocatalytic degradation performance and mechanism of AT@PbS for methylene blue (MB) were investigated. The results revealed that AT@PbS was a composite material of attapulgite nanorods (500-600 nm) and nanosquare PbS particles (80-100 nm). Additionally, AT@PbS displayed good visible light absorption, improved photo-electric properties, excellent photodegradation performance for MB, and recycling stability. Moreover, the energy band range of AT@PbS was about -0.043 V to 1.367 V. The photo-generated holes and their derived hydroxyl radicals were the main active species for MB degradation. This work not only provides a new approach to construct the composite photocatalyst, but also demonstrates the possibility of the comprehensive utilization of heavy metal adsorbents for wastewater degradation.

Effects of Healthcare Policies and Reforms at the Primary Level in China: From the Evidence of Shenzhen Primary Care Reforms from 2018 to 2019.

Countries worldwide are making efforts to achieve health equity. China focuses on the implementation of the policy goal of "improving the primary level" to eliminate the health equity gap. The main purpose of this study is to examine the effects of the healthcare reforms at the primary level in China and to analyze the key factors that can help to improve their effectiveness. From the perspectives of the policy attention mechanism and public policy analysis, this study will explore primary care reforms from policy formulation to policy implementation on the basis of grounded theory and empirical research on primary care reforms in Shenzhen, China, that was conducted from 2018 to 2019. The present study found that the government pays close attention to the medical level and service level of primary care services at the policy formulation phase but less attention to talent level and information sharing. At the same time, this study combined with empirical data from primary care centers in Shenzhen for the period covering 2018 to 2019 evaluates policy implementation and its effect. Multiple regression analysis revealed that the medical level, talent level, service level, and information sharing helped to develop primary care services and improved health equity. Nevertheless, this study reflects a deviation between policy formulation and policy implementation for the development of primary care policies. Empirical experience shows that the development of talent level and information sharing can significantly promote primary care services and health management. Therefore, this study implies that in the process of promoting the health equity at the primary level, more attention should be paid to the consistency between policy formulation and policy implementation. Additionally, the policy promotion and influence mechanism can be improved, particularly in terms of talent development and information sharing, in order to effectively promote the development of health equity at the primary level.

IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation.

Interferon regulatory factor 3 (IRF3) is an essential transductor for initiation of many immune responses. Here, we show that lncRNA-ISIR directly binds IRF3 to promote its phosphorylation, dimerization, and nuclear translocation, along with enhanced target gene productions. In vivo lncRNA-ISIR deficiency results in reduced IFN production, uncontrolled viral replication, and increased mortality. The human homolog, AK131315, also binds IRF3 and promotes its activation. More important, AK131315 expression is positively correlated with type I interferon (IFN-I) level and severity in patients with lupus. Mechanistically, in resting cells, IRF3 is bound to suppressor protein Flightless-1 (Fli-1), which keeps its inactive state. Upon infection, IFN-I-induced lncRNA-ISIR binds IRF3 at DNA-binding domain in cytoplasm and removes Fli-1's association from IRF3, consequently facilitating IRF3 activation. Our results demonstrate that IFN-I-inducible lncRNA-ISIR feedback strengthens IRF3 activation by removing suppressive Fli-1 in immune responses, revealing a method of lncRNA-mediated modulation of transcription factor (TF) activation.

E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3.

Ubiquitination is one of the most prevalent protein posttranslational modifications. Here, we show that E3 ligase Nedd4l positively regulates antiviral immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3. Deficiency of Nedd4l significantly impairs type I interferon and proinflammatory cytokine production induced by virus infection both in vitro and in vivo. Nedd4l deficiency inhibits virus-induced ubiquitination of TRAF3, the binding between TRAF3 and TBK1, and subsequent phosphorylation of TBK1 and IRF3. Nedd4l directly interacts with TRAF3 and catalyzes K29-linked ubiquitination of Cys56 and Cys124, two cysteines that constitute zinc fingers, resulting in enhanced association between TRAF3 and E3 ligases, cIAP1/2 and HECTD3, and also increased K48/K63-linked ubiquitination of TRAF3. Mutation of Cys56 and Cys124 diminishes Nedd4l-catalyzed K29-linked ubiquitination, but enhances association between TRAF3 and the E3 ligases, supporting Nedd4l promotes type I interferon production in response to virus by catalyzing ubiquitination of the cysteines in TRAF3.

Enriched environment improves post-stroke cognitive impairment and inhibits neuroinflammation and oxidative stress by activating Nrf2-ARE pathway.

INTRODUCTION: Neuroinflammation and oxidative stress are major mechanisms of post-stroke cognitive impairment (PSCI) neural injury and decreased spatial and memory capacity. Enriched environment (EE) is an effective method to improve cognitive dysfunction. However, the regulation by EE of neuroinflammation, oxidative stress and associated mechanisms in animal models remains unclear. MATERIALS AND METHODS: In this study, a rat PSCI model was established by middle cerebral artery occlusion (MCAO). Rats were randomly divided into the control group, standard environment (SE) group and EE group for 28 days. A Morris water-maze test was used to measure cognitive function at 7, 14 and 28 days after MCAO. Rats were sacrificed on the 28th day. Quantitative PCR, immunohistochemistry and ELISA were respectively used to detect mRNA expression of NF-E2-related factor 2 (Nrf2) and Nrf2 response genes, the expression of IL-1ß and levels of proinflammatory cytokines in the hippocampus. RESULTS: EE improved mNSS scores and cognitive ability in PSCI rats. EE increased mRNA expression of the Nrf2 and Nrf2 response genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). EE significantly decreased the level of malondialdehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione (GSH), in the hippocampus of PSCI rats. EE reduced the number of IL-1ß positive cells in the hippocampus, and IL-1ß levels in the hippocampus and serum. EE increased GFAP-positive astrocytes in the hippocampus, and BDNF levels in the hippocampus and serum. CONCLUSIONS: EE can improve cognitive function in PSCI rats by inhibiting neuroinflammation and oxidative stress.

Large-Area Tunable Red/Green/Blue Tri-Stacked Quantum Dot Light-Emitting Diode Using Sandwich-Structured Transparent Silver Nanowires Electrodes.

Quantum dot light-emitting diodes (QLEDs), particularly those capable of emitting light with tunable colors, have attracted the attention of researchers for their variability in lighting and displays. So far, various color-tunable QLEDs have been developed using techniques of inkjet printing or white light combining with color filters (CFs), which however suffered from difficulties in mass production. Here, by inserting an insulating resin layer between two conductive silver nanowire (AgNW) layers, a unique AgNWs/resin/AgNWs (A/R/A) sandwich-structured electrode was developed, showing rather small sheet resistances at both sides and high transparency. The as-prepared A/R/A electrode is applicable for making a large-area transparent red QLED with an external quantum efficiency (EQE) of 11.42% and a transmittance of 72.5%. Furthermore, the A/R/A electrode can be used as intermediate connecting electrodes to stack three single-colored QLEDs, forming a novel structured R/G/B tri-stacked QLED, which enables emission not only of primary colors red, green, and blue independently with the maximum EQE of 8.22, 8.07, and 2.28%, respectively, but also arbitrary hybrid colors that cover a 107% National Television System Committee (NTSC) color triangle. Such large-area full-color-tunable tri-stacked QLED offers new perspectives for the next-generation solid-state scene lighting and full-color displays.

Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses.

DNA viruses typically eject genomic DNA into the nuclei of host cells after entry. It is unclear, however, how nuclear pathogen-derived DNA triggers innate immune responses. We report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) recognizes pathogenic DNA and amplifies interferon-α/ß (IFN-α/ß) production. Upon DNA virus infection, nuclear-localized hnRNPA2B1 senses viral DNA, homodimerizes, and is then demethylated at arginine-226 by the arginine demethylase JMJD6. This results in hnRNPA2B1 translocation to the cytoplasm where it activates the TANK-binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3) pathway, leading to IFN-α/ß production. Additionally, hnRNPA2B1 facilitates N 6-methyladenosine (m6A) modification and nucleocytoplasmic trafficking of CGAS, IFI16, and STING messenger RNAs. This, in turn, amplifies the activation of cytoplasmic TBK1-IRF3 mediated by these factors. Thus, hnRNPA2B1 plays important roles in initiating IFN-α/ß production and enhancing stimulator of interferon genes (STING)-dependent cytoplasmic antiviral signaling.

Transcription factor Fli-1 positively regulates lipopolysaccharide-induced interleukin-27 production in macrophages.

IL-27 is an important regulator of TLR4-activated innate immune. The mechanism by which IL-27 production is regulated in TLR4-activated innate immune remains largely unclear. Here we show that expression of transcription factor Fli-1 at protein level is increased in macrophages following LPS stimulation. Fli-1 overexpression increases LPS-activated IL-27 production in macrophages. Consistently, Fli-1 knockdown inhibits LPS-induced IL-27 production in macrophages. Chromatin immunoprecipitation (ChIP) assay reveals that Fli-1 binds the promoter of IL-27 p28 subunit. Further experiments manifest that Fli-1 binds the region between -250 and -150 bp upstream of the transcriptional start site of p28 gene and increases p28 gene promoter-controlled transcription. These results demonstrate that Fli-1 positively regulates IL-27 production in TLR4-activated immune response by promoting transcription of IL-27 p28 gene.

Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages.

NDR/LATS kinase family is highly conserved from yeast to human. It remains unknown whether the members of this family function in innate immune responses. Here we demonstrate that Stk38 negatively regulates TLR9-mediated immune responses in macrophages. Stk38 constitutively associates with ubiquitin E3 ligase Smurf1, and facilitates Smurf1-mediated MEKK2 ubiquitination and degradation. MEKK2 is required for CpG-induced ERK1/2 activation, TNF-α and IL-6 production but not required for LPS-induced TNF-α and IL-6 production. Accordingly, Stk38 deficiency increases CpG-induced ERK1/2 activation, TNF-α and IL-6 production without significantly affecting LPS-induced TNF-α and IL-6 production. Stk38-deficient mice produce more TNF-α and IL-6, and display increased lethality than control wild-type mice upon E. coli infection. Stk38-deficient mice are also more susceptible to CLP-induced sepsis than control mice. Thus, Stk38 is important in limiting inflammatory cytokine production and necessary for protecting host from inflammatory injury during infection, possibly by negatively regulating TLR9 signalling.

Ephedrine hydrochloride protects mice from LPS challenge by promoting IL-10 secretion and inhibiting proinflammatory cytokines.

Sepsis and its derivative endotoxic shock are still serious conditions with high mortality in the intensive care unit. The mechanisms that ensure the balance of proinflammatory cytokines and anti-inflammatory cytokine production are of particular importance. As an active α- and ß-adrenergic agonist, ephedrine hydrochloride (EH) is a widely used agent for cardiovascular diseases, especially boosting blood pressure. Here we demonstrate that EH increased Toll-like receptor 4 (TLR4)-mediated production of interleukin 10 (IL-10) through p38 MAPK activation. Simultaneously, EH negatively regulated the production of proinflammatory cytokines. Consistently, EH increased lipopolysaccharide (LPS)-induced serum IL-10 and inhibited tumor necrotic factor-α (TNFα) production in vivo. As a result, EH treatment protected mice from endotoxic shock by lethal LPS challenge. In brief, our data demonstrated that EH could contribute to immune homeostasis by balancing the production of proinflammatory cytokines and anti-inflammatory cytokine in TLR4 signaling. This study provides a potential usage of EH in autoimmunologic diseases or other severe inflammations.

The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway.

Intracellular nucleic acid sensors detect microbial RNA and DNA and trigger the production of type I interferon. However, the cytosolic nucleic acid-sensing system remains to be fully identified. Here we show that the cytosolic nucleic acid-binding protein LRRFIP1 contributed to the production of interferon-beta (IFN-beta) induced by vesicular stomatitis virus (VSV) and Listeria monocytogenes in macrophages. LRRFIP1 bound exogenous nucleic acids and increased the expression of IFN-beta induced by both double-stranded RNA and double-stranded DNA. LRRFIP1 interacted with beta-catenin and promoted the activation of beta-catenin, which increased IFN-beta expression by binding to the C-terminal domain of the transcription factor IRF3 and recruiting the acetyltransferase p300 to the IFN-beta enhanceosome via IRF3. Therefore, LRRFIP1 and its downstream partner beta-catenin constitute another coactivator pathway for IRF3-mediated production of type I interferon.