Initial productive and latent HIV infections originate in vivo by infection of resting T cells.

Productively infected cells are generally thought to arise from HIV infection of activated CD4+ T cells, and these infected activated cells are thought to be a recurring source of latently infected cells when a portion of the population transitions to a resting state. We discovered and report here that productively and latently infected cells can instead originate from direct infection of resting CD4+ T cell populations in lymphoid tissues in Fiebig I, the earliest stage of detectable HIV infection. We found that direct infection of resting CD4+ T cells was correlated with the availability of susceptible target cells in lymphoid tissues largely restricted to resting CD4+ T cells in which expression of pTEFb enabled productive infection, and we documented persistence of HIV-producing resting T cells during antiretroviral therapy (ART). Thus, we provide evidence of a mechanism by which direct infection of resting T cells in lymphoid tissues to generate productively and latently infected cells creates a mechanism by which the productively infected cells can replenish both populations and maintain two sources of virus from which HIV infection can rebound, even if ART is instituted at the earliest stage of detectable infection.

Tough, recyclable and biocompatible carrageenan-modified polyvinyl alcohol ionic hydrogel with physical cross-linked for multimodal sensing.

Biocompatibility hydrogel conductors are considered as sustainable bio-electronic materials for the application of wearable sensors and implantable devices. However, they mostly face the limitations of mismatched mechanical properties with skin tissue and the difficulty of recycling. In this regard, here, a biocompatible, tough, reusable sensor based on physical crosslinked polyvinyl alcohol (PVA) ionic hydrogel modified with ι-carrageenan (ι-CG) helical network was reported. Through simulating the ion transport and network structure of biological systems, the ionic hydrogels with skin-like mechanical features exhibit large tensile strain of 640 %, robust fracture strength of 800 kPa, soft modulus and high fatigue resistance. Meanwhile, the ionic hydrogel-based sensors possess a high response to strain/pressure over a wide range and could be utilized for multimodal sensing of human activity signals. Benefit from biosafety and temperature reversibility of ι-CG and PVA endow hydrogels with not only biocompatibility, but also meaningfully recyclability. The as-prepared hydrogels could be freely reconstructed into new flexible electronics and safely integrated with the human skin. It could be anticipated that the physically cross-linked ionic hydrogel conductor could expand the options for next-generation bio-based sensors.

New insights into exogenous N-acyl-homoserine lactone manipulation in biological nitrogen removal system against ZnO nanoparticle shock.

The effects and mechanisms of three N-acyl-homoserine lactones (AHLs) (C4-HSL, C6-HSL, and C10-HSL) on responses of biological nitrogen removal (BNR) systems to zinc oxide nanoparticle (NP) shock were investigated. All three AHLs improved the NP-impaired ammonia oxidation rates by up to 50.0 % but inhibited the denitrification process via regulating nitrogen metabolism-related enzyme activities. C4-HSL accelerated the catalase activity by 13.2 %, while C6-HSL and C10-HSL promoted the superoxide dismutase activity by 26.6 % and 18.4 %, respectively, to reduce reactive oxygen species levels. Besides, the enhancements of tryptophan protein and humic acid levels in tightly-bound extracellular polymeric substance by AHLs were vital for NP toxicity attenuation. The metabonomic analysis demonstrated that all three AHLs up-regulated the levels of lipid- and antioxidation-related metabolites to advance the system's resistance to NP shock. The "dual character" of AHLs emphasized the concernment of legitimately employing AHLs to alleviate NP stress for BNR systems.

Insight into the key role of oxygen dopants over ball-milled boron nitride for efficient degradation of PFOS alternative 6:2 fluorotelomer sulfonic acid.

6:2 Fluorotelomer sulfonic acid (6:2 FTS) has been identified as an alternative to perfluorooctane sulfonic acid but has been proven to cause potential threats to humans and the environment. In this study, boron nitride (BN) photocatalysis was explored for 6:2 FTS degradation with 100% removal (kobs=1.8 h-1) and desulfurization rate of 100% as well as the defluorination rate of 57.3%. The superior performance of BN was primarily related to oxygen dopants defects (O-dopants). In addition, O-dopants contribution was confirmed by ball-milled BN (B-BN), which introduced more O-dopants and exhibited an increased 6:2 FTS degradation rate of 2.88 h-1. The decomposition of 6:2 FTS was attributed to holes (h+), hydroxyl radicals (•OH), and superoxide (•O2-) and proceeded via two pathways, the hydrogen abstraction from ethyl carbons by •OH and the C-S bond activation by h+ and •OH. To the best of our knowledge, this is the first study demonstrating that h+, •OH, and •O2- played significant roles in the heterogeneous photocatalytic degradation of 6:2 FTS.

Improved export coefficient model for identification of watershed environmental risk areas.

As a complex system under the joint action of man and nature, land use/cover directly or indirectly affects the environmental quality of the freshwater ecosystem. Studying the response of water environment quality to land use/cover change was significant to accurately simulate lake water quality and effectively enhance the management level. As an empirical model, the classical export coefficient model has been widely used and developed in agricultural non-point source pollution research because of its simple structure and convenient application. However, it assumes that the export coefficient of a particular type of land use/cover was constant, ignoring the influence of surface runoff and interception on the output intensity of pollutants in pollutant migration. This study improved the classical export coefficient model by adding factors such as precipitation, surface cover, and topography, evaluated the contribution of land use/cover to total nitrogen load into the lake in Dianchi Lake Basin, and applied the pollution assessment results to the identification of watershed environmental risk areas. The results showed that the improved export coefficient model could better simulate the relationship between land use/cover and total nitrogen load into Dianchi Lake from the basin. At the same time, spatial characteristics of the total nitrogen load contribution of the terrestrial could be represented. The high-risk areas in the basin were mainly cultivated land and construction areas with low vegetation coverage around lakes or downstream. The contribution per unit area to the TN load into the lake from areas with a high risk was 14.28 t/km2, which was 3.47 times that of medium-high-risk areas and 52.28 times that of the medium-risk area. Land use control measures in high-risk areas in the basin should be further strengthened, especially in the lakeside zone.

Metal Mesh and Narrow Band Gap Mn0.5Cd0.5S Photocatalyst Cooperation for Efficient Hydrogen Production.

A novel co-catalyst system under visible-light irradiation was constructed using high-purity metal and alloy mesh and a Mn0.5Cd0.5S photocatalyst with a narrow band gap (1.91 eV) prepared by hydrothermal synthesis. The hydrogen production rate of Mn0.5Cd0.5S changed from 2.21 to 6.63 mmol·(g·h)-1 with the amount of thioacetamide, which was used as the sulphur source. The introduction of Ag, Mo, Ni, Cu, and Cu-Ni alloy meshes efficiently improved the H2 production rate of the co-catalyst system, especially for the Ni mesh. The improvement can reach an approximately six times greater production, with the highest H2 production rate being 37.65 mmol·(g·h)-1. The results showed that some bulk non-noble metal meshes can act as good or better than some noble metal nanoparticles deposited on the main photocatalyst for H2 evolution due to the promotion of photoinduced electron transfer, increase in redox reaction sites, and prevention of the recombination of carriers.

Long-term exposure to nano-TiO2 interferes with microbial metabolism and electron behavior to influence wastewater nitrogen removal and associated N2O emission.

The extensive use of nano-TiO2 has caused concerns regarding their potential environmental risks. However, the stress responses and self-recovery potential of nitrogen removal and greenhouse gas N2O emissions after long-term nano-TiO2 exposure have seldom been addressed yet. This study explored the long-term effects of nano-TiO2 on biological nitrogen transformations in a sequencing batch reactor at four levels (1, 10, 25, and 50 mg/L), and the reactor's self-recovery potential was assessed. The results showed that nano-TiO2 exhibited a dose-dependent inhibitory effect on the removal efficiencies of ammonia nitrogen and total nitrogen, whereas N2O emissions unexpectedly increased. The promoted N2O emissions were probably due to the inhibition of denitrification processes, including the reduction of the denitrifying-related N2O reductase activity and the abundance of the denitrifying bacteria Flavobacterium. The inhibition of carbon source metabolism, the inefficient electron transfer efficiency, and the electronic competition between the denitrifying enzymes would be in charge of the deterioration of denitrification performance. After the withdrawal of nano-TiO2 from the influent, the nitrogen transformation efficiencies and the N2O emissions of activated sludge recovered entirely within 30 days, possibly attributed to the insensitive bacteria survival and the microbial community diversity. Overall, this study will promote the current understanding of the stress responses and the self-recovery potential of BNR systems to nanoparticle exposure.

Detecting Sources of Immune Activation and Viral Rebound in HIV Infection.

Anti-retroviral therapy (ART) generally suppresses HIV replication to undetectable levels in peripheral blood, but immune activation associated with increased morbidity and mortality is sustained during ART, and infection rebounds when treatment is interrupted. To identify drivers of immune activation and potential sources of viral rebound, we modified RNAscope in situ hybridization to visualize HIV-producing cells as a standard against which to compare the following assays of potential sources of immune activation and virus rebound following treatment interruption: (i) envelope detection by induced transcription-based sequencing (EDITS) assay; (ii) HIV-Flow; (iii) Flow-FISH assays that can scan tissues and cell suspensions to detect rare cells expressing env mRNA, gag mRNA/Gag protein and p24; and (iv) an ultrasensitive immunoassay that detects p24 in cell/tissue lysates at subfemtomolar levels. We show that the sensitivities of these assays are sufficient to detect one rare HIV-producing/env mRNA+/p24+ cell in one million uninfected cells. These high-throughput technologies provide contemporary tools to detect and characterize rare cells producing virus and viral antigens as potential sources of immune activation and viral rebound. IMPORTANCE Anti-retroviral therapy (ART) has greatly improved the quality and length of life for people living with HIV, but immune activation does not normalize during ART, and persistent immune activation has been linked to increased morbidity and mortality. We report a comparison of assays of two potential sources of immune activation during ART: rare cells producing HIV and the virus' major viral protein, p24, benchmarked on a cell model of active and latent infections and a method to visualize HIV-producing cells. We show that assays of HIV envelope mRNA (EDITS assay), gag mRNA, and p24 (Flow-FISH, HIV-Flow. and ultrasensitive p24 immunoassay) detect HIV-producing cells and p24 at sensitivities of one infected cell in a million uninfected cells, thereby providing validated tools to explore sources of immune activation during ART in the lymphoid and other tissue reservoirs.

Estimating the pollutant loss rate based on the concentration process and landscape unit interactions: a case study of the Dianchi Lake Basin, Yunnan Province, China.

The landscape analysis model establishes a quantitative relationship between landscape patterns and pollution processes. The spatial heterogeneity within and between landscapes affects the pollutant transmission process and originates from the superposition effect of terrestrial geographical and morphological characteristics. This study aimed to develop a new method to estimate the pollutant loss rate. From the perspective of the flow process of pollutants entering a water body, the interaction between each landscape unit and adjacent unit during pollutant migration was simulated along the pollutant migration flow path. The role of pollutants affected by external forces in the process of migration could be divided into "promoting" and "hindering." Four indices were proposed to simulate the pollutant loads entering the lake. The linear coefficients between the load of the pollutants chemical oxygen demand (CODCr), ammoniacal nitrogen (NH3-N), total nitrogen (TN), and total phosphorus (TP) entering the lake and the pollutant load emission weighted by the upstream and downstream confluence ratio index were 0.930, 0.835, 0.925, and 0.795, respectively, and the non-linear variance explanation coefficients were 87.70%, 87.50%, 87.60%, and 84.70%, respectively. When the surface resistance was integrated into the index as a parameter, the linear and nonlinear correlation coefficients were significantly improved. The linear coefficients were 0.952, 0.897, 0.919, and 0.939, respectively, and the non-linear variance explanations were 99.00%, 97.30%, 95.10%, and 97.30%, respectively. The spatial distribution of landscape surface resistance reflects the spatial movement trend of pollutants from different sources. The indices characterizing the promoting and hindering effects could be integrated to calculate the loss rate of pollutant load entering the lake from landscape units at different locations in the basin space.

The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis.

Previous studies show that 3ß-hydroxysterol-Δ24 reductase (DHCR24) has a remarked decline in the brain of AD patients. In brain cholesterol synthetic metabolism, DHCR24 is known as the heavily key synthetase in cholesterol synthesis. Moreover, mutations of DHCR24 gene result in inhibition of the enzymatic activity of DHCR24, causing brain cholesterol deficiency and desmosterol accumulation. Furthermore, in vitro studies also demonstrated that DHCR24 knockdown lead to the inhibition of cholesterol synthesis, and the decrease of plasma membrane cholesterol and intracellular cholesterol level. Obviously, DHCR24 could play a crucial role in maintaining cholesterol homeostasis via the control of cholesterol synthesis. Over the past two decades, accumulating data suggests that DHCR24 activity is downregulated by major risk factors for AD, suggesting a potential link between DHCR24 downregulation and AD pathogenesis. Thus, the brain cholesterol loss seems to be induced by the major risk factors for AD, suggesting a possible causative link between brain cholesterol loss and AD. According to previous data and our study, we further found that the reduced cholesterol level in plasma membrane and intracellular compartments by the deficiency of DHCR24 activity obviously was involved in ß-amyloid generation, tau hyperphosphorylation, apoptosis. Importantly, increasing evidences reveal that the brain cholesterol loss and lipid raft disorganization are obviously linked to neuropathological impairments which are associated with AD pathogenesis. Therefore, based on previous data and research on DHCR24, we suppose that the brain cholesterol deficiency/loss might be involved in the pathogenesis of AD.

Nucleotide-Tackified Organohydrogel Electrolyte for Environmentally Self-Adaptive Flexible Supercapacitor with Robust Electrolyte/Electrode Interface.

Hydrogel electrolytes have attracted enormous attention in flexible and safe supercapacitors. However, the interfacial contact problem between hydrogel electrolyte and electrodes, and the environmental instability are the key factors restricting the development of hydrogel-based supercapacitors. Here, a nucleotide-tackified adhesive organohydrogel electrolyte is successfully constructed and exhibits freezing resistance and water-holding ability based on the water/glycerol binary solvent system. Adenosine monophosphate enables the organohydrogels to possess outstanding adhesion and mechanical robustness. The robust adhesion can ensure close contact between the organohydrogel electrolyte and electrodes for constructing an all-in-one supercapacitor with low interfacial contact resistance. Impressively, the integrated organohydrogel-based supercapacitors display an areal specific capacitance of 163.6 mF cm-2 . Besides, the supercapacitors feature prominent environmental stability with capacitance retention of 90.6% after 5000 charging/discharging cycles at -20 °C. Furthermore, based on the strong interfacial adhesion, the supercapacitors present excellent electrochemical stability without delamination/displacement between electrolyte and electrodes even under severe deformations such as bending and twisting. It is anticipated that this work will provide an encouraging way for developing flexible energy storage devices with electrochemical stability and environmental adaptability.

Hierarchical colloidosomes self-assembled from block copolymer micelles via emulsion interfacial confinement.

Hierarchical self-assembly of polymeric building blocks into high-level colloidosomes is desirable to not only design novel nanostructures but also fabricate the complex artificial materials across many length scales with multifunctionality. Although great progress has been made in the designing the hierarchical colloidosomes, the fabrication of polymeric colloidosomes self-assembled from block copolymer (BCP) colloidal nanoparticles still remains challenge. Here, we report the fabrication of the hierarchical polymeric colloidosomes with typical hollow internal structures self-assembled from the polystyrene-block-poly (2-vinyl pyridine) (PS-b-P2VP) BCP spherical micelles through the emulsion interfacial confinement, which is constructed through the water-in-1-butanol emulsion system. Moreover, the hierarchical colloidosomes can disassemble into the original uniform spherical micelles under the acid aqueous solution, indicating that the colloidosomes possess good pH stimuli-responsibility. Finally, the stability of the colloidosomes can be greatly improved by cross-linking the P2VP corona of original spherical micelles, offering the effective templates for construction of the multifunctional materials. This finding provides a simple yet effective method for the fabrication of the hierarchical colloidosomes from the BCP building blocks.

Chitosan-driven skin-attachable hydrogel sensors toward human motion and physiological signal monitoring.

Recently, flexible and wearable sensors assembled from conductive hydrogels have attracted widespread attention. However, it is still a great challenge to make hydrogels with sufficient mechanical properties, self-adhesiveness and strain sensitivity. Here, a strong, tough, and self-adhesive hydrogel is successfully fabricated by a one-pot method, which introducing chitosan and 2-acrylamido-2-methylpropane sulfonic acid into the polyacrylamide network. The hydrogels exhibited adhesion (the peel strength reaches 798 N/m), mechanical property (The breaking strength and strain can reach 111 kPa and 2839%) and electrical conductivity (conductivity up to 0.0848 S/cm), which are suitable for wearable epidermal sensors. Besides, the hydrogels also possessed transparency. Therefore, this work would provide a novel insight on the fabrication of multi-functional self-adhesive hydrogel sensors.

DHCR24 Knock-Down Induced Tau Hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, Ser396 Epitopes and Inhibition of Autophagy by Overactivation of GSK3ß/mTOR Signaling.

Accumulating evidences supported that knock-down of DHCR24 is linked to the pathological risk factors of AD, suggesting a potential role of DHCR24 in AD pathogenesis. However, the molecular mechanism link between DHCR24 and tauopathy remains unknown. Here, in order to elucidate the relationship between DHCR24 and tauopathy, we will focus on the effect of DHCR24 on the tau hyperphosphorylation at some toxic sites. In present study, we found that DHCR24 knock-down significantly lead to the hyperphosphorylation of tau sites at Thr181, Ser199, Thr231, Ser262, Ser396. Moreover, DHCR24 knock-down also increase the accumulation of p62 protein, simultaneously decreased the ratio of LC3-II/LC3-I and the number of autophagosome compared to the control groups, suggesting the inhibition of autophagy activity. In contrast, DHCR24 knock-in obviously abolished the effect of DHCR24 knock-down on tau hyperphosphrylation and autophagy. In addition, to elucidate the association between DHCR24 and tauopathy, we further showed that the level of plasma membrane cholesterol, lipid raft-anchored protein caveolin-1, and concomitantly total I class PI3-K (p110α), phospho-Akt (Thr308 and Ser473) were significantly decreased, resulting in the disruption of lipid raft/caveola and inhibition of PI3-K/Akt signaling in silencing DHCR24 SH-SY5Y cells compared to control groups. At the same time, DHCR24 knock-down simultaneously decreased the level of phosphorylated GSK3ß at Ser9 (inactive form) and increased the level of phosphorylated mTOR at Ser2448 (active form), leading to overactivation of GSK3ß and mTOR signaling. On the contrary, DHCR24 knock-in largely increased the level of membrane cholesterol and caveolin-1, suggesting the enhancement of lipid raft/caveola. And synchronously DHCR24 knock-in also abolished the effect of DHCR24 knock-down on the inhibition of PI3-K/Akt signaling as well as the overactivation of GSK3ß and mTOR signaling. Collectively, our data strongly supported DHCR24 knock-down lead to tau hyperphosphorylation and the inhibition of autophagy by a lipid raft-dependent PI3-K/Akt-mediated GSK3ß and mTOR signaling. Taking together, our results firstly demonstrated that the decrease of plasma membrane cholesterol mediated by DHCR24 deficiency might contribute to the tauopathy in AD and other tauopathies.

Transcriptomic Analysis of High- and Low-Virulence Bovine Pasteurella multocida in vitro and in vivo.

Pasteurella multocida is a gram-negative opportunistic pathogen that causes various diseases in poultry, livestock, and humans, resulting in huge economic losses. Pasteurella multocida serotype A CQ6 (PmCQ6) is a naturally occurring attenuated strain, while P. multocida serotype A strain CQ2 (PmCQ2) is a highly virulent strain isolated from calves. Compared with PmCQ2, it was found that bacterial loads and tissue lesions of lung tissue significantly decreased and survival rates significantly improved in mice infected with PmCQ6 by intranasal infection. However, comparative genome analysis showed that the similarity between the two strains is more than 99%. To further explore the virulence difference mechanism of PmCQ2 and PmCQ6, transcriptome sequencing analysis of the two strains was performed. The RNA sequencing analysis of PmCQ2 and PmCQ6 showed a large number of virulence-related differentially expressed genes (DEGs) in vivo and in vitro. Among them, 38 virulence-related DGEs were significantly up-regulated due to PmCQ6 infection, while the number of PmCQ2 infection was 46, much more than PmCQ6. In addition, 18 virulence-related DEGs (capsule, iron utilization, lipopolysaccharide, and outer membrane protein-related genes) were up-regulated in PmCQ2 infection compared to PmCQ6 infection, exhibiting a higher intensive expression level in vivo. Our findings indicate that these virulence-related DEGs (especially capsule) might be responsible for the virulence of PmCQ2 and PmCQ6, providing prospective candidates for further studies on pathogenesis.

Heavy metal contamination in surface sediments from lakes and their surrounding topsoils of China.

Due to rapid urbanization, industrialization, agricultural development, and mining activities, soil heavy metal pollution has become a severe issue in China. To explore the regional heavy metal ecological risk of lake sediment and surrounding topsoil, we analyzed 237 lakes, with 1797 lake sediment sampling points and 1164 surrounding topsoil sampling points. Lower mean concentrations were detected for most heavy metals in soils than sediment (except for Hg). Cd and Hg in sediments and soils showed a more significant variation, with the coefficient of variation exceeding 110%. Linear regressions and Pearson's correlation analyses demonstrated that sediments and soils exhibited significant positive correlations. The principal heavy metals exceeding the Agricultural Soil Control Standard (ASCS) in sediments and soils were As and Cd, respectively. The Yunnan-Guizhou Plateau Lake Region (YGPLR) was the most seriously affected, exceeding the ASCS for Cd. The lakes with the most severe pollution were located in YGPLR impacted by the high background concentration of heavy metals in soil and mineral development activities. The Eastern Plain Lake Region, the Southeast Lake Region, and the Northeast Plain and Mountain Lake Region showed a clear anthropogenic impact. Lakes in the Inner Mongolia-Xinjiang Lake Region and the Tibetan Plateau Lake Region were estimated to have relatively low ecological risks due to their sparse population and slight environmental disturbance. The impact of geochemical factors on the ecological risk of heavy metals in lake sediments is more substantial than that of human activities at the regional scale.

Lead removal from water using organic acrylic amine fiber (AAF) and inorganic-organic P-AAF, fixed bed filtration and surface-induced precipitation.

Granular porous sorbents were normally used for heavy metals removal from water. To search for the new commercial sorbent and treatment strategy, an organic acrylic amine fiber (AAF) and phosphorus loading inorganic-organic AAF (P-AAF) were prepared and used for lead (Pb) removal from water. A new strategy of inorganic-organic coupling technology was proposed for Pb removal, based on the hypothesis of surface-induced precipitation mechanism. The AAF showed a Pb adsorption capacity of 417 mg/g from the Langmuir fitting, while the column filtration technology was further applied to measure the adsorption edge and applications. Effects of different initial Pb concentrations, hydraulic retention time, and co-existing P were considered in the filtration experiments. The presence of 0.8 mg/L P in water significantly improved the Pb breakthrough point from 15,000 to 41,000 bed volumes of water spiked with 85 µg/L Pb, while the P-AAF fixed bed showed better removal of Pb than AAF SEM/EDX and XRD spectra were employed for determining the surface functional groups and the formation of surface-induced precipitation of pyromorphite (Pb5(PO4)3OH) on AAF. This study verified the application of AAF sorbent for Pb removal and the enhanced effect of coating P on AAF, thus improved our fundamental understanding and application of the surface chemistry process of Pb with P.

Pasteurella multocida Pm0442 Affects Virulence Gene Expression and Targets TLR2 to Induce Inflammatory Responses.

Pasteurella multocida is an important pathogenic bacterium of domestic animals. However, the mechanisms of infection are still poorly understood. Here, we found that Pm0442 was dramatically up-regulated in infected mice among 67 predicted lipoproteins of P. multocida serotype A CQ2 strain (PmCQ2). To explore the role of Pm0442 in virulence and the potential of the mutant as a vaccine, Pm0442 mutant of PmCQ2 was successfully constructed. Then, the virulence characteristics, immune/inflammatory responses, and the survival rates of challenged mice were determined. As a result, it was found that the Pm0442 deletion of PmCQ2 significantly decreased bacterial loads and inflammatory responses of lung tissue in mice, resulting in improved survival. Mechanically, Pm0442 affects PmCQ2 capsular and lipopolysaccharide (LPS) synthesis and iron utilization-related genes expression affecting adhesion and phagocytosis. Furthermore, PM0442 bound directly to Toll-like receptor 2 (TLR2) to mediate the secretion of pro-inflammatory cytokine (IL-1ß, TNF-α, IL-6, and IL-12p40) in macrophages via activation of the NF-κB, ERK1/2 and p38 signaling pathways. Notably, PmCQ2Δ0442 could provide 70-80% protection to mice challenged with 3.08 × 107 CFU of PmCQ2. Our findings demonstrate that Pm0442 is a virulence-related gene of PmCQ2, which provides new guidance for the prevention and control of Pasteurellosis.

Bio-inspired adhesive and self-healing hydrogels as flexible strain sensors for monitoring human activities.

Nowadays, hydrogels have been intensively explored due to their promising potential application in bioelectronics. However, the lack of self-healing performance limits the lifespan and stability of materials. Here, a stretchable, self-healing and conductive hydrogel is prepared via physical crosslinking including hydrogen bonding, hydrophobic association and complexation effect, endowing the hydrogels with stretchability of 1150%, tensile strength of 112 kPa, flexibility and puncture resistance. Besides, the hydrogels possess extraordinary conductive property with a conductivity of 0.0720 S cm-1 and exhibit stable changes of resistance signals with a gauge factor of 2.506. Meanwhile, the hydrogels also exhibit adhesive performance due to the presence of catechol groups, and the maximum peeling adhesive strength could reach 23 N m-1. It is envisioned that the highly stretchable, self-healable, adhesive and conductive hydrogels would widen the application as the flexible strain sensors for soft robots, artificial limb, movement-monitoring equipment.

Anti-inflammatory effects of doxepin hydrochloride against LPS-induced C6-glioma cell inflammatory reaction by PI3K-mediated Akt signaling.

Recent studies have shown that tricyclic antidepressants (TCAs) may have anti-inflammatory and anticonvulsant effects in addition to its antidepressant effects. So far, the nonantidepressant effects of TCAs and their molecular pharmacological mechanisms remain completely unclear. Chronic inflammation in the brain parenchyma may be related to the pathogenesis and progression of various neurodegenerative diseases. As a common antidepressant and anti-insomnia drug, doxepin also may be a potential anti-inflammatory and anticonvulsant drug, so the study on the anti-inflammatory protective effect of doxepin and its molecular mechanism has become a very important issue in pharmacology and clinical medicine. Further elucidating the anti-inflammatory and neuroprotective effects of doxepin and its molecular mechanism may provide the important theoretical and clinical basis for the prevention and treatment of neurodegenerative disease. This study was designed to understand the glio-protective mechanism of doxepin against the inflammatory damage induced by lipopolysaccharide (LPS) exposure in C6-glioma cells. We found the treatment of C6-glioma cells with LPS results in deleterious effects, including the augmentation of inflammatory cytokine levels (tumor necrosis factor-α, interleukin-1ß), and suppresses the Akt phosphorylation. Furthermore, our outcomes demonstrated that doxepin was able to suppress these effects induced by LPS, through activation of the phosphatidylinositol-3-kinase-mediated protein kinase B (Akt) pathway. To sum up, these results highlight the potential role of doxepin against neuroinflammatory-related disease in the brain.