Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques.

SARS-CoV-2-induced hypercytokinemia and inflammation are critically associated with COVID-19 severity. Baricitinib, a clinically approved JAK1/JAK2 inhibitor, is currently being investigated in COVID-19 clinical trials. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages, and tissues was not reduced with baricitinib. Type I interferon (IFN) antiviral responses and SARS-CoV-2-specific T cell responses remained similar between the two groups. Animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of inflammatory cells, reduced NETosis activity, and more limited lung pathology. Importantly, baricitinib-treated animals had a rapid and remarkably potent suppression of lung macrophage production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for inflammation induced by SARS-CoV-2 infection.

Hydrogel delivery of purinergic enzymes improves cardiac ischemia/reperfusion injury.

RATIONALE: The innate immune response contributes to cardiac injury in myocardial ischemia/reperfusion (MI/R). Neutrophils are an important early part of the innate immune response to MI/R. Adenosine, an endogenous purine, is a known innate immune modulator and inhibitor of neutrophil activation. However, its delivery to the heart is limited by its short half-life (<30 s) and off-target side effects. CD39 and CD73 are anti-inflammatory homeostatic enzymes that can generate adenosine from phosphorylated adenosine substrate such as ATP released from injured tissue. OBJECTIVE: We hypothesize that hydrogel-delivered CD39 and CD73 target the local early innate immune response, reduce neutrophil activation, and preserve cardiac function in MI/R injury. METHODS AND RESULTS: We engineered a poly(ethylene) glycol (PEG) hydrogel loaded with the adenosine-generating enzymes CD39 and CD73. We incubated the hydrogels with neutrophils in vitro and showed a reduction in hydrogen peroxide production using Amplex Red. We demonstrated availability of substrate for the enzymes in the myocardium in MI/R by LC/MS, and tested release kinetics from the hydrogel. On echocardiography, global longitudinal strain (GLS) was preserved in MI/R hearts treated with the loaded hydrogel. Delivery of purinergic enzymes via this synthetic hydrogel resulted in lower innate immune infiltration into the myocardium post-MI/R, decreased markers of macrophage and neutrophil activation (NETosis), and decreased leukocyte-platelet complexes in circulation. CONCLUSIONS: In a rat model of MI/R injury, CD39 and CD73 delivered via a hydrogel preserve cardiac function by modulating the innate immune response.

A Hydrogel Strategy to Augment Tissue Adenosine to Improve Hindlimb Perfusion.

[Figure: see text].

Protective effects of bovine milk exosomes against oxidative stress in IEC-6 cells.

PURPOSE: Bovine milk exosomes, which are enriched with microRNAs (miRNAs) and proteins, regulate immune response and growth. In the present study, we aimed to assess the protective effects of bovine milk exosomes against oxidative stress of intestinal crypt epithelial cells (IEC-6). METHODS: Bovine milk exosomes were isolated and characterized. To assess the protective effects of exosomes, IEC-6 cells were pretreated with exosomes, followed by H2O2. Cell viability and levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPX), reactive oxidative species (ROS), and lactate dehydrogenase (LDH) were measured. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (Ho1) genes, and miR-146a, miR-155, and the HO-1 protein were also determined. RESULTS: The isolated bovine milk exosome were positive for CD63 and CD9 expression. The exosomes were approximately circular and had a diameter of about 67.23 nm. Pretreatment of IEC-6 cells with bovine milk exosomes enhanced cell viability; increased SOD and GPX activities; and reduced LDH, ROS, and MDA levels after H2O2 challenge. Further analysis showed that exosome pretreatment increased intracellular miR-146a and miR-155 levels. Exosome pretreatment inhibited the elevation of Nrf2 and Ho1 gene expression induced by H2O2, but promoted HO-1 protein expression. CONCLUSION: The results indicated that bovine milk exosomes exerted protective effects against oxidative stress in IEC-6 cells.

Solution Synthesis of Layered van der Waals (vdW) Ferromagnetic CrGeTe3 Nanosheets from a Non-vdW Cr2Te3Template.

CrGeTe3 has recently emerged as a new class of two-dimensional (2D) materials due to its intrinsic long-range ferromagnetic order. However, almost all the reported synthesis methods for CrGeTe3 nanosheets are based on the conventional mechanical exfoliation from single-crystalline CrGeTe3, which is prepared by the complicated self-flux technique. Here we report a solution-processed synthesis of CrGeTe3 nanosheets from a non-van der Waals (vdW) Cr2Te3 template. This structure evolution from non-vdW to vdW is originated from the substitution of Ge atoms on the Cr sites surrounded by fewer Te atoms in the Cr2Te3 lattice due to their smaller steric hindrance and lower energy barrier. These CrGeTe3 nanosheets present regular hexagonal structures with a diameter larger than 1 µm and excellent stability. They exhibit soft magnetic behavior with a Curie temperature lower than 67.5 K. This non-vdW to vdW synthesis strategy promotes the development of CrGeTe3 in ferromagnetism while providing an effective route to synthesize other 2D materials.

Effects of dietary nucleotide supplementation on growth in infants: a meta-analysis of randomized controlled trials.

PURPOSE: Dietary nucleotides are thought to be conditionally essential nutrients in infancy. However, studies have reported inconsistent findings regarding the association between nucleotide supplementation and infant physical growth. We conducted this meta-analysis to examine the efficacy of nucleotide supplementation of infant formula in promoting early infant growth. METHODS: Randomized controlled trials that evaluated the association between nucleotide supplementation and infant growth through June 2017 were included. Study quality was assessed using the Cochrane Collaboration's Risk of Bias tool. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using Q and I2 tests. RESULTS: Nucleotide supplementation significantly increased the rate of weight gain (SMD 0.26; 95% CI 0.06-0.47), but had no effect on weight (SMD - 0.16; 95% CI - 0.55-0.23), weight Z score (SMD, - 0.42; 95% CI - 1.64-0.81), length (SMD 0.01; 95% CI - 0.18-0.21) and length Z score (SMD 0.15; 95% CI - 0.10-0.40). Occipitofrontal head circumference (OFC) at 7-8 weeks (SMD 0.30; 95% CI 0.10-0.50) and the rate of OFC gain (SMD 0.34; 95% CI 0.09-0.58) were significantly improved with nucleotide supplementation, whereas, 16- and 20-week OFC values did not differ. CONCLUSIONS: Our meta-analysis indicated that nucleotide supplementation can increase the rate of weight gain, OFC and rate of OFC gain; however, we cannot conclude that it affects weight, weight Z score, length or length Z score. Large-scale randomized controlled trials of long-term nucleotide supplementation are needed to reach definitive conclusions.

RNase H2-Dependent Polymerase Chain Reaction and Elimination of Confounders in Sample Collection, Storage, and Analysis Strengthen Evidence That microRNAs in Bovine Milk Are Bioavailable in Humans.

Background: Evidence suggests that dietary microRNAs (miRs) are bioavailable and regulate gene expression across species boundaries. Concerns were raised that the detection of dietary miRs in plasma might have been due to sample contamination or lack of assay specificity. Objectives: The objectives of this study were to assess potential confounders of plasma miR analysis and to detect miRs from bovine milk in human plasma. Methods: Potential confounders of plasma miR analysis (circadian rhythm, sample collection and storage, calibration, and erythrocyte hemolysis) were assessed by quantitative reverse transcriptase polymerase chain reaction (PCR) by using blood from healthy adults (7 men, 6 women; aged 23-57 y). Bovine miRs were analyzed by RNase H2-dependent PCR (rhPCR) in plasma collected from a subcohort of 11 participants before and 6 h after consumption of 1.0 L of 1%-fat bovine milk. Results: The use of heparin tubes for blood collection resulted in a complete loss of miRs. Circadian variations did not affect the concentrations of 8 select miRs. Erythrocyte hemolysis caused artifacts for some miRs if plasma absorbance at 414 nm was >0.300. The stability of plasma miRs depended greatly on the matrix in which the miRs were stored and whether the plasma was frozen before analysis. Purified miR-16, miR-200c, and cel-miR-39 were stable for ≤24 h at room temperature, whereas losses equaled ≤80% if plasma was frozen, thawed, and stored at room temperature for as little as 4 h. rhPCR distinguished between bovine and human miRs with small variations in the nucleotide sequence; plasma concentrations of Bos taurus (bta)-miR-21-5p and bta-miR-30a-5p were >100% higher 6 h after milk consumption than before milk consumption. Conclusions: Confounders in plasma miR analysis include the use of heparin tubes, erythrocyte hemolysis, and storage of thawed plasma at room temperature. rhPCR is a useful tool to detect dietary miRs.

Cyclooxygenase-2 Induction by Amino Acid Deprivation Requires p38 Mitogen-Activated Protein Kinase in Human Glioma Cells.

Glioblastomas (GBMs) are malignant brain tumors that can outstrip nutrient supplies due to rapid growth. Cyclooxygenase-2 (COX-2) has been linked to GBMs and may contribute to their aggressive phenotypes. Amino acid starvation results in COX-2 mRNA and protein induction in multiple human glioma cell lines in a process requiring p38 mitogen-activated protein kinase (p38-MAPK) and the Sp1 transcription factor. Increased vascular endothelial growth factor expression results from starvation-dependent COX-2 induction. These data suggest that COX-2 induction with amino acid deprivation may be a part of the adaptation of glioma cells to these conditions, and potentially alter cellular response to anti-neoplastic therapy.

Two-Dimensional Hollow TiO2 Nanoplates with Enhanced Photocatalytic Activity.

Two-dimensional anatase TiO2 hollow nanoplates were firstly synthesized through a facile synthesis route by using α-Fe2 O3 nanoplates as removable templates. Two-dimensional hollow TiO2 nanoplates with different ratios of anatase and rutile phases were obtained by adjusting the calcining temperature. The average diameters were around 600 nm, and the shell thickness was approximately 30 nm. The photocatalytic performance of TiO2 was investigated by decomposing rhodamine B under simulated sunlight. Among the TiO2 samples, the anatase TiO2 hollow nanoplates manifested a significant enhancement in the photocatalytic performances. The excellent catalytic performance can be attributed to the unique structure of the two-dimensional anatase TiO2 hollow nanoplates, including a large surface area and increased dye-photocatalyst contact areas as well as more active sites for photodegradation.

Template-Free Synthesis of Nanorod-Assembled Hierarchical Zn1-x Mnx S Hollow Nanostructures with Enhanced Pseudocapacitive Properties.

Mixed-metal sulfide Zn1-x Mnx S nanorod-assembled hierarchical hollow spheres were synthesized by a template-free solvothermal process based on Ostwald ripening. In the reaction system, glycerol plays a key role in the formation of Znx Mn1-x S hierarchical hollow structures by a quasi-microemulsion-template mechanism. When applied as capacitor electrode material, the hierarchical Zn1-x Mnx S hollow spheres show excellent electrochemical performance. Specifically, Zn0.25 Mn0.75 S hollow spheres can deliver a high specific capacitance of 664 F g-1 at a current rate of 1 A g-1 , which is almost five times of that of MnS under the same conditions and higher than those of previously reported single Mn-based compounds.

Generalized Low-Temperature Fabrication of Scalable Multi-Type Two-Dimensional Nanosheets with a Green Soft Template.

Two-dimensional nanosheets with high specific surface areas and fascinating physical and chemical properties have attracted tremendous interests because of their promising potentials in both fundamental research and practical applications. However, the problem of developing a universal strategy with a facile and cost-effective synthesis process for multi-type ultrathin 2 D nanostructures remains unresolved. Herein, we report a generalized low-temperature fabrication of scalable multi-type 2 D nanosheets including metal hydroxides (such as Ni(OH)2, Co(OH)2, Cd(OH)2, and Mg(OH)2), metal oxides (such as ZnO and Mn3O4), and layered mixed transition-metal hydroxides (Ni-Co LDH, Ni-Fe LDH, Co-Fe LDH, and Ni-Co-Fe layered ternary hydroxides) through the rational employment of a green soft-template. The synthesized crystalline inorganic nanosheets possess confined thickness, resulting in ultrahigh surface atom ratios and chemically reactive facets. Upon evaluation as electrode materials for pseudocapacitors, the Ni-Co LDH nanosheets exhibit a high specific capacitance of 1087 F g(-1) at a current density of 1 A g(-1), and excellent stability, with 103% retention after 500 cycles. This strategy is facile and scalable for the production of high-quality ultrathin crystalline inorganic nanosheets, with the possibility of extension to the preparation of other complex nanosheets.

Ultrasonic Technology Improves Radial Artery Puncture and Cannulation in Intensive Care Unit (ICU) Shock Patients.

BACKGROUND This study observed the efficacy of ultrasonic technique with out-of-plane orientation and in-plane guidance in radial artery puncture and cannulation in intensive care unit (ICU) shock patients to elucidate the effect of this technique on the security of cannulation. MATERIAL AND METHODS A total of 88 ICU shock patients, randomized into a palpation (control) group and an ultrasound (experimental) group, received continuous intravenous sedation and analgesia. The palpation group patients underwent radial artery cannulation using the traditional palpation pulsation approach, and the ultrasound group patients underwent radial artery cannulation under out-of-plane orientation and in-plane guidance using an ultrasonic apparatus. Data were recorded and compared between the 2 groups. RESULTS (1) The success rate of the first puncture in the ultrasound group and the palpation group was 80% and 42%, respectively (P<0.05). (2) The cannulation duration in the ultrasound group and the palpation group was 8.77±6.33 s and 28.7±26.33 s, respectively (P<0.01). (3) Incidence of hematoma and staxis around stoma in the ultrasound group was 2.5% and 5%, respectively, which was significantly lower than that in the palpation group, which was 20% and 32.5%, respectively (P<0.05). (4) Time to achieve the early goal-directed therapy in the ultrasound group and the palpation group was 306.73±39.98 min and 356.75±40.97 min, respectively (P<0.01). CONCLUSIONS Compared with the traditional method, radial artery cannulation with out-of-plane orientation and in-plane guidance is a quick and secure cannulation method and is appropriate for use in clinics.

Ni/WS2/WC Composite Nanosheets as an Efficient Catalyst for Photoelectrochemical Hydrogen Peroxide Sensing and Hydrogen Evolution.

It is highly attractive to develop a photoelectrochemical (PEC) sensing platform based on a non-noble-metal nano array architecture. In this paper, a PEC hydrogen peroxide (H2O2) biosensor based on Ni/WS2/WC heterostructures was synthesized by a facile hydrothermal synthesis method and melamine carbonization process. The morphology, structural and composition and light absorption properties of the Ni/WS2/WC catalyst were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and UV-visible spectrophotometer. The average size of the Ni/WS2/WC nanosheets was about 200 nm. Additionally, the electrochemical properties toward H2O2 were studied using an electrochemical workstation. Benefiting from the Ni and C atoms, the optimized Ni/WS2/WC catalyst showed superior H2O2 sensing performance and a large photocurrent response. It was found that the detection sensitivity of the Ni/WS2/WC catalyst was 25.7 µA/cm2/mM, and the detection limit was 0.3 mmol/L in the linear range of 1-10 mM. Simultaneously, the synthesized Ni/WS2/WC electrode displayed excellent electrocatalytic properties in hydrogen evolution reaction (HER), with a relatively small overpotential of 126 mV at 10 mA/cm2 in 0.5 M H2SO4. This novel Ni/WS2/WC electrode may provide new insights into preparing other efficient hybrid photoelectrodes for PEC applications.

Alginate-Encapsulated Mesenchymal Stromal Cells Improve Hind Limb Ischemia in a Translational Swine Model.

BACKGROUND: Cellular therapies have been investigated to improve blood flow and prevent amputation in peripheral artery disease with limited efficacy in clinical trials. Alginate-encapsulated mesenchymal stromal cells (eMSCs) demonstrated improved retention and survival and promoted vascular generation in murine hind limb ischemia through their secretome, but large animal evaluation is necessary for human applicability. We sought to determine the efficacy of eMSCs for peripheral artery disease-induced limb ischemia through assessment in our durable swine hind limb ischemia model. METHODS AND RESULTS: Autologous bone marrow eMSCs or empty alginate capsules were intramuscularly injected 2 weeks post-hind limb ischemia establishment (N=4/group). Improvements were quantified for 4 weeks through walkway gait analysis, contrast angiography, blood pressures, fluorescent microsphere perfusion, and muscle morphology and histology. Capsules remained intact with mesenchymal stromal cells retained for 4 weeks. Adenosine-induced perfusion deficits and muscle atrophy in ischemic limbs were significantly improved by eMSCs versus empty capsules (mean±SD, 1.07±0.19 versus 0.41±0.16, P=0.002 for perfusion ratios and 2.79±0.12 versus 1.90±0.62 g/kg, P=0.029 for ischemic muscle mass). Force- and temporal-associated walkway parameters normalized (ratio, 0.63±0.35 at week 3 versus 1.02±0.19 preligation; P=0.17), and compensatory footfall patterning was diminished in eMSC-administered swine (12.58±8.46% versus 34.85±15.26%; P=0.043). Delivery of eMSCs was associated with trending benefits in collateralization, local neovascularization, and muscle fibrosis. Hypoxia-cultured porcine mesenchymal stromal cells secreted vascular endothelial growth factor and tissue inhibitor of metalloproteinase 2. CONCLUSIONS: This study demonstrates the promise of the mesenchymal stromal cell secretome at improving peripheral artery disease outcomes and the potential for this novel swine model to serve as a component of the preclinical pipeline for advanced therapies.

Bandgap regulation and doping modification of Ga2-x Cr x Se3 nanosheets.

Ga2Se3, an important direct wide bandgap semiconductor with excellent optoelectronic properties, has wide application potential in the fields of photodetectors, photoelectric sensors and solar cells. Herein, we describe the synthesis of Ga2Se3 semiconductor nanoparticles using a high temperature organic liquid phase method. Post-annealing treatment at different temperatures can not only improve the crystallinity of Ga2Se3 nanoparticles, but also regulate its optical band gap ranging from 2.50 to 2.80 eV. We further synthesized Ga2-x Cr x Se3 nanosheets by doping CrCl3·6H2O in the reaction process. By adjusting the Cr doping concentration, Ga2-x Cr x Se3 nanosheets can achieve a continuously tunable band gap in the range of 2.23 eV to 2.42 eV. Both Ga2-x Cr x Se3 nanosheets and Ga2Se3 nanoparticles exhibit excellent and stable photoelectric switching performance. With Cr doping, Ga2-x Cr x Se3 exhibits reduced Nyquist impedance and enhanced electrocatalytic activity, which is attributed to its ultrathin nanosheet morphology and large specific surface area. In addition, the diamagnetic behavior of pure Ga2Se3 changes to ferromagnetism with different Cr doping concentrations, and its magnetization is as high as 18.0 emu g-1 at x = 0.4. These findings demonstrate that Ga2-x Cr x Se3 nanosheets have significant potential in future optoelectronic and magnetoelectric applications.

Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production.

Both Th1 and Th17 cells have been implicated in the pathogenesis of inflammatory bowel disease and experimental colitis. However, the complex relationship between Th1 and Th17 cells and their relative contributions to the pathogenesis of inflammatory bowel disease have not been completely analyzed. Although it has been recently shown that Th17 cells can convert into Th1 cells, the underlying in vivo mechanisms and the role of Th1 cells converted from Th17 cells in the pathogenesis of colitis are still largely unknown. In this study, we report that Th17 cells from CBir1 TCR transgenic mice, which are specific for an immunodominant microbiota Ag, are more potent than Th1 cells in the induction of colitis, as Th17 cells induced severe colitis, whereas Th1 cells induced mild colitis when transferred into TCRßxδ(-/-) mice. High levels of IL-12 and IL-23 and substantial numbers of IFN-γ(+) Th1 cells emerged in the colons of Th17 cell recipients. Administration of anti-IL-17 mAb abrogated Th17 cell-induced colitis development, blocked colonic IL-12 and IL-23 production, and inhibited IFN-γ(+) Th1 cell induction. IL-17 promoted dendritic cell production of IL-12 and IL-23. Furthermore, conditioned media from colonic tissues of colitic Th17 cell recipients induced IFN-γ production by Th17 cells, which was inhibited by blockade of IL-12 and IL-23. Collectively, these data indicate that Th17 cells convert to Th1 cells through IL-17 induction of mucosal innate IL-12 and IL-23 production.

Sodium alginate microencapsulation of human mesenchymal stromal cells modulates paracrine signaling response and enhances efficacy for treatment of established osteoarthritis.

Mesenchymal stromal cells (MSCs) have shown promise as osteoarthritis (OA) treatments; however, effective translation has been limited by high variability and heterogeneity of MSCs, suboptimal delivery strategies, and poor understanding of critical quality and potency attributes. Furthermore, most pre-clinical studies of MSC therapeutics for OA have focused on delaying OA development and not on treating established OA, which brings added clinical relevance. Thus, the objective of the current study was to assess the effects of sodium alginate microencapsulation on human MSC (hMSC) secretion of immunomodulatory cytokines in an OA microenvironment and therapeutic efficacy in treating established OA. A Medial Meniscal Transection (MMT) pre-clinical model of OA was implemented. Three weeks post-surgery, after OA was established, intra-articular injections of encapsulated hMSCs or nonencapsulated hMSCs were administered. Six weeks post-surgery, microstructural changes in the knee joint were quantified using microCT. Encapsulated hMSCs reduced articular cartilage degeneration and subchondral bone remodeling. A multiplexed immunoassay panel was used to profile the in vitro secretome of hMSCs in response to IL-1ß. Nonencapsulated hMSCs showed an indiscriminate increase in all cytokines in response to IL-1ß while encapsulated hMSCs showed a targeted secretory response with increased expression of pro-inflammatory (IL-1ß, IL-6, IL-7, IL-8), anti-inflammatory (IL-1RA), and chemotactic (G-CSF, MDC, IP10) cytokines. These data show that sodium alginate microencapsulation can modulate hMSC paracrine signaling and enhance the therapeutic efficacy of the hMSCs in treating established OA. This cytokine profile provides a foundation for the identification of key factors affecting the overall potency of hMSC therapeutics for OA. STATEMENT OF SIGNIFICANCE: While there has been considerable interest in material based MSC encapsulation for treatment of OA, there are critical gaps in our translational understanding of these biomaterial-based technologies for OA. More specifically, previous studies have several important limitations: (1) they have been largely focused on preventing OA development, which limits their translational utility and (2) little prior work has been done to delineate potential routes/mechanisms by which material encapsulation alters MSC therapeutic action. In our manuscript, we aimed to fill these gaps in knowledge by testing the hypotheses that: (1) hMSC encapsulation can attenuate established disease progression, which is a more clinically relevant scenario and (2) hMSC encapsulation significantly changes the secreted paracrine factors from hMSCs.

TGF-beta promotes Th17 cell development through inhibition of SOCS3.

TGF-beta, together with IL-6 and IL-21, promotes Th17 cell development. IL-6 and IL-21 induce activation of STAT3, which is crucial for Th17 cell differentiation, as well as the expression of suppressor of cytokine signaling (SOCS)3, a major negative feedback regulator of STAT3-activating cytokines that negatively regulates Th17 cells. However, it is still largely unclear how TGF-beta regulates Th17 cell development and which TGF-beta signaling pathway is involved in Th17 cell development. In this report, we demonstrate that TGF-beta inhibits IL-6- and IL-21-induced SOCS3 expression, thus enhancing as well as prolonging STAT3 activation in naive CD4(+)CD25(-) T cells. TGF-beta inhibits IL-6-induced SOCS3 promoter activity in T cells. Also, SOCS3 small interfering RNA knockdown partially compensates for the action of TGF-beta on Th17 cell development. In mice with a dominant-negative form of TGF-beta receptor II and impaired TGF-beta signaling, IL-6-induced CD4(+) T cell expression of SOCS3 is higher whereas STAT3 activation is lower compared with wild-type B6 CD4(+) T cells. The addition of a TGF-beta receptor I kinase inhibitor that blocks Smad-dependent TGF-beta signaling greatly, but not completely, abrogates the effect of TGF-beta on Th17 cell differentiation. Our data indicate that inhibition of SOCS3 and, thus, enhancement of STAT3 activation is at least one of the mechanisms of TGF-beta promotion of Th17 cell development.

W2N/WC composite nanofibers as an efficient electrocatalyst for photoelectrochemical hydrogen evolution.

A tungsten-based electrocatalyst for hydrogen evolution reaction is vital for developing sustainable and clean energy sources. Herein, W2N/WC composite nanofibers were synthesized through electrospinning technology and simultaneous carbonization and N-doping at high temperature. The composite nanofiber has higher catalytic activity than any simple compound. It exhibits remarkable hydrogen evolution performance in acidic media with a low overpotential of -495 mV, at a current density of -50 mA cm-2. The excellent hydrogen evolution performance of the composite nanofiber could be attributed to the abundant active sites, strong light absorption and fast charge transfer. The method used in this work provides a new possibility for the fabrication of high-performance electrocatalysts rationally.

Bovine milk exosomes attenuate the alteration of purine metabolism and energy status in IEC-6 cells induced by hydrogen peroxide.

Evidence suggests that dietary depletion of bovine milk exosomes and their cargos causes a loss of circulating microRNAs and a series of health problems. The aim of the current study was to determine whether bovine milk exosomes affect purine nucleotide metabolism and energy metabolism in oxidatively stressed intestinal crypt epithelial cells (IEC-6). Cells were pretreated with exosomes, followed by H2O2 to induce oxidative stress. Reactive oxidative species (ROS) levels, purine nucleotides, purine metabolic key enzyme activities, cell energy status, and AMPK protein expression were analysed. Exosome pretreatment reduced ROS level and the activities of adenosine deaminase and xanthine oxidase induced by H2O2 in cells. Total adenine nucleotides and energy charge were increased with exosome pretreatment, while the AMPK phosphorylation level was downregulated. The results indicated that bovine milk exosomes could attenuate purine nucleotide catabolism and improve energy status in oxidatively stressed IEC-6 cells and exerted protective effects against oxidative stress.