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Flexible strain sensors have received increasing attention with the development of wearable electronic devices. However, integrating wide strain detection range, high sensitivity while maintaining relatively wide linear response range for such sensor system still remain a challenge. A fabric based flexible sensor (S-CNT/PDMS-F) was designed and fabricated, and the sensor can simultaneously achieve high sensitivity, wide linear response and strain detection range by combining self-segregated carbon nanotube (CNT)/polydimethylsiloxane (PDMS) composites and elastic medical bandage. It has been observed that this new sensor system can achieve a high sensitivity with a gauge factor of 615, a large linear responsive range of 0–100% strain (R2 ​= ​0.993) and a wide strain detection range of ∼ 200%, which is superior to almost all the reported CNT/PDMS flexible strain sensors. Compared to the similar fabric based strain sensor system deploying non self-segregated structure (C-CNT/PDMS-F), our S-CNT/PDMS-F demonstrates higher electrical conductivity and lower electrical percolation threshold and response time of 55 ​ms, as well as more stable and repeatable performance under cyclic loading conditions. The capability of the sensors in monitoring physiological activities and weight distribution has also been demonstrated.

The presence of oxygen vacancies and hydroxyl groups are both favorable for the methanol electrooxidation on Pt-based catalysts. Understanding and differentiating the enhancing mechanism between oxygen vacancies and hydroxyl groups for high activity of Pt catalysts in methanol oxidation reaction (MOR) is essential but still challenging. Herein, we developed two kinds of co-catalyst for Pt/CNTs, Pr6O11 is rich in oxygen vacancies but contains substantially no hydroxyl groups, while Pr(OH)3 possesses abundant hydroxyl groups without oxygen vacancies. After a sequence of designed experiments, it can be found that both oxygen vacancies and hydroxyl groups can improve the performance of Pt/CNTs electrocatalysts, but the enhancing mechanism and improving degree of oxygen vacancies and hydroxyl groups for the MOR are different. Since the oxygen vacancies are more conducive to increasing the intrinsic activity of the Pt catalyst, and the hydroxyl groups play a decisive role in dehydrogenation and deprotonation of methanol, the co-catalysts with both oxygen vacancies and hydroxyl groups mixed with Pt/CNTs have higher catalytic performance. Therefore, hydroxyl-rich Pr6O11·xH2O was prepared and used as MOR electrocatalyst after mixed with Pt/CNTs. Benefiting from the synergistic effect of oxygen vacancies and hydroxyl groups, the Pr6O11·xH2O/Pt/CNTs shows a high peak current density of 741 mA/mg, which is three times higher than that of Pt/CNTs. These new discoveries serve as a promising strategy for the rational design of MOR catalysts with low cost and high activity.

Cigarette smoke (CS)-caused ferroptosis was involved in the pathogenesis of COPD, but the role of ferroptosis in lung epithelial injury and inflammation is not clear. Rats were treated with CS or CUR and BEAS-2B cells were exposed to CS extract (CSE), ferrostatin-1 (Fer-1), deferoxamine (DFO), or CUR to detect reactive oxygen species (ROS) accumulation, lipid peroxidation, iron overload, and ferroptosis-related protein, which were the characteristic changes of ferroptosis. Compared with the control group, CSE-treated BEAS-2B cells had more cell death, higher cytotoxicity, and lower cell viability. The infiltration of inflammatory cell around the bronchi in the CS group of rats was more than that in the normal group. Meanwhile, CSE/CS elevated the levels of interleukin-6 and tumor necrosis factor-α in BEAS-2B cells and bronchoalveolar lavage fluid of rats. Besides, accumulative ROS and depleted glutathione was observed in vitro. In BEAS-2B cells and lung tissues of rats, CSE/CS increased malondialdehyde and iron; down-regulated solute carrier family 7, glutathione peroxidase 4, and ferritin heavy chain levels; and up-regulated transferrin receptor level. These changes were rescued by pretreatment of Fer-1 or DFO in vitro, and mitigated by CUR in vitro and in vivo. Collectively, this study reveals that ferroptosis was involved in lung epithelial cell injury and inflammation induced by CS, and CUR may alleviate CS-induced injury, inflammation, and ferroptosis of lung epithelial cell.

Transition-metal dichalcogenides (TMDs) in the 1T' phase are known high-performance catalysts for hydrogen evolution reaction (HER). Many experimental and some theoretical studies report that vacant sites play an important role in the HER on the basal plane. To provide benchmark calculations for comparison directly with future experiments on TMDs to obtain a validated detailed understanding that can be used to optimize the performance and material, we apply a recently developed grand canonical potential kinetics (GCP-K) formulation to predict the HER at vacant sites on the basal plane of the 1T' structure of WSe2 and WTe2. The accuracy of GCP-K has recently been validated for single-crystal nanoparticles. Using the GCP-K formulation, we find that the transition-state structures and the concentrations of the four intermediates (0-3 H at the selenium or tellurium vacancy) change continuously as a function of the applied potential. The onset potential (at 10 mA/cm-2) is -0.53 V for WSe2 (experiment is -0.51 V) and -0.51 V for WTe2 (experiment is -0.57 V). We find multistep reaction mechanisms for H2 evolution from Volmer-Volmer-Tafel (VVT) to Volmer-Heyrovsky (VH) depending on the applied potential, leading to an unusual non-monotonic change in current density with the applied potential. For example, our detailed understanding of the reaction mechanism suggests a strategy to improve the catalytic performance significantly by alternating the applied potential periodically.

The dissociation of a single water molecule on a ZnO(101̅0) surface has been investigated at the atomic level by low temperature STM manipulation combined with DFT calculations. The positive pulses applied from the tip inject electrons into the system and break the bonding between water and the ZnO surface, thus leading to the hopping of water molecules. Negative pulses inject holes wherein the lower energy ones split the free O-H bond pointing out of the surface whereas the higher energy ones split the second O-H bond that is directed to the surface through hydrogen bonding. Moreover, the yielded proton and hydroxyl species present distinctly charged status through different reaction pathways, manifesting their unique impacts on tailoring the surface properties of the metal oxide.

Experimental observations indicate that sulfate formation in aerosol is sensitive to the concentrations of nitric oxide (NO2). While it also widely exists as a dimer in the gas phase, previous studies focus on the monomer of NO2. In this study, we employ quantum chemical calculations and ab initio molecular dynamics simulations to investigate the reaction between the NO2 dimer (ONONO2) and sulfite (HSO3-/SO32-) in the gas phase and in an aerosol. Gas-phase reactions turn out to be barrierless. In an aerosol, the reaction between adsorbed ONONO2 and HSO3- to form ONSO3- follows a stepwise mechanism with proton and electron transfer processes. The reaction between ONONO2 and SO32- is more straightforward. Nevertheless, both reactions occur at a picosecond time scale. Decomposition of ONSO3- can form an NO molecule and SO3-, which gives a complementary pathway for sulfate formation in an aerosol. Hydrolysis of ONSO3- to form HNO and HSO4- is highly impossible in an aerosol, which calls for a revisit of the atmospheric N2O formation mechanism. The results presented in this study deepen our understanding of the interaction between NO2 and SO2 pollutants in the atmosphere.

Activation of hydrogen on oxide surface is of both practical and fundamental importance for broad fields of syngas-based chemical industries as well as clean energy utilizations. Previously we found ZnO can catalyze the heterolysis of H2, which only occurs at low temperatures (

Background Immune thrombocytopenia (ITP) is an autoimmune disease characterized as a low platelet count resulting from immune-mediated platelet destruction. Dimethyl fumarate (DMF) is widely applied for the treatment of several autoimmune diseases with immunosuppressive effect. However, whether it ameliorates ITP is unclear. This study aims to evaluate whether DMF has a preventive effect on ITP in mice. Methods DMF (30, 60 or 90 mg/kg body weight) was intraperitoneally injected into mice followed by injection of rat anti-mouse integrin GPIIb/CD41antibody to induce ITP. Peripheral blood was isolated to measure platelet count and spleen mononuclear cells were extracted to measure Th1 and Treg cells along with detecting the levels of IFN-γ, and TGFβ-1 in plasma and CD68 expression in spleen by immuohistochemical staining. Additionally, macrophage cell line RAW264.7 was cultured and treated with DMF followed by analysis of cell apoptosis and cycle, and the expression of FcγRI, FcγRIIb and FcγRIV mRNA. Results DMF significantly inhibited antiplatelet antibody-induced platelet destruction, decreased Th1 cells and the expression of T-bet and IFN-γ, upregulated Treg cells and the expression of Foxp3 and TGF-β1 as well as reduced CD68 expression in the spleen of ITP mouse. DMF-treated RAW264.7 cells showed S-phase arrest, increased apoptosis and downregulated expression of FcγRI and FcγRIV. Meanwhile, in vitro treatment of DMF also decreased the expression of cyclin D1 and E2, reduced Bcl-2 level and increased Bax expression and caspase-3 activation. Conclusions In conclusion, DMF prevents antibody-mediated platelet destruction in ITP mice possibly through promoting apoptosis, indicating that it might be used as a new approach for the treatment of ITP.

Spermine (SPM) is involved in response to abiotic stress in plants, but the potential role of SPM in regulating senescence has not been well documented. Objectives of this study were to examine the effect of changes in endogenous polyamines (PAs) by SPM application on improving heat tolerance of creeping bentgrass (Agrostis stolonifera) and explore the SPM-regulated senescence associated with alterations of water and oxidative balance, photosynthesis, and heat shock proteins under heat stress. The results showed that persistent high temperature caused severe oxidative damage and significant decreases in chlorophyll (Chl) content, photosynthetic efficiency, and leaf water content leading to premature senescence in creeping bentgrass, as reflected by a significant upregulation of transcriptions of senescence-associated genes (AsSAG39, Ash36, and Asl20). The improvement of endogenous spermidine (SPD) and SPM content induced by SPM application could significantly alleviate heat stress damage to creeping bentgrass through maintaining higher Chl content, net photosynthetic rate, photochemical efficiency, and performance index on absorption basis, promoting osmotic adjustment ability and antioxidant enzyme (superoxid dismutase, catalase, peroxidase, and ascorbate peroxidase) activities to enhance the scavenging capacity of reactive oxygen species, and upregulating transcriptions of heat shock protein (HSP) genes (HSP90-5, HSP90.1-b1, HSP82, HSP70, HSP26.7, HSP17.8, and HSP12) helping to maintain normal synthesis and functions of proteins under high temperature stress, thereby delaying heat-induced leaf senescence. These findings reveal an important role of PAs in regulating senescence in perennial plants exposed to a high temperature environment.

The NF-κB signaling pathway is an important downstream pathway of oncogenic Notch1 in T cell acute lymphoblastic leukemia (T-ALL) cells. However, the molecular mechanisms underlying the cascade activation of Notch1 in T-ALL cells are poorly understood. Here, we evaluated the role of CARMA1 in Notch1-induced NF-κB activation in T-ALL cells. CARMA1 was highly and specifically expressed in T-ALL cells and correlated with the prognosis of T-ALL patients. Interestingly, CARMA1 knockdown only inhibited the growth and proliferation of SIL-TAL1 fusion gene-negative T-ALL cells. In addition, CARMA1 knockdown arrested T-ALL cells at the G1 phase. Furthermore, CARMA1 knockdown significantly inhibited the proliferation of T-ALL cells in vivo and prolonged the survival of mice. Mechanistically, CARMA1 deficiency abolished Notch1-induced NF-κB transcriptional activation and significantly reduced expression levels of the NF-κB target genes c-Myc, Bcl-2, and CCR7. Taken together, these results of our study identify CARMA1 as one of the crucial mediators of Notch1-induced transformation of T-All cells, suggesting that CARMA1 is a promising therapeutic target for T-ALL due to its specific expression in lymphocytes.

Ionogels is a kind of hybrid materials composed of ionic liquids (ILs) and solid polymer network matrix, has been extensively investigated in the most recent decade. Due to the excellent mechanical properties and ionic conductivity, their promising applications in flexible stress and strain sensors have been proposed and explosively developed. In this review, we briefly summarize research progresses on ionogel based flexible stress and strain sensors (IFSSs) from five aspects, including material synthesis, device fabrication, working principles, characteristics and performances, and potential applications. Some outlooks and perspectives are also proposed at the end of review. The review is expected to provide reference and new insights into the research of IFSS.

Partial P-type metal ions doping(PPMID) is an alternative method to further enhance the gas sensing performance of N-type metal oxides(NMOs) in contrast to that of P-N metal oxides heterojunctions, but the influences of the introduction of PPMID on the grain size and oxygen vacancies of NMOs have been rarely investigated. Herein, a simple and effective route has been demonstrated to address this problem with Cu2+-doped SnO2 metastable solid solution nanofibers(CSMSSNs) as model and C2H2 as target molecule by combining electrospinning and calcination technique. It seems that the introduction of PPMID can also affect crystal structure and oxygen vacancies of NMOs, proven by combining X-ray diffraction(XRD) and X-ray photoelectron spectra(XPS). Thus, PPD, crystal structure and oxygen vacancies have been combined to clarify the enhanced sensing performance of Cu-doped SnO2 metastable solid solution nanofibers angainst C2H2.

Pulmonary hypertension (PH) is a life-threatening syndrome in neonates and has multiple and varied etiologies. However, few clinical studies have systematically evaluated the treatment regimens for this population. Phosphodiesterase (PDE) inhibitors, such as milrinone, tadalafil, dipyridamole, and sildenafil, are the most important regulators of vascular relaxation in the normal pulmonary vascular transition after birth, and these agents are widely used in the treatment of PH. Sildenafil, a representative PDE-5 inhibitor, has an important role as a single mode of therapy. However, the lack of evidence from pharmacokinetic and clinical trials has limited the emergence of standardized treatment regimens for sildenafil. There are also differing opinions among researchers regarding the best route of sildenafil administration. Due to the interindividual variability in the neonatal population, it is worth selecting the most suitable route of sildenafil administration according to the specific conditions of the neonatal population. These may be evaluated using the oxygenation index (OI), pulmonary artery pressure, mean blood pressure, and the serological index. This article reviews the clinical data on the use of sildenafil, focusing on the current and promising alternative routes of administration, which may affect subsequent clinical research in term and preterm neonates.

Brain-derived neurotrophic factor (BDNF), including mature BDNF (mBDNF) and precursor BDNF (proBDNF), plays a pivotal role in neuronal survival, synaptic plasticity and neurogenesis. However, the functional effect of the mBDNF/proBDNF ratio in haemorrhagic stroke remains unclear. ATP is a known mediator of BDNF production in neurons and glia. Therefore, we hypothesized that ATP could facilitate BDNF production, increase the mBDNF/proBDNF ratio and thereby alleviate cerebral haemorrhage-induced injury. In this experiment, a model of intracerebral haemorrhage (ICH) was produced by injecting 50 μL autologous blood into the right corpus striatum in healthy male rats. ATP was injected to promote BDNF production and increase the mBDNF/proBDNF ratio. After ATP pretreatment, P2X4R-shRNA and SB203580 were used to inhibit P2X4R and p38-MAPK, respectively. We provide direct evidence that ATP administration was successful in promoting mBDNF expression and increasing the mBDNF/proBDNF ratio after ICH injury. Additionally, ATP stimulation could significantly improve cerebral neurological function and alleviate neuronal damage. Furthermore, ATP injection was able to upregulate the expression of P2X4R and p-p38-MAPK. Moreover, both P2X4R-shRNA and SB203580 could effectively abolish the effect of ATP injection on the levels of P2X4R and p-p38-MAPK and the mBDNF/proBDNF ratio. Together, these findings show that ATP stimulation contributes to functional recovery after cerebral haemorrhage and that neuroprotection induced by ATP administration in ICH rats is accompanied by a strong increase in the mBDNF/proBDNF ratio. Here, we also show a significant role of P2X4R-p38-MAPK signalling in the ATP-induced increase in the mBDNF/proBDNF ratio in ICH.

Many enveloped animal viruses produce a variety of particle shapes, ranging from small spherical to long filamentous types. Characterization of how the shape of the virion affects infectivity has been difficult because the shape is only partially genetically encoded, and most pleomorphic virus structures have no selective advantage in vitro. Here, we apply virus fractionation using low-force sedimentation, as well as antibody neutralization coupled with RNAScope, single-particle membrane fusion experiments and stochastic simulations to evaluate the effects of differently shaped influenza A viruses and influenza viruses pseudotyped with Ebola glycoprotein on the infection of cells. Our results reveal that the shape of the virus particles determines the probability of both virus attachment and membrane fusion when viral glycoprotein activity is compromised. The larger contact interface between a cell and a larger particle offers a greater probability that several active glycoproteins are adjacent to each other and can cooperate to induce membrane merger. Particles with a length of tens of micrometres can fuse even when 95% of the glycoproteins are inactivated. We hypothesize that non-genetically encoded variable particle shapes enable pleomorphic viruses to overcome selective pressure and may enable adaptation to infection of cells by emerging viruses such as Ebola. Our results suggest that therapeutics targeting filamentous virus particles could overcome antiviral drug resistance and immune evasion in pleomorphic viruses.

Hanying Shen,1 Lingling Jiang,1 Linlin Nie,1 Xiaohui Fan,1 Yanqiu Xu,1 Lingling Yin,2 Linyan Xu,1,3 Jieyun Xia,2 Zhenyu Li,1– 3 Feng Zhu,1– 3 Kailin Xu1– 3 1Blood Disease Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, People’s Republic of China; 3Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu, 221000, People’s Republic of ChinaCorrespondence: Feng Zhu; Jieyun XiaDepartment of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99, West Huaihai Road, Quanshan District, Xuzhou, Jiangsu, 221002, People’s Republic of ChinaTel +86 516 8580 6985Fax +86 516 8580 1527Email frankfeng_2004@126.com; jieyunxia0315@163.comBackground: Originating from extranodal organs or tissues, primary extranodal lymphoma (PENL) acts in different primary sites with diverse clinical performances and PENL has remarkable geographical differences and lacks the relevant reports in each region.Patients and Methods: Two hundred and twenty PENL patients were enrolled, and the relevant clinical and laboratory indicators were analyzed. In addition, statistical methods were applied to analyze the effects of different factors on overall survival (OS) and progression-free survival (PFS) of patients.Results: The three most frequent primary sites of PENL are the digestive system, head and neck, and central nervous system. The patients were classified into groups based on their risk status, resulting in low-risk, medium-low-risk, medium-high-risk, and high-risk, and their respective 3-year OS values were calculated, which showed that 121 patients (55%) were in the low-risk group and 3-year OS was 85.2% (25.9% medium-low-risk, 3-year OS 66.6%; 15% medium-high-risk, 3-year OS 61.9%; 4.09% high risk, 3-year OS 45.7%). A multivariate analysis of the Cox regression demonstrated that serum beta 2-microglobulin (β2-MG) and lactate dehydrogenase (LDH) were independent prognostic factors for OS and PFS, respectively. Both the performance status and pathological subtypes were independent prognostic factors for OS and PFS.Conclusion: The correlated independent risk factors such as β2-MG, LDH, performance status, and pathological subtypes, were helpful for effectively determining the prognosis of PENL patients and guiding treatment.Keywords: beta 2-microglobulin, lactate dehydrogenase, performance status, pathological subtype, primary extranodal lymphoma, prognostic analysis

Electrospinning and calcination technique have been combined to fabricate N-doped carbon nanofibers(N-CNFs) by introducing amino grafted few-layered hexagonal boron nitride (amino@BN) into polyacrylonitrile(PAN) matrix as filler followed by carbonization. For the high N-doping level(10.7%, atomic fraction) with the final product, the as-prepared N-CNFs exhibit interesting surface wettability(superamphiphilicity in air and underwater oleophilicity). Moreover, compared with pristine PAN derived carbon nanofibers(marked as CNFs), N-CNFs exhibit higher graphic structure under fixed carbonizing temperature as well. Taking these advantages aforementioned, the as-prepared N-CNFs exhibit good specific capacitance(ca. 200.1 F/g) without activation treatment at the current density of 0.5 A/g in three-electrode configuration, which is about 149% that of CNFs(ca. 134 F/g). What’s more, our N-CNFs also display the unexpected capacity to demulsify diverse surfactant free oil-in-water emulsions by simple filtration in large scale with the high water flux ca.(23578±150) L·m−2·h−1

The inhibitors for shale gas can be divided into two categories, including inorganic inhibitors and organic inhibitors. The inorganic inhibitors usually include sodium chloride and potassium chloride, while the organic inhibitors include potassium sorbate, polyethylene glycol, polyetheramine, and diethylenetriamine. The inhibitive properties of these inhibitors for shale gas have been comprehensively compared in detail. The results show that the inhibitive effect of potassium chloride is much better than the other inorganic inhibitor sodium chloride, and polyetheramine exhibits the best inhibitive performance to other organic inhibitors. From the analysis of the inhibition mechanism, it can be found that both inorganic salt inhibitors and potassium sorbate, polyethylene glycol can effectively squeeze out the water molecules, adsorbed within clay layers, through ion exchange. As for polyetheramine and diethylenetriamine, the protonated ammonium ions can be adsorbed onto clay surface through electrostatic interaction to exchange hydrated sodium ions, thereby reduce the hydration repulsion of the clay.

Hydroxyl radicals (OH*) play a crucial role in atmospheric chemistry and biological processes. In this study, Born-Oppenheimer molecular dynamics simulations are performed under ambient conditions for a hydroxyl radical in a water nanodroplet containing 191 water molecules. Density functional theory calculations are performed at the BLYP-D3 level with some test calculations at the B3LYP-D3 level. In two 150 ps trajectories, either with OH* initially located in the interior region or at the surface of the water nanodroplet, the OH* radical ends up in the subsurface layer of the nanodroplet, which is different from the "surface preference" predicted from previous empirical force field simulations. The solvation structure of OH* contains fluctuating hydrogen bonds, as well as a two-center three-electron hemibond in some cases. The mobility of OH* is enhanced by hydrogen transfer, which has a free energy barrier of ∼4.6 kcal mol-1. The results presented in this study deepen our understanding of the structure and dynamics of OH* in aqueous solutions, especially around the air-water interface.

The original NaX zeolite is a promising material for removing organosulfur compounds from fuels. However, its utilization has been challenging owing to its limited adsorption capacity of refractory sulfur compounds. Maintaining the mesoporous structure exposed in hierarchical-NaX is crucial to obtain high desulfurization efficiency. Herein, we synthesize silver supported on hierarchical-X (AgX-CA(3.0)) with abundant mesoporous and adsorption sites to enhance the capacity of adsorption and diffusion of refractory sulfur compounds. The results demonstrate that the adsorbent can be recycled five times without any activity loss, and the framework of the X zeolite is preserved as well. This strategy that introduces mesopores on a hierarchical-NaX to remove organosulfur compounds in the fuel provides a new pathway to limit the emission of sulfur into the atmosphere.

Smart hydrogels with the capability of programmable shape memory have the potential to revolutionize medicine and soft robotics. Despite significant progress in designing hydrogels with ever more sophisticated shape memory behaviors, an ultimate goal yet to be fulfilled is programmable shape memory at subzero temperatures. Herein, an effective route has been demonstrated to address this challenge by constructing a transparent poly(vinyl alcohol)/carboxymethyl cellulose/functionalized boron nitride nanosheet glycerol-hydrogel. The resultant glycerol-hydrogel exhibited outstanding transparency (76% at 600 nm), dehydration resistance to high temperatures (60 °C) and anti-freezing performance at low temperatures (−70 °C). Furthermore, excellent programmable shape memory was demonstrated by shape memory and recovery cycles at −45 °C. Based on the shape memory capability of the glycerol-hydrogel, a through-line patterned actuator designed from the hierarchical kirigami structure could effectively carry cargoes for movement and control circuit switches by external stimuli at subzero temperatures. These outstanding programmable shape memory capabilities are expected to greatly extend the technical scope of hydrogel-based devices.

Despite advancement in the treatment of diffuse large B-cell lymphoma (DLBCL), many patients tend to relapse or become refractory after initial therapy. Therefore, it is essential to identify novel therapeutic targets and drugs, understand the molecular pathogenesis mechanism of DLBCL, and find ways to prevent and treat relapsed or refractory DLBCL. BIX-01294 is a small molecule compound that specifically inhibits EHMT2 activity. In this study, we demonstrate that BIX-01294 triggered the inhibition of human DLBCL cell proliferation, lead to G1 phase arrest via increasing P21 level and reducing cyclin E level. BIX-01294 also induced apoptosis via endogenous and exogenous apoptotic pathways. Moreover, BIX-01294 triggered autophagy and activated ER stress in human DLBCL cells. Furthermore, we showed that both key components of ER stress, ATF3, and ATF4, are required for BIX-01294-induced apoptosis and autophagy. Hence, this study provides new evidence that EHMT2 may be a new therapeutic target, and BIX-01294 may be a potential therapeutic drug for treating DLBCL.

Self-doping of oxygen vacancies (VO) states into TiO2-based nanotubes was an efficient way for improving photoelectrochemical (PEC) water splitting properties. Here we induced oxygen vacancies into Si-doped TiO2 (Ti–Si–O) nanotubes on Ti–Si alloy via a facile electrochemical surface reduction, and applied it for PEC water splitting. Systematic studies revealed that the self-doped oxygen vacancies not only promoted optical absorption of the doped nanotubes but also enhanced separation-transport processes of the photo-generated charge carriers, and thus resulted in improved PEC water splitting properties. The VO/Ti–Si–O co-doping system exhibited a higher photocurrent density of 1.63 mA/cm2 at 0 V vs. Ag/AgCl. Corresponding solar-to-hydrogen efficiency could reach 0.81%, which was about 5.4 times that of undoped TiO2. It's believed that elements doping and oxygen vacancies self-doping synergistic strategy employed in this work, may provide theoretical and practical significance for designing and fabricating efficient TiO2-based nanostructures photoanodes in PEC water splitting for boosted solar-to-hydrogen conversion.

Introduction: Somatic mutations in the calreticulin (CALR) gene occur in most myeloproliferative neoplasm (MPN) patients who lack Janus kinase 2 or thrombopoietin receptor (MPL) mutations, but the molecular pathogenesis of MPN with mutated CALR is unclear, which limited the further treatment for CALR gene mutant patients. Objectives: Previous studies showed that CALR mutations not only activated serine/threonine protein kinase (AKT) in primary mouse bone marrow cells but also mitogen-activated protein kinases (MAPKs) in MARIMO cells harboring a heterozygous 61-bp deletion in CALR exon 9, which were responsible for mutant CALR cell survival, respectively. Hence, we aimed to initially explore the mechanism of AKT activation and observe the synergistic inhibitory effect of combining AKT (MK-2206) and MAPK kinase (AZD 6244) inhibitors in MARIMO cells. Methods: We detected the expression of phosphorylated AKT in MARIMO cells treated with inhibitors for 24 or 48 h by western blotting and analyzed cell proliferation, cell cycle, and apoptosis by flow cytometry. We further examined the synergistic inhibitory effect of combining MK-2206 and AZD 6244 in MARIMO cells using the median effect principle of Chou and Talalay. Results: We found that the AKT was activated in MARIMO cells, and blocking its activity significantly inhibited MARIMO cell growth with downregulation of cyclin D and E, and accelerated cell apoptosis by decreasing Bcl-2 but increasing Bax and cleaved caspase-3 levels in a dose-dependent manner. Further analysis showed that AKT activation was dependent on mammalian target of rapamycin but not on the JAK signaling pathway in MARIMO cells, displaying that inhibition of JAK activity by ruxolitinib (RUX) did not decrease the AKT phosphorylation. Furthermore, the combination of MK-2206 and AZD 6244 produced a significantly synergistic inhibitory effect on MARIMO cells. Conclusions: AKT activation is a feature of MARIMO cells and co-targeting of AKT and MAPKs signaling pathways synergistically inhibits MARIMO cell growth.

As a new two-dimensional (2D) material with a tunable band gap and high charge carrier mobility, blue phosphorus (BlueP) has recently attracted great research interest. It is known that molecular b...

Background Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a key role in atherosclerosis. Long noncoding RNA ANRIL (lncRNA-ANRIL) is critical in vascular homeostasis. Metformin produces multiple beneficial effects in atherosclerosis. However, the underlying mechanisms need to be elucidated. Methods and results Metformin increased lncRNA-ANRIL expression and AMPK activity in cultured VSMCs, and inhibited the phenotypic switching of VSMCs to the synthetic phenotype induced by platelet-derived growth factor (PDGF). Overexpression of lncRNA-ANRIL inhibited phenotypic switching and reversed the reduction of AMPK activity in PDGF-treated VSMCs. While, gene knockdown of lncRNA-ANRIL by adenovirus or silence of AMPKγ through siRNA abolished AMPK activation induced by metformin in VSMCs. RNA-immunoprecipitation analysis indicated that the affinity of lncRNA-ANRIL to AMPKγ subunit was increased by metformin. In vivo, administration of metformin increased the levels of lncRNA-ANRIL, suppressed VSMC phenotypic switching, and prevented the development of atherosclerotic plaque in Apoe-/- mice fed with western diet. These protective effects of metformin were abolished by infecting Apoe-/- mice with adenovirus expressing lncRNA-ANRIL shRNA. The levels of AMPK phosphorylation, AMPK activity, and lncRNA-ANRIL expression were decreased in human atherosclerotic lesions. Conclusion Metformin activates AMPK to suppress the formation of atherosclerotic plaque through upregulation of lncRNA-ANRIL.

Lithium aluminosilicate (LAS), as a ceramic material with ultra-low thermal expansion, has a wide application in the field of precision instruments. But the effective integration of multiple thermal functions, including low thermal expansion and high thermal conductivity, into one material remains a huge challenge. To obtain LAS composites with high thermal conductivity, AlN was added as the reinforcing phase in LAS matrix, which can form a perfect heat conduction network and act as bridges for transferring heat. The thermal conductivity of the composite reaches 12.8 W/(m K) when the AlN content increased to 40 wt%, which is more than 5 times higher than that of bulk LAS. At the same time, the composite still maintains a low coefficient of thermal expansion of less than 3.2 × 10-6/K which matching that of silicon. Therefore, the proper combination between the components of composites is beneficial to the preparation of AlN/LAS composites with both low thermal expansion and excellent thermal conductivity.

Wearable conducting polymer-based NH3 sensors are highly desirable in real-time environmental monitoring and human health protection but still a challenge for their relatively long response/recovery time and moderate sensitivity at room temperature. Herein, we present an effective route to fulfill this challenge by constructing porous and neural network-like Au/polypyrrole (Au/PPy) electrospun nanofibrous film with hollow capsular units for NH3 sensor. Taking the unique architecture and synergistic effect between Au and PPy, our sensor exhibits not only super-rapid response/recovery time (both ∼7 s), faster than all reported sensors, but also stable and ultrahigh sensitivity (response reaches ∼2.3 for 1 ppm NH3) at room temperature even during repeated deformation. Furthermore, good selectivity has been also achieved. These outstanding properties make our sensor hold great potential in real-time NH3-related disease diagnosis and environmental monitoring at room temperature.

LncRNAs are one group of gene modulators functioning via several mechanisms in pathological and physiological conditions. We noted that LINC00472 expression level is elevated in atherosclerotic coronary tissues compared with normal coronary artery samples. LINC00472 is also upregulated in vascular smooth muscle cells (VSMCs) induced by TNF-α and PDGF-BB. Ectopic expression of LINC00472 induced VSMC migration and proliferation. The predicted binding sequence between miR-149-3p and LINC00472 was analyzed by LncBase Predicted. Overexpression of miR-149-3p decreases the luciferase activity of wild-type reporter plasmid, but not the mutant one. Ectopic expression of LINC00472 suppresses the expression of miR-149-3p in VSMCs. Furthermore, we demonstrated that miR-149-3p expression is decreased in atherosclerotic coronary tissues. MiR-149-3p was downregulated in VSMCs induced by TNF-α and PDGF-BB. Overexpression of LINC00472 induces VSMC migration and proliferation via regulating miR-149-3p. These data suggested that LINC00472 acts a critical role in the migration and proliferation of VSMCs partly via modulating miR-149-3p.

Protein phosphatase 1B (PPM1B), a member of metal‐dependent protein serine/threonine phosphatase family, is involved in the regulation of several signalling pathways. However, our understanding of its substrate interaction and physiological functions is still largely limited. There is no reported PPM1B inhibitor to date. In this study, we identified HN252, a p‐terphenyl derivative, as a potent PPM1B inhibitor (Ki = 0.52 ± 0.06 µM). HN252 binding to PPM1B displayed remarkable and specific inhibition of PPM1B in both in vitro and ex vivo. With the aid of this small molecular inhibitor, we identified 30 proteins’ serine/threonine phosphorylation as potential substrates of PPM1B, 5 of which were demonstrated by immunoprecipitation, including one known (CDK2) and 4 novel ones (AKT1, HSP90B, β‐catenin and BRCA1). Furthermore, GO and KEGG analysis of dramatically phosphorylated proteins by PPM1B inhibition indicated that PPM1B plays roles in the regulation of multiple cellular processes and signalling pathways, such as gene transcription, inflammatory regulation, ageing and tumorigenesis. Our work provides novel insights into further investigation of molecular mechanisms of PPM1B.

The adsorption of formic acid on a ZnO(1 0 −1 0) surface has been investigated with low temperature scanning tunneling microscopy (LT-STM) in combination with density-functional theory (DFT) calculations. Through high resolution STM images and in-situ exposure experiments we clearly identify that the formic acid dissociates upon adsorption even at liquid nitrogen temperature. DFT calculations reveal a preferential bidentate configuration of the formate species with the molecular plane orientating along the [1 −2 1 0] direction, while the yielded surface hydroxyl has two kinds of anchoring sites with similar energy. At elevated temperature, the adsorbed molecules were found to accumulate into short chains consisting exclusively of formate and hydroxyl and orienting along the [0 0 0 1] direction, which finally assemble into a (2 × 2) superstructure at half monolayer coverage. Careful examination of the defect structure of the saturation coverage film revealed the existence of monodentate adsorption states of formic acid but with very small probability. These results have clarified the inconsistent propositions from different spectroscopic studies. Moreover, the preferential ordering of the formate species may bring fresh insights into the understandings of the related surface reactions through formate intermediates.

Criegee intermediates and alcohols are important species in the atmosphere. In this study, we use quantum chemistry and Born-Oppenheimer molecular dynamics (BOMD) simulations to investigate the reaction between methanol/ethanol and Criegee intermediates (anti- or syn-CH3CHOO) in the gas phase and at the air-water interface. Reactions at the interface are found to be much faster than those in the gas phase. When water molecules are available, loop structures can be formed to facilitate the reaction. In addition, nonloop reaction pathways characterized by the formation of hydrated protons, although with a low possibility, are also identified at the air-water interface. Implications of our results on the fate of Criegee intermediates in the atmosphere are discussed, which deepen our understanding of Criegee intermediate-alcohol chemistry in humid environments.