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Childhood sexual abuse (CSA) is a common form of childhood maltreatment. Several studies have shown that CSA adversely affects the physical and mental health. Numerous studies have evaluated the prevalence of CSA among females using various instruments. In this meta-analysis, we estimated the rate of CSA among women using the short form of the Childhood Trauma Questionnaire for the first time. Four databases (PsycINFO, PubMed, Cochrane Library, and Embase) were systematically searched for studies published as of April 2, 2018. Forty-eight articles (53 groups of samples) covering 22,224 individuals, including women, from 16 countries were selected. Using the random-effects model, the pooled overall rate of CSA was 24% (95% confidence interval [21%, 27%]). On subgroup analyses, the rate of female CSA in people with mental illness was higher than that in the general group; this result showed variability among different geographical regions. [ABSTRACT FROM AUTHOR]

The pyruvate kinase M2 isoform (PKM2) is preferentially expressed in cancer cells to regulate anabolic metabolism. Although PKM2 was recently reported to regulate lipid homeostasis, the molecular mechanism remains unclear. Herein, we discovered an ER transmembrane protein 33 (TMEM33) as a downstream effector of PKM2 that regulates activation of SREBPs and lipid metabolism. Loss of PKM2 leads to up‐regulation of TMEM33, which recruits RNF5, an E3 ligase, to promote SREBP‐cleavage activating protein (SCAP) degradation. TMEM33 is transcriptionally regulated by nuclear factor erythroid 2‐like 1 (NRF1), whose cleavage and activation are controlled by PKM2 levels. Total plasma cholesterol levels are elevated by either treatment with PKM2 tetramer‐promoting agent TEPP‐46 or by global PKM2 knockout in mice, highlighting the essential function of PKM2 in lipid metabolism. Although depletion of PKM2 decreases cancer cell growth, global PKM2 knockout accelerates allografted tumor growth. Together, our findings reveal the cell‐autonomous and systemic effects of PKM2 in lipid homeostasis and carcinogenesis, as well as TMEM33 as a bona fide regulator of lipid metabolism. SYNOPSIS: This study identifies the endoplasmic reticulum (ER) transmembrane protein TMEM33 as a new mechanistic target of pyruvate kinase M2 (PKM2) and bona fide regulator of lipid metabolism. These findings have implications for cancer caused by elevated plasma cholesterol levels and underscore systemic functions of PKM2, opening up new avenues for therapeutic interventions. PKM2 down‐regulates TMEM33 expression in MEFs and breast cancer cells, derepressing the lipogenic transcription factor SREBP.TMEM33 is transcriptionally regulated by NRF1, whose activation depends on the PKM2/VCP axis.PKM2 loss induces TMEM33, leading it to recruit E3 ligase RNF5 for ubiquitination and degradation of SREBP‐cleavage factor SCAP.Depletion of PKM2 in mice elevates global cholesterol levels and promotes allografted growth of hepatocellular cancer. [ABSTRACT FROM AUTHOR]

Under pathological conditions, the Janus kinase (JAK)/STAT signaling pathway can regulate the proliferation, differentiation and migration of tumor cells, including colorectal cancer (CRC). CRC is the third major types of cancer among males and the second among females worldwide. In China, CRC is the fifth common cancer among both males and females. Western blotting, flow cytometry, RNA interference, immunoprecipitation, xenografts models, and immunohistochemical staining were carried out to evaluate the possible mechanisms of acton of ruxolitinib. The present data suggested that ruxolitinib can suppress CRC cell proliferation by inducing apoptosis. Firstly, JAK1/2-STAT1 was identified as the target of ruxolitinib. Then, ruxolitinib downregulated myeloid cell leukemia-1 (Mcl-1) mRNA level and decreased its protein level, which enabled Bak to trigger CRC apoptosis. Furthermore, ruxolitinib exerted potent activity against CRC xenograft growth in vivo. High expression of phosphorylated STAT1 (S727) was also confirmed in 44 pairs of human colon carcinoma and adjacent normal tissues. Taken together, the results showed that ruxolitinib decreased JAK1/2-STAT1-Mcl-1 protein level and effectively suppressed CRC cell proliferation in vitro and in vivo. Therefore, ruxolitinib could be a promising anticancer agent for CRC treatment. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma is associated with major depressive disorder (MDD) and bipolar disorder (BD) in adults. However, no meta-analysis was performed on the prevalence of different types of childhood trauma in adults with affective disorders, using the Childhood Trauma Questionnaire (CTQ).Methods: Four databases were used to search articles regarding the prevalence of childhood emotional abuse (CEA), childhood physical abuse (CPA), childhood sexual abuse (CSA), childhood physical neglect (CPN), and childhood emotional neglect (CEN) in patients with MDD and BD using the CTQ.Results: A total of 17 and 11 articles were found analyzing patients with MDD and BD, respectively. A pooled prevalence rate of 33.0% and 30.0% for CEA, 17.0% and 18.0% for CPA, 19.0% and 22.0% for CSA, 37.0% and 31.0% for CEN, and 31% and 30.0% for CPN was found in patients with MDD and BD respectively. A difference in 95% confidence interval in the CSA rate between men and women was found in patients with MDD in the gender subgroup and in the rate of some types of childhood trauma in the continent subgroup in both patient types.Limitations: A limited number of articles were included in some continents, thus, the heterogeneity in the meta-analysis was generally high.Conclusion: The prevalence of CEA, CEN, and CPN in patients with affective disorders was relatively high, whereas that of CPA and CSA was relatively low. These childhood traumas might be affected by continent and gender. [ABSTRACT FROM AUTHOR]

Renal cancer is one of the most common malignancies in urological tumors; it is necessary to develop a noninvasive and highly targeted thermal ablation method for the treatment of renal tumors. IR780 has been shown to be an effective photothermal agent for tumor thermal ablation. This study was designed to explore the feasibility of applying hyaluronic acid-IR780 nanoparticles (HA-IR780 NPs) for targeted thermal ablation of renal tumors using an in situ renal tumor model. The size of the nanoparticles was 172 ± 8.2 nm; it showed a stable spherical nanostructure with good monodispersity. HA-IR780 NPs showed high photothermal efficiency, with the 20 μg/mL HA-IR780 NPs showing a maximum temperature increase of 24.5°C with 6 min of 808 nm laser irradiation. NIR imaging showed that the nanoparticles exhibited targeted accumulation in renal tumor tissues. The treatment efficacy of the HA-IR780 NPs showed that renal tumors treated with the HA-IR780 NPs and laser irradiation were effectively ablated. Our results showed that the HA-IR780 nanoparticles that mediated the photothermal effect could generate tumor-specific heat for the destruction of a renal tumor in a minimally invasive way, which provides a novel strategy for thermal ablation of renal tumors. [ABSTRACT FROM AUTHOR]

• CTS/HMMT (chitosan/hydrophobically-modified montmorillonite) sorbent via Pickering emulsion polymerization was obtained. • HMMT coated onto the crosslinked chitosan as core-shell composite. • HMMT coat of rigidity limited crosslinked chitosan swelled effectively during iodide-ion adsorption. • CTS/HMMT composites showed the fast I− adsorption efficiency of ≥90% among the wide pH during five regenerations. • Both chitosan and HMMT favored for iodide adsorption during iodide removal. The radioactive iodine from nuclear wastes caused severe environmental contamination and public health concern. Chitosan and montmorillonite as green materials of the favorable adsorptivity were proposed for iodine treatment. Rather than intercalation, the crosslinked chitosan proposedly via Pickering emulsion polymerization was coated by hydrophobical-modified montmorillonite (HMMT) to form the micro-composite of chitosan/HMMT (CTS/HMMT) as the iodide adsorbent of eco-safety, adsorptivity combination and chitosan-swelling limitation. From pH 3 to 10, CTS/HMMTs adsorbed I127 anions no <90% during 40 min, with the maximum adsorption capacity of 0.3033 mmol/g, well-fitting with Langmuir isotherm model and the pseudo first-order kinetic model. CTS/HMMTs were also well-regenerated within the five adsorption/desorption cycles of the nearly same adsorption efficiency, performing the high stability. Nonetheless, the CTS/HMMT adsorbents were prospective for radioactive iodine removal. [ABSTRACT FROM AUTHOR]

The viral replication proteins of plus-stranded RNA viruses orchestrate the biogenesis of the large viral replication compartments, including the numerous viral replicase complexes, which represent the sites of viral RNA replication. The formation and operation of these virus-driven structures require subversion of numerous cellular proteins, membrane deformation, membrane proliferation, changes in lipid composition of the hijacked cellular membranes and intensive viral RNA synthesis. These virus-driven processes require plentiful ATP and molecular building blocks produced at the sites of replication or delivered there. To obtain the necessary resources from the infected cells, tomato bushy stunt virus (TBSV) rewires cellular metabolic pathways by co-opting aerobic glycolytic enzymes to produce ATP molecules within the replication compartment and enhance virus production. However, aerobic glycolysis requires the replenishing of the NAD+ pool. In this paper, we demonstrate the efficient recruitment of pyruvate decarboxylase (Pdc1) and alcohol dehydrogenase (Adh1) fermentation enzymes into the viral replication compartment. Depletion of Pdc1 in combination with deletion of the homologous PDC5 in yeast or knockdown of Pdc1 and Adh1 in plants reduced the efficiency of tombusvirus replication. Complementation approach revealed that the enzymatically functional Pdc1 is required to support tombusvirus replication. Measurements with an ATP biosensor revealed that both Pdc1 and Adh1 enzymes are required for efficient generation of ATP within the viral replication compartment. In vitro reconstitution experiments with the viral replicase show the pro-viral function of Pdc1 during the assembly of the viral replicase and the activation of the viral p92 RdRp, both of which require the co-opted ATP-driven Hsp70 protein chaperone. We propose that compartmentalization of the co-opted fermentation pathway in the tombusviral replication compartment benefits the virus by allowing for the rapid production of ATP locally, including replenishing of the regulatory NAD+ pool by the fermentation pathway. The compartmentalized production of NAD+ and ATP facilitates their efficient use by the co-opted ATP-dependent host factors to support robust tombusvirus replication. We propose that compartmentalization of the fermentation pathway gives an evolutionary advantage for tombusviruses to replicate rapidly to speed ahead of antiviral responses of the hosts and to outcompete other pathogenic viruses. We also show the dependence of turnip crinkle virus, bamboo mosaic virus, tobacco mosaic virus and the insect-infecting Flock House virus on the fermentation pathway, suggesting that a broad range of viruses might induce this pathway to support rapid replication. Replication of positive-strand RNA viruses, which infect plants and animals, depends on many cellular resources. These viruses subvert cellular membranes and co-opt host proteins to build replication compartments that produce the viral progeny. The viral replication process also requires cellular metabolites and energy in the form of ATP. Using plant host as well as the model host yeast, the authors discovered that tomato bushy stunt tombusvirus (TBSV) co-opts the fermentation pathway to facilitate the local generation of ATP within the replication compartments. TBSV replication induces high expression of pyruvate decarboxylase (Pdc1) and alcohol dehydrogenase (Adh1) fermentation enzymes. With the help of the viral replication protein, TBSV recruits Pdc1 and Adh1 into the viral replication compartment. The authors propose that compartmentalization of the fermentation pathway gives an evolutionary advantage for tombusviruses by facilitating rapid and efficient replication in the infected hosts. The authors also showed that the replication of five other plant viruses depends on the fermentation pathway in plants. [ABSTRACT FROM AUTHOR]

• Heat transfer experiments with axially sinusoidal heating were conducted. • The large temperature difference between the top and bottom wall was explained. • The effect of circumferential heat conduction is considered. • The local heat transfer characteristics is investigated in the horizontal tube. For a heat exchanger, the heat flux is usually non-uniform in the axial direction, and the knowledge about heat transfer of supercritical water with axially non-uniform heating is scarce. To fill the gap, experiments were conducted in a horizontal tube to study the heat transfer characteristics of supercritical water with axially sinusoidal heating. The pressures varied from 23.5 to 26.5 MPa, mass fluxes 200 to 400 kg·m−2·s−1 and average heat fluxes 50 to 150 kW·m−2. Compared with uniform heat flux, the temperature difference between the top and bottom wall is larger than that of the axially sinusoidal heat flux. The inner-wall heat flux is non-uniform along the circumference due to the temperature difference, being higher at the side wall and lower at the top wall. A relative heat flux parameter is defined to describe the relative magnitude of the local heat flux. The relative heat flux parameter of the top generatrix, which is inversely proportional to the average heat flux, decreases linearly with the increase of the temperature difference between the top and side generatrix. The non-uniform degree of heat flux along the circumference is positively correlated with the average heat flux. Additionally, the local heat transfer characteristics should be considered in horizontal tubes. On the one hand, the heat transfer deterioration may occur when the fluid temperature near the top wall is higher than the pseudo-critical temperature and it can be suppressed with increasing Reynolds number. On the other hand, the local heat transfer can be enhanced if the side and bottom wall temperatures exceed the pseudo-critical temperature. [ABSTRACT FROM AUTHOR]

This article corrects: Synergistic effect of PCPE1 and sFRP2 on the processing of procollagens via BMP1, Volume 593, Issue 1, 119–127. Article first published 09 November 2018. https://doi.org/10.1002/1873-3468.13291 Dr Daniel S. Greenspan was inadvertently omitted from the list of authors in the original publication. The correct list of authors is as shown above. Dr Daniel S. Greenspan affiliation and contact details are as follows: Department of Cell and Regenerative Biology, University of Wisconsin, Room 4503, WIMRII, 1111 Highland Ave, Madison, WI 53705, dsgreens@wisc.edu [ABSTRACT FROM AUTHOR]

A motor bearing system is a nonlinear dynamics system with nonlinear support stiffness. It is an asymmetry system, which plays an extremely important role in rotating machinery. In this paper, a center frequency method of double thresholds is proposed to improve the variational mode decomposition (VMD) method, then an adaptive VMD (called DTCFVMD) method is obtained to extract the fault feature. In the DTCFVMD method, a center frequency method of double thresholds is a symmetry method, which is used to determine the decomposed mode number of VMD according to the power spectrum of the signal. The proposed DTCFVMD method is used to decompose the nonlinear and non-stationary vibration signals of motor bearing in order to obtain a series of intrinsic mode functions (IMFs) under different scales. Then, the Hilbert transform is used to analyze the envelope of each mode component and calculate the power spectrum of each mode component. Finally, the power spectrum is used to extract the fault feature frequency for determining the fault type of the motor bearing. To test and verify the effectiveness of the DTCFVMD method, the actual fault vibration signal of the motor bearing is selected in here. The experimental results show that the center frequency method of double thresholds can effectively determine the mode number of the VMD method, and the proposed DTCFVMD method can accurately extract the clear time frequency characteristics of each mode component, and obtain the fault characteristics of characteristics; frequency, rotating frequency, and frequency doubling and so on. [ABSTRACT FROM AUTHOR]

Although ticagrelor has been demonstrated to possess an anti-atherosclerosis (AS) effect, its underlying mechanism remains unclear. In the present study, it was investigated whether ticagrelor reduces oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell apoptosis, an initial step for the development of AS, and alleviates AS in apolipoprotein-E-deficient (ApoE−/−) mice by inhibiting the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9). The human endothelial cell line EAhy926 was treated with ox-LDL, ox-LDL + ticagrelor (40 µmol/l) and ox-LDL + ticagrelor (60 µmol/l) for 24 h. Cell apoptosis was detected using Annexin V-fluorescein isothiocyanate/propidium iodide staining. The expression levels of PCSK9, apoptosis-associated proteins and signaling pathways were determined by reverse transcription-quantitative polymerase chain reaction and western blotting. ApoE−/− mice fed a high-fat diet were used to induce an AS model. After 20 weeks, ApoE−/− mice were randomly assigned to receive saline or ticagrelor intragastrically for 10 days. The formation of atherosclerotic plaques was detected by hematoxylin and eosin staining. The expression of PCSK9 in the arterial tissues was measured by immunohistochemistry. The results demonstrated that treatment with ticagrelor was able to decrease ox-LDL-induced apoptosis in a concentration-dependent manner (40 µmol/l vs. ox-LDL, 17.58±2.66 vs. 27.25±5.54%; 60 µmol/l vs. ox-LDL, 12.26±1.54 vs. 27.25±5.54%). The mRNA and protein expression level of PCSK9 significantly decreased following treatment with ticagrelor, accompanied with upregulation of B-cell lymphoma (Bcl) 2 and downregulation of Bcl-2 associated X, apoptosis regulator, caspase-3, p38, phosphorylated-(p) p38, p-c-Jun N-terminal kinases (JNK), p-extracellular signal-regulated kinases and the ratio of p-JNK to JNK. Histological analysis of arterial tissues revealed ticagrelor markedly decreased the atherosclerotic plaque area and inhibited the expression of PCSK9. The present results suggested that ticagrelor may alleviate AS via downregulation of PCSK9-mediated endothelial cell apoptosis, which may be JNK-dependent. [ABSTRACT FROM AUTHOR]

Background: The mechanisms underlying the relationship between life events and psychological distress are unclear. However, evidence of genetic involvement, including the neuropeptide S receptor gene (NPSR1), exists.Methods: A total of 600 Chinese adults were enrolled in this cross-sectional study using random cluster sampling. Demographic information, measures of life events and psychiatric symptoms, and fasting blood samples were collected.Results: Significant correlations were observed among life-event scores, somatization, and psychological distress (i.e., anxiety and depressive symptoms). Regression revealed life-event scores and somatization predicted anxiety, depressive symptoms, and psychological distress, while controlling for sex, age, income, education, and marital status. Structural equation modeling indicated that somatization mediated the association between life-event scores and psychological distress. Moreover, the mediating effect was influenced by the NPSR1 gene, suggesting that the NPSR1 polymorphisms rs324981, rs6947841, and rs6972158 influenced the association between life-event scores and somatization (ps < 0.05). The NPSR1 polymorphisms rs12673132 significantly affected the relationship of somatization with psychological distress (p < 0.05).Conclusions: In conclusion, somatization mediated the association between life-event scores and psychological distress. The current study is the first to demonstrate this relationship with a Chinese sample, whereby the NPSR1 gene affects the mediating effect of somatization on the association between life-event scores and psychological distress. [ABSTRACT FROM AUTHOR]

High‐energy‐resolution fluorescence detection (HERFD) X‐ray absorption spectroscopy at SSRL is combined with density functional theory and FEFF simulations ascribing spectral features to ethylene and CO ligands adsorbed on catalytically active iridium centers isolated on zeolite HY and on MgO, pushing detection limits below those of conventional infrared spectroscopy, and allowing XAS to identify reactionary intermediates. More information can be found in the Full Paper by D. A. Dixon, S. R. Bare, B. C. Gates et al. on page 14760. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue are the groups of David A. Dixon at the University of Alabama, Simon R. Bare at Stanford Synchrotron Radiation Lightsource and Bruce C. Gates at the University of California, Davis. The image depicts a visual representation of the key conclusion of the work. Read the full text of the article at . [ABSTRACT FROM AUTHOR]

FK228 is a selective inhibitor of histone deacetylases that exhibits marked antitumor activity in cancer cells and xenograft models. However, the effect of FK228 on the global profile of histone lysine acetylation and the proteome of EC109 cells remains poorly understood. The present study aimed at analyzing histone lysine acetylation and identifying the proteomic changes in EC109 cells following treatment with FK228, using the stable isotope labelling by amino acids in cell culture technique and a high-sensitivity mass spectrometer. In total, 87 acetylation sites and 3,515 proteins revealed changes in response to FK228 treatment. Of the 87 acetylation sites, 25 were quantifiable and 19 were quantified with ratio of >1.3. Notably, no downregulated lysine acetylation (Kac) sites were quantified in the present study and the 62 unquantified Kac sites were only identified in the FK228-treated cells. Bioinformatic analysis revealed that these quantifiable proteins were primarily involved in multiple biological functions and metabolic pathways as well as in protein complexes. The results of the present study revealed the extensive lysine acetylome and proteome in EC109 cells and expanded upon the current understanding of the anticancer mechanism of FK228 in EC109 cells. [ABSTRACT FROM AUTHOR]

Background: Previously, we reported that high expression of nipped-B-like protein (NIPBL) was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer (NSCLC). Moreover, loss of NIPBL decreased lung cancer cells proliferation, migration, invasion and promoted apoptosis as well as sensitivity to chemotherapeutic agents. However, the deep mechanisms were not explored. Purpose: The objective of this study was to identify the role of NIPBL in DNA damage response, as well as autophagy pathway, so as to interpret the mechanisms of how NIPBL knockdown enhances the chemosensitivity of lung cancer cell. Methods: Cells (NCI-H1299 and NCI-H1650) were transfected by specific siRNAs before immunofluorescence and single-cell gel electrophoresis, which were mainly used to observe the differences of DNA damage in different groups. Additionally, protein were obtained and then analyzed by western blot and mass spectroscopy. Results: In this study, we found that knockdown of NIPBL resulted in accumulation of phosphorylated H2AX (γ-H2AX) foci and higher levels of DNA damage, as revealed by comet assay. Western blot assay revealed that loss of NIPBL decreased expression of ATM/ATR, Rad3-related protein and Ku70/Ku80, but increased expression of LC3-B and depletion of p62. Using mass spectroscopy, we identified eight proteins that were significantly differentially expressed upon NIPBL knockdown. Gene Ontology analysis revealed that these proteins are mainly involved in DNA repair, mismatch repair, and binding to damaged DNA. The expression changes in two of the proteins, MSH2 and STAT1, were verified by Western blotting in NIPBL-knockdown cells. Conclusions: In summary, these results reflected that loss of NIPBL impairs the DNA damage response and promotes autophagy. And NIPBL suppression may represent a novel strategy for preventing chemotherapy resistance in lung cancer. [ABSTRACT FROM AUTHOR]

Objective:We established a novel procedure to generate a reversible partial unilateral ureteral obstruction (PUUO) in rabbit. The method allows us to reliably measure the degree of ureteral obstruction in live animals, and thus could be a useful tool for studying kidney diseases. Methods:Thirty rabbits of clean grade were divided randomly into sham control group and obstruction (PUUO) group. Each rabbit in this study received the same blocking surgery, in which the upper ureter was curvilinearly incised and inserted with two F6 ureteral catheters that were connected with a tee joint valve. Ureteral obstruction was created and released through the valve adjustment. Serum creatinine and ultrasonographic measurements were performed preoperatively, on the fifth and tenth days after obstruction surgery, and on the 10th and 20th day, respectively, after the relief of the obstruction. Pathological measurements were taken in two randomly chosen rabbits of each group on the 10th day after surgery and on the 20th day after obstruction relief. Results:Data showed that the serum creatinine went transiently up and down in the early days and then remained a little bit higher in the following days after obstruction surgery. The morphology in obstructed kidney changed significantly on the 10th day postoperatively, compared to the sham control group. The obvious differences were also observed in pathology tests. After the relief of obstruction, the volume of renal pelvis (V), renal cortical thickness (RCT), and pathological impairment were partially reversed. Conclusions:Those findings indicate our procedure generate a successful and reversible PUUO animal model. It is a reliable and simple procedure for generating an animal model for reversible PUUO. The feasibility and significance of the new method was confirmed through ultrasonographic and pathological results. [ABSTRACT FROM PUBLISHER]

• Heat transfer experiments considering local temperature were conducted. • Mechanism of heat transfer deterioration was studied. • Heat transfer was dominated by relative magnitude of buoyancy and inertia force. A comprehensive understanding of heat transfer to supercritical fluids is essential to improve the thermal efficiency of some advanced thermal systems. However, the mechanism remains unclear that how the heat transfer is affected by local temperature, especially the near-wall temperature. In this study, heat transfer experiments of supercritical water are conducted in a horizontal tube. Five local water temperatures from the near-wall region to the core in a cross-section are measured to clarify the heat transfer process with the operating pressure of 23.5–26.5 MPa, mass flux of 200–400 kg·m–2 s–1, and heat flux of 50–180 kW·m–2. The tube length and inner diameter are 6000 mm and 26 mm, respectively. The results show that the heat transfer is suppressed and the enthalpy increase is no longer linear before the pseudo-critical point. Heat transfer is dominated by the relative magnitude of buoyancy and inertia force, which are affected by heat flux and mass flux, respectively. Moreover, the heat transfer process is divided into four parts, and the heat transfer deterioration occurs at the end of part II and restores in part III. Finally, a new correlation which is suitable for supercritical heat transfer in horizontal tubes with large diameters is developed based on the present experimental data. [ABSTRACT FROM AUTHOR]

Proton exchange membrane (PEM) is a key component of proton exchange membrane fuel cells (PEMFCs) and provides proton conduction between fuel and oxidant, and it is vitally important and practical to develop PEMs with high proton conductivity through membranes. However, it is still a major challenge to develop such membranes with high through-plane proton conductivity. In this study, Nafion composite membranes with sulfonated graphene oxides (SGOs) were prepared from self-assembly sol-gel either in or not in a strong magnetic field. Microstructures, water uptake, and proton conductivity of the SGO/Nafion composite membranes have been investigated extensively. For the SGO/Nafion composite membranes recast without a magnetic field, it is found that the water uptake and in-plane proton conductivity are greatly increased with the increasing SGO content. Interestingly, SGO/Nafion composite membranes with a low SGO content of ∼ 0.5 wt% exhibit lower crystallinity and higher in-plane proton conductivity. For the SGO/Nafion composite membranes recast in a strong through-plane magnetic field, it is very appealing to find their through-plane proton conductivity is significantly higher than that of the composite membranes recast without a magnetic field. This is attributed to that the protons transport in the membranes preferentially along the water channels primarily interconnected by the aligned SGOs through-plane induced by the strong magnetic field, as confirmed by SEM. Applied in a single PEMFC, the resultant SGO/Nafion composite membrane with 1 wt% SGOs, recast in a strong magnetic field of 1.5 T, demonstrates a high power-density of 1.056 W cm-2, which is far superior to those of pristine Nafion and SGO/Nafion composite membranes recast without a magnetic field. The study provides a novel strategy for preparing proton exchanging membranes with high performances for new-generation fuel cells. [Display omitted] • The proton conductivity of sulfonated graphene oxide (SGO)/Nafion composite membranes was impacted by SGO contents. • Highly through-plane proton conductive membranes were prepared by recasting in a strong magnetic field. • A single fuel cell with optimal SGO/Nafion recast in a strong magnetic field shows a high power-density of 1.056 W cm-2. [ABSTRACT FROM AUTHOR]

Background & Aims It is proposed that p38 is involved in gluconeogenesis, however, the genetic evidence is lacking and precise mechanisms remain poorly understood. We sought to delineate the role of hepatic p38α in gluconeogenesis during fasting by applying a loss-of-function genetic approach. Methods We examined fasting glucose levels, performed pyruvate tolerance test, imaged G6Pase promoter activity, as well as determined the expression of gluconeogenic genes in mice with a targeted deletion of p38α in liver. Results were confirmed both in vivo and in vitro by using an adenoviral dominant-negative form of p38α (p38α-AF) and the constitutively active mitogen-activated protein kinase 6, respectively. Adenoviral dominant-negative form of AMP-activated protein kinase α (DN-AMPKα) was employed to test our proposed model. Results Mice lacking hepatic p38α exhibited reduced fasting glucose level and impaired gluconeogenesis. Interestingly, hepatic deficiency of p38α did not result in an alteration in CREB phosphorylation, but led to an increase in AMPKα phosphorylation. Adenoviral DN-AMPKα could abolish the effect of p38α-AF on gluconeogenesis. Knockdown of up-steam transforming growth factor β-activated kinase 1 decreased the AMPKα phosphorylation induced by p38α-AF, suggesting a negative feedback loop. Consistently, inverse correlations between p38 and AMPKα phosphorylation were observed during fasting and in diabetic mouse models. Importantly, adenoviral p38α-AF treatment ameliorated hyperglycemia in diabetic mice. Conclusions Our study provides evidence that hepatic p38α functions as a negative regulator of AMPK signaling in maintaining gluconeogenesis, dysregulation of this regulatory network contributes to unrestrained gluconeogenesis in diabetes, and hepatic p38α could be a drug target for hyperglycemia. [ABSTRACT FROM AUTHOR]

Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determined by a mass spectrometry-based method. Over ten arachidonic acid metabolites belonging to three catalytic pathways: cyclooxygenases, lipoxygenases, and cytochrome P450, were quantified simultaneously and displayed characteristic profiles under different thyroid hormone status. The level of 20-hydroxyeicosatetraenoic acid, a cytochrome P450 metabolite, was positively correlated with thyroid hormone level and possibly contributed to the elevated blood pressured in hyperthyroidism. The increased prostanoid (PG) I 2 and decreased PGE 2 levels in hypothyroid patients might serve to alleviate atherosclerosis associated with dyslipidemia. The elevated level of thromboxane (TX) A 2 , as indicated by TXB 2 , in hyperthyroid patients and mice treated with thyroid hormone might bring about pulmonary hypertension frequently found in hyperthyroid patients. In conclusion, our prospective study revealed that arachidonic acid metabolites were differentially affected by thyroid hormone status. Certain metabolites may be involved in cardiovascular disorders associated with thyroid diseases. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated the effect of toxin-antitoxin RNA pairs on clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems. Topics explored include the identification of the toxic component present in the Cascade gene cassette, the critical elements and structure of the RNA toxin gene creT, and the CRISPR repeat-like sequence observed following the mutational analysis of creT.

• The efficient & quick I− removal was achieved by silver chloride entrapped cross-linked chitosan microsphere (AgCl@CM). • The maximum adsorption capacity of I− was up to 1.5267 mmol/g in 20 min adsorption. • AgCl@CM performed wide pH adaptation from pH 2 to pH 10 for iodide ion adsorption. • AgCl@CM adsorbed I− efficient-selectively relative to Cl− and CO 3 2−. Radioactive iodine waste from nuclear plant became the severe environmental problem and led to the public health concern. The cross-linked chitosan adsorbed iodide anions through the electrical attraction, yet performing limited-efficiently. Targeting as the better adsorption, the modified chitosan sorbent as AgCl@CM (silver chloride entrapped in the cross-linked chitosan microspheres) for iodine adsorption was proposed and implemented by chemisorption from AgCl and physisorption from chitosan via the improved emulsion method (emulsions mixing-collision and polymerization). With the broad application from pH 2 to pH 10, the spherical AgCl@CM (from 0.20 g silver nitrate) performed the I127 anions (instead of radioactive iodine) adsorption efficiency of higher than 90 % in 20 min, with the maximum adsorption capacity of 1.5267 mmol/g, well-fitting with the pseudo-first-order model and Sips isothermal model. AgCl@CM also performed I127 adsorption with the significant selectivity relative to Cl−. The micro-spherical AgCl@CM sorbents were therefore prospective-effectively for iodine waste water treatment. [ABSTRACT FROM AUTHOR]

Activation of hypoxia-inducible factor 1α (HIF1α) controls the transcription of genes governing angiogenesis under hypoxic condition during tumorigenesis. Here we show that hypoxia-responsive miR-182 is regulated by HIF1α at transcriptional level. Prolyl hydroxylase domain enzymes (PHD) and factor inhibiting HIF-1 (FIH1), negative regulators of HIF1 signaling, are direct targets of miR-182. Overexpression of miR-182 in prostate cancer cells led to a reduction of PHD2 and FIH1 expression and an increase in HIF1α level either under normoxic or hypoxic condition. Consistently, inhibition of miR-182 could increase PHD2 and FIH1 levels, thereby reducing the hypoxia-induced HIF1α expression. Matrigel plug assay showed that angiogenesis was increased by miR-182 overexpression, and vice versa. miR-182 overexpression in PC-3 prostate cancer xenografts decreased PHD2 and FIH1 expression, elevated HIF1α protein levels, and increased tumor size. Lastly, we revealed that the levels of both miR-182 and HIF1α were elevated, while the expression PHD2 and FIH1 was downregulated in a mouse model of prostate cancer. Together, our results suggest that the interplay between miR-182 and HIF1α could result in a sustained activation of HIF1α pathway, which might facilitate tumor cell adaption to hypoxic stress during prostate tumor progression. [ABSTRACT FROM AUTHOR]