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Background: Gene variants are responsible for more than half of hearing loss, particularly in nonsyndromic hearing loss (NSHL). The most common pathogenic variant in SLC26A4 gene found in East Asian populations is c.919-2A > G followed by c.2168A > G (p.H723R). This study was to evaluate their variant frequencies in patients with NSHL from special education schools in nine different areas of Southwest China's Yunnan. Methods: We performed molecular characterization by PCR-products directly Sanger sequencing of the SLC26A4 c.919-2AG and c.2168 A > G variants in 1167 patients with NSHL including 533 Han Chinese and 634 ethnic minorities. Results: The SLC26A4 c.919-2A > G variant was discovered in 8 patients with a homozygous state (0.69%) and twenty-five heterozygous (2.14%) in 1167 patients with NSHL. The total carrier rate of the c.919-2A > G variant was found in Han Chinese patients with 4.50% and ethnic minority patients with 1.42%. A significant difference existed between the two groups (P < 0.05). The c.919-2A > G allele variant frequency was ranged from 3.93% in Kunming to zero in Lincang and Nvjiang areas of Yunnan. We further detected the SLC26A4 c.2168 A > G variant in this cohort with one homozygotes (0.09%) and seven heterozygotes (0.60%), which was detected in Baoshan, Honghe, Licang and Pu'er areas. Between Han Chinese group (0.94%) and ethnic minority group (0.47%), there was no statistical significance (P > 0.05). Three Han Chinese patients (0.26%) carried compound heterozygosity for c.919-2A > G and c.2168 A > G. Conclusion: These data suggest that the variants in both SLC26A4 c.919-2A > G and c.2168 A > G were relatively less frequencies in this cohort compared to the average levels in most regions of China, as well as significantly lower than that in Han-Chinese patients. These results broadened Chinese population genetic information resources and provided more detailed information for regional genetic counselling for Yunnan. [ABSTRACT FROM AUTHOR]

Urban digitalization is a key driver of regional coordinated development in modern times due to its ubiquitous and significant impact on our production, way of life, and ecosystem. Most of the current research has focused on the economic and social impacts of digitalization, while little work has been done on the efficiency of digitalization. This study investigates urban digitalization efficiency (UDE) employing the super-efficient EBM model from a viewpoint of regional coordinated development. The dynamic evolution of UDE is revealed by the Markov chain method. The convergence properties of UDE in each region are examined using the β convergence models. The findings indicate that: (1) The UDE of each city and each of the eight integrated economic zones has increased to some extent. (2) The UDE is relatively likely to remain stable, with a greater probability of shifting to a neighbouring type than to a non-neighbouring type. (3) While UDE exhibits absolute and conditional β-convergence across all areas, the causes affecting UDE convergence in various economic zones vary. The results presented in this study can help clarify the laws and characteristics of UDE and serve as a reference for developing countries to promote coordinated regional development through urban digitalization. [ABSTRACT FROM AUTHOR]

Heterostructure and phase engineering are effective method to tune the electronic structure of MoS 2 , which can activate and boost its intrinsic catalytic activity. Herein, the theoretical calculations reveal that the free energy of H∗ adsorption (ΔG H∗) for Mo 2 C (−0.65 eV) is lower than MoS 2 (2.05 eV), which is favorable for hydrogen adsorption. Inspired by the theoretical predictions, we develop a facile strategy to prepare nanostructured Mo 2 C/MoS 2 dispersed on reduced graphene oxide (rGO) via a hydrothermal preparation and carburization reaction. Since the Mo 2 C/MoS 2 -rGO nanostructures with great deal of both MoS 2 and Mo 2 C edges by heterostructure and phase engineering, which can induce massive active sites for HER on the surface of rGO, the intimate interfacial coupling effect between Mo 2 C and MoS 2 can effectively improve the charge transfer rate. The Mo 2 C/MoS 2 -rGO catalyst exhibits exceptional HER properties, delivering a high turnover frequency (TOF) of 0.209 s−1 at an overpotential of 200 mV in 0.1 M KOH. This work may open a new window for designing NPM electrocatalysts with highly efficient HER property based on earth-abundant materials. [Display omitted] • A new preparation, it is first time to fabricate Mo 2 C/MoS 2 -rGO hybrid. • The DFT calculations reveal that the synergistic effect between Mo 2 C and MoS 2 can activate the HER efficiency. • The Mo 2 C/MoS 2 -rGO presents a high TOF of 0.209 s−1 at an overpotential of 200 mV in 0.1 M KOH. • The Mo 2 C/MoS 2 -rGO shows excellent cycle stability. [ABSTRACT FROM AUTHOR]

As a crucial component of the climate system, snow cover plays an important role on surface energy budgets, hydrological cycles and socioeconomic development. This paper investigated the spatiotemporal patterns of snow depth across the Qinghai Plateau (QP) during 1980–2018 based on passive microwave (PMW) satellite observation and reanalysis products. The study identified the relationships between the changes in PMW snow depth and topographic features and revealed the impact of climatic variables (air temperature, precipitation and wind speed) and large‐scale atmospheric circulations on observed snow depth variability. The results show that the spatial pattern of snow depth climatology is similar in all datasets, except in terms of magnitude, with high values in the southern and southeastern parts of the QP and low values in the eastern and northwestern parts. Average snow depth correlates positively with precipitation, elevation and slope, and negatively with air temperature and wind speed. The long‐term trends in snow depth vary with the season and the datasets. The PMW snow depth across the QP shows a significant annual (−0.125 cm·decades−1, p <.10) and spring (−0.184 cm·decades−1, p <.05) negative trend, while snow depth for ERA5 and MERRA2 does not present significant trends. Air temperature dominates total snow depth variation over the QP, explaining 43.85, 24.88 and 47.28% of annual, winter and spring PMW snow depth variations, which significantly affects snow depth variations in most parts of the QP, yet the effects of precipitation and wind speed on snow depth variation exhibit significant regional differences, and atmospheric circulations (e.g., AMO) also have a remarkable controlling effect on some localized areas. [ABSTRACT FROM AUTHOR]

Background: Carotid body tumors (CBTs) are relatively uncommon neoplasms that rarely have malignant potential. However, malignant CBTs (MCBTs) are still associated with a poor prognosis and the treatment is still challenging clinically. Therefore, we evaluated the necessity of intraoperative level IIA lymph node dissection in patients with CBT. Methods: The clinical characteristics, intraoperative details, and pathological diagnosis of 126 CBT patients who had undergone surgery were retrospectively reviewed. The patients were divided into 2 groups according to whether level IIA lymph node dissection was performed. The prognosis was analyzed using Kaplan-Meier curves and Cox model multivariate survival analysis. Results: Among the 126 patients, 7 patients (10.3%) in the selective lymph node dissection (SLND) group (68 patients) were diagnosed with MCBTs with evidence of lymph node metastasis. Two patients (3.4%) in the lymph node nondissection (LNND) group (58 patients) were diagnosed with MCBTs later after the second operation because they could not be diagnosed as malignant initially because of the lack of lymph node pathology results although the pathology of the primary lesion showed features of malignancy. The SLND group had a significantly higher relapse-free survival rate than the LNND group (94.1% vs. 79.3%, p = 0.021). Patients with a confirmed diagnosis had a better prognosis than those with insufficient evidence of a malignancy due to the lack of lymph node information. Twenty-nine patients in the SLND group and 26 patients in the LNND group had postoperative nerve injuries, with no significant difference between the groups (p = 0.879). Conclusion: Intraoperative dissection of level IIA lymph nodes around the tumor in CBT patients can help improve the diagnosis and prognosis of MCBTs without causing additional cranial nerve injury. [ABSTRACT FROM AUTHOR]

Tuberculosis, caused by mycobacteria, continues to pose a substantial public health threat. Mycobacteria typically use cholesterol from the membranes of host macrophages as a carbon and energy source. Most genes that control cholesterol degradation are regulated by KstR, which is highly conserved in Mycobacterium tuberculosis and Mycobacterium smegmatis. Through bioinformatic analysis, we found a typical global nitrogen regulator (GlnR)‐binding motif (CCGAC‐AACAGT‐GACAC) in the promoter region of kstR of M. smegmatis, and we determined its binding activity in vitro using electrophoretic mobility shift assays. Using RT‐qPCR, we found that nine genes involved in side‐chain or sterol‐ring oxidation were upregulated in a ΔglnR M. smegmatis strain compared to the WT strain and glnR‐complemented strains under nitrogen limitation. ATP assays in macrophages revealed that coordinated GlnR–KstR regulation significantly reduced the viability of M. smegmatis in macrophages. Thus, we found that various genes involved in cholesterol catabolism are regulated by GlnR via KstR in response to environmental nitrogen, and that they further affect the invasive ability of M. smegmatis. These findings revealed a novel regulatory mechanism of cholesterol catabolism, which may be useful in the development of new strategies for controlling tuberculosis. [ABSTRACT FROM AUTHOR]

Background: The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC. Methods: ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate and multivariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In the validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. Besides, the receiver operating characteristic (ROC) curve was plotted to determine the diagnostic performance of TNFRSF4, CD4, CD8, and FOXP3 in EC. Results: Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to the prognosis in patients of EC, both verified by data from The Cancer Genome Altas (TCGA)-EC database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO). Conclusions: Collectively, TNFRSF4, a previously unrecognized key player in EC, could serve as a potential biomarker for prognosis prediction and immunomodulation of EC. [ABSTRACT FROM AUTHOR]

Background: The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC.Methods: ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate and multivariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In the validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. Besides, the receiver operating characteristic (ROC) curve was plotted to determine the diagnostic performance of TNFRSF4, CD4, CD8, and FOXP3 in EC.Results: Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to the prognosis in patients of EC, both verified by data from The Cancer Genome Altas (TCGA)-EC database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO).Conclusions: Collectively, TNFRSF4, a previously unrecognized key player in EC, could serve as a potential biomarker for prognosis prediction and immunomodulation of EC. [ABSTRACT FROM AUTHOR]

After long-term oxidation and energy storage, broken coal body borehole walls and drainage shaft walls may cause spontaneous combustion during gas extraction. The high-temperature thermal shock caused by the spontaneous combustion of coal incurs thermal damage on adjacent coal, which, in turn, causes changes in the mechanical properties of the coal. However, only a few studies have been conducted in this context, which has limited our understanding of the thermal damage characteristics of coal bodies in such situations. This study aimed to experimentally investigate the correlation between the crack evolution law and the mechanical properties of coal bodies at different temperatures (50–300°C) using heat-force loading considering Ping Mei No. 10 coal mine as the research object. The results suggest that the coal body experiences a large amount of visible damage, and becomes increasingly complex. At 50–300°C, some indexes (such as longitudinal wave velocity, Poisson's ratio, compressive strength, elastic modulus, impact energy index, and pre-peak strain) are positively correlated with temperature. In addition, the dynamic failure time and temperature show a negative correlation, and the overall change slope is small. The relationship between each index and temperature at 200–300°C is opposite to that at 50–200°C, and the overall change slope is larger. Moreover, when the oxidation temperature exceeds 200°C, the destruction of the coal body changes from elastic brittleness to ductility-plasticity. High-temperature oxidation incurs irreversible thermal damage of coal. Hence, it is necessary to focus on the changes in mechanical properties of coal after a spontaneous combustion process is extinguished. [ABSTRACT FROM AUTHOR]

The effect of porous flexible polyvinyl chloride (PVC) barriers on the kinetic properties of propane explosions is investigated based on fluid dynamics and combustion-related theory. Furthermore, using small-sized cylindrical pipes, separate experimental studies on propane deflagration are conducted with different types of flexible PVC barriers placed in the pipeline. The results show that when the conditions of the same nature as the obstacles appear at the outlet end of the pipeline and the blocking rate is low, the presence of porous flexible PVC barriers counteracts the effect of tail-end barriers on propane deflagration. In the tail-end opening experiment, the porous flexible PVC obstacle has a significant effect on the flame pattern passing through it but has a weaker effect on the flames before they pass through it. Furthermore, it only affects the degree of "fingertip" sharpening of finger-shaped flames; the fewer the number of holes in the obstacle, the higher the sharpness of the fingertip flame. The porous flexible PVC barriers can reduce the rate of flame propagation and creasing of propane deflagration. The porous flexible PVC barriers have a lifting effect on the overpressure of the blast and a delaying effect on the onset of peak overpressure; the larger the number of holes in the barrier, the stronger the delaying effect. [ABSTRACT FROM AUTHOR]

How to realize the ecological protection and high‐quality development (HQD) of the Yellow River Basin (YRB) has become a great challenge for China. Based on panel data from 100 prefecture‐level cities in the YRB from 2006 to 2018, this innovative paper employs the System Generalized Method of Moments (SYS‐GMM) panel model and takes environmental regulation as a situational factor to empirically examine the influence mechanism of industrial agglomeration on HQD in the YRB. Our findings reveal that: (i) overall, a "U‐shaped" relationship exists between industrial agglomeration and HQD in the YRB, and environmental regulation plays a vital role in augmenting their relationship. (ii) Presently, the industrial agglomeration degree prevails on the left side of the threshold value, and the upsurge of industrial agglomeration degree still limits HQD. (iii) From the perspective of river basins, the influence of industrial agglomeration on HQD in the upstream is not significant, and the strengthening effect of environmental regulation is not noticeable. We find a "U‐shaped" relationship between industrial agglomeration and HQD in the midstream, along with notable differences in the correlation between industrial agglomeration and different dimensions of HQD in downstream. This paper helps in further understanding the influence of industrial agglomeration, environmental regulation, and HQD, as well as establishes efficient policies to promote HQD in the YRB and other similar river basins through industrial agglomeration in the context of environmental constraints. [ABSTRACT FROM AUTHOR]

Lithium sulfur (Li-S) battery is considered as a promising alternative for the development of battery technologies. However, the shuttle effect seriously limits its practical use. Herein, hollow tubular graphene-like carbon nitride (Tg-C3N4) is synthesized and utilized as a functional interlayer to inhibit shuttling effect and promote catalytic kinetics. Both experiments and DFT calculations together suggest that N-doping enhances the electron transfers between Tg-C3N4 and LiPSs, leading to improved chemical adsorptions and catalytic effects towards the redox conversions of the active sulfur species. Besides, Tg-C3N4 delivers a unique hollow tubular architecture with massive ion transfer pathways and fully exposed active interfaces. In addition, the abundant C–N heteroatomic structures also impose strong chemical immobilization toward lithium polysulfides. Benefiting from these unique superiorities, the cell with the Tg-C3N4-modified separator exhibits a reversible capacity of 494 mAh g−1 after 500 cycles at 1 C with a negligible capacity decay of 0.085% per cycle, indicating an efficient strategy toward high-performance modified separators. [ABSTRACT FROM AUTHOR]

[Display omitted] • Recent successes of artificial intelligence (AI) and machine learning (ML) techniques can be leveraged to obtain quantitative insights into how intrinsically disordered proteins function. • Review highlights the use of AI/ML techniques to characterize the intrinsic statistical coupling in IDP atomistic fluctuations involved in coupled folding and binding processes using linear, non-linear, and hybrid approaches. • AI/ML methods can also be used to learn force-field parameters from long time-scale simulations as well as used to automatically coarse-grain IDP simulations. • Bayesian inference methods in conjunction with AI/ML methods can be used to integrate sparse experimental observables to obtain a comprehensive picture of how IDPs function. We outline recent developments in artificial intelligence (AI) and machine learning (ML) techniques for integrative structural biology of intrinsically disordered proteins (IDP) ensembles. IDPs challenge the traditional protein structure–function paradigm by adapting their conformations in response to specific binding partners leading them to mediate diverse, and often complex cellular functions such as biological signaling, self-organization and compartmentalization. Obtaining mechanistic insights into their function can therefore be challenging for traditional structural determination techniques. Often, scientists have to rely on piecemeal evidence drawn from diverse experimental techniques to characterize their functional mechanisms. Multiscale simulations can help bridge critical knowledge gaps about IDP structure-function relationships — however, these techniques also face challenges in resolving emergent phenomena within IDP conformational ensembles. We posit that scalable statistical inference techniques can effectively integrate information gleaned from multiple experimental techniques as well as from simulations, thus providing access to atomistic details of these emergent phenomena. [ABSTRACT FROM AUTHOR]

• PTPN1 inhibition improves LPS-induced myocardial damage and cardiac dysfunction through alleviating mitochondrial injury and dysfunction in the cardiomyocytes. • PTPN1 inhibits mitophagy in the cardiomyoblasts following LPS stimulation. • Dephosphorylation of STAT3 at Tyr705 is required for PTPN1 to inhibit mitophagy following LPS exposure. • STAT3 regulates the transcription of Pink1 and Prkn through binding to the SRE in their promoter regions. To investigate the role of protein tyrosine phosphatase non-receptor type 1 (PTPN1) in mitophagy during sepsis and its underlying mechanisms and determine the therapeutic potential of PTPN1 inhibitors in endotoxemia-induced cardiac dysfunction. A mouse model of endotoxemia was established by administering an intraperitoneal injection of lipopolysaccharide (LPS). The therapeutic effect of targeting PTPN1 was evaluated using its inhibitor Claramine (CLA). Mitochondrial structure and function as well as the expression of mitophagy-related proteins were evaluated. Rat H9c2 cardiomyocytes were exposed to mouse RAW264.7 macrophage-derived conditioned medium. Cryptotanshinone, a specific p-STAT3 (Y705) inhibitor, was used to confirm the role of STAT3 in PTPN1-mediated mitophagy following LPS exposure. Electrophoretic mobility shift and dual luciferase reporter assays were performed to discern the mechanisms by which STAT3 regulated the expression of PINK1 and PRKN. CLA alleviated LPS-induced myocardial damage, cardiac dysfunction, and mitochondrial injury and dysfunction in the mouse heart. PTPN1 upregulation exacerbated LPS-induced mitochondrial injury and dysfunction in H9c2 cardiomyocytes, but inhibited LPS-induced mitophagy. LPS promoted the interaction between PTPN1 and STAT3 and reduced STAT3 phosphorylation at Tyr705 (Y705), which was required to inhibit mitophagy by PTPN1. Upon LPS stimulation, PTPN1 negatively regulated the transcription of PINK1 and PRKN through dephosphorylation of STAT3 at Y705. STAT3 regulated the transcription of PINK1 and PRKN by binding to STAT3-responsive elements in their promoters. PTPN1 upregulation aggravates endotoxemia-induced cardiac dysfunction by impeding mitophagy through dephosphorylation of STAT3 at Y705 and negative regulation of PINK1 and PRKN transcription. [ABSTRACT FROM AUTHOR]

Chronic temporomandibular joint (TMJ) pain profoundly affects patients' quality of life. Trigeminal tumor necrosis factor-α (TNFα) plays a pivotal role in mediating TMJ pain in mice, yet the underlying epigenetic mechanisms remain enigmatic. To unravel these epigenetic intricacies, we employed a multifaceted approach. Hydroxymethylated DNA immunoprecipitation (hMeDIP) and chromatin immunoprecipitation (ChIP) followed by qPCR were employed to investigate the demethylation of TNFα gene (Tnfa) and its regulation by ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in a chronic TMJ pain mouse model. The global levels of 5-hydroxymethylcytosine (5hmc) and percentage of 5hmc at the Tnfa promoter region were measured in the trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) following complete Freund's adjuvant (CFA) or saline treatment. TET1 knockdown and pain behavioral testing were conducted to ascertain the role of TET1-mediated epigenetic regulation of TNFα in the pathogenesis of chronic TMJ pain. Our finding revealed an increase in 5hmc at the Tnfa promoter region in both TG and Sp5C of CFA-treated mice. TET1 was upregulated in the mouse TG, and the ChIP result showed TET1 direct binding to the Tnfa promoter, with higher efficiency in the CFA-treated group. Immunofluorescence revealed the predominant expression of TET1 in trigeminal neurons. TET1 knockdown in the TG significantly reversed CFA-induced TNFα upregulation and alleviated chronic TMJ pain. In conclusion, our study implicates TET1 as a vital epigenetic regulator contributing to chronic inflammatory TMJ pain via trigeminal TNFα signaling. Targeting TET1 holds promise for epigenetic interventions in TMJ pain management. [ABSTRACT FROM AUTHOR]

Palmitic acid (PA)-induced myocardial injury is considered a critical contributor to the development of obesity and type 2 diabetes mellitus (T2DM)-related cardiomyopathy. However, the underlying mechanism has not been fully understood. Here, we demonstrated that PA induced the cell death of H9c2 cardiomyoblasts in a dose- and time-dependent manner, while different ferroptosis inhibitors significantly abrogated the cell death of H9c2 cardiomyoblasts and primary neonatal rat cardiomyocytes exposed to PA. Mechanistically, PA decreased the protein expression levels of both heat shock factor 1 (HSF1) and glutathione peroxidase 4 (GPX4) in a dose- and time-dependent manner, which were restored by different ferroptosis inhibitors. Overexpression of HSF1 not only alleviated PA-induced cell death and lipid peroxidation but also improved disturbed iron homeostasis by regulating the transcription of iron metabolism-related genes (e.g., Fth1 , Tfrc , Slc40a1). Additionally, PA-blocked GPX4 protein expression was evidently restored by HSF1 overexpression. Inhibition of endoplasmic reticulum (ER) stress rather than autophagy contributed to HSF1-mediated GPX4 expression. Moreover, GPX4 overexpression protected against PA-induced ferroptosis, whereas knockdown of GPX4 reversed the anti-ferroptotic effect of HSF1. Consistent with the in vitro findings, PA-challenged Hsf 1−/− mice exhibited more serious ferroptosis, increased Slc40a1 and Fth1 mRNA expression, decreased GPX4 and TFRC expression and enhanced ER stress in the heart compared with Hsf 1+/+ mice. Altogether, HSF1 may function as a key defender against PA-induced ferroptosis in cardiomyocytes by maintaining cellular iron homeostasis and GPX4 expression. Unlabelled Image • Ferroptosis is involved in PA-induced cell death in cardiomyocytes. • HSF1 protects cardiomyocytes against PA-induced ferroptosis. • GPX4 is required for the anti-ferroptotic function of HSF1 in PA-induced cardiomyocyte death. • ER stress activation contributes to HSF1-mediated GPX4 expression in PA-challenged cardiomyocytes. [ABSTRACT FROM AUTHOR]

Myocardial ischaemia is usually accompanied by inflammatory response which plays a critical role in the myocardial healing and scar formation, while persistent inflammatory response contributes greatly to the myocardial remodeling and consequent heart failure. Metformin (Met), a widely used hypoglycemic drug, has increasingly been shown to exert remarkable cardioprotective effect on ischaemic myocardial injury such as acute myocardial infarction (AMI). However, the underlying mechanisms are still far from being fully understood. In this study, a mouse model of AMI was established through ligating the left anterior descending coronary artery (LAD), 100 mg/kg Met was given immediately after operation once daily for 3 days. It was demonstrated that Met effectively improved the cardiac haemodynamics (LVSP, LVEDP, +dp/dt, −dp/dt), diminished the infarct size, alleviated the disarrangement of myocardial cells and reduced the infiltration of inflammatory cells (macrophages, neutrophils and lymphocytes) in the heart of AMI mice. Mechanistically, Met decreased the expression of NLRP3 and enhanced the accumulation of LC3 puncta in F4/80-positive macrophages in the heart of AMI mice. Single cell suspension of cardiac macrophages was prepared from AMI mice and exhibited increased NLRP3 mRNA and protein expression. In contrast, Met decreased the expression of NLRP3 and p62, whereas increased the ratio of LC3II/LC3I. Additionally, both conditioned medium from H9c2 cardiomyocytes exposed to hydrogen peroxide (H9c2-H 2 O 2 -CM) and combination of mtDNA and ATP (mtDNA-ATP) increased the expression of NLRP3 and cleaved caspase-1 (p10) as well as intracellular ROS production in RAW264.7 macrophages, which were abrogated by Met treatment. Strikingly, chloroquine (CQ), 3-methyladenine (3-MA) and knockdown of autophagy-related gene (Atg5) abrogated the inhibitory effects of Met on H9c2-H 2 O 2 -CM and mtDNA-ATP-induced NLRP3 expression, release of IL-1β and IL-18 as well as ROS production in RAW264.7 macrophages. Collectively, these findings suggest that Met protects against ischaemic myocardial injury through alleviating autophagy-ROS-NLRP3 axis-mediated inflammatory response in macrophages. Unlabelled Image • Metformin alleviates macrophages-mediated cardiac inflammatory response after AMI. • ROS-induced NLRP3 activation initiates cardiac inflammatory response after AMI. • Autophagy activation mediates the inhibitory effect of metformin on ROS-NLRP3-triggered cardiac inflammatory response. [ABSTRACT FROM AUTHOR]

Purpose: Prediction of Fuhrman nuclear grade is crucial for making informed herapeutic decisions in clear cell renal cell carcinoma (ccRCC). The current study aimed to develop a multi-information fusion model utilizing computed tomography (CT)-based features of tumors and preoperative biochemical parameters to predict the Fuhrman nuclear grade of ccRCC in a non-invasive manner. Methods: 218 ccRCC patients confirmed by histopathology were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent predictors and establish a model for predicting the Fuhrman grade in ccRCC. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration, the 10-fold cross-validation method, bootstrapping, the Hosmer–Lemeshow test, and decision curve analysis (DCA). Results: R.E.N.A.L. Nephrometry Score (RNS) and serum tumor associated material (TAM) were identified as independent predictors for Fuhrman grade of ccRCC through multivariate logistic regression. The areas under the ROC curve (AUC) for the multi-information fusion model composed of the above two factors was 0.810, higher than that of the RNS (AUC 0.694) or TAM (AUC 0.764) alone. The calibration curve and Hosmer–Lemeshow test showed the integrated model had a good fitting degree. The 10-fold cross-validation method (AUC 0.806) and bootstrap test (AUC 0.811) showed the good stability of the model. DCA demonstrated that the model had superior clinical utility. Conclusion: A multi-information fusion model based on CT features of tumor and routine biochemical indicators, can predict the Fuhrman grade of ccRCC using a non-invasive approach. This model holds promise for assisting clinicians in devising personalized management strategies. [ABSTRACT FROM AUTHOR]

Detection of packages or storage containers relies heavily on the use of radio frequency identification (RFID) tagging, though such technology provides no means to determine the quantity of items within them. This paper presents a comprehensive study of ultra wideband (UWB) detection in the reactive near field as a low cost, low power way of detecting solid items within a package to complement RFID. For proof of concept, egg boxes within a smart fridge are used as a chosen test case. Simulations and measurements are carried out to evaluate the filtering of the UWB impulse response from which it can resolve the quantity of eggs in a box, using an array of sensors either attached to the package or placed underneath. Correlation coefficients are derived as a metric of this filtering in a reactive near field detection scenario. The robustness of the approach is further evaluated by considering other food cluttered around and above the egg box. The results show smart packages which detect an item directly above the sensor is not affected by surrounding clutter. [ABSTRACT FROM AUTHOR]

We investigate the light absorption in an ultrathin crystalline silicon solar cell with composite grating structures using three dimensional rigorous coupled wave analysis. Comparing with conventional surface gratings, the composite grating which is a superposition of two subgratings with different length scales demonstrates efficient light trapping in thin film solar cells in a broad spectral range. The light absorption is found to be close to the Yablonovitch limit in both visual and infrared regions. The optimized structure yields an ideal photocurrent density of 33.9 mA/cm 2 at an equivalent thickness of 2 µm. This is comparable to the performance of the recently proposed double-sided grating design (Wang et al., 2012 [19]). These results suggest that the composite grating structures promise efficiency enhancement in ultrathin solar cells with improved technology compatibility. [ABSTRACT FROM AUTHOR]

Membership determination of text strings has been an important procedure for analyzing textual data of a tremendous amount, especially when time is a crucial factor. Bloom filter has been a well-known approach for dealing with such a problem because of its succinct structure and simple determination procedure. As determination of membership with classification is becoming increasingly desirable, parallel Bloom filters are often implemented for facilitating the additional classification requirement. The parallel Bloom filters, however, tend to produce additional false-positive errors since membership determination must be performed on each of the parallel layers. We propose a scheme based on CMAC, a neural network mapping, which only requires a single-layer calculation to simultaneously obtain information of both the membership and classification. A hash function specifically designed for text strings is also proposed. The proposed scheme could effectively reduce false-positive errors by converging the range of membership acceptance to the minimum for each class during the neural network mapping. Simulation results show that the proposed scheme committed significantly less errors than the benchmark, parallel Bloom filters, with limited and identical memory usage at different classification levels. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of left ventricular (LV) diastolic dysfunction on left atrial (LA) phasic volume and function using dual-source CT (DSCT) and to find a viable alternative prognostic parameter of CT for LV diastolic dysfunction through quantitative evaluation of LA phasic volume and function in patients with LV diastolic dysfunction. Materials and Methods: Seventy-seven patients were examined using DSCT and Doppler echocardiography on the same day. Reservoir, conduit, and contractile function of LA were evaluated by measuring LA volume (LAV) during different cardiac phases and all parameters were normalized to body surface area (BSA). Patients were divided into four groups (normal, impaired relaxation, pseudonormal, and restrictive LV diastolic filling) according to echocardiographic findings. The LA phasic volume and function in different stages of LV diastolic function was compared using one-way ANOVA analysis. The correlations between indexed volume of LA (LAVi) and diastolic function in different stages of LV were evaluated using Spearman correlation analysis. Results: LA ejection fraction (LAEF), LA contraction, reservoir, and conduit function in patients in impaired relaxation group were not different from those in the normal group, but they were lower in patients in the pseudonormal and restrictive LV diastolic dysfunction groups (P < 0.05). For LA conduit function, there were no significant differences between the patients in the pseudonormal group and restrictive filling group (P = 0.195). There was a strong correlation between the indexed maximal left atrial volume (LAVmax, r = 0.85, P < 0.001), minimal left atrial volume (LAVmin, r = 0.91, P < 0.001), left atrial volume at the onset of P wave (LAVp, r = 0.84, P < 0.001), and different stages of LV diastolic function. The LAVi increased as the severity of LV diastolic dysfunction increased. Conclusions: LA remodeling takes place in patients with LV diastolic dysfunction. At the same time, LA phasic volume and function parameters evaluated by DSCT indicated the severity of the LV diastolic dysfunction. Quantitative analysis of LA phasic volume and function parameters using DSCT could be a viable alternative prognostic parameter of LV diastolic function. [ABSTRACT FROM AUTHOR]

Objective To observe the histological changes of lung tissues after poisoned by paraquat, and explore the expressions of hemeoxygenase-1 (HO-l) in lung of paraquat poisoning rats. Methods One hundred and fifty SD male rats were randomly divided into 3 groups: normal control group (C) 30 rats, paraquat poisoning group (PQ) 60 rats and drug intervention group (PNS) 60 rats. The PQ and PNS group rats were given paraquat by gastric perfusion (25 mg/kg) ; The C group rats were given saline by gastric perfusion. The rats in PNS group were protected by intravenous injections of penis with PNS (50 mg/kg) 15 min before exposure of paraquat, once a day until killed. The PQ and C group rats were given saline. Histological changes of lung tissues under light microscope were observed. The expression of HO-1mRNA in lung tissues of rats were measured by RT-PCR and The HO-1 protein was evaluated by western blot at different time of 6 h. 12 h. 1 d .3 d and 7d after poisoning. Results The degree of lung injury in PQ group was higher than that in C group. But in PNS group the degree of lung injury was lighter. The relative magnitude expression of HO-1 mRNA and HO-1 protein in group C were weak or no. The relative magnitude expression of HO-1 mRNA and HO-1 protein in PNS (6 h), PNS (I2h) PNS (id) and PNS (3d) subgroups were significantly higher as compared with the PQ group (P<0.05) . Conclusions PNS can effectively improve the expression of HO-1 protein and mRNA in lung tissue and reduce the pathological changes of lung tissue in rats with paraquat poisoning. [ABSTRACT FROM AUTHOR]

Objective: A recent international, multicenter, double-blinded, randomized trial shows delayed-enhanced magnetic resonance imaging (DE-MRI) using contrast doses of ≥0.2mmol/kg is effective in the detection and assessment of myocardial infarction (MI), and 0.1mmol/kg is not enough; intermediate doses between 0.1 and 0.2mmol/kg have not been tested. The aim of this study was to prospectively test the performance of DE-MRI using 0.15mmol/kg of contrast agent for the detection of MI. Materials and methods: A total of 31 consecutive patients with chronic MI underwent DE-MRI at 3.0T using both 0.15mmol/kg and 0.2mmol/kg of contrast agent in random order and on separate days. Infarction segment and infarction size were compared on DE-MRI images using a 17-segment model. Bland–Altman analysis was used to analyze correlation and agreement between global infarct sizes. Results: DE-MRI showed enhanced myocardium in all the 31 patients with chronic MI. There was no significant difference between the 0.15mmol/kg and 0.2mmol/kg images in all 31 patients based on the infarction segment (7.87±2.72 vs. 7.81±2.64, respectively; p =0.33). There was no significant difference between the infarction size obtained from 0.15mmol/kg acquisition and that from 0.2mmol/kg acquisition (16.3±7.8% vs. 16.4±7.9%, respectively; p =0.87). A strong correlation between the infarction size obtained from 0.15mmol/kg acquisition and that from 0.2mmol/kg acquisition was indicated through Bland–Altman analysis. Conclusion: DE-MRI at 3.0T using 0.15mmol/kg of contrast agent is effective for the assessment of MI. [ABSTRACT FROM AUTHOR]

Two kinds of tetranuclear Zn(ii) molecular clusters with the designed aroylhydrazone Schiff base ligand (H3L), [Zn4(HL)4]·3(DMF)·3(H2O) (1) and [Zn4(HL)2(CH3COO)4]·2(DMF)·2(CH3OH) (2), have been synthesized and studied. Molecular cluster 1 displayed a Zn4O4 boat-shaped core and 2 presented a discrete linear tetranuclear Zn(ii) structure. The luminescent properties of the two molecular clusters have been investigated, which exhibit a wide range of photo-luminescence in different organic solvents. [ABSTRACT FROM AUTHOR]

To better understand the formation mechanism of carbonate minerals by microbes, culture experiments with a duration of 70 days were performed under the mediation of strain GW-M isolated from soil using modified Lagoa Vermelha (LV, a hypersaline coastal Lagoon, Rio de Janeiro, Brazil) medium with 6:1 Mg/Ca molar ratio. The results demonstrated that strain GW-M can mediate the formations of both high-Mg calcite and aragonite and that dumbbell-, cauliflower-, rhombohedra-shaped, and irregular minerals coexist in the modified LV medium. The amount of rhombohedra-shaped crystals increased significantly with culture time. A proposed mechanism for these formations is the following. Heterogeneous nucleation on the surface of the extracellular polymeric substances (EPS) always occurred, and carbonates with irregular shape existed in experimental products at any stages. The morphologies evolved from rod to dumbbell and finally to cauliflower. At the initial stage (till day 20), hydrogen ions and EPS secreted by the bacteria only influenced the microenvironment around the cells, and carbonates were precipitated on the surface of bacterial cells. At the middle and late stages (on days 45 and 70), microbes and their secretions influenced the whole medium. Under these conditions, rhombohedra-shaped crystals were formed when homogeneous nucleation occurred. In addition, the results of energy-dispersive spectrometry (EDS) showed that Mg contents in the synthesized carbonate minerals with rhombohedra-shaped were significantly lower than those of carbonates with other shapes, though relationship between morphology and species of mineral cannot be obtained by this phenomenon alone. These results shed further light on the mechanism of carbonate precipitation in the presence of microbes. [ABSTRACT FROM PUBLISHER]

• Plasma boron-nitriding was primarily developed for 42CrMo4 steel. • Saw-tooth-shaped boron-iron compounds of FeB and Fe 2-3 B were formed. • The surface hardness was increased from 750HV0.05 to 1002HV0.05. • The effective diffusion layer was increased about 35%. • The wear rate is decreased from 3.06 mg/cm2 to 1.02 mg/cm2. In order to further enhance the performance of the components previously treated by plasma nitriding (PN) and meet the technical requirements proposed by the cooperative enterprise, plasma boron-nitriding (PNB) was primarily developed for 42CrMo4 steel at 520 °C for 6 h by adding a little Ferroboron around the samples during the process of plasma nitriding. The results show that plasma boron-nitriding (PNB) can significantly increase the surface hardness of the sample from 750HV 0.05 to 1002HV 0.05 due to the formation of very hard borides of FeB and Fe 2 B, and the thickness of compound layer is increased from 18.78um to 29.44um, the effective diffusion layer is increased from 265um to 355um, which is equivalent to an increase of nitriding efficiency by about 35%. At the same time, the wear resistance of the samples treated by PNB is significantly enhanced, the wear marks turns to be much shallower and narrower, and the wear rate is decreased from 3.06 mg/cm2 to 1.02 mg/cm2. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes an experimental investigation for physical properties of fluorinated phenyl bicyclohexane liquid crystals (LCs) mixtures. Measurements are reported of the large anisotropic dielectric properties of two structurally similar LCs (1,2-difluoro-4-[trans-4-(trans-4-propylcyclohexyl)cyclohexyl] benzene and 1-cyano-2-fluoro-4-[trans-4-(trans-4-propylcyclohexyl) cyclohexyl] benzene) mixed with a zero dielectric anisotropic LC (1-methyl-2-fluoro-4-[trans-4-(trans-4-ethylcyclohexyl) cyclohexyl] benzene). The results indicate that the mixing proportions strongly influence the dielectric constants along with the longer molecular axis. For two samples which is made from meta-para- or meta-fluorine substituted molecules, the temperature dependence of the anisotropic dielectric striking resemble that of a unitary compound with para-fluorine substituted. The threshold voltage of the mixtures relies on the element that possesses a large dielectric anisotropic. The mixing of the materials leads to a slight increase for splay elastic constants in an anti-parallel measurement cell. [Copyright &y& Elsevier]

Transverse arrangement is one of the main methods used in the polar inertial navigation system (INS). In the traditional algorithm, the calculation of using the earth ellipsoid model is complex, while using the earth sphere model cannot satisfy a high-accuracy application. Therefore, an approach based on the virtual sphere model is proposed, which has been proved in simulation experiments to reduce the computational complexity and maintain the same accuracy as the ellipsoid algorithm, but its accuracy has not yet been proved in theory. Starting from the basic principles of the ellipsoid and virtual sphere model algorithm, this paper compares the key formulations of the two. Finally, it is proved that the two arrangements are actually the same. [ABSTRACT FROM AUTHOR]

Clear cell renal carcinoma (ccRCC) is the most common histological type of renal cancer and has the highest mortality. Several studies have been conducted on the relationship between adipose tissue and ccRCC prognosis, however, the results have been inconsistent to date. The current study aimed at establishing a link between abdominal fat composition and short-term prognosis in patients with ccRCC after T-stage stratification. We retrospectively analysed 250 patients with pathologically confirmed ccRCC (173 low T-stage and 77 high T-stage) in our hospital. The computed tomography (CT) images were evaluated using ImageJ. Then, subcutaneous and visceral fat areas (SFA and VFA), total fat areas (TFA) and the relative VFA (rVFA) were measured and computed. Meanwhile, biochemical indices of blood serum were analysed. The results showed that rVFA in low T-stage cohort who had a history of short-term postoperative complications were significantly lower than those who did not. No such association was observed in the high T-stage cohort. Further investigation revealed that the correlations between biochemical indexes and fat area-related variables varied across T-stage groups. As a result, rVFA is a reliable independent predictor of short-term prognosis in patients with low T-stage ccRCC but not in patients with high T-stage ccRCC. [ABSTRACT FROM AUTHOR]

In view of the low accuracy of the motion parameters generated by the typical ship trajectory generator, and the fact that the problem of wind, current and wave interference is not considered, this paper establishes a new ship trajectory generator by analyzing the changes in the ship's attitude and speed under different motion states. Through simulation, the accuracy of the main motion parameters is significantly improved compared with the typical trajectory generator; the time-varying non-uniform wind, current and wave fields are constructed, and the interference effect of wind, current and waves on ship motion is analyzed by combining the empirical formulas of force and moment; an adaptive neuro fuzzy inference system (ANFIS) based on wind, current and wave interference is designed, and the fuzzy rules of the fuzzy system are determined by training and testing the measured data; the motion parameters of superimposed wind, current and wave interference are compared with the measured data, and the accuracy is further improved after superimposing wind, current and wave interference. [ABSTRACT FROM AUTHOR]

Myocardial perfusion magnetic resonance imaging (MRI) with sliding-window conjugate-gradient highly constrained back-projection reconstruction (SW-CG-HYPR) allows whole left ventricular coverage, improved temporal and spatial resolution and signal/noise ratio, and reduced cardiac motion-related image artifacts. The accuracy of this technique for detecting coronary artery disease (CAD) has not been determined in a large number of patients. We prospectively evaluated the diagnostic performance of myocardial perfusion MRI with SW-CG-HYPR in patients with suspected CAD. A total of 50 consecutive patients who were scheduled for coronary angiography with suspected CAD underwent myocardial perfusion MRI with SW-CG-HYPR at 3.0 T. The perfusion defects were interpreted qualitatively by 2 blinded observers and were correlated with x-ray angiographic stenoses ≥50%. The prevalence of CAD was 56%. In the per-patient analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SW-CG-HYPR was 96% (95% confidence interval 82% to 100%), 82% (95% confidence interval 60% to 95%), 87% (95% confidence interval 70% to 96%), 95% (95% confidence interval 74% to100%), and 90% (95% confidence interval 82% to 98%), respectively. In the per-vessel analysis, the corresponding values were 98% (95% confidence interval 91% to 100%), 89% (95% confidence interval 80% to 94%), 86% (95% confidence interval 76% to 93%), 99% (95% confidence interval 93% to 100%), and 93% (95% confidence interval 89% to 97%), respectively. In conclusion, myocardial perfusion MRI using SW-CG-HYPR allows whole left ventricular coverage and high resolution and has high diagnostic accuracy in patients with suspected CAD. [Copyright &y& Elsevier]

Abstract: Alcohol consumption leads to myocardial contractile dysfunction possibly due to the toxicity of ethanol and its major metabolite acetaldehyde. This study was designed to examine the influence of mitochondrial aldehyde dehydrogenase-2 (ALDH2) knockout (KO) on acute ethanol exposure-induced cardiomyocyte dysfunction. Wild-type (WT) and ALDH2 KO mice were subjected to acute ethanol (3g/kg, i.p.) challenge and cardiomyocyte contractile function was assessed 24h later using an IonOptix edge detection system. Western blot analysis was performed to evaluate ALDH2, protein phosphatase 2A (PP2A), phosphorylation of Akt, and glycogen synthase kinase-3β (GSK-3β). ALDH2 KO accentuated ethanol-induced elevation in cardiac acetaldehyde levels. Ethanol exposure depressed cardiomyocyte contractile function including decreased cell shortening amplitude and maximal velocity of shortening/relengthening as well as prolonged relengthening duration and a greater decline in peak shortening in response to increasing stimulus frequency, the effect of which was significantly exaggerated by ALDH2 KO. ALDH2 KO also unmasked an ethanol-induced prolongation of shortening duration. In addition, short-term in vitro incubation of ethanol-induced cardiomyocyte mechanical defects was exacerbated by the ALDH inhibitor cyanamide. Ethanol treatment dampened phosphorylation of Akt and GSK-3β associated with upregulated PP2A, which was accentuated by ALDH2 KO. ALDH2 KO aggravated ethanol-induced decrease in mitochondrial membrane potential. These results suggested that ALDH2 deficiency led to worsened ethanol-induced cardiomyocyte function, possibly due to upregulated expression of protein phosphatase, depressed Akt activation, and subsequently impaired mitochondrial function. These findings depict a critical role of ALDH2 in the pathogenesis of alcoholic cardiomyopathy. [Copyright &y& Elsevier]

Abstract: This paper proposes a real-time water quality monitoring scheme, which is based on judging time-series motion trajectories of live fish acquired by a CCD camera. The proposed scheme includes a floating-grid method to extract patterns in the motion trajectories and a neural network mechanism to quickly determine the frequency of pattern changes in these trajectories. To validate the proposed methods, several experiments were conducted by changing pH values of the water that houses live fish. The experimental results showed that the proposed methods could effectively differentiate motion trajectories of the fish in an efficient manner. The proposed scheme could be employed as a precautionary warning system for aquatic farms, drinking water treatment plants, and other related industries. [Copyright &y& Elsevier]

1. Cisplatin is a potent chemotherapeutic agent with broad-spectrum antineoplastic activity against various types of tumours. However, a major factor limiting treatment with cisplatin is its acute and cumulative cardiotoxicity. The aim of the present study was to explore the effect of cisplatin on myocardial contractile function and the possible underlying cellular mechanisms. 2. C57 mice were treated with cisplatin (10 mg/kg per day, i.v.) or vehicle (0.9% NaCl) for 1 week and myocardial function was assessed using the Langendorff and cardiomyocyte edge-detection systems. Transmission electron microscopy, mitochondrial membrane potential, indices of endoplasmic reticulum (ER) stress and caspase 3 activity were evaluated. 3. Cisplatin-treated mice developed myocardial contractile dysfunction, as evidenced by a reduction in left ventricular developed pressure (LVDP) and the first derivative of LVDP (+/−dP/dt). Cisplatin treatment significantly prolonged time to 90% relengthening, depressed peak shortening, maximal velocity of shortening/relengthening (+/−dL/dt) and augmented the frequency-elicited depression in peak shortening. The JC-1 fluorescent assay demonstrated that cispatin-induced cardiac dysfunction was associated with mitochondrial membrane depolarization. Transmission electron microscopy revealed that cisplatin induces ultrastructural abnormalities of the mitochondria. Following cisplatin treatment, cardiomyocytes show activation of the ER stress response, increased caspase 3 activity and increased terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL) staining. 4. The data indicate that cisplatin is cardiotoxic and may lead to left ventricular dysfunction and depressed cardiomyocyte contraction associated with mitochondrial abnormalities, enhanced ER stress and apoptosis. This work should shed some light on the management of cisplatin-induced cardiac injury. [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to evaluate the role of facilitated detoxification of acetaldehyde, the main metabolic product of ethanol, through systemic overexpression of mitochondrial aldehyde dehydrogenase-2 (ALDH2) on acute ethanol exposure-induced myocardial damage. Background: Binge drinking may exert cardiac toxicity and interfere with heart function, manifested as impaired ventricular contractility, although the underlying mechanism remains poorly defined. Methods: ALDH2 transgenic mice were produced using the chicken beta-actin promoter. Wild-type FVB (friend virus B) and ALDH2 mice were challenged with ethanol (3 g/kg, intraperitoneally), and cardiac function was assessed 24 h later using the Langendroff and cardiomyocyte edge-detection systems. Western blot analysis was used to evaluate protein phosphatase 2A and 2C (PP2A and PP2C), phosphorylation of Akt, AMP-activated protein kinase (AMPK), and the transcription factors Foxo3 (Thr32 and Ser413). Results: ALDH2 reduced ethanol-induced elevation in cardiac acetaldehyde levels. Acute ethanol challenge deteriorated myocardial and cardiomyocyte contractile function evidenced by reduction in maximal velocity of pressure development and decline (±dP/dt), left ventricular developed pressure, cell shortening, and prolonged relengthening duration, the effects of which were alleviated by ALDH2. Ethanol treatment dampened phosphorylation of Akt and AMPK associated with up-regulated PP2A and PP2C, which was abrogated by ALDH2. ALDH2 significantly attenuated ethanol-induced decrease in Akt- and AMPK-stimulated phosphorylation of Foxo3 at Thr32 and Ser413, respectively. Consistently, ALDH2 rescued ethanol-induced myocardial apoptosis, protein damage, and mitochondrial membrane potential depolarization. Conclusions: Our results suggest that ALDH2 is cardioprotective against acute ethanol toxicity, possibly through inhibition of protein phosphatases, leading to enhanced Akt and AMPK activation, and subsequently, inhibition of Foxo3, apoptosis, and mitochondrial dysfunction. [Copyright &y& Elsevier]

Abstract: Oxidative stress and endoplasmic reticulum (ER) stress have been implicated in cardiovascular diseases although the interplay between the two is not clear. This study was designed to examine the influence of oxidative stress through glutathione depletion on myocardial ER stress and contractile function in the absence or presence of the heavy metal scavenger antioxidant metallothionein (MT). FVB and MT overexpression transgenic mice received the GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mM) in drinking water for 2 weeks. Oxidative stress, ER stress, apoptosis, cardiac function and ultrastructure were assessed using GSH/GSSG assay, reactive oxygen species (ROS), immunoblotting, caspase-3 activity, Langendorff perfused heart function (LVDP and ±dP/dt), and transmission electron microscopy. BSO led to a robust decrease in the GSH/GSSG ratio and increased ROS production, consolidating oxidative stress. Cardiac function and ultrastructure were compromised following BSO treatment, the effect of which was obliterated by MT. BSO promoted overt ER stress as evidenced by upregulated BiP, calregulin, phospho-IRE1α and phospho-eIF2α without affecting total IRE1α and eIF2α. BSO treatment led to apoptosis manifested as elevated expression of CHOP/GADD153, caspase-12 and Bax as well as caspase-3 activity, reduced Bcl-2 expression and JNK phosphorylation, all of which was ablated by MT. Moreover, both antioxidant N-acetylcysteine and the ER stress inhibitor tauroursodeoxycholic acid reversed the oxidative stress inducer menadione-elicited depression in cardiomyocyte contractile function. Taken together, these data suggested that ER stress occurs likely downstream of oxidative stress en route to cardiac dysfunction. [Copyright &y& Elsevier]

The terahertz (THz) spectrum absorptions of nematic liquid crystal (LC) material, i.e. N-(p-methoxybenzylidene)-p-butylaniline (MBBA), and its relevant compounds are simulated in this paper by using the density functional theory (DFT) method. A strong absorptive frequency is located at 3.65 THz for the MBBA, which is in agreement with experimental data found in the literature. The result suggests that the DFT method is effective for dealing with the anisotropic nematic LC compounds. [ABSTRACT FROM AUTHOR]

Oxazolidin-2-one was found to be a versatile and efficient ligand for the CuI-catalyzed amidation of aryl halides and the cyclization of ortho-halobenzanilides. Notably, the less active halides could also be applied successfully in the synthesis of benzoxazoles and benzothiazoles. [ABSTRACT FROM AUTHOR]

Oxazolidin-2-one was found to be a versatile and efficient ligand for the CuI-catalyzed amidation of aryl halides and the cyclization of ORTHO-halobenzanilides. Notably, the less active halides could also be applied successfully in the synthesis of benzoxazoles and benzothiazoles. [ABSTRACT FROM AUTHOR]

Abstract: Layout has a close relationship with product cost in the vein of how to most efficiently cut product patterns from raw materials. This is the so-called “nesting problem”, which occurs frequently in sheet metal and furniture industries, wherein material utilization needs to be maximized. In this paper, a quick location and movement (QLM) algorithm is proposed to solve the situation of irregular shapes nested on multiple irregular sheets. This approach includes two major parts: it first approximates irregular shapes to a polygon with the use of a cluster of straight lines, and second, it arranges the approximated shapes one-by-one with the proposed step-by-step rule. Finally, this study investigates and compares examples presented by other authors. The results show that the QLM algorithm takes less time to calculate a layout and the material utilization efficiency is higher compared to other methods. [Copyright &y& Elsevier]

Abstract: The world wide web (WWW) has become the largest information archive in the world because of its connectivity and scalability. Web pages, identified by URLs, are the basic forms for transmitting the requested information to clients’ PC, whose number continuously explodes. There are a large portion of the web pages containing undesirable content, such as pornography, crimes, drugs and terrorisms, which makes viewers’ discretion necessary. The large number of the undesirable web pages, however, has made the blocking more difficult on a client PC, because checking through the large collection of URLs is a time-consuming task. We propose a neural network method for determining the existing status of a requested URL in the large prohibited collection. The large prohibited URL collection containing 400,000 URLs was obtained by specifying a number of keywords, e.g. “porn” or “sex”, on several commercial search engines. The simulation results show superior performances in both memory requirement and speed, comparing with a database implementation on the same PC. [Copyright &y& Elsevier]

Temperature dependence of ratio between dielectric anisotropy and order parameter of fluorinated nematic liquid crystal is investigated by using a semi-empirical molecular orbital package that can accurately calculate an angle between molecular dipole moment and long axis. We optimize the molecular conformations with three semi-empirical Hamiltonians AM1, PM3 and PM5, and then make a comparison between computational results and experimental measurements. It is shown that the results obtained from AM1 method are in good agreement with the measurements. The present study offers an applicable method to predict the dielectric properties of liquid crystal material. [ABSTRACT FROM AUTHOR]

Abstract: The SAC-CI method is used to investigate the spectroscopic properties of 7Li2(). The adiabatic potential energy curves are calculated and fitted to the analytic Murrell–Sorbie function. The spectroscopic parameters reproduced by the potential attained at cc-PVTZ are found to be very close to the experiments. With the potential obtained at the SAC-CI/cc-PVTZ level of theory, a total of 62 vibrational states is found when J =0. For each vibrational state, the vibrational level, classical turning points, inertial rotation and centrifugal distortion constants are calculated. Good agreement is obtained when they are compared with the available RKR data. [Copyright &y& Elsevier]

A synthetic investigation on oxidation of anilines to 2-amino-1,4-benzoquinone-4-phenylimides via Dess-Martin periodinane (DMP) was carried out. This facile protocol offered the advantage of short reaction times, mild reaction conditions, high yields and compatibility with a wide range of functional groups. [ABSTRACT FROM AUTHOR]

Abstract: A mild, efficient, and environmentally friendly procedure for the oxidation of alcohols with polymer-supported IBX in the presence of N(CH2CH3)3 in CH2Cl2 has been developed. This reagent has advantages over traditionally supported IBX reagents because of simplified preparation method and a high oxidation activity of 1.5mmol/g. [Copyright &y& Elsevier]

Abstract: Objectives: The objectives of this study were to investigate the vasculoprotective effects of glucose–insulin–potassium (GIK) on ischemia/reperfusion-induced coronary endothelial functional injury and to elucidate the mechanism involved. Methods: Dogs were subjected to 50 min of coronary occlusion and 4 h of reperfusion. Vehicle, GIK, or GK were intravenously infused 5 min before reperfusion, and the coronary vascular dysfunction and endothelial apoptosis were determined. In a separate study, cultured endothelial cells were subjected to simulated ischemia/reperfusion, and the signaling pathway involved in insulin''s anti-apoptotic effect was investigated. Results: In vivo ischemia/reperfusion caused significant coronary vascular endothelial dysfunction as evidenced by reduced endothelium-dependent vasorelaxation, decreased nitric oxide (NO) production, and endothelial cell apoptosis as determined by caspase 3 activation and TUNEL staining. Treatment with GIK, but not GK, markedly improved the endothelium-dependent coronary vasorelaxation (P <0.01 versus vehicle), increased total NO production (P <0.01), and attenuated endothelial apoptosis. In cultured endothelial cells, treatment with insulin also markedly increased NO production and reduced simulated ischemia/reperfusion-induced apoptosis. Moreover, pre-treatment with either Akt inhibitor or NO synthase inhibitor almost abolished the anti-apoptotic effect exerted by insulin but not by SNAP, an NO donor. Conclusion: These results demonstrate that in vivo treatment with GIK at reperfusion attenuates ischemia/reperfusion-induced coronary endothelial dysfunction and endothelial apoptosis in an Akt-dependent and NO-mediated fashion. The coronary vasculoprotective effect elicited by insulin may contribute to the previously observed cardiac protective effect of GIK. [Copyright &y& Elsevier]