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Atherosclerosis (AS) is one of the most common causes of death from cardiovascular disease, and low folic acid (FA) levels have been reported to be strongly associated with an increased risk of AS. We aimed to obtain causal estimates of the association between FA and AS and to quantify the mediating role of known modifiable risk factors. Based on the largest genome-wide association study (GWAS) from the IEU Open GWAS Project for all human studies, we conducted a two-sample Mendelian randomization (MR) study of genetically predicted FA and AS. A two-step MR design was then used to assess the causal mediating effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) on the relationship between FA and AS. This MR analysis showed that genetically determined FA levels [IVW: Odds Ratio (OR) = 0.623, 95% CI 0.421–0.924, P = 0.018] were associated with a reduced risk of AS. Inverse variance weighted (IVW) MR analysis also showed that genetically predicted FA was positively correlated with HDL-C levels (OR = 1.358, 95% CI 1.029–1.792, P = 0.031) and negatively correlated with LDL-C (OR = 0.956, 95% CI 0.920–0.994, P = 0.023) and TG levels (OR = 0.929, 95% CI 0.886–0.974, P = 0.003). LDL-C, HDL-C, and TG mediate 3.00%, 6.80%, and 4.40%, respectively, of the total impact of FA on AS. The combined effect of these three factors accounts for 13.04% of the total effect. Sensitivity analysis verifies the stability and reliability of the results. These results support a potential causal protective effect of FA on AS, with considerable mediation through many modifiable risk factors. Thus, interventions on levels of LDL-C, HDL-C, and TG have the potential to substantially reduce the burden of AS caused by low FA. [ABSTRACT FROM AUTHOR]

Fractional flow reserve (FFR) has become the gold standard for evaluating coronary lesion-specific ischemia. However, FFR is an invasive method that may cause possible complications in the coronary artery and requires expensive equipment, which limits its use. Promising noninvasive diagnostic methods, such as computed tomography angiography–derived FFR (CT-FFR) and the quantitative flow ratio (QFR), have been proposed. In this study, we evaluated the diagnostic performance of the QFR and CT-FFR in predicting coronary lesion-specific ischemia, with the FFR serving as the reference standard. Patients with suspected or known coronary artery disease who underwent coronary CT angiography revealing 30–90% diameter stenosis in the main coronary artery (≥ 2.0 mm reference diameter) were enrolled. The FFR was measured during invasive coronary angiography (within 15 days after coronary CT angiography). An FFR ≤ 0.8 was the reference standard for coronary lesion-specific ischemia. A total of 103 vessels from 92 consecutive patients (aged 59.8 ± 9.2 years; 60.9% were men) were evaluated. The diagnostic performance of a QFR ≤ 0.80 for predicting coronary lesion-specific ischemia demonstrated good diagnostic accuracy, sensitivity, and specificity (92.2%, 87.2%, and 96.4%, respectively), with an area under the receiver operating characteristic curve (AUC) of 0.987 (P < 0.0001). The diagnostic performance of a CT-FFR ≤ 0.80 for predicting coronary lesion-specific ischemia also demonstrated good diagnostic accuracy, sensitivity, and specificity (96.1%, 95.7%, and 96.4%, respectively), with an AUC of 0.967 (P < 0.0001). However, there was no significant difference in the AUC between a QFR ≤ 0.80 and a CT-FFR ≤ 0.80 for predicting coronary lesion-specific ischemia (P = 0.319). There was an excellent correlation between the QFR and FFR (r = 0.856, P < 0.0001). The CT-FFR and FFR also showed a good direct correlation (r = 0.816, P < 0.0001). The QFR and CT-FFR are strongly correlated with the FFR and can provide excellent clinical diagnostic performance for coronary lesion-specific ischemia detection. [ABSTRACT FROM AUTHOR]

Background: Specific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis. Methods: To probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host's metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota. Results: Following the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI. Conclusion: This study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB's role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies. [ABSTRACT FROM AUTHOR]

We examine the impact of digital transformation on a firm's ESG performance using data from listed firms in China. Leveraging the recent advances in textual analysis, we quantify the extent of a firm's digital transformation. The results show that digital transformation enhances a firm's ESG performance. Moreover, results remain robust after addressing endogeneity problems and several robustness tests. In addition, we validate potential mechanisms that the digital transformation mainly improves the ESG performance of firms by improving the level of environmental performance, corporate social responsibility, and corporate governance. To examine the economic consequence, we find that digital transformation gains more government subsidies and analysts' attention increasing the management's positive tone at the earnings communication conferences by improving the firm's ESG performance. Heterogeneity analysis suggests that the effect of digital transformation on ESG performance is stronger for firms in severely polluting industries and executives with information technology experience. [ABSTRACT FROM AUTHOR]

Coronary heart disease is a cardiovascular disease with high morbidity and mortality. Although great progress has been made in treatment, the prognosis is still very poor. Therefore, this project aims to screen potential diagnostic markers and therapeutic targets related to the progression of coronary heart disease. A total of 94 overlapping differentially expressed mRNAs and 70 differentially expressed miRNAs were identified from GSE20681, GSE12288, GSE49823, and GSE105449. Through a series of bioinformatics methods and experiment, we obtained 5 core miRNA-mRNA regulatory pairs, and selected miR-338-3p/RPS23 for functional analysis. Moreover, we found that RPS23 directly targets miR-338-3p by dual luciferase assay, western, and qPCR. And the expression of miR-338-3p and RPS23 is negatively correlated. The AUC value of miR-338-3p is 0.847. Downregulation of miR-338-3p can significantly inhibit the proliferation and migration of HUVEC. On the contrary, overexpression of miR-338-3p promoted the proliferation and migration of HUVEC. In addition, the interference of RPS23 expression can reverse the regulation of miR-338-3p on HUVEC proliferation. In conclusion, miR-338-3p/RPS23 may be involved in the progression of coronary heart disease, and miR-338-3p may be a diagnostic biomarker and therapeutic target for coronary heart disease. [ABSTRACT FROM AUTHOR]

Proton Exchange Membrane Fuel Cells (PEMFCs) are regarded as a promising system for power generation and energy sources in recent years. PEMFCs exhibit various advantages in comparison to other traditional energy sources especially due to their requirement for Hydrogen and air for operation while the final product is only water. Thus, the PEMFCs have received great attention for investigation of the operation under various conditions. In recent years, many researchers have done lots of mathematical modeling, but because of exact modeling absence, evolutionary optimization methods are used to adopt for parameter estimation of PEMFCs. This paper suggested a novel optimization scheme, namely, chaotic binary shark smell optimization (CBSSO), to optimize unknown parameters of PEMFC model. The CBSSO is a Meta-Heuristic algorithm which is introduced newly and has shown an appropriate ability in parameter identification and optimization cases. Moreover, the results of this proposed method are compared with some other results including typical SSO, Hybrid Artificial Bee Colony, Adaptive RNA Genetic Algorithm, Real-coded GA, Modified Particle Swarm Optimization, and Artificial Immune System. Based on the obtained results, this proposed method is very efficient in convergence and accuracy aspects compared to other famous methods. [ABSTRACT FROM AUTHOR]

Blockchain technology has the potential to reduce transaction errors and enhance the quality of reporting significantly. This article proposes a conceptual blockchain‐based protocol, labelled Smart Ledger, as a replacement for the traditional accounting information recording system. A smart ledger is a computerized algorithm that utilizes blockchain technology to perform accounting ledger functions. Its validity is based on two mechanisms within the blockchain architecture: Fractional Accounting Transactions (FAT) and Hierarchical Accounting Transaction Execution (HATE). As such, the smart ledger is a hybrid protocol that combines accounting information recording principles with the immutability of blockchain technology. If widely implemented, it could have a significant impact on accounting practices and the accounting profession. [ABSTRACT FROM AUTHOR]

Wearable temperature sensors can obtain and convey accurate temperature information on the human body and objects. However, most reported wearable temperature sensors suffer from limitations, such as high fabrication cost and low working efficiency, sensing performance, and scalability, which impede their broad application in wearable fields. In this work, a new type of metal–semiconductor–metal (MSM) self-gated device based on NiO/Ni heterostructure frameworks is fabricated and employed in wearable high-performance temperature sensors. The MSM self-gated device is prepared via a facile and controllable in situ oxidation method and demonstrates efficient charge transportation, excellent thermal conductivity [3.74 W (m K−1)], and high thermal diffusivity (9.39 mm2 s−1). The obtained temperature sensors exhibit high sensitivity (−5.04% °C−1), wide working range (−15 to 80 °C), and excellent stability (more than three months) and have been applied to monitor the temperature of objects and the human body. In particular, a flexible temperature sensor array is fabricated to measure the spatially resolved temperature distribution. The array demonstrates the bright application prospects of the sensors in the fields of human–machine interfaces and intelligent medical systems. [ABSTRACT FROM AUTHOR]

Metallic two‐dimensional conductive nanomaterials are extensively explored in stretchable strain sensors, which have promising applications ranging from health monitoring to human–machine manipulation. However, there are limited materials available in this category, and their sensing abilities need to be strengthened. Herein, a controllable deoxidation–nitridation strategy via the pyrolysis of an amine nitrogen source to synthesize oxygen‐doped vanadium nitride (VNO) nanosheets with high conductivity is reported. Its metallic characteristics and low dimensionality, together with layer‐to‐layer slippage make VNO particularly suitable for stretchable strain sensors with remarkable performance, including extraordinary sensitivity (a maximum gauge factor of 2667), wide detection range (0–100%), high durability (over 6000 cycles), and rapid response (44 ms). Furthermore, the strain sensors can capture various physiological signals; in particular, a state‐of‐the‐art wireless vehicle control system designed for differently abled people is fabricated based on the sensors. Moreover, by engineering the thickness of the VNO layer, it can behave as an elastic conductor, demonstrating its feasibility for stretchable wiring. [ABSTRACT FROM AUTHOR]

Mutations in genes related to long QT syndrome (LQTS) is recognized as an independent risk of druginduced LQTS. We previously screened a mutation F463L in a Chinese patient with LQT2, syncope, and epilepsy. Here, we planned to illustrate how F463L influences the action of dofetilide on hERG channels. F463L-hERG plasmids were transfected into the stable Human Embryonic Kidney 293 (HEK293) cells expressingWT-hERG to generate heterozygous mutant (WT1F463L-hERG).Wholecell patch clamp and laser confocal scanning microscopy were used to evaluate electrophysiological consequences and the membrane distribution of hERG protein. In comparison ofWT-hERG channels exposed to dofetilide, heterozygous F463L-hERG channels showed a reduction in the density of tail currents when exposed amidarone. F463L-hERG also altered the action of dofetilide on the gating properties of hERG channels. Images of dofetilide-treated cells expressing heterozygous F463L showed a severe retention and reduction of protein expression on the membrane compared to WT. In conclusion, dofetilide displays a powerful inhibitory effect on the currents from cells expressing heterozygous F463L, thus showing an additive suppression of currents by F463L with dofetilide. [ABSTRACT FROM AUTHOR]

Summary The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation and characterization, including single-cell RNA-seq, of neocortical and spinal cord neuroepithelial stem (NES) cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. By analyzing human NES cells, organotypic fetal brain slices, and a ZIKV-infected micrencephalic brain, we show that ZIKV infects both neocortical and spinal NES cells as well as their fetal homolog, radial glial cells (RGCs), causing disrupted mitoses, supernumerary centrosomes, structural disorganization, and cell death. ZIKV infection of NES cells and RGCs causes centrosomal depletion and mitochondrial sequestration of phospho-TBK1 during mitosis. We also found that nucleoside analogs inhibit ZIKV replication in NES cells, protecting them from ZIKV-induced pTBK1 relocalization and cell death. We established a model system of human neural stem cells to reveal cellular and molecular mechanisms underlying neurodevelopmental defects associated with ZIKV infection and its potential treatment. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to conduct an empirical examination of auditors’ interpretation of selected key uncertainty expressions, namely virtually certain, probable and unlikely, included in accounting standards. Design/methodology/approach – This paper adopts a survey research method to examine the impact of gender difference on the interpretation of uncertainty expressions. Professional auditors in China were selected to examine whether gender difference influences the interpretation of uncertainty expressions. Findings – The results show that female auditors are likely to interpret positive or negative uncertainty expressions more conservatively than male auditors. The extent of conservatism is higher when female auditors are interpreting in-context expressions. The results remain similar after controlling for additional variables, such as education and work experience, which possibly affect the interpretation of probability expressions. Originality/value – The results of this study suggest that gender difference can affect the numerical thresholds that auditors assign to uncertainty expressions. This may lead to different application of professional judgments between male and female auditors. It also provides important implications to regulators and practitioners on the quality of financial reporting and auditing across organizations within and across countries. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor (EGFR) family. In this study, the whole extracellular domain gene of HER2 was amplified by RT-PCR from human breast cancer cell line SK-BR-3. The genes of membrane-distal region (A) and membrane proximal region (B) of HER2 extracellular domain were amplified from the cloned template, and then inserted into the expression vector pET-28a and pET-30a, respectively. The recombinant expression vectors were transformed into Escherichia coli BL21 (DE3) cells and induced by isopropyl-b-D-thiogalactopyranoside (IPTG) for expression of proteins His-A and His-B. The expressed proteins were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot. The optimization of culture conditions led us to accomplish the recombinant protein induction with 1.0 mM IPTG at 37 °C for 8 h, and both proteins were expressed in the insoluble form. Both proteins were purified under the denaturing condition using Ni-NTA sepharose column. Balb/c mice were immunized with the purified proteins and then effectively produced polyclonal antibodies, which reached to a relatively high titer by ELISA testing and had good specificity by western blot detection. The HER2 ECD proteins His-A and His-B could be expressed in E. coli and were suitable for production of high titer antibodies against HER2 ECD. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effects of allitridin on human ether-à-go-go-related gene (hERG) channels. Methods: We used whole-cell patch clamping and laser confocal scanning microscopy to evaluate the effects of allitridin on hERG currents and the membrane expression of the hERG protein expressed in HEK 293 cells. Results: The amplitude of IKr showed a concentration-dependent decrease with increasing allitridin concentration. Additionally, alterations in the gating properties of hERG channels were also confirmed. Allitridin does not alter the voltage- and time-dependent activation of hERG channels, the gating properties of hERG channel inactivation over time or the recovery from inactivation, but allitridin does cause alterations in the steady-state inactivation and the deactivation of hERG channels. We further evaluated the influence of allitridin on membrane expression of the hERG protein. Images of allitridin-treated cells showed a reduction in hERG protein on the membrane and retention in the cytoplasm. Conclusions: To the best of our knowledge this is the first study to show that allitridin reduces the IKr current by impairing the trafficking of hERG channels. The results may demonstrate that allitridin could be a promising candidate for the prevention and treatment of arrhythmia-related diseases. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]