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The auditing industry will be strongly affected by emerging technology, as many of the auditing processes can be carried out automatically. Responding to this challenge, students in auditing majors must be trained in applying information technology to their work. In this teaching case, students will learn to analyze a large dataset of simulated SMEs survey to identify the tax risk of small and medium enterprises (SMEs), and to use technology (i.e CAATs, Computer Assisted Audit Techniques) to figure out the issues. Learning through a specific situation helps students to not only understand the process of applying technology to auditing, but also to develop analytical skills to assess what technology can and can-not do. These essential skills are needed for long-term career growth. &nbsp

BACKGROUND: Dysfunction of endothelial cells is now considered a vital contributor to the pathogenesis of atherosclerosis (AS). Moreover, circular RNA (circRNA) circ_0029589 has been found to be involved in the regulation of oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell damage. Nevertheless, its molecular mechanism in ox-LDL-triggered endothelial cell injury is poorly defined. METHODS: Human umbilical vein endothelial cells (HUVECs) treated with ox-LDL were applied as cell models of AS. Circ_0029589, microRNA-1197 (miR-1197), and Ras-related protein Rab-22A (RAB22A) expression were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, angiogenesis, and invasion were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, tube formation, and transwell assays. Western blot analysis of Cleaved-caspase-3, B-cell lymphoma-2 related X protein (Bax), and RAB22A. IL-6, IL-1β, and Tumor necrosis factor α (TNF-α) levels were gauged using ELISA kits. Superoxide Dismutase (SOD) activity and Malondiahyde (MDA) level were assessed using special kits. Bioinformatics software predicted the binding between miR-1197 and circ_0029589 or RAB22A, which was proved using dual-luciferase reporter and RNA pull-down assays. RESULTS: Circ_0029589 and RAB22A expression were strengthened, and miR-1197 was reduced in ox-LDL-treated HUVECs. Importantly, circ_0029589 silencing ameliorated ox-LDL-triggered HUVEC damage via promoting cell proliferation, tube formation ability, invasion, and repressing cell apoptosis, inflammation, and oxidative stress. Mechanical analysis suggested that circ_0029589 might affect RAB22A content through sponging miR-1197. CONCLUSION: Circ_0090231 might protect against ox-LDL-mediated HUVEC injury via the miR-1197/RAB22A axis, which provides a therapeutic strategy for endothelial cell damage of AS.

PURPOSE Immune checkpoint inhibitors combined with antiangiogenic therapy reportedly have potential synergistic antitumor activity. We investigated the activity and safety of this regimen for recurrent/metastatic nasopharyngeal carcinoma (NPC). METHODS This single-arm, Simon two-stage study enrolled patients with recurrent/metastatic NPC who were refractory to at least first-line systemic therapy and treatment-naive to immune checkpoint inhibitors. The patients received camrelizumab 200 mg once every 3 weeks and apatinib 250 mg once per day. The primary end point was the objective response rate. Key secondary end points included disease control rate, progression-free survival, duration of response, overall survival, and safety. RESULTS Between October 14, 2020, and December 23, 2021, 58 patients were enrolled, and all were included in the efficacy and safety analysis set. The objective response rate was 65.5% (95% CI, 51.9 to 77.5), and the disease control rate was 86.2% (95% CI, 74.6 to 93.9). The median duration of response was not reached, and the median progression-free survival was 10.4 months (95% CI, 7.2 to 13.6), with a median follow-up duration of 12.4 months (range, 2.1-19.9 months). Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 34 (58.6%) patients, with the most common being hypertension (19.0%), nasopharyngeal necrosis (15.5%), headache (12.1%), AST elevation (10.3%), and creatine phosphokinase elevation (10.3%). Sixteen (27.6%) patients discontinued apatinib treatment before progression because of unbearable TRAEs, and the most common complication was nasopharyngeal necrosis (9/16; 56.3%). Recurrent nasopharyngeal lesions (odds ratio, 5.94 [95% CI, 1.45 to 24.24]) and reirradiation (odds ratio, 5.33 [95% CI, 1.15 to 24.79]) were significantly positively correlated with nasopharyngeal necrosis. CONCLUSION Camrelizumab plus apatinib had promising antitumor activity in patients with refractory recurrent/metastatic NPC who failed first-line therapy. Moderate to severe TRAEs were experienced by 58.6%, including nasopharyngeal necrosis associated with local recurrence and a history of reirradiation.

Jie Chen,1,* Yen-Ming Huang,1– 3,* Hsun-Yu Chan,4 Mon-Chiao Chen,5 Yunn-Fang Ho1,2 1School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 100025, Taiwan; 2Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, 100025, Taiwan; 3Department of Pharmacy, National Taiwan University Hospital, Taipei, 100229, Taiwan; 4Department of Industrial Education, National Taiwan Normal University, Taipei, 106308, Taiwan; 5Adam’s Drug Store, Taipei, 111049, Taiwan*These authors contributed equally to this workCorrespondence: Yunn-Fang Ho, Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, No. 33, Linsen South Road, Zhongzheng District, Taipei, 100025, Taiwan, Tel +886 2 33668794, Fax +886 2 33668780, Email yfho@ntu.edu.twBackground: Easy and adequate access to community pharmacies is key to eliminating primary barriers to the utilization of medicines and healthcare services. The location of community pharmacies is important for patients and providers when choosing and opening a pharmacy, but only a handful of studies investigate factors associated with the geographical distribution of pharmacies. This study aimed to identify decisive factors for location selection when starting a pharmacy among districts/townships in Taiwan.Methods: This cross-sectional mixed mode study employed an explanatory sequential design, beginning with a quantitative analysis of national datasets, and followed by a qualitative analysis of structured interviews. The national data were extracted from the Taiwan government database of 2020, and the qualitative interviews were conducted with 10 community pharmacists through a snowball sampling in 2021. A multiple linear regression was conducted to identify salient predictors of the number of community pharmacies in each of the 368 districts/townships in Taiwan, including population density, median annual household income, number of physician offices, area, and proportion of female residents of each district/township. Ten chief pharmacists were interviewed to share viewpoints on the decision-making process of their selection of current pharmacy practice sites. Inductive thematic analysis was performed to extract factors pertinent to location selection for pharmacy operations and services.Results: Confirmed by quantitative and qualitative data, population density, numbers of physician offices, median annual household income, pharmacy operation type, and type of retail locations are key determinants for site selection in considering opening a new community pharmacy.Conclusion: The study uncovers salient factors associated with the choice of community pharmacy location in Taiwan and proposes the adequate number of physician offices that a community pharmacy can collaborate with. In addition, pharmacists should prudently consider if their preferred service features match the needs of residents.Keywords: community pharmacy, physician office, location, mixed mode

Energy is one of the vital needs for humans. Indonesia as a developing country faces problems in ensuring the availability of energy. The aim of this research is to explore the development of practice energy management disclosure in accordance with GRI 302 (energy) in energy sub-sector companies listed on the Indonesia Stock Exchange (IDX) through disclosures issued by each company. This study uses secondary data collected from reports published by energy sub-sector companies listed on the Indonesia Stock Exchange (IDX) and can be accessed online. Data analysis was carried out using the data analysis model of Miles and Huberman (1992), namely data reduction, data presentation, drawing conclusions, and verification. The results of this study indicate that only thirty-six out of 74 energy subsector companies (49%) report energy management disclosure according to GRI 302 (energy) for three consecutive years (2020-2022). Nineteen out of thirty-six companies attach a GRI Index Reference to their GRI 302 (energy) reports. Meanwhile, the other thirty-eight companies did not attach the GRI Index Reference in their reports. The company is expected to develop a power plant that uses renewable energy as its energy source. By using renewable energy, companies can reduce consumption of non-renewable energy, and play a role in reducing CO2 emissions in the environment.

Epitranscriptomic RNA modifications constitute a critical gene regulatory component that can affect cancer progression. Among these, the RNA N4-acetylcytidine (ac4C) modification, which is mediated by the ac4C writer N-acetyltransferase 10 (NAT10), regulates the stabilization of mRNA. Here, we identified that the ac4C modification is induced upon cisplatin treatment and correlates with chemoresistance in bladder cancer. Both in vitro and in vivo, NAT10 promoted cisplatin chemoresistance in bladder cancer cells by enhancing DNA damage repair (DDR). Mechanistically, NAT10 bound and stabilized AHNAK mRNA by protecting it from exonucleases, and AHNAK-mediated DDR was required for NAT10-induced cisplatin resistance. Clinically, NAT10 overexpression was associated with chemoresistance, recurrence, and worse clinical outcome in patients with bladder cancer. Cisplatin-induced NFκB signaling activation was required for the upregulation of NAT10 expression, and NFκB p65 directly bound to the NAT10 promoter to activate transcription. Moreover, pharmacological inhibition of NAT10 with Remodelin sensitized bladder cancer organoids and mouse xenografts to cisplatin. Overall, the present study uncovered a mechanism of NAT10-mediated mRNA stabilization in bladder cancer, laying the foundation for NAT10 as a therapeutic target to overcome cisplatin resistance in bladder cancer. Significance: The mRNA ac4C writer NAT10 stimulates DNA damage repair to promote cisplatin chemoresistance in bladder cancer, identifying NAT10 inhibition as a potential therapeutic approach to enhance cisplatin sensitivity.

Intermittent fasting (IF) is an eating pattern in which individuals go extended periods with little or no energy intake after consuming regular food in intervening periods. IF has several health-promoting effects. It can effectively reduce weight, fasting insulin levels, and blood glucose levels. It can also increase the antitumor activity of medicines and cause improvement in the case of neurological diseases, such as memory deficit, to achieve enhanced metabolic function and prolonged longevity. Additionally, IF activates several biological pathways to induce autophagy, encourages cell renewal, prevents cancer cells from multiplying and spreading, and delays senescence. However, IF has specific adverse effects and limitations when it comes to people of a particular age and gender. Hence, a more systematic study on the health-promoting effects and safety of IF is needed. This article reviewed the research on the health-promoting effects of IF, providing a theoretical basis, direction for subsequent basic research, and information related to the clinical application of IF.

Background Medication adherence is one of the crucial attempts in primary stroke prevention. The available evidence lacks comprehensive reviews exploring the association of medication adherence with stroke prevention. Objectives To investigate the effects of non-adherence to medications used to treat the modifiable risk of diseases on stroke-associated outcomes in primary stroke prevention. Methods Study records were searched from PubMed, Embase, and CINAHL. Those studies reported risks relevant to stroke-associated outcomes and medication non-adherence for patients diagnosed with four modifiable stroke-related diseases (atrial fibrillation [AF], hyperlipidemia, hypertension, and type 2 diabetes mellitus) but without stroke history were included for meta-analysis and further subgroup, sensitivity, and publication bias analyses. A random effect model was performed to analyse the pooled risk estimates of relative risk (RR) and 95% confidence intervals (CIs). Results Thirty-nine studies (with 2,117,789 participants in total) designed as cohort or case–control studies were included. Those patients presenting with four stroke-related diseases and categorised as medication non-adherent tended to result in stroke and/or associated death (all pooled RR ≥ 1 and 95% CI did not include 1). The findings of stratification and sensitivity analysis for each stroke-related disease showed a similar trend. Non-adherent patients with AF were prone to stroke occurrence (RR 1.852; 95% CI 1.583–2.166) but inclined to reduced bleeding (RR 0.894; 95% CI 0.803–0.996). The existence of publication bias warrants further interpretation. Conclusions Non-adherence to medications for the four stroke-related diseases contributes to the development of stroke and/or mortality in primary stroke prevention. More efforts are needed to improve patients’ medication adherence.

Wake losses are a critical consideration in wind farm design. The ability to steer and deform wakes can result in increased wind farm power density and reduced energy costs and can be used to optimize wind farm designs. This study investigates the wake deflection of a vertical axis wind turbine (VAWT) experimentally, emphasizing the effect of different load distributions on the wake convection and mixing. A trailing vortex system responsible for the wake topology is hypothesized based on a simplified vorticity equation that describes the relationship between load distribution and its vortex generation; the proposed vorticity system and the resulting wake topology are experimentally validated in the wind tunnel via stereoscopic particle image velocimetry measurements of the flow field at several wake cross-sections. Variations in load distribution are accomplished by a set of fixed blade pitches. The experimental results not only validate the predicted vorticity system but also highlight the critical role of the streamwise vorticity component in the deflection and deformation of the wake, thus affecting the momentum and energy recoveries. The evaluation of the various loading cases demonstrates the significant effect of the wake deflection on the wind power available to a downwind turbine, even when the distance between the two turbines is only three diameters.

Antibody-mediated autoimmune pathologies like membranous nephropathy are difficult to model, particularly in the absence of local target antigen expression in model organisms such as mice and rats; as is the case for phospholipase A2 receptor 1 (PLA2R1), the major autoantigen in membranous nephropathy. Here, we generated a transgenic mouse line expressing the full-length human PLA2R1 in podocytes, which has no kidney impairment after birth. Beginning from the age of three weeks, these mice spontaneously developed anti-human PLA2R1 antibodies, a nephrotic syndrome with progressive albuminuria and hyperlipidemia, and the typical morphological signs of membranous nephropathy with granular glomerular deposition of murine IgG in immunofluorescence and subepithelial electron-dense deposits by electron microscopy. Importantly, human PLA2R1-expressing Rag2

Aim: The study aims to investigate the combined effects of chrysin and cisplatin on hepatoma(HepG2) cell lines in vivo and in vitro. Objective: Studies have suggested that chrysin can enhance the sensitivity of tumor cells to apoptosis. Drug resistance in tumor cells reduced the effectiveness of chemotherapy drugs such as cisplatin. We investigated whether the combination of chrysin and cisplatin can induce more apoptosis than chrysin alone and cisplatin alone. Methods: HepG2 cells were pretreated with chrysin for 2 h, followed by the addition of cisplatin for another 24 h. The morphologic changes were observed under inverted microscope and the cell viability was measured using the MTT test. The protein and cleavage of caspase-3,8,9, PARP, and cFLIP were determined by Western blotting. Results: The cell viability of the HepG2 cell can be reduced by the combination of chrysin pretreatment for 2 h and cisplatin addition for 24 h; Caspase-3,8,9 and PARP were cleaved after 12 h treatment with chrysin and cisplatin; Pancaspase inhibitor, Z-VAD-fmk, could reverse the apoptosis induced by chrysin and cisplatin in HepG2 cells; cFLIP was down-regulated by the combination of chrysin and cisplatin, and could be reversed by Z-VAD-fmk; the xenografted HepG2 cells formed a tumor in one week; At the end of the experiment, there were significant differences in relative tumor volume (RTV) and relative tumor proliferation rate between the combined group and the control group, the chrysin group and the cisplatin group; Western blotting showed that the levels of PARP, cFLIP, and caspase-3 proteins in isolated tumor tissues also decreased under the combined action of chrysin and cisplatin. Conclusion: The combination of chrysin and cisplatin induces apoptosis of hepatic tumor in vivo and in vitro. It downregulates cFLIP and then activates caspase-8, which triggers caspase-mediated apoptosis of HepG2 cell.

This is the first time to explore the self-assembly process of double butterfly-shaped lanthanide high-nucleus clusters and propose their possible assembly mechanism.

Luminescent nanoaggregates of Re(i) metallacycles were used as potential probes for the sensitive and selective detection of explosives and antibiotics that contain nitro groups.

A great improvement in the thermoelectric and mechanical properties of a TiNiSn-based compound has been achieved by entropy engineering.

Platinum (Pt) is the most commonly used counter electrode material for DSSCs. However, as Pt is a noble metal and expensive, researchers have tried to replace the Pt counter electrode with a variety of materials. In this study, graphene oxide (GO) powders were added to solvents of different polarities as precursor solutions for the counter electrode. The solvents were deionized water, dimethylformamide, isopropanol, and chlorobenzene in descending order of polarity. The prepared GO precursor solutions were coated on the Florine doped Tin Oxide (FTO) glass substrate via spin coating, then coated substrate subjected to thermal reduction reaction to obtain reduced graphene oxide, which was used as the counter electrode of the DSSC. The photoelectric conversion efficiency (PCE) of DSSC using deionized water as the dispersing solvent was 2.70%, which was five times higher than that of DSSC using chlorobenzene.

Accurately predicting ultimate strength of composite laminate is still a great challenge, especially only based on the constituent properties. In this paper, the micromechanics Bridging Model and systematic failure criteria for the constituent materials with emphasis on matrix failures subjected to three dimensional (3D) loads are compiled into a UMAT subroutine for ABAQUS to analyze failures of a laminated composite structure. The main purpose of this research is to greatly reduce calculation costs for loading conditions of in-plane tension or compression by introducing a simplified 3D finite element model based on the Pipes-Pagano theory. In all calculation cases, only the constituent properties together with the transverse tensile strength of unidirectional composite are needed as input data. Later in this paper, sufficient illustrations of 81 different composite laminates composed of 14 material systems are analyzed to confirm the practicability of this model.

It has been reported that miR-217 can inhibit the oncogenic activity and progression of bladder cancer (BCa) cells, but it has not been explored whether miR-217 is involved in the regulation of ferroptosis. In the present study, RNA transfection, real-time PCR, flow cytometry, Western blotting assays, immunofluorescence and ELISA were performed to explore the effects and mechanisms of miR-217 in BCa tissue-derived exosomes. We found that extracellular fluid from bladder cancer tissue promoted the growth and miR-217 expression of T24 cells and inhibited ferroptosis. MiR-217 was confirmed to inhibit ferroptosis in bladder cancer cells by RNA interference and functional assays. By cell membrane fluorescence probe (CM-Dil) labeling, inhibiting exosome secretion by GW4689 and exosome extraction, we determined that BCa tissue-derived exosomes transport miR-217 into T24 cells. Culture of T24 cells with extracellular fluid after RNA interference showed that exosomes carrying miR-217 derived from BCa tissues inhibited ferroptosis of T24 cells. We conclude that bladder cancer tissue-derived exosomes inhibit ferroptosis of T24 bladder cancer cells by transporting miR-217. The results of our study provide a new insight into the progression of bladder cancer.