Discovery of selective Orai channel blockers bearing an indazole or a pyrazole scaffold.

The calcium release activated calcium (CRAC) channel is highly expressed in T lymphocytes and plays a critical role in regulating T cell proliferation and functions including activation of the transcription factor nuclear factor of activated T cells (NFAT), cytokine production and cytotoxicity. The CRAC channel consists of the Orai pore subunit and STIM (stromal interacting molecule) endoplasmic reticulum calcium sensor. Loss of CRAC channel mediated calcium signaling has been identified as an underlying cause of severe combined immunodeficiency (SCID), leading to drastically weakened immunity against infections. Gain-of-function mutations in Orai and STIM have been associated with tubular aggregated myopathy (TAM), a skeletal muscle disease. While a number of small molecules have shown activity in inhibiting the CRAC signaling pathway, the usefulness of those tool compounds is limited by their off-target activity against TRPM4 and TRPM7 ion channels, high lipophilicity, and a lack of understanding of their mechanism of action. We report structure-activity relationship (SAR) studies that resulted in the characterization of compound 4k [1-(cyclopropylmethyl)-N-(3-fluoropyridin-4-yl)-1H-indazole-3-carboxamie] as a fast onset, reversible, and selective CRAC channel blocker. 4k fully blocked the CRAC current (IC50: 4.9 µM) and the nuclear translocation of NFAT at 30 and 10 µM, respectively, without affecting the electrophysiological function of TRPM4 and TRPM7 channels. Computational modeling appears to support its direction binding to Orai proteins that form the transmembrane CRACchannel.

Primary gastrointestinal stromal tumor of the liver: a case report.

Introduction and importance: Primary gastrointestinal stromal tumors of the liver are exceedingly rare entities, presenting diagnostic and therapeutic challenges. The authors present a case of a 64-year-old male with a primary gastrointestinal stromal tumor (GIST) of the liver, emphasizing the importance of comprehensive diagnostic evaluation and multidisciplinary management in such uncommon cases. Case presentation: The patient presented with persistent hypochondriac pain, leading to the discovery of a hepatic mass. Diagnostic work-ups, including imaging studies and biopsy, confirmed the diagnosis of primary GIST in the liver. Following thorough multidisciplinary consultation, the patient underwent right anterior segmentectomy of the liver, performed by our experienced surgeon. Postoperative pathology confirmed the diagnosis of GIST, and the patient was advised to use adjuvant imatinib. Clinical discussion: Primary GISTs of the liver pose diagnostic challenges due to their rarity and varied clinical presentations. Imaging modalities, immunohistochemistry, and molecular genotyping are crucial in accurate diagnosis and treatment planning. Surgical resection remains the cornerstone of treatment for localized GISTs, with adjuvant therapy considered based on recurrence risk factors and molecular characteristics. Conclusion: This case highlights the need for multidisciplinary consultation in managing primary GISTs of the liver. Accurate diagnosis, surgical expertise, and personalized adjuvant therapy are crucial for better patient outcomes. Further research is necessary to enhance our understanding of prognostic factors and treatment strategies for these rare tumors.

Facile Fabrication of SERS Substrates by the Electrodeposition Method to Detect Pesticides with High Enhancement Effect and Long-Term Stability.

In this study, surface-enhanced Raman scattering substrates were investigated by the electrodeposition method to detect low concentrations of pesticides via the electrodeposition method with different agents from silver and gold precursors on APTES-modified ITO glass. A dual-potential method supplied three electrodes and was performed with a nucleation potential of 0.7 V for 2 s and a growth potential of -0.2 V for 500 s. The Ag film produced by the electrodeposition approach has great surface uniformity and good SERS signal amplification for the thiram insecticide at low concentrations. Interestingly, the ITO/APTES/Ag substrate extensively increased the sensitivity than the other investigated ones, thanks to the adequate assistance of amino groups of APTES in the denser and hierarchical deposition of Ag NPs. These observations were additionally elucidated via finite-difference time-domain (FDTD) calculation. For thiram, the detection was set at 10-8 M with an enhancement factor of up to 3.6 × 107 times. Comparing the SERS spectra of thiram at concentrations of 10-3, 10-4, and 10-5 M with a relative standard deviation (RSD) of less than 7.0% demonstrates excellent reproducibility of the ITO/APTES/Ag substrate. In addition, the special selectivity of the ITO/APTES/Ag substrate for thiram demonstrates that these nanostructures can identify pesticides with extreme sensitivity.

English as a foreign language students' acceptance of Google Classroom in writing classes: A case study in Vietnam.

Google Classroom is a virtual education platform created by Google that allows both instructors and learners to actively participate in educational environments inside and outside of the classroom in an innovative way. This research aims to determine how university students perceived the adoption of Google Classroom in writing classes. This research was a convergent parallel mix-methods approach in which data were gathered through a 5-point Likert scale questionnaire and semi-structured interviews. The participants of this study included 130 university students in Vietnam. The results revealed that students expressed their approval of using Google Classroom in writing classes and that they had a positive view since it benefited them greatly in their learning writing process. This study suggests practical implications for language educators to use Google Classroom in writing classes.

A cross-sectional study of sleep disturbance among middle-aged cancer patients at Vietnam National Cancer Hospital.

AIM: Sleep disorders are common in cancer patients and have negative consequences for patient well-being and treatment outcomes. This study aimed to investigate sleep quality and related factors in Vietnamese middle-aged cancer patients. METHODS: A cross-sectional study was conducted on 246 middle-aged in-patient cancer patients at Vietnam National Cancer Hospital (VNCH) from 1/2021 to 7/2021. Sleep was measured by the Pittsburgh Sleep Quality Index (PSQI), with a cutoff of 5. RESULTS: The results showed a male/female ratio of 0.85 with an average age of 52. The five most prevalent cancer types were breast, colorectal, lung, and esophagus-stomach cancer, primarily in the late stage and treated with chemotherapy. The prevalence of sleep disturbances was 58.5%. The mean PSQI score was 7.5, with sleep duration and latency of 5.4 h and 1 h, respectively. Approximately 44% of participants reported poor sleep quality, nearly 9% had daytime dysfunction, and 10.6% used sleep medication. The multivariate logistic regression results indicate that people with depression were 8.89 times more likely to have poor sleep than those without depression (95% CI:2.63-28.27, p < .001). CONCLUSION: Sleep problems are common among middle-aged people with cancer in Vietnam, especially individuals with depression. It is necessary to have more effective approaches to sleep management for cancer patients with limited resources.

Does income inequality moderate the effect of fintech development on renewable energy consumption?

Fintech development is generally considered as an effective mechanism to promote the consumption of renewable energy sources. The relationship between fintech development and renewable energy consumption have been examined in previous studies. However, the moderating effect of income inequality on this relationship has largely been ignored in the existing literature. As such, this study is conducted to shed light on this moderating effect. Two estimation techniques, including the two-step system generalized method of moments (GMM) and the method of moments quantile regression (MMQR), were used on a sample of 65 countries from 2013 to 2019. Our findings reveal that fintech development plays a vital role in promoting the consumption of renewable energy sources. However, it is crucial to recognize that rising income inequality may hinder the potential positive effects of fintech development on renewable energy consumption. A threshold of income inequality should be maintained to ensure that the positive effect of fintech development on increased renewable energy consumption is not compromised. Policy implications have emerged based on the findings from this study regarding promoting fintech development towards green economic growth and sustainable development.

Flexible, high-performance and facile PVA/cellulose/Ag SERS chips for in-situ and rapid detection of thiram pesticide in apple juice.

Flexible surface-enhanced Raman scattering (SERS) sensors have gained significant attention for their practical applications in detecting chemical and biological molecules. However, the fabrication of flexible SERS chips is often complex and requires advanced techniques. In this study, we present a simple and rapid method to design a flexible SERS chip based on polyvinyl alcohol (PVA), cellulose, and silver nanoparticles (AgNPs) using mechanical stirring and drying methods. Benefiting from the abundant hydroxide groups on cellulose, AgNPs easily adhere and distribute evenly on the cellulose surface. The combination of PVA and cellulose forms a bendable film-like SERS chip. This chip allows convenient immersion in liquid analyte samples. We demonstrate its effectiveness by using it to detect the thiram pesticide in apple juice using the "dip and dry" method, achieving an outstanding detection limit of 1.01 × 10-8 M. The Raman signals on the SERS chips exhibit high repeatability and reproducibility, with relative standard deviation values below 10%. These findings show that the flexible PVA/cellulose/Ag SERS chips is a strong candidate for real-world analysis.

Boosting the ultraviolet shielding and thermal retardancy properties of unsaturated polyester resin by employing electrochemically exfoliated e-GO nanosheets.

In this work, a series of unsaturated polyester resin (UPRs)/electrochemically exfoliated graphene oxide (e-GO) polymer nanocomposites with different ratios of e-GO (0.05, 0.1, 0.15, and 0.2 wt%) were prepared via an in situ polymerization method. The surface morphology and structural and chemical properties of the original UPR and UPR/e-GO nanocomposites were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). The positive influence of e-GO nanosheets on the mechanical properties, thermal stability, and anti-UV aging performance of UPR/e-GO nanocomposites was demonstrated by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). The obtained results showed that the incorporation of e-GO nanosheets within the UPR matrix, despite the addition of e-GO at as low as 0.2 wt% comprehensively improves the advanced functional properties of UPR/e-GO nanocomposites as compared to the original UPR. In addition, artificial weathering testing of quartz-based artificial stone using UPR/e-GO 0.2 wt% showed excellent UV-resistant efficiency, supporting the use of e-GO nanosheets as an additive in manufacturing the industrial-scale UPRs-based artificial quartz stone samples for real outdoor applications.

The long-run effects of financial development on income inequality: Evidence from the Asia-Pacific countries.

Income inequality is a vexing developmental challenge for governments and policymakers as it impedes social transformation and economic growth and development. Meanwhile, promoting financial development is generally regarded as an effective way to achieve inclusive and sustainable growth. This study examines the long-run effects of financial development, economic growth, and their combined effects on income inequality for 12 Asia-Pacific countries from 1990 to 2021. This paper employs various econometric techniques and different financial development proxies to ensure the findings' robustness. The paper also constructs a financial development index using the principal component analysis to fully capture the comprehensive effect of financial development on income inequality. Empirical results reveal that the impact of financial development on income inequality follows the inverted U-shaped relationship - financial development widens income inequality and only reduces income when surpassing its turning point. Findings further reveal that the nonlinear effect of financial development on income inequality is contingent upon the level of per capita income. Thus, policies promoting financial development to reduce income inequality should consider the existing level of per capita income.

Tuned Transport Path of Perovskite MAPbI3 -based Memristor Structure.

In this study, the features of resistive random access memory (RRAM) employing a straightforward Cr/MAPbI3 /FTO three-layer structure have been examined and clarified. The device displays various resistance switching (RS) behavior at various sweep voltages between 0.5 and 5 V. The RS effect has a conversion in the direction of the SET and RESET processes during sweeping for a number of cycles at a specific voltage. The directional change of the RS processes corresponds to the dominant transition between the generation/recombination of iodide ion and vacancy in the MAPbI3 perovskite layer and the electrochemical metallization of the Cr electrode under the influence of an electric field, which results in the conductive filament (CF) formation/rupture. At each stage, these processes are controlled by specific charge conduction mechanisms, including Ohmic conduction, space-charge-limited conduction (SCLC), and variable-range hopping (VRH). By identifying the biased voltage and the quantity of voltage sweep cycles, one can take a new approach to control or modulate the pathways for effective charge transport. This new approach is made possible by an understanding of the RS characteristics and the corresponding mechanisms causing the variation of RS behavior in the structure.