Stumbling Block in Providing Physical Activity Support Among Parents of Children with Autism Spectrum Disorder: A Moderated Mediation Analysis.

Physical activity (PA) benefits children with autism spectrum disorder (ASD). Evidence suggests that some barriers impede parents from providing PA support for their children with ASD. Parental perceived stigma is one of these barriers. However, few studies have explored how parental perceived stigma influences parental PA support. This study aimed to investigate the relationship between parental perceived stigma and parental PA support, the mediating role of parental self-efficacy, and the moderating effect of having other typically developing children or not. A total of 274 participants were recruited to participate in the study. The results showed that parental self-efficacy mediated the association between parental perceived stigma and parental PA support and the moderating effect of having other typically developing children or not.

2-Aminopyrimidine derivatives as selective dual inhibitors of JAK2 and FLT3 for the treatment of acute myeloid leukemia.

Dual inhibitors of JAK2 and FLT3 can synergistically control the development of acute myeloid leukemia (AML), and overcome secondary drug resistance of AML that is associated with FLT3 inhibition. We therefore designed and synthesized a series of 4-piperazinyl-2-aminopyrimidines as dual inhibitors of JAK2 and FLT3, and improved their selectivity for JAK2. Screening cascades revealed that compound 11r exhibited inhibitory activity with IC50 values of 2.01, 0.51, and 104.40 nM against JAK2, FLT3, and JAK3, respectively. Compound 11r achieved a high selectivity for JAK2 at a ratio of 51.94, and also showed potent antiproliferative activity in HEL (IC50 = 1.10 µM) and MV4-11 (IC50 = 9.43 nM) cell lines. In an in vitro metabolism assay, 11r exhibited moderate stability in human liver microsomes (HLMs), with a half-life time of 44.4 min, and in rat liver microsomes (RLMs), with a half-life of 143 min. In pharmacokinetic studies, compound 11r showed moderate absorption (Tmax = 5.33 h), with a peak concentration of 38.7 ng/mL and an AUC of 522 ng h/mL in rats, and an oral bioavailability of 25.2%. In addition, 11r induced MV4-11 cell apoptosis in a dose-dependent manner. These results indicate that 11r is a promising selective JAK2/FLT3 dual inhibitor.

ICT literacy, resilience and online learning self-efficacy between Chinese rural and urban primary school students.

In the process of large-scale online education during the COVID-19 pandemic, students' online learning has caused widespread public concerns. This study investigated the relationships between Chinese rural and urban primary school students' information communications technology (ICT) literacy, student resilience, and online learning self-efficacy in a large-scale online education environment during the pandemic in China. We compared 5,037 primary school students in rural areas to 5,045 primary school students in urban areas with matching gender and grade in nine regions in China's Guangdong province, using a survey comprising an ICT literacy scale, a student resilience scale, an online learning self-efficacy scale, and an ICT devices scale. The ICT literacy, resilience and online learning self-efficacy of primary school students in rural areas were significantly lower than those in urban areas (p < 0.01). The primary school students' ICT literacy was significantly associated with student resilience and online learning self-efficacy. Student resilience played a mediating role between ICT literacy and online learning self-efficacy, while the rural/urban area factor moderated the relationship between ICT literacy and student resilience. These findings suggest that ICT literacy is more scarce and important for primary school students in rural areas of China than for those in urban areas. Improving ICT literacy among primary school students can enhance students' resilience and thus improve their online learning self-efficacy, especially in rural areas.

Broadband Acoustic Sensing with Optical Nanofiber Couplers Working at the Dispersion Turning Point.

Herein, a broadband ultrasensitive acoustic sensor based on an optical nanofiber coupler (ONC) attached to a diaphragm is designed and experimentally demonstrated. The ONC is sensitive to axial strain and works as the core transducing element to monitor the deformation of the diaphragm driven by acoustic waves. We first theoretically studied the sensing property of the ONC to axial strain and the deformation of the diaphragm. The results reveal that ONC working at the dispersion turning point (DTP) shows improved ultra-sensitivity towards axial strain, and the largest deformation of the circular diaphragm occurs at the center. Guided by the theoretical results, we fabricated an ONC with a DPT at 1550 nm, and we fixed one end of the ONC to the center of the diaphragm and the other end to the edge to construct the acoustic sensor. Finally, the experimental results show that the sensor can achieve accurate measurement in the broadband acoustic wave range of 30~20,000 Hz with good linearity. Specifically, when the input acoustic wave frequency is 120 Hz, the sensitivity reaches 1923 mV/Pa, the signal-to-noise ratio is 42.45 dB, and the minimum detectable sound pressure is 330 µPa/Hz1/2. The sensor has the merits of simple structure, low cost, and high performance, and it provides a new method for acoustic wave detection.

Covalent CDK7 Inhibitor THZ1 Inhibits Myogenic Differentiation.

Covalent CDK7 inhibitor THZ1 is a newly discovered anti-tumor drug.THZ1 affects the function of transcription factor TFIIH by inhibiting CDK7, which in turn affects RNA polymerase II, and ultimately affects transcription initiation. Study found that THZ1 could inhibit proliferation and promote apoptosis of several tumor cell lines. However, there is no report of the potential side effect of THZ1 in normal tissues. In the course of cancer, the muscle consumption of cachexia needs to be supplemented by the differentiation of muscle cells. However, the effect of THZ1 on myogenic differentiation remains unclear. Our study in this article found that THZ1 could both inhibit the differentiation of C2C12 cells and mouse primary myoblasts, also repressing the expression of differentiation-related transcription factors and muscle structural proteins, such as and myogenin, myh3 and MCK. Moreover, THZ1 could inhibit C2C12 cell proliferation and migration, increase its oxidative stress and promote its apoptosis. Our data indicates that THZ1 inhibits myogenic differentiation, suggesting that therapies based on THZ1 might have potential side effects on muscle functions.

Synthesis of polysubstituted pyrazoles by a platinum-catalyzed sigmatropic rearrangement/cyclization cascade.

A highly efficient Pt-catalyzed [3,3] sigmatropic rearrangement/cyclization cascade of N-propargylhydrazones is reported. The process provides expedient access to a variety of highly functionalized pyrazoles. The substrate has good substituted group compatibility, and the bioactive 3-CF3 pyrazoles could be synthesized easily with this method.