Design, Synthesis, and Biological Evaluation of Novel Orally Available Covalent CDK12/13 Dual Inhibitors for the Treatment of Tumors.

Cyclin-dependent kinases 12 and 13 (CDK12/13) safeguard genomic integrity by preferentially regulating gene expression in the DNA damage response (DDR). The CDK12/13-mediated upregulation of DDR genes and pathways significantly contributes to both tumorigenesis and the development of resistance to antitumor therapies. Thus, the functional inhibition of CDK12/13 offers an attractive strategy to combat carcinogenesis, particularly for refractory and treatment-resistant cancers.

Translation and validation of the caregiving burden scale for family caregivers of children with cancer in chinese population.

Background: Effective response and reducing the burden of family care for children with cancer is critical, and China currently lacks a specific assessment tool.

Aims: This study aimed to translate and validate the Caregiving Burden Scale for Family Caregivers of Children with Cancer (CBSFC-CC) and then test and implement the tool.

Methods: According to the Beaton cross-cultural debugging guide, preliminary Chinese version of CBSFC-CC scale was formed, which was suitable for Chinese language environment and clinical context.

Synthesis and structure-activity optimization of azepane-containing derivatives as PTPN2/PTPN1 inhibitors.

Protein tyrosine phosphatases PTPN2 and PTPN1 (also known as PTP1B) have been implicated in a number of intracellular signaling pathways of immune cells. The inhibition of PTPN2 and PTPN1 has emerged as an attractive approach to sensitize T cell anti-tumor immunity. Two small molecule inhibitors have been entered the clinic.

Employment intention and career planning of male nursing students in different levels of colleges and universities: A qualitative study.

Aim: To explore the employment intention and career planning of male nursing students at different levels of colleges and universities and provide references for formulating individualized training content.

Design: Phenomenological research method in qualitative research.

Methods: Using a phenomenological research method, 15 male nursing students from three levels of colleges and universities were interviewed in a one-to-half structure, and the data were analysed using NVivo12.

Transcription Elongation Machinery Is a Druggable Dependency and Potentiates Immunotherapy in Glioblastoma Stem Cells.

Glioblastoma (GBM) is the most lethal primary brain cancer characterized by therapeutic resistance, which is promoted by GBM stem cells (GSC). Here, we interrogated gene expression and whole-genome CRISPR/Cas9 screening in a large panel of patient-derived GSCs, differentiated GBM cells (DGC), and neural stem cells (NSC) to identify master regulators of GSC stemness, revealing an essential transcription state with increased RNA polymerase II-mediated transcription. The YY1 and transcriptional CDK9 complex was essential for GSC survival and maintenance and .

The effectiveness of the laid-back position on lactation-related nipple problems and comfort: a meta-analysis.

Background: The importance of breastfeeding for maternal and child health is agreed upon worldwide. However, lactation-related nipple problems are common and are important factors affecting breastfeeding. Multiple studies recommended laid-back breastfeeding, but they are of various levels of quality, and the results are inconclusive.

Mediator MED23 regulates inflammatory responses and liver fibrosis.

Liver fibrosis, often associated with cirrhosis and hepatocellular carcinomas, is characterized by hepatic damage, an inflammatory response, and hepatic stellate cell (HSC) activation, although the underlying mechanisms are largely unknown. Here, we show that the transcriptional Mediator complex subunit 23 (MED23) participates in the development of experimental liver fibrosis. Compared with their control littermates, mice with hepatic Med23 deletion exhibited aggravated carbon tetrachloride (CCl4)-induced liver fibrosis, with enhanced chemokine production and inflammatory infiltration as well as increased hepatocyte regeneration.

A Pharmacogenomic Landscape in Human Liver Cancers.

Liver cancers are highly heterogeneous with poor prognosis and drug response. A better understanding between genetic alterations and drug responses would facilitate precision treatment for liver cancers. To characterize the landscape of pharmacogenomic interactions in liver cancers, we developed a protocol to establish human liver cancer cell models at a success rate of around 50% and generated the Liver Cancer Model Repository (LIMORE) with 81 cell models.

Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin.

Understanding stage-dependent oncogenic mechanisms is critical to develop not only targeted therapies, but also diagnostic markers and preventive strategies. The mechanisms acting during cancer initiation remain elusive, largely owing to a lack of suitable animal models and limited availability of human precancerous lesions. Here we show using genetic mouse models specific for liver cancer initiation, that survival of initiated cancer cells is controlled by c-Jun, independently of p53, through suppressing c-Fos-mediated apoptosis.

Successful pregnancy following the transfer of vitrified blastocyst which developed from poor quality embryos on day 3.

Background: The selection of pre-embryos for transferred is based on morphological appearance. But some poor quality cleaved embryos also can be cultured to the blastocyst stage and implanted.

Objective: To assess the clinical pregnancy outcomes of blastocyst transfer which developed from poor quality embryos.

Sorafenib inhibits transforming growth factor β1-mediated epithelial-mesenchymal transition and apoptosis in mouse hepatocytes.

Epithelial-mesenchymal transition (EMT) is a physiological process that has been recognized to occur during the progression of an increasingly large number of human diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. The activation of transforming growth factor β (TGF-β) signaling is considered a critical event during EMT, and efforts have been made to screen small molecules that interfere with the TGF-β signaling pathway during EMT. Here we report the identification of sorafenib, a clinical agent that inhibits TGF-β signaling.

Mitogen-activated protein kinases in hepatocellular carcinoma development.

Hepatocellular carcinoma (HCC) is among the most frequently occurring cancers and the leading causes of cancer mortality worldwide. Identification of the signaling pathways regulating liver carcinogenesis is critical in developing novel chemoprevention and targeted therapies. Mitogen-activated protein kinases (MAPKs), comprising a family of serine and threonine kinases of ERK, JNK, and p38, are important signaling components which convert external stimuli into a wide range of cellular responses, such as proliferation, survival, differentiation and migration.

Effect of the size of zona pellucida thinning by laser assisted hatching on clinical outcome of human frozen-thawed embryo transfers.

Of 122 consecutive procedures, 31 were not assisted hatching (AH), which served as the control group, 34 were AH with 40 microm thinning of the zona, and 57 were AH with 80 microns of the zona thinning. The pregnancy and implantation rates were significantly higher in 80 microns thinning group compared to control group (40.3 vs.

Nitric oxide suppresses transforming growth factor-beta1-induced epithelial-to-mesenchymal transition and apoptosis in mouse hepatocytes.

Unlabelled: Nitric oxide (NO) is a multifunctional regulator that is implicated in various physiological and pathological processes. Here we report that administration of NO donor S-nitroso-N-acetylpenicillamine (SNAP) inhibited transforming growth factor-beta1 (TGF-beta1)-induced epithelial-to-mesenchymal transition (EMT) and apoptosis in mouse hepatocytes. Overexpression of inducible NO synthase (iNOS) by transfection of the iNOS-expressing vector, which increased NO production, also inhibited the TGF-beta1-induced EMT and apoptosis in these cells.

Maternal confidence in China: association with infant neurobehaviors but not sociodemographic variables.

Objective: To examine the relations of sociodemographic factors and infant neurobehaviors to maternal confidence in China.

Methods: The Brazelton Neonatal Behavioral Assessment Scale, Family APGAR, and Maternal Confidence in Caring for the Newborn scales were administered to 40 healthy, full-term neonates.

Results: Range and regulation of state, autonomic stability, and reflex cluster scores were positively correlated; the autonomic stability cluster score was negatively correlated with maternal confidence in meeting the infant's social and instrumental needs.