res of each cell type or subtypes allows for study, precise capture and manipulation of specific cell type(s) in heart and will provide insights into the development of therapeutics for cardiovascular diseases. Vascular smooth muscle cells (VSMCs) normally exhibit a very low proliferative rate. VX-548 Vessel injury triggers VSMC proliferation, in part, through focal adhesion kinase (FAK) activation, which increases transcription of cyclin D1, a key activator for cell cycle-dependent kinases (CDKs). At the same time, we also observe that FAK regulates the expression of the CDK inhibitors (CDKIs) p27 and p21. However, the mechanism of how FAK controls CDKIs in cell cycle progression is not fully understood. We found that pharmacological and genetic FAK inhibition increased p27 and p21 by reducing stability of S-phase kinase-associated protein 2 (Skp2), which targets the CDKIs for degradation. FAK N-terminal domain interacts with Skp2 and an APC/C E3 ligase activator, fizzy-related 1 (Fzr1) in the nucleus, which promotes ubiquitination and degradation of both Skp2 and Fzr1. Notably, overexpression of cyclin D1 alone failed to promote proliferation of genetic FAK kinase-dead (KD) VSMCs, suggesting that the FAK-Skp2-CDKI sip2 protein expression by proteasomal degradation, thereby increasing theexpression of cell cycle inhibitors p27 and p21 and blocking cell cycle progression. This studyhas demonstrated the potential for FAK inhibitors in blocking VSMC proliferation to treat vessel narrowing diseases.Increased VSMC proliferation contributes to pathological vessel narrowing in atherosclerosisand following vascular interventions. Blocking VSMC proliferation will reduce atherosclerosisprogression and increase patency of vascular interventions. We found that forced nuclear FAKlocalization by FAK inhibition reduced VSMC proliferation upon vessel injury. Nuclear FAKdecreased Skp2 protein expression by proteasomal degradation, thereby increasing theexpression of cell cycle inhibitors p27 and p21 and blocking cell cycle progression. This studyhas demonstrated the potential for FAK inhibitors in blocking VSMC proliferation to treat vessel narrowing diseases.Glioblastoma (GBM) is the most malignant and lethal intracranial tumor, with extremely limited treatment options. Immunotherapy has been widely studied in GBM, but none can significantly prolong the overall survival (OS) of patients without selection. Considering that GBM cancer stem cells (CSCs) play a non-negligible role in tumorigenesis and chemoradiotherapy resistance, we proposed a novel stemness-based classification of GBM and screened out certain population more responsive to immunotherapy. The one-class logistic regression algorithm was used to calculate the stemness index (mRNAsi) of 518 GBM patients from The Cancer Genome Atlas (TCGA) database based on transcriptomics of GBM and pluripotent stem cells. Based on their stemness signature, GBM patients were divided into two subtypes via consensus clustering, and patients in Stemness Subtype I presented significantly better OS but poorer progression-free survival than Stemness Subtype II. Genomic variations revealed patients in Stemness Subtype I had higher somatic mutation loads and copy number alteration burdens. Additionally, two stemness subtypes had distinct tumor immune microenvironment patterns. Tumor Immune Dysfunction and Exclusion and subclass mapping analysis further demonstrated patients in Stemness Subtype I were more likely to respond to immunotherapy, especially anti-PD1 treatment. The pRRophetic algorithm also indicated patients in Stemness Subtype I were more resistant to temozolomide therapy. Finally, multiple machine learning algorithms were used to develop a 7-gene Stemness Subtype Predictor, which were further validated in two external independent GBM cohorts. This novel stemness-based classification could provide a promising prognostic predictor for GBM and may guide physicians in selecting potential responders for preferential use of immunotherapy.Batch effect correction is an essential step in the integrative analysis of multiple single-cell RNA-sequencing (scRNA-seq) data. One state-of-the-art strategy for batch effect correction is via unsupervised or supervised detection of mutual nearest neighbors (MNNs). However, both types of methods only detect MNNs across batches of uncorrected data, where the large batch effects may affect the MNN search. To address this issue, we presented a batch effect correction approach via iterative supervised MNN (iSMNN) refinement across data after correction. Our benchmarking on both simulation and real datasets showed the advantages of the iterative refinement of MNNs on the performance of correction. Compared to popular alternative methods, our iSMNN is able to better mix the cells of the same cell type across batches. In addition, iSMNN can also facilitate the identification of differentially expressed genes (DEGs) that are relevant to the biological function of certain cell types. These results indicated that iSMNN will be a valuable method for integrating multiple scRNA-seq datasets that can facilitate biological and medical studies at single-cell level. Chemosensitivity testing, including collagen gel droplet-embedded culture drug sensitivity test, has proven to be a useful tool in therapeutic decision-making. This retrospective analysis investigated chemosensitivity testing of peritoneal metastases collected during cytoreductive surgery (CRS), and its impact on survival in patients with colorectal cancer. All patients with peritoneal metastasis from colorectal cancer who underwent CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) between November 2008 and October 2014 were included. The growth inhibition rate was expressed as the ratio between the image density after treatment (T) and that before treatment (control, C). Tumours with a reduction in T/C ratio of less than 20 per cent were defined as resistant and those with a reduction of 20 per cent or more as sensitive. Groups were compared for overall (OS) and disease-free (DFS) survival. Of 84 eligible patients, 81 received neoadjuvant chemotherapy (NACT), including 56 patients with an oxaliplatin-based regimen.