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Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1. ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein (HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells (RGCs) by using an artificial intelligence (AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing (scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1

Background Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, subjective, and costly, making them inaccessible to many families. In this study, we aimed to investigate the use of parent-child interaction as a potential screening tool for identifying children with ASD. Methods We recruited 85 preschool ASD children with development delay (DD), ASD children without DD and typically developing (TD) children, along with their caregivers, to engage in parent-child interaction while simultaneously recording EEG and video signals. Results We found that the behavioral indicators of both ASD groups were worse than TD group and correlated with the severity of the symptoms of ASD. Both theta and alpha band PSD values increased in both ASD groups compared to TD children, primarily correlated with social behavior rather than IQ level. Conclusion Our results verified the behavioral paradigm of parent-child interaction as an efficient method for identifying children with ASD, further validated by the PSD of alpha and theta bands.

Multiple regression analysis of tankyrase inhibitor sensitivities and genetic mutations in colorectal cancer cell lines

Figure S6 shows that inhibition of GPER1 by G-15 reverses Sin1 expression and Sin1-mTORC2-AKT mediated hepatocyte proliferation.

In most colorectal cancers, Wnt/β-catenin signaling is activated by loss-of-function mutations in the adenomatous polyposis coli (APC) gene and plays a critical role in tumorigenesis. Tankyrases poly(ADP-ribosyl)ate and destabilize Axins, a negative regulator of β-catenin, and upregulate β-catenin signaling. Tankyrase inhibitors downregulate β-catenin and are expected to be promising therapeutics for colorectal cancer. However, colorectal cancer cells are not always sensitive to tankyrase inhibitors, and predictive biomarkers for the drug sensitivity remain elusive. Here we demonstrate that the short-form APC mutations predict the sensitivity of colorectal cancer cells to tankyrase inhibitors. By using well-established colorectal cancer cell lines, we found that tankyrase inhibitors downregulated β-catenin in the drug-sensitive, but not resistant, colorectal cancer cells. The drug-sensitive cells showed higher Tcf/LEF transcriptional activity than the resistant cells and possessed “short” truncated APCs lacking all seven β-catenin-binding 20-amino acid repeats (20-AARs). In contrast, the drug-resistant cells possessed “long” APC retaining two or more 20-AARs. Knockdown of the long APCs with two 20-AARs increased β-catenin, Tcf/LEF transcriptional activity and its target gene AXIN2 expression. Under these conditions, tankyrase inhibitors were able to downregulate β-catenin in the resistant cells. These results indicate that the long APCs are hypomorphic mutants, whereas they exert a dominant-negative effect on Axin-dependent β-catenin degradation caused by tankyrase inhibitors. Finally, we established 16 patient-derived colorectal cancer cells and confirmed that the tankyrase inhibitor–responsive cells harbor the short-form APC mutations. These observations exemplify the predictive importance of APC mutations, the most common genetic alteration in colorectal cancers, for molecular targeted therapeutics. Mol Cancer Ther; 16(4); 752–62. ©2017 AACR.

Supplementary Figure S1: Full scans of the immunoblots shown in Figs. 1C, 2A and 4A. Supplementary Figure S2: Basal expression of tankyrase, Axins, and β-catenin and intracellular localization of β-catenin in CRC cell lines used in this study. Supplementary Figure S3: Response of colorectal cancer SW480 cells to tankyrase inhibitors. Supplementary Figure S4: Depletion of long APC enhances β-catenin signaling and restores tankyrase inhibitor-mediated downregulation of the signal. Supplementary Figure S5: Long but not short APC represses Wnt/β-catenin signal and its knockdown sensitizes β-catenin to tankyrase inhibitor-mediated downregulation. Supplementary Figure S6: Schematic models for the differential effects of the "short" and "long" APC mutants on tankyrase inhibitor (TNKSi)-mediated downregulation of β-catenin. Supplementary Figure S7: APC mutations and sensitivity to tankyrase inhibitors of the patient-derived CRC cells. Supplementary Figure S8: Effects of a tankyrase inhibitor G007-LK on colony formation and β-catenin knockdown on proliferation of patient-derived CRC cells (PDCs).

Supplementary Figure 1. Brief schematic of the strategy to identify salivary miRNA biomarkers to detect resectable pancreatic cancer.

Supplementary Figure Legends 1-8

Early surgery is vital in the treatment of pancreatic cancer, which is often fatal. However, there is currently no useful noninvasive biomarker to screen for pancreatic cancer. Studies have documented that many salivary molecules can be used to detect systemic diseases. We investigated whether salivary miRNAs are useful biomarkers for detecting resectable pancreatic cancer. Using an Agilent microarray, salivary miRNAs were profiled from saliva samples of 8 patients with resectable pancreatic cancer and 8 healthy controls. Candidate biomarkers identified in the profiles were subjected to validation using quantitative PCR and an independent sample set of 40 patients with pancreatic cancer, 20 with benign pancreatic tumors (BPT), and 40 healthy controls. The validated salivary miRNA biomarkers were evaluated within three discriminatory categories: pancreatic cancer versus healthy control, pancreatic cancer versus BPT, and pancreatic cancer versus noncancer (healthy control + BPT). miR-3679-5p showed significant downregulation in the pancreatic cancer group within the three categories (P = 0.008, 0.007, and 0.002, respectively), whereas miR-940 showed significant upregulation in pancreatic cancer (P = 0.006, 0.004, and 0.0001, respectively). Logistic regression models combining the two salivary miRNAs were able to distinguish resectable pancreatic cancer within the three categories, showing sensitivities of 72.5%, 62.5%, and 70.0% and specificities of 70.0%, 80.0%, and 70.0%, respectively. Salivary miR-3679-5p and miR-940 possess good discriminatory power to detect resectable pancreatic cancer, with reasonable specificity and sensitivity. This report provides a new method for the early detection of pancreatic cancer and other systemic diseases by assessing salivary miRNAs. Cancer Prev Res; 8(2); 165–73. ©2014 AACR.

Legends for Supplementary Figure S1-S8

Supplementary material 4. Normalised microarray data in the discovery phase.

Supplementary material 3. Detailed demographic, clinical and experimental information of the enrolled participants including patients with resectable pancreatic cancer and benign pancreatic tumor, and healthy controls.

Supplementary material 2. Pancreatic cancer staging based on The American Joint Committee on Cancer: 7th Edition on Cancer Staging.

Supplementary table 1. Demographic and clinical information of enrolled participants.

Supplementary material 1. The definition of pancreatic cancers deemed resectable or borderline resectable according to the National Comprehensive Cancer Network: Practice Guidelines in Oncology (v. 2.2010).

The Revised International Staging System (R-ISS) is a simple and powerful prognostic tool for multiple myeloma (MM). However, heterogeneity in R-ISS stage is still poorly characterised, hampering improvement of treatments. We used single-cell RNA-seq to examine novel cellular heterogeneity and regular networks in nine MM patients stratified by R-ISS. Plasma cells were clustered into nine groups (P1-P9) based on gene expression, where P1-P5 were almost enriched in stage III.PDIA6 was significantly upregulated in P3 and LETM1 was enriched in P1, and they were validated to be upregulated in the MM cell line and in 22 other patients' myeloma cells. Furthermore, in progression, PDIA6 was newly found and verified to be activated by UQCRB through oxidative phosphorylation, while LETM1 was activated by STAT1 via the C-type lectin receptor-signalling pathway. Finally, a subcluster of monocytes was exclusively found in stage III specifically expressed chemokines modulated by ATF3. A few ligand-receptor pairs (CCL3/CCL5/CCL3L1-CCR1) were obviously active in monocyte-plasma communications in stage III. Herein, this study identified novel molecules, networks and crosstalk pairs in different R-ISS stages of MM, providing significant insight for its prognosis and treatment.

Because protein is readily degraded in the environment, it is unknown whether “protein-like substances” in environments are a group of intact proteins or a mixture of peptides and even amino acids....