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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

This work studied the wind load acting on a point focus solar furnace composed of a 110 m2 heliostat and a 77 m2 concentrator through wind tunnel testing. Based on wind tunnel test data under 305 different working conditions, the variation laws of the wind pressure coefficient, power spectral density, and wind load coefficient of the heliostat and concentrator were analyzed. The results showed that due to the interaction between the concentrator and heliostat, the wind speed near the heliostat and concentrator decreased but the turbulence intensity increased, which caused the peak wind load coefficient to rise slightly. The results suggested that a safety factor of 1.1–1.2 should be considered for structural design and optimization of solar furnaces.

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

Figure S5 proves that Sin1 expression is induced in hepatocytes from acute liver injury.

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.

Figure S7 demonstates that gender difference of HCC is seen in mouse and human.

Figure S2 demonstrates that Sin1 is specifically induced by estrogen, but not by androgen, in HCC cells.

Figure S8 shows the model of GPER1-mediated Sin1 in regulation of cell proliferation via mTORC2-AKT signaling in HCC.

Legends for Supplementary Figure S1-S8

Figure S4 reveals tha estrogen promotes the nuclear accumulation of Sin1.

Figure S1 shows that SIN1 is upregulated and co-expressed with GPER1 in HCC.

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).

IC50 values of colorectal cancer cell lines and colorectal cancer patient-derived cells

Figure S3 tells that GPER1-E2 signaling does not affect apoptosis of HCC cells.

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....

The cost of operating Chinese football clubs has increased, prompting the need to examine their operating efficiency. Hence, this study proposes an integrated approach to analyse the efficiency of ...

Understanding the reactions taking place in the hematite-oxalic acid system is important in order to clean iron oxides from filters and to remove iron from mineral concentrates. Previous studies reported the formation of an unwanted solid phase during this process. The objective of the current work, therefore, was to visualize and rationalize the iron dissolution steps taking place in the hematite–oxalic acid reaction by combining density functional theory (DFT) calculations and experimental data. The results of DFT calculations indicated that a precipitate was formed in this reaction; XRD analysis of the solid phase after the dissolution experiment revealed the formation of humboldtine as the precipitate. The attachment of oxalate on the hematite surface and the reduction of Fe(III) to Fe(II) were key steps for humboldtine formation. Both simulations and the experimental results showed that greater oxalic acid concentrations yielded more precipitate, suggesting a simple and novel route to synthesize humboldtine, a material which is relevant to the demand for clean energy.

Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells.

Background To evaluate the possibilty of preventing recurrent vitreous hemorrhage (RVH) after vitrectomy in proliferative diabetic retinopathy (PDR) patients with unabsorbed vitreous hemorrhage (VH) by intravitreal injection of viscoelastic agent (VA) at the end of the surgery and compared its effect with triamcinolone acetonide (TA). Methods This was a pilot prospective, observational study. PDR patients with VH who underwent vitrectomy were assigned to 3 groups according to the tamponade applicated at the end of the surgery, including VA group (intravitreally injected 1 ml VA if the retina was prone to bleed during the operation), TA group (intravitreally injected 2 mg TA when there was much exudates), or balanced salt solution (BSS) group (no tamponade). Then postoperative follow-up was performed routinely until 6 months after surgery. The primary outcome was the incidence of RVH, secondary outcome were the best-corrected visual acuity (BCVA) and introcular pressure (IOP). Cataract formation and other complication were also assessed. Results A total of 68 eyes, from 68 patients, were included. 18,18,32 eyes were enrolled in the VA group, TA group and BSS group, respectively. The integral incidence of RVH after vitrectomy was 5.6%, 5.6% and 12.5% respectively (P = 0.602). There was no early RVH in VA or TA group, whereas 3 early RVHs were identified in BSS group, however there was no significant difference (P = 0.171). Every group had one late RVH case. In all groups, final BCVA showed significant improvement compared to baseline. BCVA at any postoperative visit showed no significant differences among 3 groups. Mean IOP was higher 1 week after surgery in VA group compared with the other groups; however, in other times the differences were not significant. No cataract formation and other complication was noted in 3 groups. Conclusion Intravitreal injection of VA or TA at the end of vitrectomy for PDR patients with unabsorbed VH tend to reduce the incidence of early RVH after vitrectomy similarly. As VA was preferred to applicate in the eyes that were prone to bleed, intravitreal injection of VA at the end of vitrectomy might be a promising method for preventing RVH in PDR patients.

Artificial intelligence (AI) software in radiology is becoming increasingly prevalent and performance is improving rapidly with new applications for given use cases being developed continuously, oftentimes with development and validation occurring in parallel. Several guidelines have provided reporting standards for publications of AI-based research in medicine and radiology. Yet, there is an unmet need for recommendations on the assessment of AI software before adoption and after commercialization. As the radiology AI ecosystem continues to grow and mature, a formalization of system assessment and evaluation is paramount to ensure patient safety, relevance and support to clinical workflows, and optimal allocation of limited AI development and validation resources before broader implementation into clinical practice. To fulfil these needs, we provide a glossary for AI software types, use cases and roles within the clinical workflow; list healthcare needs, key performance indicators and required information about software prior to assessment; and lay out examples of software performance metrics per software category. This conceptual framework is intended to streamline communication with the AI software industry and provide healthcare decision makers and radiologists with tools to assess the potential use of these software. The proposed software evaluation framework lays the foundation for a radiologist-led prospective validation network of radiology AI software. Learning Points: The rapid expansion of AI applications in radiology requires standardization of AI software specification, classification, and evaluation. The Canadian Association of Radiologists' AI Tech & Apps Working Group Proposes an AI Specification document format and supports the implementation of a clinical expert evaluation process for Radiology AI software.