WNT16 as a promising biomarker for systemic lupus erythematosus and its role in regulating cell proliferation and apoptosis.

OBJECTIVES: To investigate the expression and function of WNT16, a member of the WNT family protein, in the context of systemic lupus erythematosus (SLE). METHODS: WNT16 expression was assessed in peripheral blood mononuclear cells (PBMCs) from 35 SLE patients and 25 healthy individuals using quantitative polymerase chain reaction. Additionally, serum WNT16 protein levels were quantified via enzyme-linked immunosorbent assay in 162 SLE patients, 96 healthy controls (HC), and disease controls comprised 154 individuals with rheumatoid arthritis (RA) and Sjögren's syndrome (SS). We investigated the associations between WNT16 protein levels and clinical manifestations, laboratory indices, and disease activity in SLE patients. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of serum WNT16 for SLE. Furthermore, we performed a knockdown assay on Jeko-1 cells and assessed cell proliferation and apoptosis using Cell Counting Kit-8 and flow cytometry. RESULTS: WNT16 mRNA in SLE patients' PBMCs were significantly lower than those in HC. Furthermore, serum WNT16 in SLE patients were markedly reduced compared to HC, RA, and SS cohorts. ROC curve analysis indicated that plasma WNT16 levels could serve as a potential biomarker for SLE identification (AUC=0.809, SLE vs. HC; AUC=0.760, SLE vs. RA; AUC=0.710, SLE vs. SS). Notably, a weak positive correlation was observed between WNT16 protein and both alkaline phosphatase and lymphocyte percentages. Conversely, a weak negative correlation existed between WNT16 and low-density lipoprotein, neutrophil percentage, and the incidence of pleurisy and disease activity. Additionally, our study confirmed that WNT16 knockdown impairs cell proliferation and enhances apoptosis. CONCLUSIONS: Serum WNT16 levels effectively differentiate SLE patients from healthy controls and individuals with other autoimmune disorders. WNT16 serves as a potential biomarker with high sensitivity. The diminished expression of WNT16 in SLE may have a significant role in its pathogenesis through the regulation of cell proliferation and apoptosis.

The relation between effortful control and executive function training in preschoolers.

In recent years, the question of whether executive function (EF) is malleable has been widely documented. Despite using the same training tasks, transfer effects remain uncertain. Researchers suggested that the inconsistency might be attributed to individual differences in temperamental traits. In the current study, we investigated how effortful control, a temperamental trait, would affect EF training outcomes in children. Based on parent rating, 79 6-year-old preschoolers were identified as having higher or lower effort control and were assigned to three conditions: working memory (WM) training, inhibitory control (IC) training, and a business-as-usual control group. Children completed assessments at baseline, 1 week after intervention (posttest), and 3 months after intervention (follow-up). As compared with the control group, the WM and IC training groups showed improvement in both trained tasks and nontrained measures. At baseline, children with higher effortful control scores showed greater WM capacity and better IC. Furthermore, effortful control was positively correlated with training gain in both training groups, with children with higher effortful control benefitting more through training. In the WM training group, effortful control was positively correlated with near transfer on WM outcomes both immediately and longitudinally. At posttest, the WM and IC training groups showed a positive correlation between effortful control and fluid intelligence performance. Our results underscore the importance of individual differences in training benefits, in particular the role of effortful control, and further illustrate the potential avenues for designing more effective individualized cognitive training programs to foster learning and optimize children's development.

Revisiting artificial intelligence diagnosis of hepatocellular carcinoma with DIKWH framework.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high morbidity and fatality rate. Traditional diagnostic methods for HCC are primarily based on clinical presentation, imaging features, and histopathology. With the rapid development of artificial intelligence (AI), which is increasingly used in the diagnosis, treatment, and prognosis prediction of HCC, an automated approach to HCC status classification is promising. AI integrates labeled clinical data, trains on new data of the same type, and performs interpretation tasks. Several studies have shown that AI techniques can help clinicians and radiologists be more efficient and reduce the misdiagnosis rate. However, the coverage of AI technologies leads to difficulty in which the type of AI technology is preferred to choose for a given problem and situation. Solving this concern, it can significantly reduce the time required to determine the required healthcare approach and provide more precise and personalized solutions for different problems. In our review of research work, we summarize existing research works, compare and classify the main results of these according to the specified data, information, knowledge, wisdom (DIKW) framework.

WD repeat domain 48 promotes hepatocellular carcinoma progression by stabilizing c-Myc.

The role of protein members containing the WD40 repeat domain in many diseases, including cancer, is well documented. However, the role of WD repeat domain 48 (WDR48) in hepatocellular carcinoma (HCC) and its molecular basis remain to be further investigated. In the present study, we report that WDR48 is downregulated in clinical HCC samples and evaluate the relationship between its expression and clinical features of HCC. In vitro experiments showed that WDR48 positively regulated the proliferation, invasion and metastasis of HCC cells and in vivo experiments showed that downregulation of WDR48 significantly inhibited the tumorigenicity of HCC cells. Mechanistically, WDR48 binds to the proto-oncogene transcriptional regulator c-Myc and stabilizes c-Myc expression by mediating its deubiquitination, thereby enhancing cell proliferation and EMT signalling. Our study demonstrates the oncogenic role of WDR48 and suggests that WDR48 can be an important target in HCC.

Artificial Intelligence Meets Whole Slide Images: Deep Learning Model Shapes an Immune-Hot Tumor and Guides Precision Therapy in Bladder Cancer.

Background: To construct and validate a deep learning cluster from whole slide images (WSI) for depicting the immunophenotypes and functional heterogeneity of the tumor microenvironment (TME) in patients with bladder cancer (BLCA) and to explore an artificial intelligence (AI) score to explore the underlying biological pathways in the developed WSI cluster. Methods: In this study, the WSI cluster was constructed based on a deep learning procedure. Further rerecognition of TME features in pathological images was applied based on a neural network. Then, we integrated the TCGA cohort and several external testing cohorts to explore and validate this novel WSI cluster and a corresponding quantitative indicator, the AI score. Finally, correlations between the AI cluster (AI score) and classical BLCA molecular subtypes, immunophenotypes, functional heterogeneity, and potential therapeutic method in BLCA were assessed. Results: The WSI cluster was identified associated with clinical survival (P < 0.001) and was proved as an independent predictor (P = 0.031), which could also predict the immunology and the clinical significance of BLCA. Rerecognition of pathological images established a robust 3-year survival prediction model (with an average classification accuracy of 86%, AUC of 0.95) for BLCA patients combining TME features and clinical features. In addition, an AI score was constructed to quantify the underlying logic of the WSI cluster (AUC = 0.838). Finally, we hypothesized that high AI score shapes an immune-hot TME in BLCA. Thus, treatment options including immune checkpoint blockade (ICB), chemotherapy, and ERBB therapy can be used for the treatment of BLCA patients in WSI cluster1 (high AI score subtype). Conclusions: In general, we showed that deep learning can predict prognosis and may aid in the precision medicine for BLCA directly from H&E histology, which is more economical and efficient.

DNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with ß-catenin to promote its ubiquitin degradation pathway.

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic ß-catenin destruction complex (GSK-3ß and Axin), promotes the ubiquitination degradation of ß-catenin, and inhibits its nuclear transfer, thus, decreasing c-Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

[Clinical Characteristics and Risk Factors Analysis for Visceral Pleural Invasion in 
Mixed Ground-glass Nodular Lung Adenocarcinoma].

BACKGROUND: Lung cancer is still the malignant tumor with the highest morbidity and mortality in China. Lung adenocarcinoma is the most common subtype, and the number of lung cancer presenting as mixed ground glass nodule (mGGN) in imaging is gradually increasing. Visceral pleural invasion (VPI) is an important factor affecting the prognosis of mGGN type lung adenocarcinoma. The aim of the study is to explore and analyze the risk factors for VPI in mGGN type lung adenocarcinoma. METHODS: From November 2016 to November 2019, 128 patients with mGGN lung adenocarcinoma underwent radical surgical resection in the First Affiliated Hospital of Nanjing Medical University. Their clinical data, including imaging, pathological and biological features, were collected and analyzed retrospectively. There were 40 males and 88 females, aged 60.3±9.3 years ranging from 30 to 81 years. Single factor Chi-square test and multivariate Logistic regression were used to analyze the risk factors of VPI in mGGN type lung adenocarcinoma. RESULTS: Among 128 mGGN patients who met the inclusion criteria, 57 cases were pathologically confirmed with pleural invasion. Between the VPI (+) and VPI (-) group (P<0.05), there were significant differences in gender, maximum diameter of solid component, consolidation tumor ratio (CTR), spicule sign, history of lung disease, family history of hypertension, relation of lesion to pleura (RLP), coursing relationship between bronchi and nodules. In multivariate Logistic regression analysis, RLP (OR=3.529, 95%CI: 1.430-8.713, P=0.006) and coursing relationship between bronchi and nodules (OR=3.993, 95%CI: 1.517-10.51, P=0.005) were found to be independent risk factors for VPI (P<0.05). CONCLUSIONS: The possibility of VPI in m GGN lung adenocarcinoma should be evaluated by combining these parameters in clinical diagnosis and treatment. As independent risk factors, RLP and coursing relationship between bronchi and nodules are instructive to identify VPI in mGGN type lung adenocarcinoma.

Identification of Immune-Related Genes and Small-Molecule Drugs in Interstitial Cystitis/Bladder Pain Syndrome Based on the Integrative Machine Learning Algorithms and Molecular Docking.

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, severely distressing clinical syndrome characterized by bladder pain and pressure perceptions. The origin and pathophysiology of IC/BPS are currently unclear, making it difficult to diagnose and formulate successful treatments. Our study is aimed at investigating the role of immune-related genes in the diagnosis, progression, and therapy of IC/BPS. Method: The gene expression datasets GSE11783, GSE11839, GSE28242, and GSE57560 were retrieved from the GEO database for further analysis. Immune-related IC/BPS differentially expressed genes (DEGs) were identified by limma. Three distinct machine learning approaches, least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF), were used to find the immune-related IC characteristic genes. Nomogram and receiving operator curves (ROC) were plotted to measure characteristic effectiveness. Using the CMap database and the molecular docking approach, potential small-molecule medicines were found and verified. Consensus cluster analysis was also performed to separate the IC/BPS samples into immunological subtypes. Results: A total of 24 immune-related IC/BPS-DEGs were identified. When compared to the normal control group, the IC/BPS cohort had significantly more immune cell infiltration. Integrative machine learning methods discovered 5 IC/BPS characteristic genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) that may predict IC/BPS diagnosis and immune cell infiltration. Furthermore, two immunological subgroups with substantial variations in immune cell infiltration across IC/BPS samples were identified, which were named cluster1 and cluster2, with the hallmark genes having greater expression in cluster2. Finally, bumetanide was shown to have the potential to be a medication for the treatment of IC/BPS, and it performed well in terms of its molecular binding with RASGRP1. Conclusion: We found and validated 5 immune-related IC/BPS genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) and 2 IC/BPS immune subtypes. In addition, bumetanide was discovered to be a potential drug for treating IC/BPS, which may provide new insight into the diagnosis and immune therapy of IC/BPS patients.

In vitro Antimicrobial Activity of Fosfomycin, Rifampin, Vancomycin, Daptomycin Alone and in Combination Against Vancomycin-Resistant Enterococci.

PURPOSE: The emergence of vancomycin resistant Enterococci (VRE) is shortening the choices for clinical anti-infective therapy. The aim of this study was to investigate the mechanism of vancomycin resistance and evaluate the effect of fosfomycin (FM), rifampin (RIF), vancomycin (VAN), linezolid (LNZ), daptomycin (DAP) alone or in combination against VRE. METHODS: Eight VRE isolates were collected. A total of 18 antibiotics susceptibility tests were further done for VRE. Whole genome sequencing and bioinformatics analysis were performed. The effect of FM, RIF, VNA, LNZ, DAP alone or in combination was determined using anti-biofilm testing and the time-kill assay. RESULTS: All isolates were susceptible to LNZ and DPA. The high-level resistance determinant of VAN in these strains was due to VanA-type cassette. MLST revealed two different STs for vancomycin-resistant Enterococcus faecium (VREm) and four different STs for vancomycin-resistant E. faecalis (VREs). Virulence genes in VREs were more than VREm, especially for 4942 isolated from blood. Gene acm and uppS were only identified in VREm, while virulence genes related to cytolysin were only found in E. faecalis. Further in vitro studies indicated FM (83 mg/L) combined with DAP (20.6 mg/L) and DAP monotherapy (47.1 mg/L) had bactericidal effect against VRE isolates at 24h. CONCLUSION: High-level resistance determinant of VAN in tested isolates was due to VanA-type cassette. FM combined with DAP is a potential therapeutic option for VRE infections.

Analysis of Clinical Characteristics, Radiological Predictors, Pathological Features, and Perioperative Outcomes Associated with Perinephric Fat Adhesion Degree.

BACKGROUND: To assess the clinical characteristics, radiological predictors, and pathological features of perinephric fat adhesion degree (PFAD) graded based on fixed criteria and to determine the impact of adherent perinephric fat (APF) on retroperitoneal laparoscopic partial nephrectomy (RLPN) outcomes. METHODS: 84 patients undergoing RLPN were included and graded into 4 groups based on PFAD. Univariate and multivariate analyses were performed for clinical characteristics and radiological predictors of PFAD. Perioperative data were compared between APF groups and non-APF groups. Masson staining determined collagen fibers. Immunohistochemistry detected CD45 immune cells and CD34 vessels. RESULTS: 20, 28, 18, and 18 patients were graded as normal perinephric fat (NPF), mild adherent perinephric fat (MiPF), moderate adherent perinephric fat (MoPF), and severe adherent perinephric fat (SPF), respectively. Multivariate analysis revealed that gender (p < 0.001), age (p = 0.003), and hypertension (p = 0.006) were significant clinical risk factors of PFAD, while radiological predictors included perinephric stranding (p = 0.001), posterior perinephric fat thickness (p = 0.009), and perinephric fat density (p = 0.02). APF was associated with drain output (p = 0.012) and accompanied by immune cells gathering in renal cortex near thickened renal capsule with many vessels. CONCLUSIONS: Clinical characteristics and radiological predictors can evaluate PFAD and may assist to guide preoperative surgical option. Pathological features of APF reflect decapsulation and bleeding during kidney mobilization at RLPN.

Start-up performance of anaerobic/aerobic/anoxic-sequencing batch reactor (SBR) augmented with denitrifying polyphosphate-accumulating organism (DPAO) and their gene analysis.

This paper was aimed at investigating the bio-augmentation performance of anaerobic/aerobic/anoxic-type sequencing batch reactor (SBR) during its start-up period by introducing a strain of denitrifying polyphosphate-accumulating organism (DPAO). Two SBR reactors were inoculated to study the start-up performance, with one for DPAO introduction and the other as the control specimen. A comparison, of microbial community diversity based on the reactor which obtained a better performance, was made between polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analyses encoded by 16S rRNA and functional genes (nirS, nirK). The results indicated that the introduction of DPAO had a positive effect on the biological system, including a reduction of the start-up period, the improvement of sludge characteristics and the removal efficiency of nutrients, especially for phosphorus. By comparing the phylogenetic relationship of 16S rRNA and functional genes (nirS, nirK) of the reactor augmented with DPAO, it could be found that the phylogenetic relationship of these genes were remarkably inconsistent with each other. Therefore, 16SrRNA should not be used to determine the microbial community diversity of functional bacteria which could accomplish denitrification, and gene nirK should not be neglected when determining functional bacteria.

Three-dimensional reconstructive methods in the visualization of anterolateral thigh flap.

INTRODUCTION: Developments in the field of digitalized technique and three-dimensional (3D) reconstruction methods allowed a precise description of anatomy structures. With the development of computer reconstructive techniques, we could get more precise anatomic images. Digitized visible models of these structures can be as a useful tool in clinical training. The purpose of this study was to observe the anatomy of arteria circumflexa femoris lateralis (ACFL) flap and to discuss the methods in the visualization of anterolateral thigh (ATL) flap by digitalized technique. METHODS: Six adults volunteer underwent contrast-enhanced CT angiography of pelvic and lower limbs utilizing a 64-row multi-slice spiral CT after median cubital vein injection with Ultravist (3.5 ml/s). 2D images from these data in Dicom format were transformed into computer. Next two adult fresh cadaver specimens, one male and one female, were subject to radiographic CT scanning before and after perfused with lead oxide-gelatine mixture, whose collimation are 0.5 mm (120 kV, 110 mA, 512 x 512 matrix). Through Amira 3.1 (TGS) software, the 2D images in Dicom format were transformed into the 3D models of the entire region. The structures of arteria circumflexa femoris lateralis (ACFL) were observed and the digitized visible models of ALT flap were established through 3D computerized reconstructions methods from these data using Amira 3.1 software. Then merging volume rendering with surface rendered reconstruction from lead oxide-gelatine mixture perfusion database. RESULTS: The 3D reconstructed visible models established from these datasets perfectly displayed the characteristic of ACFL and ALT flap anatomy. CONCLUSION: The digitized models could offer the anatomy of ALT flap perfectly, and the reconstructed methods may be used in other flap reconstruction with 3D demonstration.