Clinical features and familial mutations in the coexistence of Wilson's disease and Alport syndrome: A case report

BackgroundAlport syndrome (AS) and Wilson's disease (WD) are genetic diseases that could lead to kidney damage. Herein, we report the clinical features and gene variants in a patient with WD and X-linked AS.Case presentationThe proband was a 12-year-old boy diagnosed with AS coexisting with WD at the age of 11 years. The patient underwent a medical check-up when he was 4 years and 8 months. Laboratory tests revealed elevated liver enzymes, decreased serum ceruloplasmin, increased 24-h urinary copper excretion, and one variant in the ATP7B gene. Then, the patient was diagnosed with WD. After 2 months of treatment with D-penicillamine and zinc salt, his liver function had recovered to normal levels, but he presented with microscopic hematuria. The hematuria did not resolve after switching to dimercaptosuccinic acid from D-penicillamine. In addition, he presented with proteinuria 3 years later. A renal biopsy was performed more than 6 years after the patient was diagnosed with WD, and electron microscopy showed that the basement membrane thickness was uneven, layered, and focal torn. Copper staining was negative. A genetic analysis identified a hemizygous variant (c.1718G > A, p. Gly573Asp) in COL4A5 and a homozygous variant (c.2975C > T, p. Pro992leu) in ATP7B. The patient’s urine protein–creatinine ratio was less than 1.0 mg/mg after a 1 year of follow-up, after enalapril was administered for treating AS.ConclusionThis case highlights a lack of improvement in renal function after conventional treatment provides a possible indication for performing renal biopsy or genetic testing to determine the etiology in order to facilitate subsequent clinical management. Clinicians should prevent the occurrence of diagnostic inaccuracies caused by diagnostic anchoring because an accurate diagnosis is essential for achieving precise treatment and improved prognosis

Genistein suppresses FLT4 and inhibits human colorectal cancer metastasis

Dietary consumption of genistein, found in soy, has been associated with a potentially protective role in colorectal cancer (CRC) development and progression. Herein we demonstrate that genistein will inhibit human CRC cell invasion and migration, that it does so at non-cytotoxic concentrations and we demonstrate this in multiple human CRC cell lines. After orthotopic implantation of human CRC tumors into mice, oral genistein did not inhibit tumor growth, but did inhibit distant metastasis formation, and was non-toxic to mice. Using a qPCR array, we screened for genistein-induced changes in gene expression, followed by Western blot confirmation, demonstrating that genistein downregulated matrix metalloproteinase 2 and Fms-Related Tyrosine Kinase 4 (FLT4; vascular endothelial growth factor receptor 3). After demonstrating that genistein suppressed neo-angiogenesis in mouse tumors, we examined FLT4 expression in primary CRC and adjacent normal colonic tissue from 60 human subjects, demonstrating that increased FLT4 significantly correlates with increased stage and decreased survival. In summary, we demonstrate for the first time that genistein inhibits human CRC metastasis at dietary, non-toxic, doses. FLT4 is identified as a marker of metastatic disease, and as a response marker for small molecule therapeutics that inhibit CRC metastasis

Uric acid predicts recovery of left ventricular function and adverse events in heart failure with reduced ejection fraction: Potential mechanistic insight from network analyses

Background and Aims: Heart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF. Methods: HFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016-2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and cardiovascular events were identified. Network-based analysis was utilized to examine the relationship between recovery of LVEF and hyperuricemia, and we further elucidated the underlying mechanisms for the impact of hyperuricemia on HFrEF. Results: After adjusting confounding factors by propensity score matching, hyperuricemia was a determinant of HFrEF [OR 1.247 (1.172-1.328); Conclusion: Lower baseline UA value predicted the LVEF recovery and less long-term adverse events in HFrEF patients. Our results provide new insights into underlying mechanistic relationship between hyperuricemia and HFrEF

Deregulation of manganese superoxide dismutase (SOD2) expression and lymph node metastasis in tongue squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Lymph node metastasis is a critical event in the progression of tongue squamous cell carcinoma (TSCC). The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making. Previous studies showed that deregulation of manganese superoxide dismutase (SOD2) expression is a frequent event in TSCC and may be associated with enhanced cell invasion. The purpose of this study is to further evaluate whether the expression level of SOD2 is correlated with the metastatic status in TSCC patients.</p> <p>Methods</p> <p>We first examined the SOD2 expression at mRNA level on 53 TSCC and 22 normal control samples based on pooled-analysis of existing microarray datasets. To confirm our observations, we examined the expression of SOD2 at protein level on an additional TSCC patient cohort (n = 100), as well as 31 premalignant dysplasias, 15 normal tongue mucosa, and 32 lymph node metastatic diseases by immunohistochemistry (IHC).</p> <p>Results</p> <p>The SOD2 mRNA level in primary TSCC tissue is reversely correlated with lymph node metastasis in the first TSCC patient cohort. The SOD2 protein level in primary TSCC tissue is also reversely correlated with lymph node metastasis in the second TSCC patient cohort. Deregulation of SOD2 expression is a common event in TSCC and appears to be associated with disease progression. Statistical analysis revealed that the reduced SOD2 expression in primary tumor tissue is associated with lymph node metastasis in both TSCC patient cohorts examined.</p> <p>Conclusions</p> <p>Our study suggested that the deregulation of SOD2 in TSCC has potential predictive values for lymph node metastasis, and may serve as a therapeutic target for patients at risk of metastasis.</p

Artificial Intelligence tool for fire safety design (IFETool): Demonstration in large open spaces

Fire modelling is a common practice in building fire safety analysis, but it is costly. This work develops an AI software, Intelligent Fire Engineering Tool (IFETool), to speed up the fire safety analysis and quickly identify design limits. A big numerical atrium-fire database is firstly formed by considering key building and fire parameters. Then, a deep learning model is trained to predict the evolution of tenable smoke visibility, temperature and CO concentration with an accuracy of 97%. The tenability descending profile is further processed to assess the available safe egress time (ASET) and the fire safety of the atriums that have complex roof shapes and slab extensions. This AI design software is able to make a quick assessment of the proposed atrium fire engineering design and give valuable suggestions for potential improvement. Finally, the operation guidelines of IFETool are provided for common design tasks of atrium fire safety

Data from: Body size response to warming: time of the season matters in a tephritid fly

Whether shrinking body size is a universal response to climate change remains controversial. Moreover, the mechanisms underlying body size shifts are poorly understood. Here, assuming that life history traits evolve to maximize fitness according to life history plasticity theory, we hypothesized that under global warming temperate multivoltine insects should emerge earlier with a smaller body mass in the early growing season, but emerge later with a larger body mass in the late season. We tested this hypothesis by conducting two field artificial warming experiments in an alpine meadow: 1) with one pre-dispersal seed predator species (tephritid flies, Tephritis femoralis) and its two host-plant species flowering in early and late growing seasons, respectively, and 2) with the tephritid flies and one host species with a flowering season that occupies parts of both the early and late growing seasons. These experiments were complemented by a microcosm chamber warming experiment, in which increasing and decreasing temperature trends were set to simulate temperature variation pattern in early and late growing seasons, respectively, but photoperiod was held constant. Warming generally advanced the adult emergence and decreased the body size (adult body mass) in the early season but delayed the emergence and increased the size in the late season in both field experiments, indicating that the seasonally different effects of warming on the fly body size was constant regardless of host-plant identity. The chamber warming resulted in consistent responses of emerging timing and body size to the simulated seasonal warming, demonstrating that the temperature increase per se and its interaction with direction of temperature change, but not other correlated effects, should be primarily responsible for the observed contrasting shifts of body size at different times of the season. Our results indicate that taking into account temperate seasonal patterns of temperature variation could be of general importance for predicting animal body size changes in the warmed future

Data for the observtional field experiment, controlled field experiment, and the microcosm experiment

Data for the observtional field experiment, controlled field experiment, and the microcosm experimen