Image2_Case report: A novel c.1842_1845dup mutation of ETFDH in two Chinese siblings with multiple acyl-CoA dehydrogenase deficiency.jpeg

This article reports the characterization of two siblings diagnosed with late-onset multiple Acyl-CoA dehydrogenase deficiency (MADD) caused by mutations in electron transfer flavoprotein(ETF)-ubiquinone oxidoreductase (ETF-QO) (ETFDH) gene. Whole exome sequencing (WES) was performed in the proband's pedigree. Clinical phenotypes of Proband 1 (acidosis, hypoglycemia, hypotonia, muscle weakness, vomiting, hypoglycemia, hepatomegaly, glutaric acidemia, and glutaric aciduria) were consistent with symptoms of MADD caused by the ETFDH mutation. However, Proband 2 presented with only a short stature. The patients (exhibiting Probands 1 and 2) showed identical elevations of C6, C8, C10, C12, and C14:1. c.1842_1845 (exon13)dup, and c.250 (exon3) G > A of the ETFDH gene were compound heterozygous variants in both patients. The novel variant c.1842_1845dup was rated as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines (ACMG). This is the first report on the c.1842_1845dup mutation of the ETFDH gene in patients with late-onset MADD, and the data described herein may help expand the mutation spectrum of ETFDH.</p

Image1_Case report: A novel c.1842_1845dup mutation of ETFDH in two Chinese siblings with multiple acyl-CoA dehydrogenase deficiency.jpeg

This article reports the characterization of two siblings diagnosed with late-onset multiple Acyl-CoA dehydrogenase deficiency (MADD) caused by mutations in electron transfer flavoprotein(ETF)-ubiquinone oxidoreductase (ETF-QO) (ETFDH) gene. Whole exome sequencing (WES) was performed in the proband's pedigree. Clinical phenotypes of Proband 1 (acidosis, hypoglycemia, hypotonia, muscle weakness, vomiting, hypoglycemia, hepatomegaly, glutaric acidemia, and glutaric aciduria) were consistent with symptoms of MADD caused by the ETFDH mutation. However, Proband 2 presented with only a short stature. The patients (exhibiting Probands 1 and 2) showed identical elevations of C6, C8, C10, C12, and C14:1. c.1842_1845 (exon13)dup, and c.250 (exon3) G > A of the ETFDH gene were compound heterozygous variants in both patients. The novel variant c.1842_1845dup was rated as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines (ACMG). This is the first report on the c.1842_1845dup mutation of the ETFDH gene in patients with late-onset MADD, and the data described herein may help expand the mutation spectrum of ETFDH.</p

Studying Different Binding and Intracellular Delivery Efficiency of ssDNA Single-Walled Carbon Nanotubes and Their Effects on LC3-Related Autophagy in Renal Mesangial Cells via miRNA-382

Single-walled carbon nanotubes (SWCNTs) have been used to deliver single-stranded (ssDNA). ssDNA in oligonucleotide can act as an inhibitor of microRNA to regulate cellular functions. However, these ssDNA are difficult to bind carbon nanotubes with low transferring efficiency to cells. To this end, we designed ssDNA with regulatory and functional units to form ssDNA-SWCNT hybrids to study their binding effects and transferring efficiency. The functional unit on ssDNA mimics the inhibitor (MI) of miRNA-382, which plays a crucial role in the progress of many diseases such as renal interstitial fibrosis. After verification of overexpression of miRNA-382 in a coculture system, we designed oligonucleotide sequences (GCG)₅-MI, (TAT)₅-MI, and N₂₃-MI as regulatory units added to the 5′-terminal end of the functional DNA fragment, respectively. These regulatory units lead to different secondary structures and thus exhibit different affinity ability to SWCNTs, and finally decide their deliver efficacy to cells. Autophagy, apoptosis and necrosis were observed in renal mesangial cells

Additional file 2 of Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Additional file 2: Figure S1. DNA sequencing to verify V367F and N354D mutations in the pseudovirus genome

Additional file 6 of Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Additional file 6: Figure S5. Network graphic of SARS-CoV-2 isolates worldwide during 1 July and 31 August 2020. Isolates were aligned by the Force Atlas model in Gephi. In the network, each node represented an isolate of SARS-CoV-2. Each color represented a country. Lines inherit colors from their origin clades. Distances between clades represented evolutionary distance

Additional file 3 of Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Additional file 3: Figure S2. Network graphic of SARS-CoV-2 isolates worldwide during 9 and 31 March 2020. Isolates were aligned by the Force Atlas model in Gephi. In the network, each node represented an isolate of SARS-CoV-2. Each color represented a country. Lines inherit colors from their origin clades. Distances between clades represented evolutionary distance

Additional file 4 of Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Additional file 4: Figure S3. Network graphic of SARS-CoV-2 isolates worldwide during 1 and 30 April 2020. Isolates were aligned by the Force Atlas model in Gephi. In the network, each node represented an isolate of SARS-CoV-2. Each color represented a country. Lines inherit colors from their origin clades. Distances between clades represented evolutionary distance

Additional file 1 of Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Additional file 1: Table S1. Sequences included for detecting genetic recombination relevant to SARS-CoV-2

Additional file 5 of Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Additional file 5: Figure S4. Network graphic of SARS-CoV-2 isolates worldwide during 1 May and 30 June 2020. Isolates were aligned by the Force Atlas model in Gephi. In the network, each node represented an isolate of SARS-CoV-2. Each color represented a country. Lines inherit colors from their origin clades. Distances between clades represented evolutionary distance

Table_4_Epidemiological Characteristics of Primary Liver Cancer in Mainland China From 2003 to 2020: A Representative Multicenter Study.docx

BackgroundThe contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to primary liver cancer (PLC) and their association with cancer aggressiveness remains uncertain in China, a country with half of global PLC. We aimed to characterize this using data from four representative medical centers.MethodsIn total, 15,801 PLC patients were enrolled from the centers distributed in Easter5n, Southern, Northern, and Western China from 2003 to 2020. Of those, 7585 with curative surgery were involved in survival analysis. A nomogram was constructed using preoperative parameters to predict postoperative survival.ResultsHepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma accounted for 93.0%, 4.3%, and 1.6% in PLC, respectively. The seropositivities of HBV and HCV were 84.4% and 3.2% in HCC, respectively. The seropositivity of anti-HCV antibody was significantly higher in HBV-negative than in HBV-positive HCC patients (13.2% vs. 1.1%). Compared to HCV-positive HCC (HCV-HCC), HBV-positive HCC (HBV-HCC) was associated with 12-year earlier onset, higher proportions of males, high α-fetoprotein, large tumor size, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and vascular tumor thrombus. The proportions of HCC and HBV seropositivity increased, whereas that of anti-HCV decreased, from 2003 to 2020. Postoperative five-year survival rate was 73.5%, 64.1%, 34.9%, and 19.7% in HCC at BCLC stage 0, A, B, and C, respectively. The multivariate Cox regression analysis showed that HBV seropositivity, incomplete tumor capsule, vascular tumor thrombus, tumor diameter (≥3 cm), advanced BCLC stage (B+C), α-fetoprotein (≥20ng/ml), and direct bilirubin (>8µmol/L) contributed independently to shorter overall survival (OS); whereas post-operative radiofrequency ablation and second resection independently improved OS in HCC. HCV-HCC had a more favorable prognosis than did HBV-HCC (Log-rank test, PConclusionHBV contributes to 84.4% of HCC in China, and actively promotes hepatocarcinogenesis and HCC progression. A favorable postoperative survival obtained in patients at the early BCLC stage highlights the importance of screening for early HCC in high-risk populations. Our preoperative prognosis prediction model is important in clinical decision-making.</p