Background: Whether the patients with coronavirus disease 19 (COVID-19) infected by severe acute respiratory syndrome (SARS)-CoV-2 would commonly develop acute kidney injury (AKI) is an important issue worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients. Methods: One hundred sixteen COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was detected by real-time reverse transcription-polymerase chain reaction. Results: Twelve (10.8%) patients showed mild increase of blood urea nitrogen or creatinine (<26 μmol/L within 48 h), and 8 (7.2%) patients showed trace or 1+ albuminuria in 111 COVID-19-confirmed patients without chronic kidney disease (CKD). All these patients did not meet the diagnostic criteria of AKI. In addition, 5 patients with CKD who were undergone regular continuous renal replacement therapy (CRRT) before admission were confirmed infection of SARS-CoV-2 and diagnosed as COVID-19. In addition to therapy for COVID-19, CRRT was also applied 3 times weekly during hospitalization for these 5 patients with CKD. In the course of treatment, the renal function indicators showed stable state in all 5 patients with CKD, without exacerbation of CKD, and pulmonary inflammation was gradually absorbed. All 5 patients with CKD were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without CKD, and 1 patient had a positive for SARS-CoV-2 open reading frame 1ab from 5 cases with CKD. Conclusion: AKI was uncommon in COVID-19. SARS-CoV-2 infection does not result in AKI, or aggravate CKD in the COVID-19 patients.

Genetic mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS), and the increased presence of TDP-43 in the cytoplasm is a prominent histopathological feature of degenerating neurons in various neurodegenerative diseases. However, the molecular mechanisms by which TDP-43 contributes to ALS pathophysiology remain elusive. Here, we have found that TDP-43 accumulates in mitochondria in neurons of subjects with ALS or frontotemporal dementia (FTD). Disease-associated mutations increase TDP-43 mitochondrial localization. Within mitochondria, wild type (WT) and mutant TDP-43 preferentially bind mitochondria-transcribed messenger RNAs (mRNAs) encoding respiratory complex I subunit ND3 and ND6, impair their expression and specifically cause complex I disassembly. Suppression of TDP-43 mitochondrial localization abolishes WT and mutant TDP-43-induced mitochondrial dysfunction and neuronal loss, and improves phenotypes of transgenic mutant TDP-43 mice. Thus, our studies link TDP-43 toxicity directly to mitochondrial bioenergetics and propose targeting TDP-43 mitochondrial localization as a promising therapeutic approach for neurodegeneration.

This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods: The clinical records, laboratory findings and radiological assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Results: The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-dimer, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. Conclusions: The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.

Parkinson disease (PD) is a common neurodegenerative disorder caused by environmental and genetic factors. We have previously shown linkage of PD to chromosome 8p. Subsequently, fibroblast growth factor 20 (FGF20) at 8p21.3-22 was identified as a risk factor in several association studies. To identify the risk-conferring polymorphism in FGF20, we performed genetic and functional analysis of single-nucleotide polymorphisms within the gene. In a sample of 729 nuclear families with 1089 affected and 1165 unaffected individuals, the strongest evidence of association came from rs12720208 in the 3' untranslated region of FGF20. We show in several functional assays that the risk allele for rs12720208 disrupts a binding site for microRNA-433, increasing translation of FGF20 in vitro and in vivo. In a cell-based system and in PD brains, this increase in translation of FGF20 is correlated with increased alpha-synuclein expression, which has previously been shown to cause PD through both overexpression and point mutations. We suggest a novel mechanism of action for PD risk in which the modulation of the susceptibility gene's translation by common variations interfere with the regulation mechanisms of microRNA. We propose this is likely to be a common mechanism of genetic modulation of individual susceptibility to complex disease.

Background: Tet methylcytosine dioxygenase converts 5-mC to 5-hmC in DNA. Results: Ascorbate significantly and specifically enhances Tet-mediated generation of 5-hmC. Conclusion: Our findings suggest that ascorbate enhances 5-hmC generation, most likely by acting as a co-factor for Tet methylcytosine dioxygenase to generate 5-hmC. Significance: The availability of ascorbate could have significant consequences for health and diseases by modulating the epigenetic control of genome activity.

Emerging evidence suggests that ascorbate, the dominant form of vitamin C under physiological pH conditions, influences the genome activity via regulating epigenomic processes. Ascorbate serves as a cofactor for ten-eleven translocation (TET) dioxygenases that catalyze the oxidation of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), further to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), which are ultimately replaced by unmodified cytosine. The JmjC domain-containing histone demethylases also require ascorbate as a cofactor for histone demethylation. Thus, by primarily participating in the demethylation of both DNA and histones, ascorbate appears to be a mediator of the interface between the genome and environment. Furthermore, redox status has a profound impact on the bioavailability of ascorbate in the nucleus. In order to bridge the gap between redox biology and genomics, we suggest an interdisciplinary research field that can be termed “Redox Genomics” to study dynamic redox processes in health and diseases. This review examines the evidence and potential molecular mechanism of ascorbate in demethylation of the genome, while highlighting potential epigenetic roles of ascorbate in various diseases.

Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. For the novel SPG31 locus on chromosome 2p12, we identified six different mutations in the receptor expression-enhancing protein 1 gene (REEP1). REEP1 mutations occurred in 6.5% of the patients with HSP in our sample, making it the third-most common HSP gene. We show that REEP1 is widely expressed and localizes to mitochondria, which underlines the importance of mitochondrial function in neurodegenerative disease.

SummaryParkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies implicated several genes as PD risk loci with strong, but not genome-wide significant, associations.In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990, p-value = 6.7 × 10 −8 ; genome-wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17-1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the MAPT region (rs11012, p-value = 5.6 × 10 −8 ; genome-wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62-0.79] T vs. C allele, PAR% = 8%) were genomewide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD.