Genotypes and Phylogenetic Analysis of Human Adenovirus in Hospitalized Pneumonia and Influenza-Like Illness Patients in Jiangsu Province, China (2013-2021).

Background: Human adenovirus (HAdV) is common pathogens that cause various respiratory diseases. The genetic diversity of viruses caused by recombination is considered to be the main source of emerging outbreaks. The aim of this study is to explore the evolutionary relationship and recombination events of HAdV genome in respiratory tract infections in Jiangsu Province. Methods: Whole-genome sequencing (WGS) technology was used to sequence 66 patients with HAdV infection (37 patients with influenza-like illness (ILI) and 29 hospitalized patients with pneumonia) from Jiangsu Province. Epidemiological analysis was performed on hospitalized pneumonia and ILI patients infected with HAdV. Subsequently, phylogenetic, recombination, and nucleotide and amino acid identity analyses were performed. Results: Epidemiological analysis of patients undergoing WGS showed that 75.7% of ILI patients were infected with the HAdVB strain and 69.0% of hospitalized pneumonia patients were infected with the HAdVC strain. Moreover, the hospitalized pneumonia and ILI patients infected with HAdV were different in region and time. The strains of HAdVB3 and HAdVB7 genotypes were mainly infected in 2015 and 2017, and the strains of HAdVC1 and HAdVC2 genotypes were mainly infected in 2020. The results of histogram analysis showed that the HAdV strain mainly infected children under 5 years old. In addition, 36 novel recombinant strains were identified. The discovery of these recombinant strains may contribute to understanding the epidemiology of HAdV and research on related vaccines. Furthermore, the percentage of nucleotide and amino acid identities revealed a high level of genetic conservation within isolates from HAdVB3, HAdVB7, HAdVC1, HAdVC2 and HAdVC5 genotypes. Conclusion: The WGS analysis reveals the evolutionary relationships and recombination events of HAdV strains in Jiangsu Province, which is helpful to deepen the understanding of HAdV epidemiology and evolution. In addition, it provides a basis for the formulation of public health strategies in Jiangsu Province.

27-hydroxycholesterol causes cognitive deficits by disturbing Th17/Treg balance and the related immune responses in mild cognitive impairment patients and C57BL/6J mice.

BACKGROUND: Cognitive impairment is associated with dysregulated immune responses. Emerging evidence indicates that Th17 cells and their characteristic cytokine-IL-17 are receiving growing interest in the pathogenesis of cognitive decline. Here, we focus on the involvement of Th17 cells in mild cognitive impairment (MCI) and the possible mechanism of cholesterol metabolite-27-hydroxycholesterol (27-OHC). METHODS: 100 individuals were recruited into the nested case-control study who completed cognition assessment and the detection of oxysterols and Th17-related cytokines in serum. In addition, mice were treated with 27-OHC and inhibitors of RORγt and Foxp3 (Th17 and Treg transcription factors), and the factors involved in Th17/Treg balance and amyloidosis were detected. RESULTS: Our results showed there was enhanced 27-OHC level in serum of MCI individuals. The Th17-related cytokines homeostasis was altered, manifested as increased IL-17A, IL-12p70, IL-23, GM-CSF, MIP-3α and TNF-α but decreased IL-13, IL-28A and TGF-ß1. Further, in vivo experiments showed that 27-OHC induced higher immunogenicity, which increased Th17 proportion but decreased Treg cells in peripheral blood mononuclear cells (PBMCs); Th17 proportions in hippocampus, and IL-17A level in serum and brain were also higher than control mice. The fluorescence intensity of amyloid-ß (Aß) and the precursor of amyloid A amyloidosis-serum amyloid A (SAA) was increased in the brain of 27-OHC-treated mice, and worse learning and memory performance was supported by water maze test results. While by inhibiting RORγt in 27-OHC-loaded mice, Th17 proportions in both PBMCs and hippocampus were reduced, and expressions of IL-17A and TGF-ß1 were down- and up-regulated, respectively, along with a decreased amyloidosis in brain and improved learning and memory decline. CONCLUSIONS: Altogether, our results demonstrate that excessive 27-OHC aggravates the amyloidosis and leads to cognitive deficits by regulating RORγt and disturbing Th17/Treg balance.

Sulforaphene suppressed cell proliferation and promoted apoptosis of COV362 cells in endometrioid ovarian cancer.

Aim: N6-methyladenosine (m6A) RNA methylation exerts a regulatory effect on endometrioid ovarian cancer (EOC), but the specific m6A regulator genes in EOC remain to be explored. This study investigated that sulforaphene (Sul) is implicated in EOC development by regulating methyltransferase-like 3 (METTL3). Methods: The dysregulated m6A RNA methylation genes in EOC were determined by methylated RNA immunoprecipitation (MeRIP-seq) and RNA sequencing. The roles of METTL3 and/or Sul on viability, proliferative ability, cell cycle, and apoptosis of EOC cells were determined by MTT, colony formation, flow cytometry, and TUNEL staining assay, respectively. The expression of METTL3 and apoptosis-related proteins in EOC cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. Results: Five m6A RNA methylation regulators (METTL3, ELF3, IGF2BP2, FTO, and METTL14) were differentially expressed in EOC, among which METTL3 had the highest expression level. Silencing METTL3 reduced the clonal expansion and viability of EOC cells, and caused the cells to arrest in the G0/G1 phase. This also promoted apoptosis in the EOC cells and activated the FAS/FADD and mitochondrial apoptosis pathways. In contrast, overexpressing METTL3 had the opposite effect. Sul, in a dose-dependent manner, reduced the viability of EOC cells but promoted their apoptosis. Sul also increased the levels of IGF2BP2 and FAS, while decreasing the levels of KRT8 and METTL3. Furthermore, Sul was able to reverse the effects of METTL3 overexpression on EOC cells. Conclusions: Sul could suppress cell proliferation and promote apoptosis of EOC cells by inhibiting the METTL3 to activate the FAS/FADD and apoptosis-associated pathways.

Vitamin D, Folic Acid and Vitamin B12 Can Reverse Vitamin D Deficiency-Induced Learning and Memory Impairment by Altering 27-Hydroxycholesterol and S-Adenosylmethionine.

The cholesterol-oxidized metabolite 27-hydroxycholesterol (27-OHC) is synthesized by CYP27A1, which is a key factor in vitamin D and oxysterol metabolism. Both vitamin D and 27-OHC are considered to play important roles in Alzheimer's disease (AD). The study aims to research the effects of co-supplementation of vitamin D, folic acid, and vitamin B12 on learning and memory ability in vitamin D-deficient mice, and to explore the underlying mechanism. In this study, C57BL/6J mice were fed a vitamin D-deficient diet for 13 weeks to establish a vitamin D-deficient mice model. The vitamin D-deficient mice were then orally gavaged with vitamin D (VD), folic acid (FA), and vitamin B12 (VB12) alone or together for eight weeks. Following the gavage, the learning and memory ability of the mice were evaluated by Morris Water Maze and Novel object recognition test. The CYP27A1-related gene and protein expressions in the liver and brain were determined by qRT-PCR. The serum level of 27-OHC was detected by HPLC-MS. Serum levels of 25(OH)D, homocysteine (Hcy), and S-Adenosylmethionine (SAM) were measured by ELISA. After feeding with the vitamin D-deficient diet, the mice performed longer latency to a platform (p < 0.001), lower average speed (p = 0.026) in the Morris Water Maze, a lower time discrimination index (p = 0.009) in Novel object recognition, and performances were reversed after vitamin D, folic acid and vitamin B12 supplementation alone or together (p < 0.05). The gene expressions of CYP27A1 in the liver and brain were upregulated in the vitamin D-deficiency (VDD) group compared with the control (CON) group (p = 0.015), while it was downregulated in VDD + VD and VDD + VD-FA/VB12 groups compared with the VDD group (p < 0.05), with a similar trend in the protein expression of CYP27A1. The serum levels of 27-OHC were higher in the VDD group, compared with CON, VDD + VD, and VDD + VD-FA/VB12 group (p < 0.05), and a similar trend was found in the brain. The serum 25(OH)D levels were significantly decreased in the vitamin D-deficiency group (p = 0.008), and increased in the vitamin D-supplemented group (p < 0.001). The serum levels of SAM were higher in the B vitamins-supplemented group, compared with CON and VDD groups (p < 0.05). This study suggests that CYP27A1 expression may be involved in the mechanism of learning and memory impairment induced by vitamin D deficiency. Co-supplementation with vitamin D, folic acid, and vitamin B12 significantly reverses this effect by affecting the expression of CYP27A1, which in turn regulates the metabolism of 27-OHC, 25(OH)D, and SAM.

Disparities in diagnosis, treatment and survival between Black and White Parkinson patients.

INTRODUCTION: Racial disparities in diagnosis, treatment and survival in Black patients with Parkinson's disease (PD) compared to White patients have not been well studied, largely due to limited number of studies and information on Black patients in healthcare systems. Studying racial disparities and identifying underlying factors in large populations are important to understand PD and improve care. METHODS: We retrospectively identified PD patients on both races from 1/1/2006 to 10/31/2017 and compared demographics, socioeconomic status (educations, incomes and insurances), comorbidities (all categories, including mood, cognition and psychosis), treatment (medications for parkinsonism and major non-motor symptoms, and frequency and locations of healthcare) and survival, and identified factors associated with medication usage and survival. RESULTS: We retrospectively studied 2033 PD patients, of whom 725 were Black. Black patients lacked male predominance, were 4 years older at first diagnosis here, more likely to smoke and live in a low education and income community, and possessed limited insurances compared to White patients. Black patients also had more comorbidities and were more likely to receive care through emergency or inpatient service, but less likely to be on medications for parkinsonism and mood disorders. Race, age, smoking status, insurance type, frequency and locations of healthcare and comorbidities were associated with medication usage. Black race, older age, inpatient admission and malignancy were associated with increased risk of death. CONCLUSION: We revealed racial disparities in diagnosis, treatment and survival, and factors associated with medication usage and survival in the largest reported Black PD cohort from a single center.

Effect of Deep Brain Stimulation on Swallowing Function: A Systematic Review.

The effect of deep brain stimulation (DBS) on swallowing function in movement disorders is unclear. Here, we systematically reviewed this topic by searching keywords following PICOS strategy of problem (swallowing or swallow or dysphagia or aspiration) and intervention (deep brain stimulation, or DBS) in the PubMed and Web of Science in English in April 2020, with comparators [subthalamic nucleus (STN), globus pallidus interna (GPi), ventralis intermedius, (ViM), post-subthalamic area, or caudal zona incerta (PSA/cZi); ON/OFF DBS state/settings, ON/OFF medication state, Parkinson's disease (PD), dystonia, tremor], outcomes (swallowing function measures, subjective/objective) and study types (good quality original studies) in mind. We found that STN DBS at usual high-frequency stimulation could have beneficial effect (more so on subjective measures and/or OFF medication), no effect, or detrimental effect (more so on objective measures and/or ON medication) on swallowing function in patients with PD, while low-frequency stimulation (LFS) could have beneficial effect on swallowing function in patients with freezing of gait. GPi DBS could have a beneficial effect (regardless of medication state and outcome measures) or no effect, but no detrimental effect, on swallowing function in PD. GPi DBS also has beneficial effects on swallowing function in majority of the studies on Meige syndrome but not in other diseases with dystonia. PSA/cZi DBS rarely has detrimental effect on swallowing functions in patients with PD or tremor. There is limited information on ViM to assess. Information on swallowing function by DBS remains limited. Well-designed studies and direct comparison of targets are further needed.

Simultaneous detection of hemagglutinin and neuraminidase genes of novel influenza A (H7N9) by duplex real-time reverse transcription polymerase chain reaction.

A novel reassortant influenza A (H7N9) virus emerged recently in China. In this study, a duplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assay was developed for the simultaneous detection of hemagglutinin (HA) and neuraminidase (NA) genes of H7N9 influenza viruses. The sensitivity of the assay was determined to be 10 RNA copies per reaction for both HA and NA genes. No cross-reactivity was observed with other influenza virus subtypes or respiratory tract viruses. One hundred and forty-six clinical and environmental specimens were tested and compared with reference methods and were found to be consistent. The assay is suitable for large-scale screening due to short turnaround times and high specificity, sensitivity, and reproducibility.