Background: Since mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai.Methods: Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features. Results:Of 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5 o C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure. Conclusions:In this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5 o C, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease. MethodsPatients. We obtained epidemiological, demographic, clinical, laboratory and management data from the medical records of patients infected with SARS-Cov-2. On Jan 20, 2020, the first human case of in Shanghai was confirmed. Since then all hospitals in Shanghai have opened special fever clinics to screen suspected patients, and laboratory confirmed patients were then admitted to a single designated hospital in Shanghai (Shanghai Public Health Clinical Centre). Laboratory confirmation of COVID-19 was done by the Chinese Centre for Disease Control and Prevention. Throat-swab specimens from the upper respiratory tract were obtained from all patients at admission and maintained in viral transport medium. COVID-19 was confirmed by real-time RT-PCR using the same protocol as described previously 3 . Confirmed patients were hospitalized into negative pressure wards for further medical observation and treatment. We collected data from patients who were admitted from Jan. 20 up to Feb. 15. All the data collected from the included cases have been shared with the WHO. Data Collection. Epidemiological exposure data, patient characteristics, clinical symptoms, laboratory and imaging findings and medical history were extracted from electronic medical records and analysed by licensed physicians. Laboratory data were recorded in standardized form. Initial investigations included a complete blood count, routine urinalysis, blood gases, coagulation...

Parkinson’s disease (PD) is a common neurodegenerative disorder without effective disease-modifying therapeutics. Here, we establish a chemogenetic dopamine (DA) neuron ablation model in larval zebrafish with mitochondrial dysfunction and robustness suitable for high-content screening. We use this system to conduct an in vivo DA neuron imaging-based chemical screen and identify the Renin-Angiotensin-Aldosterone System (RAAS) inhibitors as significantly neuroprotective. Knockdown of the angiotensin receptor 1 (agtr1) in DA neurons reveals a cell-autonomous mechanism of neuroprotection. DA neuron-specific RNA-seq identifies mitochondrial pathway gene expression that is significantly restored by RAAS inhibitor treatment. The neuroprotective effect of RAAS inhibitors is further observed in a zebrafish Gaucher disease model and Drosophila pink1-deficient PD model. Finally, examination of clinical data reveals a significant effect of RAAS inhibitors in delaying PD progression. Our findings reveal the therapeutic potential and mechanisms of targeting the RAAS pathway for neuroprotection and demonstrate a salient approach that bridges basic science to translational medicine.

Vitamin D deficiency is a common health issue around the world. We therefore evaluated the associations of semen quality with both serum and seminal plasma vitamin D levels and studied the mechanisms underlying these by incubating spermatozoa with 1,25(OH) 2 D in vitro . Two hundred and twenty-two men were included in our study. Vitamin D was detected using an electrochemiluminescence method. Spermatozoa used for in vitro experiments were isolated by density gradient centrifugation. Positive relationships of serum 25(OH)D with semen volume and seminal plasma fructose were identified. Seminal plasma 25(OH)D level showed no relationship with serum 25(OH)D level, while it was inversely associated with sperm concentration and positively correlated with semen volume and sperm kinetic values. In vitro , sperm kinetic parameters increased after incubation with 1,25(OH) 2 D, especially upon incubation for 30 min with it at a concentration of 0.1 nmol l −1 . Under these incubation conditions, the upward migration of spermatozoa increased remarkably with increasing adenosine triphosphate (ATP) concentration. The concentration of cyclic adenosine monophosphate (cAMP) and the activity of protein kinase A (PKA) were both elevated, and the PKA inhibitor, N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89) reversed the increase of ATP production. The concentrations of cytoplasmic calcium ions and nicotinamide adenine dinucleotide (NADH) were both enhanced, while mitochondrial calcium uniporter (MCU) inhibitor, Ruthenium 360 (Ru360) did not reverse the increase of ATP production. Therefore, seminal plasma vitamin D may be involved in regulating sperm motility, and 1,25(OH) 2 D may enhance sperm motility by promoting the synthesis of ATP both through the cAMP/PKA pathway and the increase in intracellular calcium ions.