Background: A novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. Methods: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. Results: None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cordlike shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. Conclusions: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.

Here we report on remarkably high lipophilicity of perfluoroalkyl carboxylate and sulfonate. A lipophilic nature of this emerging class of organic pollutants has been hypothesized as an origin of their bioaccumulation and toxicity. Both carboxylate and sulfonate, however, are considered hydrophilic while perfluroalkyl groups are not only hydrophobic but also oleophobic. Partition coefficients of homologous series of perfluoroalkyl and alkyl carboxylates between water and noctanol were determined as a measure of their lipophilicity by ion-transfer cyclic voltammetry. Very similar lipophilicity of perfluoroalkyl and alkyl chains with the same length is demonstrated experimentally for the first time by fragment analysis of the partition coefficients. This finding is important for pharmaceutical and biomedical applications of perfluoroalkyl compounds. Interestingly, ∼2 orders of magnitude higher lipophilicity of a perfluoroalkyl carboxylate or sulfonate in comparison to its alkyl counterpart is ascribed nearly exclusively to their oxoanion groups. The higher lipophilicity originates from a strong electron-withdrawing effect of the perfluoroalkyl group on the adjacent oxoanion group, which is weakly hydrated to decrease its hydrophilicity. In fact, the inductive effect is dramatically reduced for a fluorotelomer with an ethylene spacer between perfluorohexyl and carboxylate groups, which is only as lipophilic as its alkyl counterpart, nonanoate, and is 400 times less lipophilic than perfluorononanoate. The high lipophilicity of perfluoroalkyl carboxylate and sulfonate implies that their permeation across such a thin lipophilic membrane as a bilayer lipid membrane is limited by their transfer at a membrane/water interface. The limiting permeability is lower and less dependent on their lipophilicity than the permeability controlled by their diffusion in the membrane interior as assumed in the classical solubility-diffusion model.

Alzheimer’s Disease (AD), the most prevalent neurodegenerative disease of aging, affects one in eight older Americans. Nearly all drug treatments tested for AD today have failed to show any efficacy. There is a great need for therapies to prevent and/or slow the progression of AD. The major challenge in AD drug development is lack of clarity about the mechanisms underlying AD pathogenesis and pathophysiology. Several studies support the notion that AD is a multifactorial disease. While there is abundant evidence that amyloid plays a role in AD pathogenesis, other mechanisms have been implicated in AD such as tangle formation and spread, dysregulated protein degradation pathways, neuroinflammation, and loss of support by neurotrophic factors. Therefore, current paradigms of AD drug design have been shifted from single target approach (primarily amyloid-centric) to developing drugs targeted at multiple disease aspects, and from treating AD at later stages of disease progression to focusing on preventive strategies at early stages of disease development. Here, we summarize current strategies and new trends of AD drug development, including pre-clinical and clinical trials that target different aspects of disease (mechanism-based versus non-mechanism based, e.g. symptomatic treatments, lifestyle modifications and risk factor management).

We report on the application of scanning electrochemical microscopy (SECM) for the measurement of the ion-selective permeability of porous nanocrystalline silicon membrane as a new type of nanoporous material with potential applications in analytical, biomedical, and biotechnology device development. The reliable measurement of high permeability in the molecularly thin nanoporous membrane to various ions is important for greater understanding of its structure-permeability relationship and also for its successful applications. In this work, this challenging measurement is enabled by introducing two novel features into amperometric SECM tips based on the micropipetsupported interface between two immiscible electrolyte solutions (ITIES) to reveal the important ion-transport properties of the ultrathin nanopore membrane. The tip of a conventional heat-pulled micropipet is milled using focused ion beam (FIB) technique to be smoother, better aligned, and subsequently, approach closer to the membrane surface, which allows for more precise and accurate permeability measurement. The high membrane permeability to small monovalent ions is determined using FIB-milled micropipet tips to establish a theoretical formula for the membrane permeability that is controlled by free ion diffusion across water-filled nanopores. Moreover, the ITIES tips are rendered selective for larger polyions with biomedical importance, i.e., polyanionic pentasaccharide Arixtra and polycationic peptide protamine, to yield the membrane permeability that is lower than the corresponding diffusion-limited permeability. The hindered transport of the respective polyions is unequivocally ascribed to electrostatic and steric repulsions from the wall of the nanopores, i.e., the charge and size effects.The fast and selective transport of molecules across porous nanocrystalline silicon (pnc-Si) membranes 1 is attractive potentially for various important applications such as nanofiltration, 2, 3 biomedical device development, 4, 5 and nanofluidics for medical diagnostics and drug discovery. [6][7][8][9][10] The high permeability of the molecularly thin nanoporous membrane is also essential for its successful applications as cell culture and tissue engineering substrates. 11 This novel solid-state membrane features well-defined nanopores with an average diameter of ~10 nm and a length of ~15 nm. The nanopore membrane is nearly as thin as biological membranes * To whom correspondence should be addressed. amemiya@pitt.edu. # Current address: Shandong Entry-Exit Inspection and Quarantine Bureau, P. R. China SUPPORTING INFORMATION AVAILABLE Additional information as noted in text. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Access Author ManuscriptAnal Chem. Author manuscript; available in PMC 2011 September 1. and is ~1000 times thinner than widely used nanopore membranes such as aluminum oxide membranes and polycarbonate track etch membranes. Despite the molecular thickness, the nanopore silicon membrane wi...

Dopamine is an important neurotransmitter in mammalian central and peripheral nervous systems and is also a medicament to cure some neuropsychosis. In this work, ion transfer (IT), facilitated ion transfer (FIT) of protonated dopamine, and electron transfer (ET) between dopamine and ferrocene are investigated at the water/1,2-dichloroethane (W/DCE) interface. The IT and FIT reactions of protonated dopamine can be observed simultaneously within the same potential window. The experimental results demonstrate that dibenzo-18-crown-6, dibenzo-24-crown-8, and benzo-15-crown-5 work well with the protonated dopamine. The amperometric detection of dopamine based on either the IT or the FIT of protonated dopamine can get rid of the interference of ascorbic acid, and the lowest concentration that can be determined is approximately 0.05 microM by differential pulse voltammetry. For the ET reaction, its kinetics can be evaluated by scanning electrochemical microscopy, and the results show that the relationship between rate constants and driving force at the unmodified W/DCE interface obeys the Butler-Volmer equation in a rather wide potential region. When the W/DCE interface is modified by egg lecithin, the ET rate constants decrease with increasing concentration of egg lecithin, which indicates that egg lecithin hinders the ET reaction. When the driving force is increased to a certain degree, the linear relationship between ET rate constants and the driving force is distorted. These results will be helpful to understand both the pharmacodynamics and the neural signal transmission mechanism of dopamine at biological membranes and also provide a novel way to detect dopamine.

Electrochemically controlled molecular recognition of a synthetic heparin mimetic, Arixtra, at nitrobenzene/water microinterfaces was investigated to obtain a greater understanding of interfacial recognition and sensing of heparin and its analogues with biomedical importance. In contrast to unfractionated heparin, this synthetic pentasaccharide that mimics the unique Antithrombin III binding domain of heparin possesses well-defined structure and ionic charge to enable quantitative interpretation of cyclic voltammetric/chronoamperometric responses based on the interfacial recognition at micropipet electrodes. Arixtra is electrochemically extracted from the water phase into the bulk nitrobenzene phase containing highly lipophilic ionophores, methyltridodecylammonium or dimethyldioctadecylammonium. Numerical analysis of the kinetically controlled cyclic voltammograms demonstrates for the first time that formal potentials and standard rate constants of polyion transfer at liquid/liquid interfaces are ionophore dependent. Moreover, octadecylammonium and octadecylguanidinium are introduced as new, simple ionophores to model recognition sites of heparin-binding proteins at liquid/liquid interfaces. In comparison to octadecyltrimethylammonium, the best ionophore for heparin recognition at liquid/liquid interfaces reported so far, these new ionophores dramatically facilitate Arixtra adsorption at the interfaces. With a saline solution at physiological pH, an Arixtra molecule is selectively and cooperatively bound to 5 molecules of the guanidinium ionophore, suggesting hydrogen-bond-directed interactions of each guanidinium with a few of 10 negatively charged sulfo or carboxyl groups of Arixtra at the interfaces.

Background and Purpose: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. Methods: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. Results: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56–73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55–72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P =0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213–2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065–2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325–3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085–3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098–2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222–13.385]). Conclusions: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03370939.

Highlights A high prevalence of probable PTSD (20.87%) was found about six months after the first local outbreak of COVID-19 among healthcare workers at the Central Hospital of Wuhan. Healthcare workers with negative COVID-19 tests, those with high Social Support Self-Rating Scale (SSRS) scores, and HCWs whose family members tested negative were less likely to have probable PTSD. High levels of psychiatric and somatic illness and insomnia were associated with probable PTSD.