BACKGROUND & AIMS:Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. METHODS:We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin. RESULTS:Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P [ .027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09 -4.79 days) than patients with normal liver function (12.76 -4.14 days) (P [ .021). CONCLUSIONS:More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.

b Dysbiosis in the intestinal microbiota of persons with inflammatory bowel disease (IBD) has been described, but there are still varied reports on changes in the abundance of Bifidobacterium and Lactobacillus organisms in patients with IBD. The aim of this investigation was to compare the compositions of mucosa-associated and fecal bacteria in patients with IBD and in healthy controls (HCs). Fecal and biopsy samples from 21 HCs, 21 and 15 Crohn's disease (CD) patients, and 34 and 29 ulcerative colitis (UC) patients, respectively, were analyzed by quantitative real-time PCR targeting the 16S rRNA gene. The bacterial numbers were transformed into relative percentages for statistical analysis. The proportions of bacteria were uniformly distributed along the colon regardless of the disease state. Bifidobacterium was significantly increased in the biopsy specimens of active UC patients compared to those in the HCs (4.6% versus 2.1%, P ‫؍‬ 0.001), and the proportion of Bifidobacterium was significantly higher in the biopsy specimens than in the fecal samples in active CD patients (2.7% versus 2.0%, P ‫؍‬ 0.012). The Lactobacillus group was significantly increased in the biopsy specimens of active CD patients compared to those in the HCs (3.4% versus 2.3%, P ‫؍‬ 0.036). Compared to the HCs, Faecalibacterium prausnitzii was sharply decreased in both the fecal and biopsy specimens of the active CD patients (0.3% versus 14.0%, P < 0.0001 for fecal samples; 0.8% versus 11.4%, P < 0.0001 for biopsy specimens) and the active UC patients (4.3% versus 14.0%, P ‫؍‬ 0.001 for fecal samples; 2.8% versus 11.4%, P < 0.0001 for biopsy specimens). In conclusion, Bifidobacterium and the Lactobacillus group were increased in active IBD patients and should be used more cautiously as probiotics during the active phase of IBD. Butyrate-producing bacteria might be important to gut homeostasis.

Two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in both animals and plants as organellar cation channels. Here, we present the first crystal structure of a vacuolar two-pore channel from Arabidopsis thaliana, AtTPC1, which functions as a homodimer. AtTPC1 activation requires both voltage and cytosolic Ca2+. Ca2+ binding to the cytosolic EF-hand domain triggers conformational changes coupled to the pair of pore-lining inner helices (IS6 helices) from the first 6-TM domains, whereas membrane potential only activates the second voltage-sensing domain (VSD2) whose conformational changes are coupled to the pair of inner helices (IIS6 helices) from the second 6-TM domains. Luminal Ca2+ or Ba2+ can modulate voltage activation by stabilizing VSD2 in the resting state and shifts voltage activation towards more positive potentials. Our Ba2+ bound AtTPC1 structure reveals a voltage sensor in the resting state, providing hitherto unseen structural insight into the general voltage-gating mechanism among voltage-gated channels.

We propose an efficient method to propagate the hierarchical quantum master equations based on a reformulation of the original formalism and the incorporation of a filtering algorithm that automatically truncates the hierarchy with a preselected tolerance. The new method is applied to calculate electron transfer dynamics in a spin-boson model and the absorption spectra of an excitonic dimmer. The proposed method significantly reduces the number of auxiliary density operators used in the hierarchical equation approach and thus provides an efficient way capable of studying real time dynamics of non-Markovian quantum dissipative systems in strong system-bath coupling and low temperature regimes.

Ion selectivity is one of the basic properties that define an ion channel. Most tetrameric cation channels, which include the K+, Ca2+, Na+ and cyclic nucleotide-gated channels, probably share a similar overall architecture in their ion-conduction pore, but the structural details that determine ion selection are different. Although K+ channel selectivity has been well studied from a structural perspective, little is known about the structure of other cation channels. Here we present crystal structures of the NaK channel from Bacillus cereus, a non-selective tetrameric cation channel, in its Na+- and K+-bound states at 2.4 A and 2.8 A resolution, respectively. The NaK channel shares high sequence homology and a similar overall structure with the bacterial KcsA K+ channel, but its selectivity filter adopts a different architecture. Unlike a K+ channel selectivity filter, which contains four equivalent K+-binding sites, the selectivity filter of the NaK channel preserves the two cation-binding sites equivalent to sites 3 and 4 of a K+ channel, whereas the region corresponding to sites 1 and 2 of a K+ channel becomes a vestibule in which ions can diffuse but not bind specifically. Functional analysis using an 86Rb flux assay shows that the NaK channel can conduct both Na+ and K+ ions. We conclude that the sequence of the NaK selectivity filter resembles that of a cyclic nucleotide-gated channel and its structure may represent that of a cyclic nucleotide-gated channel pore.

Objectives: To describe the clinical characteristics of patients in a Fangcang Hospital. Methods: Non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests admitted between 7 February and 12 February 2020 to Dongxihu Fangcang Hospital, which was promptly constructed because of the rapid, exponential increase in COVID-19 patients in Wuhan, China, were included; clinical course through to 22 February was recorded. Results: A total of 1012 non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests were included in the study. Thirty (of 1012, 3.0%) individuals were asymptomatic on admission. During hospitalization, 16 of 30 (53.3%) asymptomatic individuals developed different symptoms. Fourteen of 1012 patients (1.4%) remained asymptomatic from exposure to the end of follow up, with a median duration of 24 days (interquartile range 22e27). Fever (761 of 1012, 75.2%) and cough (531 of 1012, 52.4%) were the most common symptoms. Small patchy opacities (355 of 917, 38.7%) and ground-glass opacities (508 of 917, 55.4%) were common imaging manifestations in chest CT scans. One hundred patients (9.9%) were transferred to designated hospitals due to aggravation of illness. Diarrhoea emerged in 152 of 1012 patients (15.0%). Male, older age, diabetes, cardiovascular diseases, chills, dyspnoea, SO 2 value of 93%, white blood cell counts of >10 Â 10 9 /L and large consolidated opacities on CT images were all risk factors for aggravation of illness. Conclusions: Non-critically ill individuals had different clinical characteristics from critically ill individuals. Asymptomatic infections only accounted for a small proportion of COVID-19. Although with a low incidence, diarrhoea was observed in patients with COVID-19, indicating the possibility of faecal eoral transmission.

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The impact of dynamic disorder arising from the thermal fluctuations on the charge transport in organic semiconductors is studied by a multi-scale approach combining molecular dynamics, electronic structure calculations and kinetic Monte Carlo simulations for pentacene crystal of thin-film phase. It is found that for 1-D arrays, such fluctuations severely reduce charge mobility as temperature increases. However, when going from an 1-D array to an 2-D herringbone layer, for a wide range of temperatures, the charge transport property is found to be unaffected by such disorders from our multiscale computational study. And in some extreme cases, when the fluctuations of the hopping integral are even larger than their average values, the dynamic disorders can increase the charge mobility. In addition, we point out that the "band-like" behavior concluded by the experiment can be reproduced by quantum charge transfer involving nuclear vibration tunneling effects within a hopping model.