Hypercytokinemia is a critically fatal factor in COVID-19. However, underlying pathogenic mechanisms are unknown. Here we show that brinogen and leukotriene-A4 hydrolase (LTA4H), two of the most potent in ammatory contributors, are elevated by 67.7 and astonishing 227.7% in the plasma of patients infected by SARS-CoV-2 and admitted to intensive care unit in comparison with healthy control, respectively. Conversely, transferrin identi ed as a brinogen immobilizer in our recent work and Spink6 are down-regulated by 40.3 and 25.9%, respectively. Furthermore, we identify Spink6 as the rst endogenous inhibitor of LTA4H, a pro-in ammatory enzyme catalyzing nal and rating limited step in biosynthesis of leukotriene-B4 that is an extremely in ammatory mediator and a target to design superior anti-in ammatory drugs. Additionally, virus Spike protein is found to evoke LTA4H and brinogen expression in vivo. Collectively, these ndings identify the imbalance between in ammatory drivers and antagonists, which likely contributes to hypercytokinemia in COVID-19. Spink6 may have superior antiin ammatory function because it speci cally targets epoxide hydrolase of LTA4H to inhibit leukotriene-B4 biosynthesis without effecting LTA4H's aminopeptidase activity.

Background: The coronavirus disease 2019 outbreak is evolving rapidly worldwide. Objective: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. Methods: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. Results: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. Conclusion: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes. This article has supplementary material available from

Background: Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods:We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29 th , 2020. Results:The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%).Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10. 1101 /2020 admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions:The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes. Abstract: 249 words; main text: 2677 words : medRxiv preprint Clinical outcomesThe percentages of patients being admitted to the ICU, requiring invasive ventilation and death were 5.00%, 2.18% and 1.36%, respectively. This corresponded to 67 (6.10%) of patients having reached to the composite endpoint ( Table 3).Results of the univariate competing risk model are shown in Table E1 in Supplementary Appendix. Severe pneumonia cases (SDHR, 9.803; 95%CI, 4.06 to 23.67), leukocyte count greater than 4,000/mm 3 (SDHR, 4.01; 95%CI, 1.53 to 10.55) and interstitial abnormality on chest X-ray (SDHR, 4.31; 95%CI, 1.73 to 10.75) were associated with the composite endpoint (Fig. 2, see Table E2 in Supplementary Appendix). Sensitivity analyses are shown in Figure E2 in Supplementary Appendix. DiscussionThis study has shown that fever occurred in only 43.8% of patients with 2019-nCoV ARD on presentation but developed in 87.9% following hospitalization. Severe pneumonia occurred in 15.7% of cases. No radiolo...

The strong interest in graphene has motivated the scalable production of high-quality graphene and graphene devices. As the large-scale graphene films synthesized so far are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient chemical vapour deposition on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman 'D' peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.

@ERSpublications These data showed that age ⩾65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3 + CD8 + T-cells ⩽75 cells·μL −1 and cardiac troponin I ⩾0.05 ng·mL −1 were four risk factors predicting high mortality of COVID-19 pneumonia patients https://bit.ly/2Rh6NqvABSTRACT The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ⩾65 years (OR 3.765, 95% CI 1.146-17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755-8.044; p=0.007), CD3 + CD8 + T-cells ⩽75 cells·μL −1 (OR 3.982, 95% CI 1.132-14.006; p<0.001) and cardiac troponin I ⩾0.05 ng·mL −1 (OR 4.077, 95% CI 1.166-14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age-and comorbid illness-matched case-control study, CD3 + CD8 + T-cells ⩽75 cells·μL −1 and cardiac troponin I ⩾0.05 ng·mL −1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ⩾65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3 + CD8 + T-cells ⩽75 cells·μL −1 and cardiac troponin I ⩾0.05 ng·mL −1 . The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.

BACKGROUND:The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain.RESEARCH QUESTION: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model. STUDY DESIGN AND METHODS:A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. RESULTS:In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age $ 75 years (hazard ratio [HR], 7.86; 95% CI, 2. 44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI,, procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI,, and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation. INTERPRETATION:The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.

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Spin-orbit coupling (SOC) is central to many physical phenomena, including fine structures of atomic spectra and topological phases in ultracold atoms. Whereas, in general, SOC is fixed in a system, laser-atom interaction provides a means to create and control synthetic SOC in ultracold atoms 1 . Despite significant experimental progress in this area 2-8 , two-dimensional (2D) synthetic SOC, which is crucial for exploring two-and threedimensional topological phases, is lacking. Here, we report the experimental realization of 2D SOC in ultracold 40 K Fermi gases using three lasers, each of which dresses one atomic hyperfine spin state. Through spin-injection radiofrequency (rf) spectroscopy 4 , we probe the spin-resolved energy dispersions of the dressed atoms, and observe a highly controllable Dirac point created by the 2D SOC. These results constitute a step towards the realization of new topological states of matter.There have been many theoretical proposals for creating multi-dimensional SOC in ultracold atoms 9-14 , so as to access novel macroscopic quantum phenomena and quantum topological states [15][16][17][18][19][20][21][22][23][24] . Whereas these proposals have not been realized in laboratories, physicists have also just begun to explore topological phenomena in optical lattices [25][26][27][28] . Here, we use the Raman scheme to produce a highly controllable 2D synthetic SOC for an ultracold Fermi gas of 40 K. Such SOC allows us to create and manipulate a single stable Dirac point on a 2D plane, which is detected by spin-injection rf spectroscopy 4 .We apply three far-detuned lasers propagating on the x-y plane to couple three ground hyperfine spin states, within the 4 2 S 1/2 ground electronic manifold, |1 = |F = 9/2, m F = 3/2 , |2 = |F = 9/2, m F = 1/2 and |3 = |F = 7/2, m F = 1/2 , where (F, m F ) are the quantum numbers for hyperfine spin states as shown in Fig. 1a, to the electronically excited states. Unlike the tripod scheme, where a single excited state is considered [9][10][11][15][16][17][18] , in the 40 K used here the excited states include a fine-structure doublet 4 2 P 1/2 (D 1 line) and 4 2 P 3/2 (D 2 line) with a finestructure splitting of ∼3.4 nm. Each of two D-line components also has hyperfine structures. After adiabatically eliminating excited states, the ring scheme proposed in ref. 12 is realized for three cyclically coupled states, with a generalization to arbitrary laser configurations. The Hamiltonian is written as( 1) where p denotes the momentum of atoms, k i (|k i | = 2π/λ i ) and ω i are the wavevectors and frequencies of the three lasers, Ω i are the Rabi frequencies, i, j are the indices for the three ground hyperfine spin and the excited states respectively, ε i and E j are the ground and excited state energies, n is the total number of the excited states and M ij is the matrix element of the dipole transition. Different from refs 9,10,15, each hyperfine ground spin state here is dressed by only one laser field, regardless of the excited states it is coupled to. A gau...