Background: Recently, dyslipidaemia was observed in patients with coronavirus disease 2019 (COVID-19), especially in severe cases. This study aimed to explore the predictive value of blood lipid levels for COVID-19 severity. Methods: All patients with COVID-19 admitted to HwaMei Hospital, University of Chinese Academy of Sciences, from January 23 to April 20, 2020, were included in this retrospective study. General clinical characteristics and laboratory data (including blood lipid parameters) were obtained, and their predictive values for the severity were analysed. Results: In total, 142 consecutive patients with COVID-19 were included. The non-severe group included 125 cases, and 17 cases were included in the severe group. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (ApoA1) at baseline were signi cantly lower in the severe group. ApoA1 and interleukin-6 (IL-6) were recognized as independent risk factors for COVID-19 severity. ApoA1 had the highest area under the receiver operator characteristic curve (AUC) among all the single markers (AUC: 0.896, 95% CI: 0.834-0.941). Moreover, the risk model established using ApoA1 and IL-6 enhanced the predictive value (AUC: 0.977, 95% CI: 0.932-0.995). On the other hand, ApoA1 levels were elevated in the severe group during treatment, and there was no signi cant difference between the severe and non-severe groups during the recovery stage of the disease. Conclusion: The blood lipid pro le in severe COVID-19 patients is quite different from that in non-severe cases. Serum ApoA1 could severe as a good indictor to re ect the severity of COVID-19.
The beginning of the twenty-rst century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The current pandemic COVID-19 (Coronavirus disease 2019) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a rapid infection rate, it is a global threat endangering the livelihoods of millions worldwide. Currently, and despite the collaborative efforts of governments, researchers, and the pharmaceutical industries, there are no substantially signi cant treatment protocols for the disease. To address the need for such an immediate call of action, we leveraged the largest dataset of drug-induced transcriptomic perturbations, public SARS-CoV-2 transcriptomic datasets, and expression pro les from normal lung transcriptomes. Our unbiased systems biology approach not only shed light on previously unexplored molecular details of SARS-CoV-2 infection (e.g., interferon signaling, in ammation and ACE2 co-expression hallmarks in normal and infected lungs) but most importantly prioritized more than 50 repurposable drug candidates (e.g., Corticosteroids, Janus kinase and Bruton kinase inhibitors). Further clinical investigation of these FDA approved candidates as monotherapy or in combination with an antiviral regimen (e.g., Remdesivir) could lead to promising outcomes in COVID-19 patients.
Highlights d 11,394 proteins are quantified in autopsy samples from 7 organs in 19 COVID-19 patients d Elevated expression of cathepsin L1 is detected in the COVID-19 lung tissue d Dysregulation of angiogenesis, coagulation, and fibrosis is detected in multiple organs d Systemic metabolic dysregulation is detected in multiple organs
The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report an in-depth multi-organ proteomic landscape of COVID-19 patient autopsy samples. By integrative analysis of proteomes of seven organs, namely lung, spleen, liver, heart, kidney, thyroid and testis, we characterized 11,394 proteins, in which 5336 were perturbed in COVID-19 patients compared to controls. Our data showed that CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. Dysregulation of protein translation, glucose metabolism, fatty acid metabolism was detected in multiple organs. Our data suggested upon SARS-CoV-2 infection, hyperinflammation might be triggered which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart and thyroid. Evidence for testicular injuries included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. In summary, this study depicts the multi-organ proteomic landscape of COVID-19 autopsies, and uncovered dysregulated proteins and biological processes, offering novel therapeutic clues.
A new computational method for the identification of regulatory motifs from large genomic datasets is presented here
In this work, a bubble-sheet-like hollow interface design on Al foil anode to improve the cycling stability and rate performance of aluminum anode based dual-ion battery is reported, in which, a carbon-coated hollow aluminum anode is used as both anode materials and current collector. This anode structure can guide the alloying position inside the hollow nanospheres, and also confine the alloy sizes within the hollow nanospheres, resulting in significantly restricted volumetric expansion and ultrastable solid electrolyte interface (SEI). As a result, the battery demonstrates an excellent long-term cycling stability within 1500 cycles with ≈99% capacity retention at 2 C. Moreover, this cell displays an energy density of 169 Wh kg even at high power density of 2113 W kg (10 C, charge and discharge within 6 min), which is much higher than most of conventional lithium ion batteries. The interfacial engineering strategy shown in this work to stabilize SEI layer and control the alloy forming position could be generalized to promote the research development of metal anodes based battery systems.
Cell membrane chromatography (CMC) derived from pathological tissues is ideal for screening specific components acting on specific diseases from complex medicines owing to the maximum simulation of in vivo drug-receptor interactions. However, there are no pathological tissue-derived CMC models that have ever been developed, as well as no visualized affinity comparison of potential active components between normal and pathological CMC columns. In this study, a novel comparative normal/failing rat myocardium CMC analysis system based on online column selection and comprehensive two-dimensional (2D) chromatography/monolithic column/time-of-flight mass spectrometry was developed for parallel comparison of the chromatographic behaviors on both normal and pathological CMC columns, as well as rapid screening of the specific therapeutic agents that counteract doxorubicin (DOX)-induced heart failure from Acontium carmichaeli (Fuzi). In total, 16 potential active alkaloid components with similar structures in Fuzi were retained on both normal and failing myocardium CMC models. Most of them had obvious decreases of affinities on failing myocardium CMC compared with normal CMC model except for four components, talatizamine (TALA), 14-acetyl-TALA, hetisine, and 14-benzoylneoline. One compound TALA with the highest affinity was isolated for further in vitro pharmacodynamic validation and target identification to validate the screen results. Voltage-dependent K+ channel was confirmed as a binding target of TALA and 14-acetyl-TALA with high affinities. The online high throughput comparative CMC analysis method is suitable for screening specific active components from herbal medicines by increasing the specificity of screened results and can also be applied to other biological chromatography models.
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