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 most common inherited form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motoneurons, is caused by dominant mutations in the ubiquitously expressed Cu 2؉ ͞Zn 2؉ superoxide dismutase (SOD1). Recent studies suggest that glia may contribute to motoneuron injury in animal models of familial ALS. To determine whether the expression of mutant SOD1 (mSOD1 G93A ) in CNS microglia contributes to motoneuron injury, PU.1 ؊/؊ mice that are unable to develop myeloid and lymphoid cells received bone marrow transplants resulting in donor-derived microglia. Donor-derived microglia from mice overexpressing mSOD1 G93A , an animal model of familial ALS, transplanted into PU.1 ؊/؊ mice could not induce weakness, motoneuron injury, or an ALS-like disease. To determine whether expression of mSOD1 G93A in motoneurons and astroglia, as well as microglia, was required to produce motoneuron disease, PU.1 ؊/؊ mice were bred with mSOD1 G93A mice. In mSOD1 G93A ͞PU.1 ؊/؊ mice, wild-type donorderived microglia slowed motoneuron loss and prolonged disease duration and survival when compared with mice receiving mSOD1 G93A expressing cells or mSOD1 G93A mice. In vitro studies confirmed that wild-type microglia were less neurotoxic than similarly cultured mSOD1 G93A microglia. Compared with wild-type microglia, mSOD1 G93A microglia produced and released more superoxide and nitrite؉nitrate, and induced more neuronal death. These data demonstrate that the expression of mSOD1 G93A results in activated and neurotoxic microglia, and suggests that the lack of mSOD1 G93A expression in microglia may contribute to motoneuron protection. This study confirms the importance of microglia as a double-edged sword, and focuses on the importance of targeting microglia to minimize cytotoxicity and maximize neuroprotection in neurodegenerative diseases.bone marrow transplant ͉ neuroprotection ͉ superoxide dismutase ͉ nitric oxide ͉ motoneurons

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.

Emerging evidences suggest that gut microbiota dysbiosis plays a role in Parkinson's disease (PD). However, the alterations in fecal microbiome in Chinese PD patients remains unknown. This case-control study was conducted to explore fecal microbiota compositions in Chinese PD patients. Microbiota communities in the feces of 45 patients and their healthy spouses were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene. The relationships between fecal microbiota and PD clinical characteristics were analyzed. The structure and richness of the fecal microbiota differed between PD patients and healthy controls. Genera Clostridium IV, Aquabacterium, Holdemania, Sphingomonas, Clostridium XVIII, Butyricicoccus and Anaerotruncus were enriched in the feces of PD patients after adjusting for age, gender, body mass index (BMI), and constipation. Furthermore, genera Escherichia/Shigella were negatively associated with disease duration. Genera Dorea and Phascolarctobacterium were negatively associated with levodopa equivalent doses (LED). Among the non-motor symptoms (NMSs), genera Butyricicoccus and Clostridium XlVb were associated with cognitive impairment. Overall, we confirmed that gut microbiota dysbiosis occurs in Chinese patients with PD. A well-controlled population involved was beneficial for the identification of microbiota associated with diseases. Additionally, the fecal microbiota was closely related to PD clinical characteristics. Elucidating these differences in the fecal microbiome will provide a foundation to improve our understanding the pathogenesis of PD and to support the potentially therapeutic options modifying the gut microbiota.

Objective Gut microbiota changes before the onset of Alzheimer's disease (AD) and the alterations could be detected in the stage of mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers before the onset of dementia. Background AD is the most common cause of dementia, and MCI is the predementia state. Recent studies suggest the alterations in the gut microbial communities associated with AD, whereas the microbiota in MCI before the onset of dementia has not been discovered and characterized in humans. New/Updated Hypothesis We hypothesize that the dysbiosis happens in the MCI stage. Patients with AD and MCI have decreased microbial diversity, and changes in gut microbiota could be detected for early detection of AD. In our preliminary study, we identified differences between AD and normal controls in 11 genera from the feces and 11 genera from the blood. No difference in genera between AD and MCI was detected. Using the diagnostic model from fecal samples with all different genera input, 93% (28 in 30) of patients with MCI could be identified correctly. Major Challenges for the Hypothesis The diagnosis of MCI and AD in the study was based on symptoms and neuroimaging, and AD biomarkers should be included for precise diagnosis in further validating studies. Besides, as the microbiota changes longitudinally, their relationship with the progress of dementia needs to be studied in the prospective studies. Linkage to Other Major Theories Escherichia was observed increased at genus level in both fecal and blood samples from AD and MCI. For AD biomarker, postmortem brain tissue from patients with AD showed lipopolysaccharides and gram‐negative Escherichia coli fragments colocalize with amyloid plaque. In this way, the amyloid pathogenesis for AD would be triggered during MCI by gut microbiota shifting. Besides, systemic inflammatory reactions caused by compounds secreted by bacteria may impair the blood‐brain barrier and promote neuroinflammation and/or neurodegeneration. Furthermore, abnormal metabolites caused by microbial gene functions have an impact on neurodegeneration.

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

Exhaled breath samples had the highest positive rate (26.9%, n=52), followed by surface swabs (5.4%, n=242), and air samples (3.8%, n=26). COVID-19 patients recruited in Beijing exhaled millions of SARS-CoV-2 RNA copies into the air per hour. Exhaled breath emission may play an important role in the COVID-19 transmission.

Recent studies suggest that motor neuron (MN) death may be non-cell autonomous, with cell injury mediated by interactions involving non-neuronal cells, such as microglia and astrocytes. To help define these interactions, we used primary MN cultures to investigate the effects of microglia activated by lipopolysaccharide or IgG immune complexes from patients with amyotrophic lateral sclerosis. Following activation, microglia induced MN injury, which was prevented by a microglial iNOS inhibitor as well as by catalase or glutathione. Glutamate was also required since inhibition of the MN AMPA/kainate receptor by CNQX prevented the toxic effects of activated microglia. Peroxynitrite and glutamate were synergistic in producing MN injury. Their toxic effects were also blocked by CNQX and prevented by calcium removal from the media. The addition of astrocytes to cocultures of MN and activated microglia prevented MN injury by removing glutamate from the media. The protective effects could be reversed by inhibiting astrocytic glutamate transport with dihydrokainic acid or pretreating astrocytes with H2O2. Astrocytic glutamate uptake was also decreased by activated microglia or by added peroxynitrite. These data suggest that free radicals released from activated microglia may initiate MN injury by increasing the susceptibility of the MN AMPA/kainate receptor to the toxic effects of glutamate.