This retrospective study was designed to explore whether neutrophil to lymphocyte ratio (NLR) is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). A cohort of patients with COVID-19 admitted to the Tongren Hospital of Wuhan University from 11 January 2020 to 3 March 2020 was retrospectively analyzed. Patients with hematologic malignancy were excluded. The NLR was calculated by dividing the neutrophil count by the lymphocyte count. NLR values were measured at the time of admission. The primary outcome was all-cause in-hospital mortality. A multivariate logistic analysis was performed. A total of 1004 patients with COVID-19 were included in this study. The mortality rate was 4.0% (40 cases). The median age of nonsurvivors (68 years) was significantly older than survivors (62 years). Male sex was more predominant in nonsurvival group (27; 67.5%) than in the survival group (466; 48.3%). NLR value of nonsurvival group (median: 49.06; interquartile range [IQR]: 25.71-69.70) was higher than that of survival group (median: 4.11; IQR: 2.44-8.12; P < .001). In multivariate logistic regression analysis, after adjusting for confounding factors, NLR more than 11.75 was significantly correlated with all-cause in-hospital mortality (odds ratio = 44.351; 95% Xisheng Yan and Fen Li contributed equally to this work.

Corona Virus Disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2. Emerging genetic and clinical evidence suggests similarities between COVID-19 patients and those with severe acute respiratory syndrome and Middle East respiratory syndrome. Hematological changes such as lymphopenia and thrombocytopenia are not rare in COVID-19 patients, and a smaller population of these patients had leukopenia. Thrombocytopenia was detected in 5-41.7% of the patients with COVID-19. Analyzing the dynamic decrease in platelet counts may be useful in the prognosis of patients with COVID-19. However, the mechanisms underlying the development of thrombocytopenia remain to be elucidated. This review summarizes the hematological changes in patients infected with SARS-CoV-2 and possible underlying mechanisms of thrombocytopenia development. Coronavirus types and their receptorsSix types of human CoVs have been identified till date: HCoV-NL63 and HCoV-229E are Alphacoronaviruses and HCoV-OC43, HCoVHKU1, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) are Betacoronaviruses (Table I) [6-10]. SARS-CoV-2 is the seventh member of the RNA-containing enveloped CoV family. SARS-CoV-2 and SARS-CoV reside on different branches of the phylogenetic tree, but the genome of SARS-CoV-2 shares more than 85% homology with that of SARS-CoV [7]. HCoV-229E, OC43, NL63, and HKU1 cause mild respiratory diseases. The last two decades have seen fatal infections caused by SARS-CoV and MERS-CoV [8].CoVs use cell surface receptors to enter host cells [9]. SARS-CoV primarily binds to the angiotensin-converting enzyme 2 (ACE2) [10], whereas MERS-CoV interacts with dipeptidyl peptidase 4 (DPP4; also known as CD26; Table I). Similar to SARS-CoV, COVID-19 develops upon binding of SARS-CoV-2 viral particles to ACE2, but not to other CoV receptors, such as aminopeptidase N and DPP4 [7]. SARS-CoV has similar antigenic characteristics as human 12]. HCoV-229E enters monocytes and macrophages via CD13 and induces cell apoptosis [13]. In addition, Betacoronaviruses can utilize CEACAMla (CD66a) as receptors [4,14]. Clinical manifestations and treatment of COVID-19Patients with COVID-19 can be divided into four categories based on their clinical manifestations: light, common, severe, and critical. Guan et al. performed a retrospective study (n = 1099) demonstrated that COVID-19 is associated with a wide range of symptoms [1]. Fever

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world at an unprecedented rate. In the present study, 4 marine sulfated...

The first manganese(I)-catalyzed C-H allylations with ample scope were achieved by carboxylate assistance. The highly selective C-H/C-O functionalizations proved viable with densely substituted allyl carbonates, and the organometallic C-H allylation strategy set the stage for expedient late-stage diversification with excellent levels of positional selectivity.

Acute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8+ T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8+ T lymphocytes in the setting of acute myocardial infarction.

Thymoquinone (TQ, 2‐methyl‐5‐isopropyl‐1,4‐benzoquinone), a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti‐tumor efficiency in various cancers. Autophagy is a self‐digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786‐O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model. Meanwhile, we observed LC3 puncta and detected the expression of LC3 in TQ‐treated RCC cells, and then found that autophagy was induced by TQ in 786‐O and ACHN cell lines. In addition, TQ inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy‐dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. In conclusion, our findings provide a novel therapeutic strategy that aims at TQ‐induced autophagy in RCC treatment.

miR-124, a brain-specific microRNA, was originally considered as a key regulator in neuronal differentiation and the development of the nervous system. Here we showed that miR-124 expression was suppressed in patients with epilepsy and rats after drug induced-seizures. Intrahippocampal administration of a miR-124 duplex led to alleviated seizure severity and prolonged onset latency in two rat models (pentylenetetrazole- and pilocarpine-induced seizures), while miR-124 inhibitor led to shortened onset latency in pilocarpine-induced seizure rat models. Moreover, the result of local field potentials (LFPs) records further demonstrated miR-124 may have anti-epilepsy function. Inhibition of neuronal firing by miR-124 was associated with the suppression of mEPSC, AMPAR- and NMDAR-mediated currents, which were accompanied by decreased surface expression of NMDAR. In addition, miR-124 injection resulted in decreased activity and expression of cAMP-response element-binding protein1 (CREB1). a key regulator in epileptogenesis. A dual-luciferase reporter assay was used to confirm that miR-124 targeted directly the 3′UTR of CREB1 gene and repressed the CREB1 expression in HEK293T cells. Immunoprecipitation studies confirmed that the CREB1 antibody effectively precipitated CREB1 and NMDAR1 but not GLUR1 from rat brain hippocampus. These results revealed a previously unknown function of miR-124 in neuronal excitability and provided a new insight into molecular mechanisms underlying epilepsy.

Nanozymes are artificial enzymes, which can substitute traditional biological enzymes for multifield applications. However, to date, it remains challenging to search novel mimic enzymes or multienzyme mimics. Herein, a facile and green method for preparing monodisperse, homogeneous copper nanoclusters (Cu NCs) with smaller size was developed, which used cysteamine as a template and hydrazine hydrate as a reductant to reduce Cu 2+ . The as-prepared Cu NCs exhibited excellent tetraenzyme-like activities, including peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-, and ascorbic acid oxidase (AAO)-mimic activities. The mechanisms, kinetics, and catalytic performances of Cu NCs were systematically studied. Moreover, based on the POD-like activity of Cu NCs, sensitive and simple colorimetric sensing glutathione (GSH) was explored, with the low limit of detection of 0.89 μM GSH (S/N = 3). Additionally, a novel fluorimetric ascorbic acid (AA) sensor was developed with the linear range of 0.5−30 μM and limit of detection (LOD) of 0.144 μM, on the basis of the principle that AA is oxidized to dehydroascorbic acid (DHAA) specifically catalyzed by the AAO-like activity of Cu NCs, while DHAA can further react with ophenylenediamine (OPDA) to generate a highly fluorescent quinoxaline (DFQ) derivative. The as-proposed colorimetric GSH sensor and the fluorimetric AA sensor were capable of detecting GSH and AA, respectively, in real samples accurately and reproducibly. Thus, the Cu NCs-based multienzyme mimic is a promising candidate for biocatalysis and biosensing.