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Pseudotyped viruses are useful virological tools because of their safety and versatility. On the basis of a vesicular stomatitis virus (VSV) pseudotyped virus production system, we developed a pseudotyped virus-based neutralization assay against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in biosafety level 2 facilities. Compared with the binding antibody test, the neutralization assay could discriminate the protective agents from the antibody family. This protocol includes production and titration of the SARS-CoV-2 S pseudotyped virus and the neutralization assay based on it. Various types of samples targeting virus attachment and entry could be evaluated for their potency, including serum samples derived from animals and humans, monoclonal antibodies and fusion inhibitors (peptides or small molecules). If the pseudotyped virus stock has been prepared in advance, it will take 2 days to get the potency data for the candidate samples. Experience in handling cells is needed before implementing this protocol. The production and titration of the SARS-CoV-2 S pseudotyped virus using a VSV-based pseudovirus production system in this protocol enable its use under biosafety level 2 conditions as well as in a neutralization assay to assess the level of neutralizing antibodies or molecular inhibitors in a sample.

The classical Wiener lemma and its various generalizations are important and have numerous applications in numerical analysis, wavelet theory, frame theory, and sampling theory. There are many different equivalent formulations for the classical Wiener lemma, with an equivalent formulation suitable for our generalization involving commutative algebra of infinite matrices W:={(a(j−j′))j,j′∈Zd: ∑j∈Zd|a(j)|>∞}{\\mathcal W}:=\\{(a(j-j’))_{j,j’\\in \\mathbf {Z}^d}: \\ \\sum _{j\\in \\mathbf {Z}^d} |a(j)|>\\infty \\}. In the study of spline approximation, (diffusion) wavelets and affine frames, Gabor frames on non-uniform grid, and non-uniform sampling and reconstruction, the associated algebras of infinite matrices are extremely non-commutative, but we expect those non-commutative algebras to have a similar property to Wiener’s lemma for the commutative algebra W{\\mathcal W}. In this paper, we consider two non-commutative algebras of infinite matrices, the Schur class and the Sjöstrand class, and establish Wiener’s lemmas for those matrix algebras.

Pseudoviruses are useful virological tools because of their safety and versatility, especially for emerging and re-emerging viruses. Due to its high pathogenicity and infectivity and the lack of effective vaccines and therapeutics, live SARS-CoV-2 has to be handled under biosafety level 3 conditions, which has hindered the development of vaccines and therapeutics. Based on a VSV pseudovirus production system, a pseudovirus-based neutralization assay has been developed for evaluating neutralizing antibodies against SARS-CoV-2 in biosafety level 2 facilities. The key parameters for this assay were optimized, including cell types, cell numbers, virus inoculum. When tested against the SARS-CoV-2 pseudovirus, SARS-CoV-2 convalescent patient sera showed high neutralizing potency, which underscore its potential as therapeutics. The limit of detection for this assay was determined as 22.1 and 43.2 for human and mouse serum samples respectively using a panel of 120 negative samples. The cutoff values were set as 30 and 50 for human and mouse serum samples, respectively. This assay showed relatively low coefficient of variations with 15.9% and 16.2% for the intra- and inter-assay analyses respectively. Taken together, we established a robust pseudovirus-based neutralization assay for SARS-CoV-2 and are glad to share pseudoviruses and related protocols with the developers of vaccines or therapeutics to fight against this lethal virus.

From an average (ideal) sampling/reconstruction process, the question arises whether the original signal can be recovered from its average (ideal) samples and, if so, how. We consider the above question under the assumption that the original signal comes from a prototypical space modeling signals with a finite rate of innovation, which includes finitely generated shift-invariant spaces, twisted shift-invariant spaces associated with Gabor frames and Wilson bases, and spaces of polynomial splines with nonuniform knots as its special cases. We show that the displayer associated with an average (ideal) sampling/reconstruction process, which has a well-localized average sampler, can be found to be well-localized. We prove that the reconstruction process associated with an average (ideal) sampling process is robust, locally behaved, and finitely implementable, and thus we conclude that the original signal can be approximately recovered from its incomplete average (ideal) samples with noise in real time. Most of our results in this paper are new even for the special case when the original signal comes from a finitely generated shift-invariant space.

Acute myocardial infarction (AMI) is one of the most serious complications of coronary heart disease. Although morbidity and mortality have been decreasing year by year, acute coronary syndrome still has a high mortality rate and disability rate. To search for accurate and effective biomarkers, we explore the diagnostic and prognostic value of microRNAs (miRNAs) and the monocyte to high-density lipoprotein cholesterol ratio (MHR) in patients with AMI. By referring to the relevant literature, miR-486-5p, miR-451a and miR-21-5p were reportedly altered in the blood of patients with ischemic heart disease. These miRNAs were selected and validated in 40 AMI patients, 22 unstable angina pectoris (UAP) and 22 healthy groups (HC) by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). All patients with AMI underwent primary percutaneous coronary intervention (PCI) and were followed up 3 months after the operation. MHR and miR-451a expression were markedly elevated in plasma samples of AMI patients compared with the UAP and HC groups, but the expressions of miR-486-5p and miR-21-5p were significantly decreased. The expression level of miRNA-451a increased gradually among the three groups ( p  < 0.05). However, the expression of miRNA-21-5p showed a downward trend ( p  < 0.05). More importantly, MHR was significantly different before and after PCI in AMI patients ( p  < 0.05). Receiver operating characteristic (ROC) analysis indicated that MHR, miR-486-5p, miR-451a and miR-21-5p could diagnose and predict AMI. MiR-451a was a more reliable biomarker for AMI diagnosis among these miRNAs. Moreover, the combination of MHR and miRNAs had higher diagnostic value for AMI. We further demonstrated that miR-21-5p had a strong predictive ability for the occurrence of major adverse cardiovascular events (MACE) after 3 months. The results showed that circulating miR-486-5p, miR-451a, miR-21-5p and MHR may play critical roles in the early phase of AMI, and may be used as potential predictors for AMI diagnosis. Importantly, miR-451a was a more reliable biomarker in diagnosing AMI patients. Circulating miR-21-5p may be used as a predictor of MACE occurrence.

Background Currently, acute myocardial infarction (AMI) represents a serious cardiovascular disease with high morbidity and mortality. Therefore, this study aimed to systematically evaluate the roles of miRNA‐499 and miRNA‐22 as potential biomarkers for AMI. Methods According to the inclusion and exclusion criteria, we measured circulating levels of miRNAs in 50 AMI patients and 50 non‐MI populations. The expression levels of plasma miRNA‐499 and miRNA‐22 were analyzed by real‐time fluorescent quantitative polymerase chain reaction (qRT‐PCR). A statistical analysis of clinical data of AMI patients was conducted by 90‐day follow‐up. Results Real‐time PCR analysis showed that the relative expression level of miRNA‐499 increased gradually among the three groups (P < .05). However, the expression of miRNA‐22 showed a downward trend (P < .05). According to logistic analysis, the relative levels of miRNA‐499 and miRNA‐22 were important predictors of AMI. When the miRNA‐499 and miRNA‐22 levels were 0.377 and 0.946 separately, the diagnostic value of miRNA‐499 and miRNA‐22 for AMI was 86.00% and 86.00% for sensitivity, and 98.00% and 94.00% for specificity, respectively. In addition, compared to the baseline GRACE scoring system, the combination of miRNA‐499, miRNA‐22, and GRACE scores had a stronger discriminating power for MACE occurrence, with a sensitivity of 100.00% and a specificity of 79.40%. Conclusions The results showed that plasma miRNA‐499 and miRNA‐22 were more sensitive and specific for the diagnosis of AMI, suggesting that they can be used as potential biomarkers for clinical diagnosis of AMI.

Abstract The aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and neutrophil-to-lymphocyte*platelet ratio (NLRP) are novel indices that simultaneously reflect the inflammatory and immune status. However, the role of these indices in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) remains unclear. We aimed to elucidate the predictive value of AISI, SIRI, and NLRP in patients with ACS undergoing PCI. A total of 1558 patients with ACS undergoing PCI were consecutively enrolled from January 2016 to December 2018. The AISI, SIRI, NLRP, systemic immune-inflammatory index, derived neutrophil-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio cutoff values for predicting major adverse cardiovascular events (MACE) were calculated using receiver-operating characteristic curves, and Spearman's test was used to analyze correlations between these indices. Kaplan–Meier curves and Cox regression models were used for survival analyses, and the endpoint was a MACE, which included all-cause mortality and rehospitalization for severe heart failure during the follow-up period. The Kaplan–Meier curves showed that higher AISI, SIRI, and NLRP values were associated with a higher risk of MACE (all P < .001). The association between AISI, SIRI, and NLRP and ACS prognosis was stable in various subgroups according to sex, age, smoking, dyslipidemia, hypertension, diabetes mellitus, history of stroke, and heart failure (P for interaction > .05). Increasing tertiles of AISI, SIRI, and NLRP significantly increased the MACE risk (P for trend < .05). AISI, SIRI, and NLRP may be suitable laboratory markers for identifying high-risk patients with ACS after PCI.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma, and the tumour growth and metastasis of ccRCC are related to prognosis. N4-acetylcytidine (ac4C) is one of the major modifications of RNA and is known to be mediated by N-acetyltransferase 10 (NAT10). The role of NAT10 in cancer is gradually being revealed, although the role of NAT10-mediated RNA ac4C modification in ccRCC has not been reported. In this study, NAT10 was found to be upregulated in ccRCC tissues and associated with a poor prognosis in patients. HIF-1α activated NAT10 expression at the transcriptional level. CCK8, EdU, Transwell and scratch assays after NAT10 knockdown or overexpression showed that NAT10 promoted cell proliferation and migration. The results of subcutaneous xenograft and caudal vein injection showed that NAT10 promoted tumour growth and metastasis in vivo, while Remodelin inhibited tumour growth. The acRIP-seq, RIP, RNA stability and dual luciferase reporter experiments showed that NAT10 activated ac4C acetylation of NFE2L3 mRNA and promoted NFE2L3 mRNA stability. The ChIP-seq results showed that NFE2L3 regulated the expression of LASP1 and thus activated the AKT/GSK3β signalling pathway. In summary, our results suggest that NAT10 mediates ac4C acetylation of NFE2L3 mRNA, promotes its mRNA stability, regulates the LASP1-AKT/GSK3β/β-catenin axis and promotes the progression of renal clear cell carcinoma.

Introduction An accurate assessment of prognostic risk is widely recognized to be important in improving the survival of patients with acute coronary syndrome (ACS). This study aimed to investigate the roles of neutrophil-to-lymphocyte * platelet (NLPR) and neutrophil-lymphocyte (NLR) ratios with high- and (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels in predicting the risk of major adverse cardiovascular events (MACEs) in patients with ACS undergoing percutaneous coronary intervention (PCI). Results Overall, 1,263 patients with ACS undergoing PCI between January 2016 and December 2018 were consecutively enrolled. The patients were divided into MACEs ( n  = 54) and non-MACEs ( n  = 1,209) groups. The study endpoints were MACEs, including cardiac-related mortality and re-hospitalization for severe heart failure (HF), myocardial infarction (MI), and in-stent restenosis (ISR). The Kaplan–Meier curve showed the low NLPR and NLR groups had higher cumulative survival than the high NLPR and NLR group. Patients with high NLPR/HDL-C, NLPR×LDL-C, NLR/HDL-C, and NLR×LDL-C also had significantly lower cumulative survival. Conclusion NLPR ≥ 2.843, NLPR/HDL-C ≥ 1.977, NLPR*LDL-C ≥ 4.608, NLR ≥ 0.025, NLR/HDL-C ≥ 0.030, and NLR*LDL-C ≥ 0.038 were all independent prognostic risk factors in patients with ACS undergoing PCI, which may be useful markers for long prognosis.

Purpose: The decreased advanced lung cancer inflammation index (ALI), defined as body mass index (BMI) * albumin (Alb)/neutrophil-to-lymphocyte ratio (NLR), is an independent prognostic risk factor for overall survival in gastric, lung, and colorectal cancers. This study aimed to investigate the value of ALI in predicting the risk of major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Patients and Methods: A total of 1624 patients with ACS undergoing percutaneous coronary intervention (PCI) were consecutively enrolled between January 2016 and December 2018. Follow-up data were collected at 1, 3, 6, and 12 months and annually thereafter. The primary endpoints were MACEs. All endpoints were defined as all-cause mortality, recurrent angina pectoris, restenosis/intra stent thrombosis, stroke, heart failure, and all-cause bleeding. Results: The MACEs group and non-MACEs group showed significant differences in patients with age >65 years (28 [50.0%] vs 319 [23.7%]), history of heart failure (16 [28.6%] vs 127 [9.4%]), history of ischemic stroke (14 [25.0%] vs 186 [13.8%]), history of cardiogenic shock (6 [10.71%] vs 16 [1.19%]), left ventricular ejection fraction <40% (8 [14.29%] vs 33 [2.46%]), and ALI <343.96 (44 [78.65%] vs 680 [50.60%]) (all p<0.001). The optimal cut-off value for ALI was 334.96. The area under the curve (AUC) of the 1-, 2-, 3-, and 5-year was 0.560, 0.577, 0.665, and 0.749, respectively. The survival rate was significantly lower in the low ALI group than in the high ALI group (log-rank p<0.001). Low ALI was an independent risk factor for the long-term prognosis of patients with ACS after PCI, univariate HR: 3.671, 95% CI: 1.938-6.953, p<0.001; multivariate HR: 3.009, 95% CI: 1.57-5.769, p=0.001. Conclusion: ALI score less than 334.96 is an independent prognostic risk factor for patients with ACS undergoing PCI and may be a novel marker for clinical practice. Keywords: acute coronary syndrome, advanced lung cancer inflammation index, prognosis, percutaneous coronary intervention