Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients

The global coronavirus disease 2019 (COVID-19) pandemic has lasted for over 2 years now and has already caused millions of deaths. In COVID-19, leukocyte pyroptosis has been previously associated with both beneficial and detrimental effects, so its role in the development of this disease remains controversial. Using transcriptomic data (GSE157103) of blood leukocytes from 126 acute respiratory distress syndrome patients (ARDS) with or without COVID-19, we found that COVID-19 patients present with enhanced leukocyte pyroptosis. Based on unsupervised clustering, we divided 100 COVID-19 patients into two clusters (PYRcluster1 and PYRcluster2) according to the expression of 35 pyroptosis-related genes. The results revealed distinct pyroptotic patterns associated with different leukocytes in these PYRclusters. PYRcluster1 patients were in a hyperinflammatory state and had a worse prognosis than PYRcluster2 patients. The hyperinflammation of PYRcluster1 was validated by the results of gene set enrichment analysis (GSEA) of proteomic data (MSV000085703). These differences in pyroptosis between the two PYRclusters were confirmed by the PYRscore. To improve the clinical treatment of COVID-19 patients, we used least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model based on differentially expressed genes between PYRclusters (PYRsafescore), which can be applied as an effective prognosis tool. Lastly, we explored the upstream transcription factors of different pyroptotic patterns, thereby identifying 112 compounds with potential therapeutic value in public databases

Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1

Global genetic diversity, introgression, and evolutionary adaptation of indicine cattle revealed by whole genome sequencing

Indicine cattle, also referred to as zebu (Bos taurus indicus), play a central role in pastoral communities across a wide range of agro-ecosystems, from extremely hot semiarid regions to hot humid tropical regions. However, their adaptive genetic changes following their dispersal into East Asia from the Indian subcontinent have remained poorly documented. Here, we characterize their global genetic diversity using high-quality whole-genome sequencing data from 354 indicine cattle of 57 breeds/populations, including major indicine phylogeographic groups worldwide. We reveal their probable migration into East Asia was along a coastal route rather than inland routes and we detected introgression from other bovine species. Genomic regions carrying morphology-, immune-, and heat-tolerance-related genes underwent divergent selection according to Asian agro-ecologies. We identify distinct sets of loci that contain promising candidate variants for adaptation to hot semi-arid and hot humid tropical ecosystems. Our results indicate that the rapid and successful adaptation of East Asian indicine cattle to hot humid environments was promoted by localized introgression from banteng and/or gaur. Our findings provide insights into the history and environmental adaptation of indicine cattle

AMOS-based analysis of factors influencing customer loyalty

In order to better reduce the cost of e-commerce operations and save resources for marketing promotion, e-commerce merchants must adopt a reasonable and effective way to screen customers and improve the competitiveness of their own products. This paper takes the measurement of latent variable customer loyalty as the starting point, collects data through the design of questionnaires as the research basis, and uses Analysis of Moment Structure (AMOS) to construct structural equation model to conduct a validating factor analysis. It was found that the hypotheses proposed from the three subjects of business, customers themselves and logistics are all basically valid, and all three have a positive impact on loyalty. Ecommerce businesses should improve the service quality of their stores, ensure that their products can meet the needs of most customers, and build a good brand image, and should also carefully choose logistics companies that are reliable and new to customers to cooperate with

Prescribed-Time Convergent Adaptive ZNN for Time-Varying Matrix Inversion under Harmonic Noise

Harmonic noises widely exist in industrial fields and always affect the computational accuracy of neural network models. The existing original adaptive zeroing neural network (OAZNN) model can effectively suppress harmonic noises. Nevertheless, the OAZNN model’s convergence rate only stays at the exponential convergence, that is, its convergence speed is usually greatly affected by the initial state. Consequently, to tackle the above issue, this work combines the dynamic characteristics of harmonic signals with prescribed-time convergence activation function, and proposes a prescribed-time convergent adaptive ZNN (PTCAZNN) for solving time-varying matrix inverse problem (TVMIP) under harmonic noises. Owing to the nonlinear activation function used having the ability to reject noises itself and the adaptive term also being able to compensate the influence of noises, the PTCAZNN model can realize double noise suppression. More importantly, the theoretical analysis of PTCAZNN model with prescribed-time convergence and robustness performance is provided. Finally, by varying a series of conditions such as the frequency of single harmonic noise, the frequency of multi-harmonic noise, and the initial value and the dimension of the matrix, the comparative simulation results further confirm the effectiveness and superiority of the PTCAZNN model

Prescribed-Time Convergent Adaptive ZNN for Time-Varying Matrix Inversion under Harmonic Noise

Harmonic noises widely exist in industrial fields and always affect the computational accuracy of neural network models. The existing original adaptive zeroing neural network (OAZNN) model can effectively suppress harmonic noises. Nevertheless, the OAZNN model’s convergence rate only stays at the exponential convergence, that is, its convergence speed is usually greatly affected by the initial state. Consequently, to tackle the above issue, this work combines the dynamic characteristics of harmonic signals with prescribed-time convergence activation function, and proposes a prescribed-time convergent adaptive ZNN (PTCAZNN) for solving time-varying matrix inverse problem (TVMIP) under harmonic noises. Owing to the nonlinear activation function used having the ability to reject noises itself and the adaptive term also being able to compensate the influence of noises, the PTCAZNN model can realize double noise suppression. More importantly, the theoretical analysis of PTCAZNN model with prescribed-time convergence and robustness performance is provided. Finally, by varying a series of conditions such as the frequency of single harmonic noise, the frequency of multi-harmonic noise, and the initial value and the dimension of the matrix, the comparative simulation results further confirm the effectiveness and superiority of the PTCAZNN model

Double integral‐enhanced Zeroing neural network with linear noise rejection for time‐varying matrix inverse

Abstract In engineering fields, time‐varying matrix inversion (TVMI) issue is often encountered. Zeroing neural network (ZNN) has been extensively employed to resolve the TVMI problem. Nevertheless, the original ZNN (OZNN) and the integral‐enhanced ZNN (IEZNN) usually fail to deal with the TVMI problem under unbounded noises, such as linear noises. Therefore, a neural network model that can handle the TVMI under linear noise interference is urgently needed. This paper develops a double integral‐enhanced ZNN (DIEZNN) model based on a novel integral‐type design formula with inherent linear‐noise tolerance. Moreover, its convergence and robustness are verified by derivation strictly. For comparison and verification, the OZNN and the IEZNN models are adopted to resolve the TVMI under multiple identical noise environments. The experiments proved that the DIEZNN model has excellent advantages in solving TVMI problems under linear noises. In general, the DIEZNN model is an innovative work and is proposed for the first time. Satisfyingly, the errors of DIEZNN are always less than 1 × 10−3 under linear noises, whereas the error norms of OZNN and IEZNN models are not convergent to zero. In addition, these models are applied to the control of the controllable permanent magnet synchronous motor chaotic system to indicate the superiority of the DIEZNN

Antibacterial activity and mechanism of a scorpion venom peptide derivative in vitro and in vivo.

BmKn2 is an antimicrobial peptide (AMP) characterized from the venom of scorpion Mesobuthus martensii Karsch by our group. In this study, Kn2-7 was derived from BmKn2 to improve the antibacterial activity and decrease hemolytic activity. Kn2-7 showed increased inhibitory activity against both gram-positive bacteria and gram-negative bacteria. Moreover, Kn2-7 exhibited higher antibacterial activity against clinical antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). In addition, the topical use of Kn2-7 effectively protected the skin of mice from infection in an S. aureus mouse skin infection model. Kn2-7 exerted its antibacterial activity via a bactericidal mechanism. Kn2-7 killed S. aureus and E. coli rapidly by binding to the lipoteichoic acid (LTA) in the S. aureus cell wall and the lipopolysaccharides (LPS) in the E. coli cell wall, respectively. Finally, the hemolytic activity of Kn2-7 was significantly decreased, compared to the wild-type peptide BmKn2. Taken together, the Kn2-7 peptide can be developed as a topical therapeutic agent for treating bacterial infections

Hp1404, a new antimicrobial peptide from the scorpion Heterometrus petersii.

Antimicrobial peptides have attracted much interest as a novel class of antibiotics against a variety of microbes including antibiotics resistant strains. In this study, a new cationic antimicrobial peptide Hp1404 was identified from the scorpion Heterometrus petersii, which is an amphipathic α-helical peptide and has a specific inhibitory activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus. Hp1404 can penetrate the membrane of S. aureus at low concentration, and disrupts the cellular membrane directly at super high concentration. S. aureus does not develop drug resistance after multiple treatments with Hp1404 at sub MIC concentration, which is possibly associated with the antibacterial mechanism of the peptide. In addition, Hp1404 has low toxicity to both mammalian cells (HC₅₀  =  226.6 µg/mL and CC₅₀ > 100 µg/mL) and balb-c mice (Non-toxicity at 80 mg/Kg by intraperitoneal injection and LD₅₀  =  89.8 mg/Kg by intravenous injection). Interestingly, Hp1404 can improve the survival rate of the MRSA infected balb-c mice in the peritonitis model. Taken together, Hp1404 may have potential applications as an antibacterial agent