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The coronavirus disease 2019 (COVID-19) global pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been marked by severe cases demonstrating a "cytokine storm", an upsurge of pro-inflammatory cytokines in the bloodstream. NLRP3 inflammasomes, integral to the innate immune system, are speculated to be activated by SARS-CoV-2 within host cells. This review investigates the potential correlation between NLRP3 inflammasomes and COVID-19, exploring the cellular and molecular mechanisms through which SARS-CoV-2 triggers their activation. Furthermore, promising strategies targeting NLRP3 inflammasomes are proposed to mitigate the excessive inflammatory response provoked by SARS-CoV-2 infection. By synthesizing existing studies, this paper offers insights into NLRP3 as a therapeutic target, elucidating the interplay between COVID-19 and its pathophysiology. It serves as a valuable reference for future clinical approaches in addressing COVID-19 by targeting NLRP3, thus providing potential avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Enterovirus A71, a non-enveloped single-stranded (+) RNA virus, enters host cells through three stages: attachment, endocytosis and uncoating. In recent years, receptors/co-receptors anchored on the host cell membrane and involved in this process have been continuously identified. Among these, hSCARB-2 was the first receptor revealed to specifically bind to a definite site of the EV-A71 viral capsid and plays an indispensable role during viral entry. It actually acts as the main receptor due to its ability to recognize all EV-A71 strains. In addition, PSGL-1 is the second EV-A71 receptor discovered. Unlike hSCARB-2, PSGL-1 binding is strain-specific; only 20% of EV-A71 strains isolated to date are able to recognize and bind it. Some other receptors, such as sialylated glycan, Anx 2, HS, HSP90, vimentin, nucleolin and fibronectin, were discovered successively and considered as "co-receptors" because, without hSCARB-2 or PSGL-1, they are not able to mediate entry. For cypA, prohibitin and hWARS, whether they belong to the category of receptors or of co-receptors still needs further investigation. In fact, they have shown to exhibit an hSCARB-2-independent entry. All this information has gradually enriched our knowledge of EV-A71's early stages of infection. In addition to the availability of receptors/co-receptors for EV-A71 on host cells, the complex interaction between the virus and host proteins and various intracellular signaling pathways that are intricately connected to each other is critical for a successful EV-A71 invasion and for escaping the attack of the immune system. However, a lot remains unknown about the EV-A71 entry process. Nevertheless, researchers have been continuously interested in developing EV-A71 entry inhibitors, as this study area offers a large number of targets. To date, important progress has been made toward the development of several inhibitors targeting: receptors/co-receptors, including their soluble forms and chemically designed compounds; virus capsids, such as capsid inhibitors designed on the VP1 capsid; compounds potentially interfering with related signaling pathways, such as MAPK-, IFN- and ATR-inhibitors; and other strategies, such as siRNA and monoclonal antibodies targeting entry. The present review summarizes these latest studies, which are undoubtedly of great significance in developing a novel therapeutic approach against EV-A71. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a complex disorder characterized by insufficient insulin production or insulin resistance, which results in a lifelong dependence on glucose-lowering drugs for almost all patients. During the fight with diabetes, researchers are always thinking about what characteristics the ideal hypoglycemic drugs should have. From the point of view of the drugs, they should maintain effective control of blood sugar, have a very low risk of hypoglycemia, not increase or decrease body weight, improve β-cell function, and delay disease progression. Recently, the advent of oral peptide drugs, such as semaglutide, brings exciting hope to patients with chronic diabetes. Legumes, as an excellent source of protein, peptides, and phytochemicals, have played significant roles in human health throughout human history. Some legume-derived peptides with encouraging anti-diabetic potential have been gradually reported over the last two decades. Their hypoglycemic mechanisms have also been clarified at some classic diabetes treatment targets, such as the insulin receptor signaling pathway or other related pathways involved in the progress of diabetes, and key enzymes including α-amylase, α-glucosidase, and dipeptidyl peptidase-IV (DPP-4). This review summarizes the anti-diabetic activities and mechanisms of peptides from legumes and discusses the prospects of these peptide-based drugs in type 2 diabetes (T2D) management. [ABSTRACT FROM AUTHOR]

Simple Summary: The high expression of signal-induced proliferation-associated 1 (SIPA1) in breast cancer could aggravate cancer cell metastasis, but how the tumour microenvironment is involved in this incident is unknown. In this study, we investigated whether breast cancer cells with high SIPA1 expression recruited macrophages into the tumour microenvironment. We also found that extracellular vesicles (EVs) derived from MDA-MB-231 cells significantly enhanced macrophage migration, compared with that from SIPA1-knockdown MDA-MB-231 cells both in vitro and in vivo. In terms of the mechanism, SIPA1 in cancer cells modulated the key protein myosin-9 in EVs and promoted macrophage infiltration via EVs. We confirmed that either down-regulating SIPA1 expression or blocking myosin-9 by its inhibitor, blebbistatin, led to the suppression of macrophage infiltration. These findings contribute to a deep understanding of how SIPA1 regulates the tumour microenvironment in breast cancer to facilitate tumour metastasis and provide a basis for the development of therapeutics against breast cancer metastasis. Tumour cell metastasis can be genetically regulated by proteins contained in cancer cell-derived extracellular vesicles (EVs) released to the tumour microenvironment. Here, we found that the number of infiltrated macrophages was positively correlated with the expression of signal-induced proliferation-associated 1 (SIPA1) in invasive breast ductal carcinoma tissues and MDA-MB-231 xenograft tumours. EVs derived from MDA-MB-231 cells (231-EVs) significantly enhanced macrophage migration, compared with that from SIPA1-knockdown MDA-MB-231 cells (231/si-EVs) both in vitro and in vivo. We revealed that SIPA1 promoted the transcription of MYH9, which encodes myosin-9, and up-regulated the expression level of myosin-9 in breast cancer cells and their EVs. We also found that blocking myosin-9 by either down-regulating SIPA1 expression or blebbistatin treatment led to the suppression of macrophage infiltration. Survival analysis showed that breast cancer patients with high expression of SIPA1 and MYH9 molecules had worse relapse-free survival (p = 0.028). In summary, SIPA1high breast cancer can enhance macrophage infiltration through EVs enriched with myosin-9, which might aggravate the malignancy of breast cancer. [ABSTRACT FROM AUTHOR]

In this work, SiO2-encapsulated copper particles/PA12 (Cu-SiO2/PA12) composite powders were prepared by electroless composite plating, and the laser sintering behavior was investigated. Results showed that Cu, Cu2O, CuO, and SiO2 (Cu-SiO2) composite particles were plated on the surface of KH550-modified PA12 powders. The Cu-SiO2 particles existed independently on PA12 surface, and the size was around 200 nm. The melting temperature and crystallization temperature of Cu-SiO2/PA12 composite powders were 183∘C and 150∘C. The results indicate that the selective laser sintering (SLS) process involved the contact of Cu-SiO2/PA12 powders, the formation of sintering neck, the growth of sintering neck, and the formation of fused solid. The Cu-SiO2 composite particles uniformly dispersed in the part due to surface tension, and the contact interface was good due to their similar polarity. The Cu-SiO2/PA12 SLS parts had excellent dimensional precision. The tensile strength of the 15 W-sintered Cu-SiO2/PA12 specimen was 48 MPa. [ABSTRACT FROM AUTHOR]

Background: Enterovirus 71 (EV71) is the main pathogen of hand-foot-mouth disease (HFMD) and sometimes causes several neurological complications. However, the underlying mechanism of the host response to the virus infection remains unclear. Objective: To reveal the cell-specific transcriptional response of cultured RD cells following infection with EV71, and better understand the molecular mechanisms of virus-host interactions. Methods: The RD cells were infected with or without EV71 for 24 h, and then transcriptome sequencing and qRT-PCR were performed to analyze the transcriptome difference of functional genes. Results: More than 15000 genes were identified in transcriptome sequencing. In comparison with uninfected RD cells, 329 DEGs were identified in cells infected with EV71. GO and KEGG pathway enrichment analysis showed that most of the DEGs were related to DNA binding, transcriptional regulation, immune response and inflammatory response, apoptosis inducing factors and enriched in JAK-STAT and MAPK signaling pathways. TXNIP (thioredoxin-interacting protein) gene was further demonstrated to play an important role participating in cellular apoptosis induced by EV71, and the apoptosis and death mediated by TXNIP during EV71 infection was triggered by viral 2A protease (2Apro), not 3C protease (3Cpro). Conclusion: Our study demonstrated that RD cells have a significant response to EV71 infection, including immune response and apoptosis. 2Apro might be a key inducer relative to the cellular apoptosis and death mediated by TXNIP during EV71 infection. These data would contribute to preferably understand the process at the molecular level and provide theoretical foundation for diagnosis and treatment of EV71-related diseases. [ABSTRACT FROM AUTHOR]

Poly(trimethylene terephthalate)/poly(propylene glycol) (PTT/PPG) copolymers with different PPG molecular weights (400–4,000 g /mol) were successfully synthesized and characterized. Double melting endotherms during isothermal melt crystallization were observed by differential scanning calorimetry. Middle-temperature melting endotherms in all copolymers were stronger than that in PTT homopolymer and became smaller with the increasing PPG molecular weight. Nonisothermal crystallization kinetics of all samples were analyzed by Ozawa and Mo models. Polarized optical microscopy micrographs revealed that ring-banded spherulitic morphology was relatively easier to be observed in copolymers with higher PPG molecular weight at lower crystallization temperature, and PPG molecular weight nearly had no influence on the band spacing. [ABSTRACT FROM AUTHOR]

In this work, the effects of plating time on structural properties of Ni-plating coating on Nylon 12 (PA12) powders modified with 3-amino-propyltriethoxysilane (KH550) solution were investigated systematically using scanning electron microscopy and X-ray diffraction. Results showed amine groups attached on surface of KH550-modified PA12 powders, which could adsorb Sn and Pd used as sensitizer and activator, respectively. The relative concentration of Sn and Pd on sensitized and activated PA12 surface were 0.15 and 0.04%. When the plating time increased from 1 to 60 min, the crystallinity of Ni-plating coating enhanced and Ni-particle deposited content increased from 3.8 to 28%. Moreover, the Ni-plating particles firstly showed discrete distribution on the PA12 surface, average Ni-particle size was little changed at about 0.18 μm, and then showed continuous distribution with the average size increased to 0.32 μm. [ABSTRACT FROM AUTHOR]

Poly(trimethylene terephthalate)/ZnO nanocomposites were successfully prepared by dual in situ polymerization. Firstly, ZnO nanoparticles were synthesized by a simple polyol method using 1,3-propanediol (PDO) as solvent and stabilizer. Then, PTT/ZnO nanocomposites were prepared by in situ polymerization. The results of Fourier transform infrared spectra showed that PTT molecular chains were grafted to the surface of ZnO nanoparticles. The results of 1H NMR spectra confirmed that propyl ester molecules (as reaction product) were incorporated into PTT molecular chains. It was found that the intrinsic viscosity and molecular weight of synthesized PTT decreased with the addition of ZnO nanoparticles and the incorporation of propyl ester molecules. TEM results showed that ZnO nanoparticles with particle size of 20 ~ 30 nm were well dispersed and fully distributed in the polymer matrix. Besides, the melting temperatures and crystallization temperature decreased gradually and then increased slightly with the increasing loading of ZnO nanoparticles. Because of the strong interaction between ZnO nanoparticles and PTT matrix, the thermal stability of PTT/ZnO nanocomposites was improved. Interestingly, the results of Polarized Optical Microscopy showed that banded spherulites morphology can be observed in all PTT/ZnO nanocomposite samples. However, at higher loading of ZnO nanoparticles, band spacing became larger and was finally disturbed. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Coxsackievirus B3 (CVB3) is the most common cause of acute and chronic viral myocarditis, primarily in children, while human adenovirus infections represent a significant cause of morbidity and mortality worldwide, in people of all ages. A series of novel 2-benzoxyl-phenylpyridine derivatives were evaluated for their potential antiviral activities against CVB3 and adenovirus type 7 (ADV7). Preliminary assays indicated that some of these compounds exhibited excellent antiviral effects on both CVB3 and ADV7 viruses; they could effectively inhibit virus-induced cytopathic effects, reduce viral progeny yields, and had similar or superior antiviral activities compared with the control drug, ribavirin. Further, these compounds targeted the early stages of CVB3 replication in cells, including viral RNA replication and protein synthesis, rather than inactivating the virus directly, inhibiting virus adsorption/entry, or affecting viral release from cells. Our data demonstrate that the tested 2-benzoxyl-phenylpyridine derivatives are effective inhibitors of CVB3 and ADV7, raising the possibility that these compounds might be feasible candidates for anti-viral agents. [ABSTRACT FROM AUTHOR]

Review: data from 2009 to 2015; 192 refs. [ABSTRACT FROM AUTHOR]

C language is one of the most popular languages for software systems. In order to verify safety, reliability and security properties of such systems written in C, a tool UMC4M for runtime verification at code level based on Modeling, Simulation and Verification Language (MSVL) and its compiler MC is employed. To do so, a C program P has to be translated to an MSVL program M and the negation of a desired property Q is also translated to an MSVL program M', then "M and M'" is compiled and executed armed with MC. Whether P violates Q is checked by evaluating whether there exists an acceptable execution of new MSVL program "M and M'". Therefore, how to translate a C program to an MSVL program is a critical issue. However, in general, C is of complicated structures with goto statement. In this paper, we confine the syntax of C in a suitable subset called Xd-C without loss of expressiveness. Further, we present a translation algorithm from an Xd-C program to an MSVL program based on translation algorithms for expressions and statements. Moreover, the equivalences between expressions and statements involved in Xd-C and MSVL programs are inductively proved. Subsequently, the equivalence between the original Xd-C program and the translated MSVL program is also proved. In addition, the proposed approach has been implemented by a tool called C 2 M. A benchmark of experiments including 13 real-world Xd-C programs is conducted. The results show that C 2 M works effectively. [ABSTRACT FROM AUTHOR]

A series of 2-Benzoxyl-Phenylpyridine derivatives were evaluated for their potential antiviral activities against EV71. The preliminary assays indicated that some of these compounds exhibited excellent antiviral effects on EV71, they could effectively inhibit virus-induced cytopathic effects (CPEs), reduce progeny viral yields, and present similar or better antiviral activities compared to the positive control drug ribavirin. Among these derivatives, compounds WY7, WY13 and WY14 showed the most potency against EV71. Investigation of the underlying mechanism of action revealed that these compounds target EV71 replication in cells post infection, they could profoundly inhibit viral RNA replication and protein synthesis, and inhibit virus-induced cell apoptosis. Further experiments demonstrated that compound WY7 potently inhibited the activity of the EV71 3C protease (3Cpro), and to some extent, it affected the activity of 3D polymerase (3Dpol), thus blocking viral replication, but not the activity of the 2A proteinase (2Apro). Modeling of the molecular binding of the 3Cpro-WY7 complex revealed that compound WY7 was predicted to insert into the substrate-binding pocket of EV71 3Cpro, blocking substrate recognition and thereby inhibiting EV71 3Cpro activity. These results indicate that these compounds might be feasible therapeutic agents against EV71 infection and that these compounds may provide promising lead scaffolds for the further design and synthesis of potential antiviral agents. [Display omitted] [ABSTRACT FROM AUTHOR]