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Porcine reproductive and respiratory syndrome virus (PRRSV) has become widespread in China particularly the highly pathogenic porcine reproductive and respiratory syndromes (HP-PRRSV), NADC30, and NADC34 strains, and has posed a threat to the swine industry for over 20 years. To monitor genetic variation in PRRSV-2 GP3 strains in China, we analyzed 618 strains isolated between 1996 to 2023 and constructed phylogenetic trees. Additionally, 60 selected strains were used to analyze nucleotide and amino acid homology. PRRSV GP3 gene exhibited nucleotide identity ranging from 78.2% to 100.0% and amino acid similarity ranging from 74.9% to 99.6%. The GP3 gene in the 60 selected strains consisted of 254 amino acids, and amino acid mutations in the strains primarily occurred in B-cell epitopes, T-cell epitopes, and highly variable regions. The glycosylation sites of the strains used for amino acid sequence comparisons remained unaltered, except for the N 29 site in the GD20220303-2022 strain. PRRSV-2 strains in China belong to lineages 1, 3, 5, and 8. Recombination analysis detected two recombination events, involving lineages 1 and 8. In conclusion, this study investigated multiple strains of the PRRSV-2 GP3 gene to explore the prevalence and genetic diversity of the GP3 gene in China from a gene family perspective. The results of the analyses provide a basis for clinical prevention strategies and vaccine development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lv, Zheng, Liu, Li, Luo, Zhang, Sha, Wang, Kong and Zhao.)

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV exhibits genetic diversity and complexity in terms of immune responses, posing challenges for eradication. The nucleocapsid (N) protein of PRRSV, an alkaline phosphoprotein, is important for various biological functions. This review summarizes the structural characteristics, genetic evolution, impact on PRRSV replication and virulence, interactions between viral and host proteins, modulation of host immunity, detection techniques targeting the N protein, and progress in vaccine development. The discussion provides a theoretical foundation for understanding the pathogenic mechanisms underlying PRRSV virulence, developing diagnostic techniques, and designing effective vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Li, Luo, Sha, Zhang, Wang, Kong, Liao and Zhao.)

The aim of this study was to screen the active regions and transcription factor binding sites in the promoter of the CBD103 gene related to Arctic fox coat color, and to provide a basis for revealing the molecular genetic mechanism of CBD103 gene regulating the coat color formation. The 5'-flanking region fragment 2 123 bp of Arctic fox CBD103 gene was cloned, and 4 truncated promoter reporter vectors of different lengths were constructed. The promoter activity was detected by the dual-luciferase reporter assay system. Point mutations were performed on the 3 predicted specificity protein 1 (Sp1) transcription factor binding sites in the highest promoter active region, and 3 mutant vectors were constructed. The activity was then detected by the dual-luciferase reporter assay system. The results showed that the region 1 656 (-1 604/+51) had the highest activity in the 4 truncated promoters of different lengths, and the promoter activity of the three mutant vectors constructed in this region were significantly lower than that of the wild type (fragment 1 656). The region of -1 604 /+51 was the core promoter region of CBD103 gene in Arctic fox and -1 552/-1 564, -1 439/-1 454 and -329/-339 regions were positive regulatory regions. This study successfully obtained the core promoter region and positive regulation regions of the Arctic fox CBD103 gene, which laid a foundation for further study on the molecular genetic mechanism of this gene regulating Arctic fox coat color.

An interferon-mediated antiviral protein, 2'-5' oligoadenylate synthetase 2, plays an important role in the antiviral response of interferons. In this study, 2'-5' oligoadenylate synthetase 2 genes were cloned from Chinese domestic pigs. Bioinformatics analysis revealed that the 2024-bp long open reading fame encodes 707 amino acids. There are two conserved regions in this protein: the nucleotidyltransferase domain, and the 2'-5' oligoadenylate synthetase domain (OAS). Genetic evolution analysis showed that the 2'-5' oligoadenylate synthetase 2 gene in domestic pigs is closely related to that of cattle. There are multiple antigenic sites, no signal peptide, and no transmembrane region in the gene, which is predicted to be a hydrophilic protein. Secondary structures were found to be mainly alpha helix-based; its tertiary structure is close to that of humans and cattle, but not that of mice. Tissue distribution results indicated that this protein is distributed in multiple organs, with high distribution in the liver; it is mainly localized in the cytoplasm. PRRSV infection, interferon-beta, and Poly(I: C) treatment all promoted 2'-5' oligoadenylate synthetase 2 gene expression. Overexpression and RNA silencing of porcine OAS2 inhibited and promoted PRRSV replication in cells, respectively. The inhibitory effect of porcine OAS2 was mainly dependent on RNase L, similar to what was predicted. This study has laid the foundation for future antiviral studies in pig, and provided a new way of preventing and treating PRRSV in the future., Competing Interests: Compliance with Ethical StandardsThe authors declare that they have no conflict of interest.

TWIST protein is critical to development and is activated in many cancers. TWIST regulates epithelial-mesenchymal transition, and is linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance. The majority of epithelial ovarian cancer (EOC) patients with metastatic disease respond well to first-line chemotherapy but most relapse with disease that is both metastatic and drug resistant, leading to a five-year survival rate under 20%. We are investigating the role of TWIST in mediating these relapses. We demonstrate TWIST-siRNA (siTWIST) and a novel nanoparticle delivery platform to reverse chemoresistance in an EOC model. Hyaluronic-acid conjugated mesoporous silica nanoparticles (MSN-HAs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro. Mice treated with siTWIST-MSN-HA and cisplatin exhibited specific tumor targeting and reduction of tumor burden. This platform has potential application for overcoming clinical challenges of tumor cell targeting, metastasis and chemoresistance in ovarian and other TWIST overexpressing cancers., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Phase change materials such as pseudobinary GeTe-Sb 2 Te 3 (GST) alloys are an essential part of existing and emerging technologies. Here, we investigate the electrical and optical properties of epitaxial phase change materials: α-GeTe, Ge 2 Sb 2 Te5 (GST225), and Sb 2 Te 3 . Temperature-dependent Hall measurements reveal a reduction of the hole concentration with increasing temperature in Sb 2 Te 3 that is attributed to lattice expansion, resulting in a non-linear increase of the resistivity that is also observed in GST225. Fourier transform infrared spectroscopy at room temperature demonstrates the presence of electronic states within the energy gap for α-GeTe and GST225. We conclude that these electronic states are due to vacancy clusters inside these two materials. The obtained results shed new light on the fundamental properties of phase change materials such as the high dielectric constant and persistent photoconductivity and have the potential to be included in device simulations.

In Mycobacterium tuberculosis-infected macrophages, cyclooxygenase-2 (COX-2) expression considerably increases to defend the body against mycobacteria by regulating adaptive immunity and restoring the mitochondrial inner membrane. Moreover, in cancer cells, COX-2 enhances the autophagy machinery, an important bactericidal mechanism. However, the association between M. tuberculosis-induced COX-2 and autophagy-mediated antimycobacterial response has not been explored. Here, COX-2 expression silencing reduced the autophagy and bactericidal activity against intracellular M. tuberculosis, while COX-2 overexpression reversed the above effects. In addition, enhancement of bactericidal activity was suppressed by inhibiting autophagy in COX-2-overexpressing cells, indicating that COX-2 accelerated mycobacterial elimination by promoting autophagy. Furthermore, the regulatory effects of COX-2 on autophagy were mediated by its catalytic products, which functioned through inhibiting the protein kinase B/mammalian target of rapamycin pathway. Thus, COX-2 contributes to host defense against mycobacterial infection by promoting autophagy, establishing the basis for development of novel therapeutic agents against tuberculosis by targeting COX-2.

Objective: To study the relationship between HLA allele frequencies in peripheral blood mononuclear cells (PBMCs) and the susceptibility to tuberculosis in southern Chinese population., Methods: The polymorphisms of HLA-A and HLA-DRB1 loci in the PBMCs were analyzed in 294 patients with active tuberculosis using polymerase chain reaction-sequence based typing (PCT-SBT). The allele frequencies in the patients were compared with the data from 644 control southern Chinese subjects obtained from the online database Allele Frequencies in Worldwide Population., Results: The frequencies of HLA-A * 0101 and HLA-DRB1 * 1454 alleles in the patient cohort with pulmonary tuberculosis were significantly higher than those in the control group (2.4% vs 0.6%, χ 2 =10.788, P =0.001, P c =0.016; 7.5% vs 0%, χ 2 =69.850, P < 0.0001); the frequencies of HLA-DRB1 * 1202 and HLA-DRB1 * 1401 alleles were significantly lower in this patient cohort than in the control group (10.4% vs 16.1%, χ 2 =9.845, P =0.002, P c =0.044; 0% vs 3.1%, χ 2 =18.520, P < 0.001)., Conclusions: The frequencies of HLA-A and HLA-DRB1 alleles are correlated with the susceptibility to active tuberculosis in this southern Chinese population. HLA-A * 0101, HLA-DRB1 * 1454 and the other 3 alleles are likely susceptible genes to tuberculosis, while HLA-DRB1 * 1202, HLA-DRB1 * 1401 and the other 4 alleles can be protective genes in this population.

Phase-change materials based on GeSbTe show unique switchable optoelectronic properties and are an important contender for next-generation non-volatile memories. Moreover, they recently received considerable scientific interest, because it is found that a vacancy ordering process is responsible for both an electronic metal-insulator transition and a structural cubic-to-trigonal transition. GeTe-Sb 2 Te 3 based superlattices, or specifically their interfaces, provide an interesting platform for the study of GeSbTe alloys. In this work such superlattices have been grown with molecular beam epitaxy and they have been characterized extensively with transmission electron microscopy and X-ray diffraction. It is shown that the van der Waals gaps in these superlattices, which result from vacancy ordering, are mobile and reconfigure through the film using bi-layer defects and Ge diffusion upon annealing. Moreover, it is shown that for an average composition that is close to GeSb 2 Te 4 a large portion of 9-layered van der Waals systems is formed, suggesting that still a substantial amount of random vacancies must be present within the trigonal GeSbTe layers. Overall these results illuminate the structural organization of van der Waals gaps commonly encountered in GeSbTe alloys, which are intimately related to their electronic properties and the metal-insulator transition.

Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders because of their powerful anti-inflammatory properties; however, their effects on macrophage-mediated immune responses are not completely understood. In the present study, we found that GCs decreased LPS-mediated TBK1 activation and the expression of IFN-β, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1 activity and cytokine expression were not affected by GCs treatment. Furthermore, GCs decreased the expression of key autophagy-related genes (ATGs), including ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS stimulation. However, GCs had no effect on poly(dA:dT)-mediated autophagy and ATG expression in macrophages. Collectively, this study demonstrates that GCs inhibit the TLR4-mediated innate immune response, but do not affect the cytosolic DNA sensing pathway. This provides new insights into the immunomodulatory mechanisms of GCs in macrophages, which may provide useful information for the clinical use of GCs in treating chronic inflammatory disorders., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy on account of its late stage at diagnosis and frequency of drug resistant recurrences. Novel therapies to overcome these barriers are urgently needed. TWIST is a developmental transcription factor reactivated in cancers and linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance, making it a promising therapeutic target. In this work, we demonstrate the efficacy of TWIST siRNA (siTWIST) and two nanoparticle delivery platforms to reverse chemoresistance in EOC models. Polyamidoamine dendrimers and mesoporous silica nanoparticles (MSNs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro. Mice treated with cisplatin plus MSN-siTWIST exhibited lower tumor burden than mice treated with cisplatin alone, with most of the effect coming from reduction in disseminated tumors. This platform has potential application for overcoming the clinical challenges of metastasis and chemoresistance in EOC and other TWIST overexpressing cancers., (Copyright © 2016 Elsevier Inc. All rights reserved.)