Zinc-finger CCHC-type containing protein 8 promotes RNA virus replication by suppressing the type-I interferon responses.

Host cells have evolved an intricate regulatory network to fine tune the type-I interferon responses. However, the full picture of this regulatory network remains to be depicted. In this study, we found that knock out of zinc-finger CCHC-type containing protein 8 (ZCCHC8) impairs the replication of influenza A virus (IAV), Sendai virus (Sev), Japanese encephalitis virus (JEV), and vesicular stomatitis virus (VSV). Further investigation unveiled that ZCCHC8 suppresses the type-I interferon responses by targeting the interferon regulatory factor 3 (IRF3) signaling pathway. Mechanistically, ZCCHC8 associates with phosphorylated IRF3 and disrupts the interaction of IRF3 with the co-activator CREB-binding protein (CBP). Additionally, the direct binding of ZCCHC8 with the IFN-stimulated response element (ISRE) impairs the ISRE-binding of IRF3. Our study contributes to the comprehensive understanding for the negative regulatory network of the type-I interferon responses and provides valuable insights for the control of multiple viruses from a host-centric perspective.IMPORTANCEThe innate immune responses serve as the initial line of defense against invading pathogens and harmful substances. Negative regulation of the innate immune responses plays an essential role in avoiding auto-immune diseases and over-activated immune responses. Hence, the comprehensive understanding of the negative regulation network for innate immune responses could provide novel therapeutic insights for the control of viral infections and immune dysfunction. In this study, we report that ZCCHC8 negatively regulates the type-I interferon responses. We illustrate that ZCCHC8 impedes the IRF3-CBP association by interacting with phosphorylated IRF3 and competes with IRF3 for binding to ISRE. Our study demonstrates the role of ZCCHC8 in the replication of multiple RNA viruses and contributes to a deeper understanding of the negative regulation system for the type-I interferon responses.

Inhibition of RAN attenuates influenza a virus replication and nucleoprotein nuclear export.

Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti-IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participate in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified that bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral target.

The recombinant vaccine of Lactobacillus plantarum elicits immune protection against H1N1 and H9N2 influenza virus infection.

Influenza A virus (IAV) causes annual epidemics and occasional pandemics, resulting in significant economic losses and numerous fatalities. Current vaccines, typically administered through injection, provide limited protection due to the frequent antigenic shift and drift of IAV strains. Therefore, the development of alternative broad-spectrum vaccine strategies is imperative. Lactic acid bacteria (LAB) represent promising candidates for vaccine engineering due to their low cost, high safety profile, and suitability for oral administration. In this study, we identified a strain of Lactobacillus plantarum (Lp) that is resistant to acid and bile salts and capable of colonizing the intestines of mice. Subsequently, we employed the RecE/T gene editing system to integrate headless hemagglutinins (mini-HA) into the genome of Lp, generating Lp-mini-HA-SP. Remarkably, immunization with Lp-mini-HA-SP elicited serum IgG antibody responses and conferred immune protection against H9N2 and H1N1 influenza virus challenges. Collectively, our findings offer a novel approach for the development of orally administered IAV vaccines and hold significant potential for future drug development endeavors.

Seroprevalence of the novel swine acute diarrhea syndrome coronavirus in China assessed by enzyme-linked immunosorbent assay.

The endemic outbreak of SADS-CoV has resulted in economic losses and potentially threatened the safety of China's pig industry. The molecular epidemiology of SADS-CoV in pig herds has been investigated in many provinces in China. However, there are no data over a long-time span, and there is a lack of extensive serological surveys to assess the prevalence of SADS-CoV in Chinese swine herds since the discovery of SADS-CoV. In this study, an indirect anti-SADS-CoV IgG enzyme-linked immunosorbent assay (ELISA) based on the SADS-CoV S1 protein was established to investigate the seroprevalence of SADS-CoV in Chinese swine herds. Cross-reactivity assays, indirect immunofluorescence, and western blotting assays showed that the developed ELISA had excellent SADS-CoV specificity. In total, 12,978 pig serum samples from 29 provinces/municipalities/autonomous regions in China were tested from 2022 to 2023. The results showed that the general seroprevalence of SADS-CoV in China was 59.97%, with seroprevalence ranging from 16.7% to 77.12% in different provinces and from 42.61% to 68.45% in different months. SADS-CoV is widely prevalent in China, and its seroprevalence was higher in Northeast China, North China, and Central China than in other regions. Among the four seasons, the prevalence of SADS-CoV was the highest in spring and the lowest in autumn. The results of this study provide the general seroprevalence profile of SADS-CoV in China, facilitating the understanding of the prevalence of SADS-CoV in pigs. More importantly, this study is beneficial in formulating preventive and control measures for SADS-CoV and may provide directions for vaccine development.

Saccharomyces cerevisiae oral immunization in mice using multi-antigen of the African swine fever virus elicits a robust immune response.

African swine fever virus (ASFV) is one of the most complex viruses. ASFV is a serious threat to the global swine industry because no commercial vaccines against this virus are currently available except in Vietnam. Moreover, ASFV is highly stable in the environment and can survive in water, feed, and aerosols for a long time. ASFV is transmitted through the digestive and respiratory tract. Mucosal immunity is the first line of defense against ASFV. Saccharomyces cerevisiae (SC), which has been certified by the U.S. Food and Drug Administration and has a generally recognized as safe status in the food industry, was used for oral immunization in this study. ASFV antigens were effectively expressed in recombinant SC strains with high DNA copy numbers and stable growth though surface display technology and chromosome engineering (δ-integration). The recombinant SC strains containing eight ASFV antigens-KP177R, E183L, E199L, CP204L, E248R, EP402R, B602L, and B646L- induced strong humoral and mucosal immune responses in mice. There was no antigenic competition, and these antigens induced Th1 and Th2 cellular immune responses. Therefore, the oral immunization strategy using recombinant SC strains containing multiple ASFV antigens demonstrate potential for future testing in swine, including challenge studies to evaluate its efficacy as a vaccine against ASFV.

How public environmental appeals affect the collaborative governance in pollution and carbon reduction: Evidence from spatial effects across Chinese cities.

China has always adhered to the strategy of sustainable development. It is prevalent the public want a good living environment, which requires local governments and businesses to enhance their environmental governance capabilities. Using the panel data from Chinese cities from 2012 to 2019 and econometrics models, we examine the impact mechanisms of public environmental appeals (PEA) on efficiency of collaborative governance in pollution reduction and carbon mitigation (GPC). Results indicate that there is a positive spatial clustering of GPC across cities, with high-high clustering is notably concentrated in the southern regions of China and low-low clustering is prevalent in the northern regions. Spatial econometrics model results reveal that the stronger PEA, the higher GPC. The result of mechanism analysis shows the mediation of environmentally friendly technological innovation is crucial. Subsequent inquiry uncovers that the digital economy positively moderates the impact of PEA on GPC. The Belt and Road policy region exhibits heightened sensitivity to PEA, thereby enhancing the positive impact of PEA on GPC.

Whole-genome resequencing of Chinese indigenous sheep provides insight into the genetic basis underlying climate adaptation.

BACKGROUND: Chinese indigenous sheep are valuable resources with unique features and characteristics. They are distributed across regions with different climates in mainland China; however, few reports have analyzed the environmental adaptability of sheep based on their genome. We examined the variants and signatures of selection involved in adaptation to extreme humidity, altitude, and temperature conditions in 173 sheep genomes from 41 phenotypically and geographically representative Chinese indigenous sheep breeds to characterize the genetic basis underlying environmental adaptation in these populations. RESULTS: Based on the analysis of population structure, we inferred that Chinese indigenous sheep are divided into four groups: Kazakh (KAZ), Mongolian (MON), Tibetan (TIB), and Yunnan (YUN). We also detected a set of candidate genes that are relevant to adaptation to extreme environmental conditions, such as drought-prone regions (TBXT, TG, and HOXA1), high-altitude regions (DYSF, EPAS1, JAZF1, PDGFD, and NF1) and warm-temperature regions (TSHR, ABCD4, and TEX11). Among all these candidate genes, eight ABCD4, CNTN4, DOCK10, LOC105608545, LOC121816479, SEM3A, SVIL, and TSHR overlap between extreme environmental conditions. The TSHR gene shows a strong signature for positive selection in the warm-temperature group and harbors a single nucleotide polymorphism (SNP) missense mutation located between positions 90,600,001 and 90,650,001 on chromosome 7, which leads to a change in the protein structure of TSHR and influences its stability. CONCLUSIONS: Analysis of the signatures of selection uncovered genes that are likely related to environmental adaptation and a SNP missense mutation in the TSHR gene that affects the protein structure and stability. It also provides information on the evolution of the phylogeographic structure of Chinese indigenous sheep populations. These results provide important genetic resources for future breeding studies and new perspectives on how animals can adapt to climate change.

Application of Recombinant Lactic Acid Bacteria (LAB) Live Vector Oral Vaccine in the Prevention of F4+ Enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in piglets. The current primary approach for ETEC prevention and control relies on antibiotics, as few effective vaccines are available. Consequently, an urgent clinical demand exists for developing an effective vaccine to combat this disease. Here, we utilized food-grade Lactococcus lactis NZ3900 and expression plasmid pNZ8149 as live vectors, together with the secreted expression peptide Usp45 and the cell wall non-covalent linking motif LysM, to effectively present the mutant LTA subunit, the LTB subunit of heat-labile enterotoxin, and the FaeG of F4 pilus on the surface of recombinant lactic acid bacteria (LAB). Combining three recombinant LAB as a live vector oral vaccine, we assessed its efficacy in preventing F4+ ETEC infection. The results demonstrate that oral immunization conferred effective protection against F4+ ETEC infection in mice and piglets lacking maternal antibodies during weaning. Sow immunization during late pregnancy generated significantly elevated antibodies in colostrum, which protected piglets against F4+ ETEC infection during lactation. Moreover, booster immunization on piglets during lactation significantly enhanced their resistance to F4+ ETEC infection during the weaning stage. This study highlights the efficacy of an oral LAB vaccine in preventing F4+ ETEC infection in piglets by combining the sow immunization and booster immunization of piglets, providing a promising vaccination strategy for future prevention and control of ETEC-induced diarrhea in piglets.

Whole-Genome Scanning for Selection Signatures Reveals Candidate Genes Associated with Growth and Tail Length in Sheep.

Compared to Chinese indigenous sheep, Western sheep have rapid growth rate, larger physique, and higher meat yield. These excellent Western sheep were introduced into China for crossbreeding to expedite the enhancement of production performance and mutton quality in local breeds. Here, we investigated population genetic structure and genome-wide selection signatures among the Chinese indigenous sheep and the introduced sheep based on whole-genome resequencing data. The PCA, N-J tree and ADMIXTURE results showed significant genetic difference between Chinese indigenous sheep and introduced sheep. The nucleotide diversity (π) and linkage disequilibrium (LD) decay results indicated that the genomic diversity of introduced breeds were lower. Then, Fst & π ratio, XP-EHH, and de-correlated composite of multiple signals (DCMS) methods were used to detect the selection signals. The results showed that we identified important candidate genes related to growth rate and body size in the introduced breeds. Selected genes with stronger selection signatures are associated with growth rate (CRADD), embryonic development (BVES, LIN28B, and WNT11), body size (HMGA2, MSRB3, and PTCH1), muscle development and fat metabolism (MSTN, PDE3A, LGALS12, GGPS1, and SAR1B), wool color (ASIP), and hair development (KRT71, KRT74, and IRF2BP2). Thus, these genes have the potential to serve as candidate genes for enhancing the growth traits of Chinese indigenous sheep. We also identified tail-length trait-related candidate genes (HOXB13, LIN28A, PAX3, and VEGFA) in Chinese long-tailed breeds. Among these genes, HOXB13 is the main candidate gene for sheep tail length phenotype. LIN28A, PAX3, and VEGFA are related to embryonic development and angiogenesis, so these genes may be candidate genes for sheep tail type traits. This study will serve as a foundation for further genetic improvement of Chinese indigenous sheep and as a reference for studies related to growth and development of sheep.

Analysis of the efficacy of blunt separation combined with uncrosslinked sodium hyaluronate composite solution for the treatment of tear trough deformity in Asians.

BACKGROUND: Filling therapy is becoming increasingly popular for correcting tear trough deformities (TTD). However, its therapeutic effect and retention time are limited. AIMS: To improve the clinical efficacy and safety of TTD treatment in Asians, we used a blunt separation technique to break the adhesion site of periorbital subcutaneous tissue, and while repairing skin dermis after injury, it was combined with uncrosslinked hyaluronic acid compound solution to promote collagen regeneration and treat TTDs. PATIENTS/METHODS: Twenty-six Chinese patients (21 women and 5 men) with TTD, with a mean age of 34.54 ± 9.21 (range, 20-56) years, were enrolled. Symptom improvement, recurrence rates, treatment safety, and patient satisfaction were evaluated. RESULTS: All patients' tear trough rating scale (TTRS) scores decreased significantly immediately after treatment. The TTRS scores at 1, 3, and 6 months, and 1 year after treatment demonstrated significant differences from those before treatment (all p < 0.05). All patients' experienced mild pain, erythema, and swelling during the treatment. Three patients developed postinjection bruising after treatment, which lasted for 6-7 days and subsequently disappeared. No other adverse reactions were observed during the follow-up. There were no recurrent cases, and patient satisfaction was very high. CONCLUSIONS: Blunt separation combined with an uncrosslinked sodium hyaluronate composite solution is safe and effective for treating TTDs in Asians with few side effects and has good clinical application prospects.

2023 International African Swine Fever Workshop: Critical Issues That Need to Be Addressed for ASF Control.

The 2023 International African Swine Fever Workshop (IASFW) took place in Beijing, China, on 18-20 September 2023. It was jointly organized by the U.S.-China Center for Animal Health (USCCAH) at Kansas State University (KSU) and the Chinese Veterinary Drug Association (CVDA) and sponsored by the United States Department of Agriculture Foreign Agricultural Service (USDA-FAS), Harbin Veterinary Research Institute, and Zoetis Inc. The objective of this workshop was to provide a platform for ASF researchers around the world to unite and share their knowledge and expertise on ASF control and prevention. A total of 24 outstanding ASF research scientists and experts from 10 countries attended this meeting. The workshop included presentations on current ASF research, opportunities for scientific collaboration, and discussions of lessons and experiences learned from China/Asia, Africa, and Europe. This article summarizes the meeting highlights and presents some critical issues that need to be addressed for ASF control and prevention in the future.