Damage on intestinal barrier function and microbial detoxification of deoxynivalenol:A review

Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.

Identification of two novel linear epitopes on the p30 protein of African swine fever virus

African swine fever(ASF) is a hemorrhagic disease caused by African swine fever virus(ASFV), which belongs to the Asfarviridae family. ASF has become prevalent in Africa since it was first reported in Kenya in 1921(Rowlands et al. 2008;Costard et al. 2009). In 1957, it was introduced to Portugal in Europe, after which ASFV rapidly spread to other European countries and has already been eradicated in several countries except Sardinia(Mur et al. 2016). In 2007, ASF was introduced to Georgia and has continued its spread to other countries in Europe(Smietanka et al. 2016;Kolbasov et al. 2018;Garigliany et al. 2019;Linden et al. 2019). In China, an ASF outbreak was first reported on August 3, 2018 in a pig farm in Shenyang, Liaoning Province(Zhou et al. 2018). Since then, the dramatic spread of ASF throughout China has caused huge economic losses to the swine industry(Jiang et al. 2021).

Toxoplasma gondii adhesion and apoptosis of chicken erythrocytes

Toxoplasma gondi is thought to infect all nucleated cells in warm-blooded animals,including poultry,mammals,and humans.However,it is unclear whether T.gondi can infect chicken erythrocytes due to the nucleated nature of these cells.Due to the special role of chicken erythrocytes in innate immunity,we investigated the cell-cell interaction between T.gondi and erythrocytes to elucidate the role of chicken erythrocytes in T.gondi infection.Cellular apoptosis was analyzed by transwell assay and flow cytometry.An immunofluorescence method was used to examine the reorganization of vimentin during T.gondi infection in both Vero cells and chicken erythrocytes.The reorganization of actin was evaluated to further examine the invasion capacity of tachyzoites on chicken erythrocytes during infection.We discovered that T.gondi can adhere to but not invade chicken erythrocytes and eventually cause apoptosis in chicken erythrocytes.When tachyzoites were cocultured with chicken erythrocytes in vitro,the transcrip-tional levels of T.gondi MIC3,ROP16,and ROP18 were significantly decreased.In addition,the rearrangement of host cell vimentin,a type Il cytoskeleton protein regulated by T.gondii infection,was not observed.Similarly,the parasite-induced ring-shaped actin structure was not formed in the host-parasite junction.T.gondi(RH strain)tachyzoites pref-erentially invaded Vero cells and replicated in chicken blood monocytes,but they were not found in chicken erythro-cytes.These findings showed that although T.gondi could attach to the surface of chicken erythrocytes,but couldn't invade successfully.Interestingly,we found that the T.gondii secretome,lysates,and intact tachyzoites could cause apoptosis of chicken erythrocytes,which suggested a complex mechanism involved in the apoptosis of chicken erythrocytes induced by T.gondi.This study elucidated that T.gondi could not infect nucleated chicken erythrocytes and enriched our understanding of the transmission mechanism of T.gondii among avian species.

Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii

The biology of Toxoplasma gondii,the causative pathogen of one of the most widespread parasitic diseases(toxoplasmosis),remains poorly understood.Lactate,which is derived from glucose metabolism,is not only an energy source in a variety of organisms,including T.gondii,but also a regulatory molecule that participates in gene activation and protein function.Lysine lactylation(Kla)is a type of post-translational modifications(PTMs)that has been recently associated with chromatin remodeling;however,Kla of histone and non-histone proteins has not yet been studied in T.gondii.To examine the prevalence and function of lactylation in T.gondii parasites,we mapped the lactylome of proliferating tachyzoite cells and identified 1964 Kla sites on 955 proteins in the T.gondii RH strain.Lactylated proteins were distributed in multiple subcellular compartments and were closely related to a wide variety of biological processes,including mRNA splicing,glycolysis,aminoacyl-tRNA biosynthesis,RNA transport,and many signaling pathways.We also performed a chromatin immunoprecipitation sequencing(ChIP-seq)analysis using a lactylationspecific antibody and found that the histones H4K12la and H3K14la were enriched in the promoter and exon regions of T.gondii associated with microtubule-based movement and cell invasion.We further confirmed the delactylase activity of histone deacetylases TgHDAC2–4,and found that treatment with anti-histone acetyltransferase(TgMYST-A)antibodies profoundly reduced protein lactylation in T.gondii.This study offers the first dataset of the global lactylation proteome and provides a basis for further dissecting the functional biology of T.gondii.

Dihydroartemisinin regulates the immune system by promotion of CD8^+T lymphocytes and suppression of B cell responses

Artemisia annua is an anti-fever herbal medicine first described in traditional Chinese medicine 1,000 years ago.Artemisinin,the extract of A.annua,and its derivatives(dihydroartemisinin(DHA),artemether,and artesunate)have been used for the treatment of malaria with substantial efficacy.Recently,DHA has also been tested for the treatment of lupus erythematosus,indicating that it may function to balance the immune response in immunocompromised individuals.In the present study,the regulatory effect of artemisinin on the murine immune system was systematically investigated in mice infected with two different protozoan parasites(Toxoplasma gondii and Plasmodium berghei).Our results revealed that the mouse spleen index significantly increased(spleen enlargement)in the healthy mice after DHA administration primarily due to the generation of an extra number of lymphocytes and CD8^+T lymphocytes in both the spleen and circulation.DHA could increase the proportion of T helper cells and CD8^+T cells,as well as decrease the number of splenic and circulatory B cells.Further,DHA could reduce the production of proinflammatory cytokines.Our study revealed that apart from their anti-parasitic activity,artemisinin and its derivatives can also actively modulate the immune system to directly benefit the host.

Distribution of the COVID-19 epidemic and correlation with population emigration from Wuhan,China

Background:The ongoing new coronavirus pneumonia(Corona Virus Disease 2019,COVID-19)outbreak is spreading in China,but it has not yet reached its peak.Five million people emigrated from Wuhan before lockdown,potentially representing a source of virus infection.Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks.Methods:The official case report on the COVID-19 epidemic was collected as of January 30,2020.Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software.Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi,and their correlation with the number of cases was analyzed.Results:The COVID-19 confirmed and death cases in Hubei province accounted for 59.91%(5806/9692)and 95.77%(204/213)of the total cases in China,respectively.Hot spot provinces included Sichuan and Yunnan,which are adjacent to Hubei.The time risk of Hubei province on the following day was 1.960 times that on the previous day.The number of cases in some cities was relatively low,but the time risk appeared to be continuously rising.The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943.The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases.Conclusions:The population that emigrated from Wuhan was the main infection source in other cities and provinces.Some cities with a low number of cases showed a rapid increase in case load.Owing to the upcoming Spring Festival return wave,understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.

TatD DNases of African trypanosomes confer resistance to host neutrophil extracellular traps

African trypanosomatid parasites escape host acquired immune responses through periodic antigenic variation of their surface coat.In this study,we describe a mechanism by which the parasites counteract innate immune responses.Two Tat D DNases were identified in each of Trypanosoma evansi and Trypanosoma brucei.These DNases are bivalent metal-dependent endonucleases localized in the cytoplasm and flagella of the parasites that can also be secreted by the parasites.These enzymes possess conserved functional domains and have efficient DNA hydrolysis activity.Host neutrophil extracellular traps(NETs)induced by the parasites could be hydrolyzed by native and recombinant Tat D DNases.NET disruption was prevented,and the survival rate of parasites was decreased,in the presence of the DNase inhibitor aurintricarboxylic acid.These data suggest that trypanosomes can counteract host innate immune responses by active secretion of Tat D DNases to degrade NETs.

From severe acute respiratory syndrome-associated coronavirus to 2019 novel coronavirus outbreak:similarities in the early epidemics and prediction of future trends

Emerging infectious diseases represent a serious threat for human public health worldwide.[1,2]The 2019 novel coronavirus(2019-nCoV)caused a pneumonia outbreak,which is spreading around the country and has affected 32 provinces and regions of China as of January 27,2020.[3,4]Countries outside China,including Japan,the United States,Thailand,and South Korea,have also reported cases imported from other countries.[5]With the joint efforts of Chinese scientists,health workers,and related departments,the pathogen causing this epidemic was quickly identified as a new type of coronavirus,10 days after the first official report.After confirming the pathogen,specific detection methods were rapidly developed,with improvement in etiological diagnosis.As of January 22,2020,it has been confirmed that the new coronavirus came from wild bats and belonged to group 2b of the beta coronavirus,which includes severe acute respiratory syndrome-associated coronavirus(SARS-CoV).[6]Although 2019-nCoV and SARS-CoV belong to the same sub-group of beta coronaviruses,the similarity at the genome level is only 80%,[7,8]meaning that the new virus is genetically different from SARS-CoV[Supplementary Figure 1A,http://links.lww.com/CM9/A209].Rapid discovery of the causative agent and development of diagnostic reagents demonstrated that technology has greatly improved in the 17 years since the SARS outbreak.However,no effective anti-viral medication or vaccines are available for this new virus,and many of its aspects remain to be explored.Similar to the SARS outbreak,this outbreak also occurred during the spring festival,the most important of the Chinese traditional festivals,when 3 billion people travel throughout the country.[9]This unexpectedly provides beneficial conditions for the transmission of this highly infectious disease and correspondingly poses great challenges for the prevention and control of the outbreak.

Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation

Artemisinin(ART)and dihydroartemisinin(DHA),apart from their profound anti-malaria effect,can also beneficially modulate the host immune system;however,the underlying molecular mechanisms remain unclear.Here,we report that DHA selectively induced T-cell activation,with an increased proportion of Ki67^(+)CD4^(+)T cells,CD25^(+)CD4^(+)T cells,interferon(IFN)-γ-producing CD8^(+)T cells,Brdu^(+)CD8^(+)T cells and neutrophils,which was found to enhance cellular immunity to experimental malaria and overcome immunosuppression in mice.We further revealed that DHA upregulated the expression of cell proliferation-associated proteins by promoting the phosphorylation of mitogen-activated protein kinase(MAPK),cyclin-dependent kinases(CDKs),and activator protein 1 in the spleen.This study is the first to provide robust evidence that DHA selectively induced the expansion of subsets of splenic T cells through phosphorylated CDKs and MAPK to enhance cellular immune responses under non-pathological or pathological conditions.The data significantly deepened our knowledge in the mechanism underlying DHA-mediated immunomodulation.

Mechanisms by which microbial enzymes degrade four mycotoxins and application in animal production:A review

Mycotoxins are toxic compounds that pose a serious threat to animal health and food safety.Therefore,there is an urgent need for safe and efficient methods of detoxifying mycotoxins.As biotechnology has continued to develop,methods involving biological enzymes have shown great promise.Biological enzymatic methods,which can fundamentally destroy the structures of mycotoxins and produce degradation products whose toxicity is greatly reduced,are generally more specific,efficient,and environmentally friendly.Mycotoxin-degrading enzymes can thus facilitate the safe and effective detoxification of mycotoxins which gives them a huge advantage over other methods.This article summarizes the newly discovered degrading enzymes that can degrade four common mycotoxins(aflatoxins,zearalenone,deoxynivalenol,and ochratoxin A)in the past five years,and reveals the degradation mechanism of degrading enzymes on four mycotoxins,as well as their positive effects on animal production.This review will provide a theoretical basis for the safe treatment of mycotoxins by using biological enzyme technology.

Dihydroartemisinin beneficially regulates splenic immune cell heterogeneity through the SOD3-JNK-AP-1 axis

The immunomodulatory potential of dihydroartemisinin(DHA) has recently been highlighted;however, the potential mechanism remains to be clarified. Single-cell RNA sequencing was explored in combination with cellular and biochemical approaches to elucidate the immunomodulatory mechanisms of DHA. In this study, we found that DHA induced both spleen enlargement and rearrangement of splenic immune cell subsets in mice. It was revealed that DHA promoted the reversible expansion of effective regulatory T cells and interferon-γ^(+)cytotoxic CD8^(+)T cells in the spleen via induction of superoxide dismutase 3(SOD3) expression and increased phosphorylation of c-Jun N-terminal kinases(JNK) and its downstream activator protein 1(AP-1) transcription factors. Further, SOD3 knockout mice were resistant to the regulatory effect of DHA. Thus, DHA,through the activation of the SOD3-JNK-AP-1 axis, beneficially regulated immune cell heterogeneity and splenic immune cell homeostasis to treat autoimmune diseases.