The Mycobacterium tuberculosis prolyl dipeptidyl peptidase cleaves the N-terminal peptide of the immunoprotein CXCL-10.

Dipeptidyl peptidases constitute a class of non-classical serine proteases that regulate an array of biological functions, making them pharmacologically attractive enzymes. With this work, we identified and characterized a dipeptidyl peptidase from Mycobacterium tuberculosis (MtDPP) displaying a strong preference for proline residues at the P1 substrate position and an unexpectedly high thermal stability. MtDPP was also characterized with alanine replacements of residues of its active site that yielded, for the most part, loss of catalysis. We show that MtDPP catalytic activity is inhibited by well-known human DPP4 inhibitors. Using MALDI-TOF mass spectrometry we also describe that in vitro, MtDPP mediates the truncation of the C-X-C motif chemokine ligand 10, indicating a plausible role in immune modulation for this mycobacterial enzyme.

Prevalence and factors associated with post-traumatic stress disorder in healthcare workers exposed to COVID-19 in Wuhan, China: a cross-sectional survey.

BACKGROUND: The COVID-19 pandemic has posed significant threats to both the physical and psychological health of healthcare workers working in the front-line combating COVID-19. However, studies regarding the medium to long term impact of COVID-19 on mental health among healthcare workers are limited. Therefore, we conducted this cross-sectional survey to investigate the prevalence, factors and impact of post-traumatic stress disorder (PTSD) in healthcare workers exposed to COVID-19 8 months after the end of the outbreak in Wuhan, China. METHODS: A web-based questionnaire was delivered as a link via the communication application WeChat to those healthcare workers who worked at several COVID-19 units during the outbreak (from December 2019 to April 2020) in Wuhan, China. The questionnaire included questions on social-demographic data, the post-traumatic stress disorder checklist-5 (PCL-5), the family care index questionnaire (Adaptation, Partnership, Growth, Affection and Resolve, APGAR), and the quality-of-life scale (QOL). The prevalence, risk and protective factors, and impact of PTSD on healthcare workers were subsequently analyzed. RESULTS: Among the 659 participants, 90 healthcare workers were still suffering from PTSD 8 months after the end of the outbreak of COVID-19 in Wuhan, in which avoidance and negative impact were the most affected dimensions. Suffering from chronic disease, experiencing social isolation, and job dissatisfaction came up as independent risk factors for PTSD, while obtaining COVID-19 related information at an appropriate frequency, good family function, and working in well-prepared mobile cabin hospitals served as protective factors. The impact of PTSD on COVID-19 exposed healthcare workers was apparent by shortened sleeping time, feeling of loneliness, poorer quality of life and intention to resign. CONCLUSIONS: Eight months after the end of the COVID-19 outbreak in Wuhan, the level of PTSD in healthcare workers exposed to COVID-19 was still high. Apart from the commonly recognized risk factors, comorbid chronic disease was identified as a new independent risk factor for developing PTSD. For countries where the pandemic is still ongoing or in case of future outbreaks of new communicable diseases, this study may contribute to preventing cases of PTSD in healthcare workers exposed to infectious diseases under such circumstances.

Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19).

OBJECTIVES: To assess the efficacy of corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19). DESIGN, SETTING: Observational study in the two COVID-19-designated hospitals in Wuhu, Anhui province, China, 24 January - 24 February 2020. PARTICIPANTS: Thirty-one patients infected with the severe acute respiratory coronavirus 2 (SARS-CoV-2) treated at the two designated hospitals. MAIN OUTCOME MEASURES: Virus clearance time, length of hospital stay, and duration of symptoms, by treatment type (including or not including corticosteroid therapy). RESULTS: Eleven of 31 patients with COVID-19 received corticosteroid treatment. Cox proportional hazards regression analysis indicated no association between corticosteroid treatment and virus clearance time (hazard ratio [HR], 1.26; 95% CI, 0.58-2.74), hospital length of stay (HR, 0.77; 95% CI, 0.33-1.78), or duration of symptoms (HR, 0.86; 95% CI, 0.40-1.83). Univariate analysis indicated that virus clearance was slower in two patients with chronic hepatitis B infections (mean difference, 10.6 days; 95% CI, 6.2-15.1 days). CONCLUSIONS: Corticosteroids are widely used when treating patients with COVID-19, but we found no association between therapy and outcomes in patients without acute respiratory distress syndrome. An existing HBV infection may delay SARS-CoV-2 clearance, and this association should be further investigated.

Advances in freshwater risk assessment: improved accuracy of dissolved organic matter-metal speciation prediction and rapid biological validation.

Speciation modeling of bioavailability has increasingly been used for environmental risk assessment (ERA). Heavy metal pollution is the most prevalent environmental pollution issue globally, and metal bioavailability is strongly affected by its chemical speciation. Dissolved organic matter (DOM) in freshwater will bind heavy metals thereby reducing bioavailability. While speciation modeling has been shown to be quite effective and is validated for use in ERA, there is an increasing body of literature reporting problems with the accuracy of metal-DOM binding in speciation models. In this study, we address this issue for a regional-scale field area (Lake Tai, with 2,400 km2 surface area and a watershed of 36,000 km2) where speciation models in common use are not highly accurate, and we tested alternative approaches to predict metal-DOM speciation/bioavailability for lead (Pb) in this first trial work. We tested five site-specific approaches to quantify Pb-DOM binding that involve varying assumptions about conditional stability constants, binding capacities, and different components in DOM, and we compare these to what we call a one-size-fits-all approach that is commonly in use. We compare model results to results for bioavailable Pb measured using a whole-cell bioreporter, which has been validated against speciation models and is extremely rapid compared to many biological methods. The results show that all of the site-specific approaches we use provide more accurate estimates of bioavailability than the default model tested, however, the variation of the conditional stability constant on a site-specific basis is the most important consideration. By quantitative metrics, up to an order of magnitude improvement in model accuracy results from modeling active DOM as a single organic ligand type with site-specific variations in Pb-DOM conditional stability constants. Because the biological method is rapid and parameters for site-specific tailoring of the model may be obtained via high-throughput analysis, the approach that we report here in this first regional-scale freshwater demonstration shows excellent potential for practical use in streamlined ERA.

The NS1 gene from bat-derived influenza-like virus H17N10 can be rescued in influenza A PR8 backbone.

Influenza A viruses have the potential to cause pandemics due to the introduction of novel subtypes against which human hosts have little or no preexisting immunity. Such viruses may result from reassortment between human and animal influenza viruses. Recently, new influenza-like viruses were identified in bats, raising the concern for a new reservoir of potentially harmful influenza viruses that could form reassortants with categorized human influenza A viruses. However, until now, it has not been possible to generate a recombinant reassortant virus containing a single functional gene or domain from H17N10 that could propagate. Here, we demonstrate that a recombinant A/Puerto Rico/8/1934 (H1N1) virus with NS1 gene from H17N10 influenza-like virus can be successfully rescued. We used luciferase reporter assays and quantitative reverse transcriptase PCR to show that the NS1 protein from H17N10 inhibited Sendai-virus (SeV)-induced activation of IFN-ß expression with an efficiency similar to NS1 from an H5N1 strain. Moreover, the crystal structure of the NS1 (H17N10) RNA-binding domain is also similar to that of other NS1s. These results demonstrate that H17N10 influenza-like virus indeed contains functional genes that are compatible with categorized influenza A viruses. Although the chance of this particular event occurring in nature seems negligible, further research is needed to address the possibility of the natural formation of reassortants.

Nα-terminal acetylation for T cell recognition: molecular basis of MHC class I-restricted nα-acetylpeptide presentation.

As one of the most common posttranslational modifications (PTMs) of eukaryotic proteins, N(α)-terminal acetylation (Nt-acetylation) generates a class of N(α)-acetylpeptides that are known to be presented by MHC class I at the cell surface. Although such PTM plays a pivotal role in adjusting proteolysis, the molecular basis for the presentation and T cell recognition of N(α)-acetylpeptides remains largely unknown. In this study, we determined a high-resolution crystallographic structure of HLA (HLA)-B*3901 complexed with an N(α)-acetylpeptide derived from natural cellular processing, also in comparison with the unmodified-peptide complex. Unlike the α-amino-free P1 residues of unmodified peptide, of which the α-amino group inserts into pocket A of the Ag-binding groove, the N(α)-linked acetyl of the acetylated P1-Ser protrudes out of the groove for T cell recognition. Moreover, the Nt-acetylation not only alters the conformation of the peptide but also switches the residues in the α1-helix of HLA-B*3901, which may impact the T cell engagement. The thermostability measurements of complexes between N(α)-acetylpeptides and a series of MHC class I molecules derived from different species reveal reduced stability. Our findings provide the insight into the mode of N(α)-acetylpeptide-specific presentation by classical MHC class I molecules and shed light on the potential of acetylepitope-based immune intervene and vaccine development.

The N-terminal domain of PA from bat-derived influenza-like virus H17N10 has endonuclease activity.

Influenza imposes a great burden on society, not only in its seasonal appearance that affects both humans and domesticated animals but also through the constant threat of potential pandemics. Migratory birds are considered to be the reservoir hosts for influenza viruses, but other animals must also be considered. The recently identified influenza-like virus genome, from H17N10 in bats, was shown to be markedly different from genomes of other known influenza viruses, as both its surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) do not have canonical functions. However, no studies on other individual proteins from this particular virus have been reported until now. Here, we describe the structure of the N-terminal domain of PA from H17N10 influenza-like virus at 2.7-Å resolution and show that it has a fold similar to those of homologous PA domains present in more familiar influenza A virus strains. Moreover, we demonstrate that it possesses endonuclease activity and that the histidine residue in the active site is essential for this activity. Although this particular influenza virus subtype is probably not infectious for humans (even its virus state has not been confirmed in bats, as only the genome has been sequenced), reassortment of canonical influenza viruses with certain segments from H17N10 cannot be ruled out at this stage. Therefore, further studies are urgently needed for the sake of influenza prevention and control.

Identification and functional analysis of two Golgi-localized UDP-galactofuranose transporters with overlapping functions in Aspergillus niger.

BACKGROUND: Galactofuranose (Galf)-containing glycoconjugates are present in numerous microbes, including filamentous fungi where they are important for morphology, virulence and maintaining cell wall integrity. The incorporation of Galf-residues into galactomannan, galactomannoproteins and glycolipids is carried out by Golgi-localized Galf transferases. The nucleotide sugar donor used by these transferases (UDP-Galf) is produced in the cytoplasm and has to be transported to the lumen of the Golgi by a dedicated nucleotide sugar transporter. METHODS: Based on homology with recently identified UDP-Galf-transporters in A. fumigatus and A. nidulans, two putative UDP-Galf-transporters in A. niger were found. Their function and localization was determined by gene deletions and GFP-tagging studies, respectively. RESULTS: The two putative UDP-Galf-transporters in A. niger are homologous to each other and are predicted to contain eleven transmembrane domains (UgtA) or ten transmembrane domains (UgtB) due to a reduced length of the C-terminal part of the UgtB protein. The presence of two putative UDP-Galf-transporters in the genome was not unique for A. niger. From the twenty Aspergillus species analysed, nine species contained two additional putative UDP-Galf-transporters. Three of the nine species were outside the Aspergillus section nigri, indication an early duplication of UDP-Galf-transporters and subsequent loss of the UgtB copy in several aspergilli. Deletion analysis of the single and double mutants in A. niger indicated that the two putative UDP-Galf-transporters (named UgtA and UgtB) have a redundant function in UDP-Galf-transport as only the double mutant displayed a Galf-negative phenotype. The Galf-negative phenotype of the double mutant could be complemented by expressing either CFP-UgtA or CFP-UgtB fusion proteins from their endogenous promoters, indicating that both CFP-tagged proteins are functional. Both Ugt proteins co-localize with each other as well as with the GDP-mannose nucleotide transporter, as was demonstrated by fluorescence microscopy, thereby confirming their predicted localization in the Golgi. CONCLUSION: A. niger contains two genes encoding UDP-Galf-transporters. Deletion and localization studies indicate that UgtA and UgtB have redundant functions in the biosynthesis of Galf-containing glycoconjugates.

Human T cell activation results in extracellular signal-regulated kinase (ERK)-calcineurin-dependent exposure of Tn antigen on the cell surface and binding of the macrophage galactose-type lectin (MGL).

The C-type lectin macrophage galactose-type lectin (MGL) exerts an immunosuppressive role reflected by its interaction with terminal GalNAc moieties, such as the Tn antigen, on CD45 of effector T cells, thereby down-regulating T cell receptor signaling, cytokine responses, and induction of T cell death. Here, we provide evidence for the pathways that control the specific expression of GalNAc moieties on human CD4(+) T cells. GalNAc epitopes were readily detectable on the cell surface after T cell activation and required de novo protein synthesis. Expression of GalNAc-containing MGL ligands was completely dependent on PKC and did not involve NF-κB. Instead, activation of the downstream ERK MAPK pathway led to decreased mRNA levels and activity of the core 1 ß3GalT enzyme and its chaperone Cosmc, favoring the expression of Tn antigen. In conclusion, expression of GalNAc moieties mirrors the T cell activation status, and thus only highly stimulated T cells are prone to the suppressive action of MGL.

We need to plan streamlined environmental impact assessment for the future X-Press Pearl disasters.

The X-Press Pearl disaster illustrates the urgent needs for streamlined environmental impact assessment to inform decision making. The environmental contamination caused by the disaster is complex, and the biological impact of different environmental stressors, and at different biological scales, needs to be determined. Traditional methods for analyzing complex environmental stressors are often inefficient and do not reflect the biological impact of pollution. The combination of chemical stressors and biological impacts is the key to environmental impact assessment based on integrated monitoring. Whole-cell bioreporters are tools for rapid, efficient and quantitative detection of the bioavailability, stressor effects, and toxicity of pollutants, i.e., spanning a wide range of applications. Here we propose the view that using whole-cell bioreporter technology to streamline short-term environmental impact assessment for maritime disasters such as the X-Press Pearl is more fit-for-purpose/practical than other approaches in use.

Toxins from harmful algal blooms: How copper and iron render chalkophore a predictor of microcystin production.

Research on harmful algal blooms has focused on macronutrients, yet recent research increasingly indicates that understanding micronutrient roles is also important in the development of effective environmental management interventions. Here, we report results on metallophore production from mesocosms amended with copper and iron (enzymatic co-factors in photosynthetic electron transport) to probe questions of how cyanobacteria navigate the divide between copper nutrition, copper toxicity, and issues with iron bioavailability. These experiments utilized Microcystis, Chlorella and Desmodesmus spp., in mono- and mixed-cultures in lake water from a large, hypereutrophic lake (Taihu, China). To initiate experiments, copper and iron amendments were added to mesocosms containing algae that had been acclimated to achieve a state of copper and iron limitation. Mesocosms were analyzed over time for a range of analytes including algal growth parameters, algal assemblage progression, copper/iron concentrations and biomolecule production of chalkophore, siderophore and total microcystins. Community Trajectory Analysis and other multivariate methods were used for analysis resulting in our findings: 1) Microcystis spp. manage copper/iron requirements though a dynamically phased behavior of chalkophore/siderophore production according to their copper and iron limitation status (chalkophore correlates with Cu concentration, R2 = 0.99, and siderophore correlates with the sum of Cu and Fe concentrations, R2 = 0.98). 2) A strong correlation was observed between the production of chalkophore and the cyanobacterial toxin microcystin (R2 = 0.76)-Chalkophore is a predictor of microcystin production. 3) Based on our results and literature, we posit that Microcystis spp. produces microcystin in response to copper/iron availability to manage photosystem productivity and effect an energy-saving status. Results from this work underscore the importance of micronutrients in influencing harmful algal bloom progression and represents a major advance in understanding the ecological function for the cyanobacterial toxin microcystin as a hallmark of micronutrient limitation stress.

Intravenous Polymyxin B as Adjunctive Therapy to High-Dose Tigecycline for the Treatment of Nosocomial Pneumonia Due to Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae: A Propensity Score-Matched Cohort Study.

Although the combination of polymyxin and tigecycline is widely used in treating carbapenem-resistant bacterial infections, the benefit of this combination is still uncertain. To assess whether adding polymyxin B to the high-dose tigecycline regimen would result in better clinical outcomes than the high-dose tigecycline therapy in patients with pneumonia caused by carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, we conducted a propensity score-matched cohort study in a single center between July 2019 and December 2021. Of the 162 eligible patients, 102 were included in the 1:1 matched cohort. The overall 14-day mortality in the matched cohort was 24.5%. Compared with high-dose tigecycline, the combination therapy was not associated with better clinical outcomes, and showed similar 14-day mortality (OR, 0.72, 95% CI 0.27-1.83, p = 0.486), clinical cure (OR, 1.09, 95% CI 0.48-2.54, p = 0.823), microbiological cure (OR, 0.96, 95% CI 0.39-2.53, p = 0.928) and rate of nephrotoxicity (OR 0.85, 95% CI 0.36-1.99, p = 0.712). Subgroup analyses also did not demonstrate any statistical differences. Based on these results, it is reasonable to recommend against adding polymyxin B to the high-dose tigecycline regimen in treating pneumonia caused by carbapenem-resistant K. pneumoniae and A. baumannii.

Galactofuranose in eukaryotes: aspects of biosynthesis and functional impact.

Galactofuranose (Galf) is the five-membered ring form of galactose. It is widely distributed among several branches of the eukaryotic kingdom. This review highlights recent advances in our understanding of the biosynthesis and function of Galf-containing glycoconjugates in fungal Aspergillus spp. and the protozoan trypanosomatid parasites. We give an overview of the biosynthetic pathways leading to the production of glycolipids, glycoproteins and polysaccharides containing Galf in these species and their biological relevance. Remarkably, modification of the cell surface caused by Galf absence often results in morphological abnormalities and an impaired cell wall function in these organisms. Galf-deficient mutants are generally hypersensitive to drugs, exhibit a constitutive osmotic stress phenotype and/or have an attenuated virulence. Since Galf has never been found in mammals and higher plants, Galf-biosynthetic pathways have raised much interest as targets for drug development to combat microbial infections.

Fungal α-arabinofuranosidases of glycosyl hydrolase families 51 and 54 show a dual arabinofuranosyl- and galactofuranosyl-hydrolyzing activity.

Aspergillus niger possesses a galactofuranosidase activity, however, the corresponding enzyme or gene encoding this enzyme has never been identified. As evidence is mounting that enzymes exist with affinity for both arabinofuranose and galactofuranose, we investigated the possibility that α-L-arabinofuranosidases, encoded by the abfA and abfB genes, are responsible for the galactofuranosidase activity of A. niger. Characterization of the recombinant AbfA and AbfB proteins revealed that both enzymes do not only hydrolyze p-nitrophenyl-α-L-arabinofuranoside (pNp-α-Araf) but are also capable of hydrolyzing p-nitrophenyl-ß-D-galactofuranoside (pNp-ß-Galf). Molecular modeling of the AbfB protein with pNp-ß-Galf confirmed the possibility for AbfB to interact with this substrate, similarly as with pNp-α-Araf. We also show that galactomannan, a cell wall compound of A. niger, containing ß-linked terminal and internal galactofuranosyl moieties, can be degraded by an enzyme activity that is present in the supernatant of inulin-grown A. niger. Interestingly, purified AbfA and AbfB did not show this hydrolyzing activity toward A. nigergalactomannan. In summary, our studies demonstrate that AbfA and AbfB, α-L-arabinofuranosidases from different families, both contain a galactofuranose (Galf)-hydrolyzing activity. In addition, our data support the presence of a Galf-hydrolase activity expressed by A. niger that is capable of degrading fungal galactomannan.

From speciation to toxicity: Using a "Two-in-One" whole-cell bioreporter approach to assess harmful effects of Cd and Pb.

Due to the sheer number of contaminated sites, bioavailability-based measurement and modeling of toxicity is used to triage response; despite advances, both remain relatively cumbersome. Cadmium (Cd) and lead (Pb) are two of the most toxic and globally prevalent pollutants, disproportionately impacting disadvantaged communities. Here we demonstrate the use of high throughput lights-on bioreporter technology to measure both speciation and toxicity. The organism's response is fit-for-purpose to parameterize the Biotic Ligand Model used in risk assessment of aquatic ecotoxicity and setting environmental Water Quality Criteria. Toxicity endpoints for analogous Cd and Pb models reported in literature average 71st and 44th rank-percentile sensitivity of Genus Mean Acute Values for acute toxicity (i.e., insensitive) in comparison to the bioreporter, the unique dual-mode measurement ability of which can predict toxicity endpoints from below the 5th percentile up to the 50th rank-percentile. These results are extensible to other reporters, paving the way to cost-efficient environmental risk assessment of aquatic ecotoxicity for a wide range of priority toxic pollutants.

Whole-cell biosensors for determination of bioavailable pollutants in soils and sediments: Theory and practice.

The bioavailability of pollutants is a key factor affecting environmental risk. Whole-cell bioreporters are a demonstratedly effective tool for the investigation of pollutant bioavailability in water and soil/sediment. Unlike aqueous samples, transmittance of bioreporter optical signal is reduced in direct-contact assays with soil/sediment, which affects the accuracy of bioreporter-detected pollutant bioavailability. No studies have measured the magnitude and variability of soil/sediment effects on signal in direct-contact assays or how associated uncertainties influence results. In this study, we investigate the optical effects of soil/sediment particles in suspensions on bioreporter signal transmittance and quantify how variable these optical effects are from sample-to-sample. We find that neglecting bioreporter signal diminution by soil/sediment, as many studies do, can lead to order-of-magnitude errors in results, underestimating risk. Correction based on methods in ad hoc use (e.g. comparison to signal from non-inducible reporter or use of reference soil/sediment) are also problematic for some types of experiment, and could lead to errors in excess of 30%. Our findings have a sound basis in theory, and we provide recommendations concerning the most suitable type of approach to use for different experimental settings. Generally, if best accuracy is not needed to quantify bioavailability, for samples that have been ground, sieved, and are of reasonably uniform color, it may be possible to use a single or average correction factor, particularly for experiments performed at a single slurry concentration. For investigations studying bioavailability under varying solid-phase:water ratios (e.g., sorption/desorption), detailed compensation measurements are needed for independent variables, including each specific soil/sediment sample, slurry concentration, and in some cases bioreporter signal intensity. Our measurements and calculations indicate that best results are obtained when working in the region of ballistic photon transmittance. Findings herein will be useful in areas that require information on bioavailability, such as ecotoxicology and environmental risk assessment.

Pragmatic Comparison of Piperacillin/Tazobactam versus Carbapenems in Treating Patients with Nosocomial Pneumonia Caused by Extended-Spectrum ß-Lactamase-Producing Klebsiella pneumoniae.

The effectiveness of piperacillin/tazobactam for managing nosocomial pneumonia caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is unknown. To answer this question, we conducted a retrospective cohort study in two tertiary teaching hospitals of patients admitted between January 2018 and July 2021 with a diagnosis of nosocomial pneumonia caused by ESBL-producing K. pneumoniae receiving either piperacillin/tazobactam or carbapenems within 24 h from the onset of pneumonia for at least 72 h. Clinical outcomes, including 28-day mortality and 14-day clinical and microbiological cure, were analyzed. Of the 136 total patients, 64 received piperacillin/tazobactam and 72 received carbapenems. The overall 28-day mortality was 19.1% (26/136). In the inverse probability of treatment weighted cohort, piperacillin/tazobactam therapy was not associated with worse clinical outcomes, as the 28-day mortality (OR, 0.82, 95% CI, 0.23-2.87, p = 0.748), clinical cure (OR, 0.94, 95% CI, 0.38-2.35, p = 0.894), and microbiological cure (OR, 1.10, 95% CI, 0.53-2.30, p = 0.798) were comparable to those of carbapenems. Subgroup analyses also did not demonstrate any statistical differences. In conclusion, piperacillin/tazobactam could be an effective alternative to carbapenems for treating nosocomial pneumonia due to ESBL-producing K. pneumoniae when the MICs are ≤8 mg/L.

Glycan microarray profiling of parasite infection sera identifies the LDNF glycan as a potential antigen for serodiagnosis of trichinellosis.

Diagnostic methods for parasite infections still highly depend on the identification of the parasites by direct methods such as microscopic examination of blood, stool and tissue biopsies. Serodiagnosis is often carried out to complement the direct methods; however, few synthetic antigens with sufficient sensitivity and specificity are available. Here we evaluated a glycan microarray approach to select for synthetic glycan antigens that could be used for serodiagnosis of parasitic infections. Using a glycan array containing over 250 different glycan antigens, we identified GalNAcß1-4(Fucα1-3)GlcNAc-R (LDNF) as a glycan antigen that is recognized by antibodies from Trichinella-infected individuals. We synthesized a neoglycoconjugate, consisting of five LDNF molecules covalently coupled to bovine serum albumin (BSA), and used this neoglycoconjugate as an antigen to develop a highly sensitive total-Ig ELISA for serological screening of trichinellosis. The results indicate that glycan microarrays constitute a promising technology for fast and specific identification of parasite glycan antigens to improve serodiagnosis of different parasitic infections, either using an ELISA format, or parasite-specific glycan arrays.

ZIKV viral proteins and their roles in virus-host interactions.

The re-emergence of Zika virus (ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related studies have successively reported the role of various viral proteins of ZIKV in the process of ZIKV infection and pathogenicity. These studies have provided significant insights for the treatment and prevention of ZIKV infection. Here we review the current research advances in the functional characterization of the interactions between each ZIKV viral protein and its host factors.