Research progress on the N protein of porcine reproductive and respiratory syndrome virus.

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.

Inhibition of Lck/Fyn kinase activity promotes the differentiation of induced Treg cells through AKT/mTOR pathway.

Regulatory T (Treg) cells are indispensable in maintaining the immune homeostasis and preventing autoimmune diseases. Regulatory T (Treg) cells include thymus derived Treg cells (tTregs) and peripherally induced Treg cells (iTreg), which are differentiated from antigen stimulated CD4+ naïve T cells in presence of TGFß. tTregs are quite stable, and more immune suppressive, while iTreg cells are less stable, and are prone to differentiate into inflammatory T cells. Therefore, identification of small molecules that could promote the differentiation of iTreg cells is an attractive strategy for autoimmune diseases. Inhibition of AKT/mTOR pathway promotes their differentiation. Whether inhibition of Lck/Fyn kinase activity (upstream of AKT/mTOR pathway) can be used to promote the differentiation of iTreg cells has not been determined. Here, we showed that Srci1, a small molecular inhibitor of Lck/Fyn, promoted the differentiation of FOXP3+ iTreg cells. Srci1 treatment resulted in inhibition of phosphorylation of key components of AKT/mTOR pathway, including mTOR, p70 S6K, 4EBP1, and promoted the expression of Foxp3 and its target genes, thereby promoted differentiation of in vitro iTreg cells. Srci1 treated iTreg cells showed more similar gene expression profile to that of tTreg cells. Our results thus suggest that inhibition of Lck/Fyn kinase activity can promote the differentiation of iTreg cells, and may have implication in autoimmune diseases.

Appearance comparison on social networking sites and body shame: The role of negative body talk and perceived sociocultural influences on body image.

Social media platforms play a significant role in the lives of young people. While the usage of these platforms has grown, research exploring the challenges of body image remains limited. This study investigated whether initiating negative body talk functioned as an indirect pathway between appearance comparison on social media and body shame and whether perceived sociocultural influences from parents, friends, and media on body image moderated this indirect effect. An online cross-sectional survey of 795 Chinese college students (Mage = 20.17, SD = 1.65; 60% female, 40% male) was conducted. Negative body talk was a partial indirect pathway in the association, and this indirect effect was significant among those experiencing higher sociocultural pressures from all three sources. This study highlights the need for health psychology in understanding and addressing the mental health consequences associated with digital media and sociocultural influences on body image perception.

Research Progress on the NSP10 Protein of Porcine Reproductive and Respiratory Syndrome Virus.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious and pathogenic infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). It manifests as reproductive disorders in sows and respiratory disorders in piglets. PRRSV infects swine herds with symptoms such as abortions, stillbirths, and mummified fetuses in gestating sows. Piglets mainly experience abdominal respiration and respiratory symptoms. To date, the prevention of PRRS relies primarily on vaccination and the implementation of various preventive and control measures. Swine deaths caused by PRRS have resulted in significant economic losses to the pig industry worldwide. Non-structural protein 10 (NSP10) has helicase and adenosine triphosphatase (ATPase) activities that unwind DNA and RNA and play important roles in viral replication and transcription. Hence, it can be potentially used to develop novel reagents for the detection of PPRSV. This article reviews genetic variations, interaction with viral and host proteins, effects on PRRSV replication, immunomodulation, apoptosis, and viral virulence of NSP10, with the aim of providing a theoretical basis for the prevention and control of PRRS and drug development in the future.

TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation.

TH17 differentiation is critically controlled by "signal 3" of cytokines (IL-6/IL-23) through STAT3. However, cytokines alone induced only a moderate level of STAT3 phosphorylation. Surprisingly, TCR stimulation alone induced STAT3 phosphorylation through Lck/Fyn, and synergistically with IL-6/IL-23 induced robust and optimal STAT3 phosphorylation at Y705. Inhibition of Lck/Fyn kinase activity by Srci1 or disrupting the interaction between Lck/Fyn and STAT3 by disease-causing STAT3 mutations selectively impaired TCR stimulation, but not cytokine-induced STAT3 phosphorylation, which consequently abolished TH17 differentiation and converted them to FOXP3+ Treg cells. Srci1 administration or disrupting the interaction between Lck/Fyn and STAT3 significantly ameliorated TH17 cell-mediated EAE disease. These findings uncover an unexpected deterministic role of TCR signaling in fate determination between TH17 and Treg cells through Lck/Fyn-dependent phosphorylation of STAT3, which can be exploited to develop therapeutics selectively against TH17-related autoimmune diseases. Our study thus provides insight into how TCR signaling could integrate with cytokine signal to direct T cell differentiation.

Identification of the Linear Fc-Binding Site on the Bovine IgG1 Fc Receptor (boFcγRIII) Using Synthetic Peptides.

The bovine IgG1 Fc receptor (boFcγRIII) is a homologue to human FcγRIII (CD16) that binds bovine IgGI with medium-low affinity. In order to identify the Fc-binding site on the bovine IgG1 Fc receptor (boFcγRIII), peptides derived from the second extracellular domain (EC2) of boFcγRIII were synthesized and conjugated with the carrier protein. With a Dot-blot assay, the ability of the peptides to bind bovine IgG1 was determined, and the IgG1-binding peptide was also identified via truncation and mutation. The minimal peptide AQRVVN corresponding to the sequence 98-103 of boFcγRIII bound bovine IgG1 in Dot-blot, suggesting that it represents a linear ligand-binding site located in the putative A-B loop of the boFcγRIII EC2 domain. Mutation analysis of the peptide showed that the residues of Ala98, Gln99, Val101, Val102 and Asn103 within the Fc-binding site are critical for IgG1 binding on boFcγRIII. The functional peptide identified in this paper is of great value to the IgG-Fc interaction study and FcR-targeting drug development.

Critical fractions in reclaimed water responsible for membrane fouling: Isolation, fouling characteristics, quantitative and qualitative variations in practical application.

Considering the different fouling characteristics between model foulants and organic components in real reclaimed water, it is of great importance to identify the critical foulants responsible for membrane fouling. This study identified and isolated the fraction with molecular weight (MW) > 100 kDa as the critical foulant in secondary effluent by MW cut-off membrane of 100 kDa with high efficiency. This fraction accounted for 92.2% membrane fouling of raw water, including 28.7%, 29.7% and 33.8% fouling contribution by subfractions with MW between 100-300, 300-500 and > 500 kDa. Specifically, the critical fraction with MW > 100 kDa were mainly distributed in two parts: < 0.22 µm and > 0.45 µm, corresponding to 41.9% and 56.9% fouling contribution of this fraction. Furthermore, both total organic carbon (TOC) and fouling potential of fraction with MW > 100 kDa were monitored, presenting about threefold increase from September to January in next year. Membrane fouling contribution of this critical fraction in raw secondary effluent were mainly distributed in 85∼95% throughout the 5 months, demonstrating its predominant fouling propensity. Moreover, the TOC concentration of fraction with MW > 100 kDa presented distinct positive correlation with the fouling potential of raw secondary effluent (R2 = 0.947), which was promising to be a surrogate for predicting membrane fouling in practical application.

How COVID-19 prevention burnout impacts emotional symptoms among Chinese college students: A moderated mediation model.

The current study investigated the relationship between COVID-19 prevention burnout and emotional symptoms (depression and anxiety) among 1,837 Chinese college students and the underlying mechanisms. Results from moderated mediation analysis revealed that the association between COVID-19 prevention burnout and emotional symptoms was mediated by psychological inflexibility (ß = 0.20, 95%CI = [0.10, 0.19]). Also, COVID-19 prevention burnout's direct and indirect effects on emotional symptoms were more substantial for students with high susceptibility to emotional contagion than those with low susceptibility. These findings contribute to understanding how COVID-19 prevention burnout relates to emotional symptoms and provide a new perspective for interventions promoting students' psychological flexibility, particularly those with higher susceptibility to emotional contagion.

Quantitative health risk assessment of microbial hazards from water sources for community and self-supply drinking water systems.

In low and medium income countries (LMIC) drinking water sources (wells and boreholes) often contain a high number of pathogenic microorganisms, that can pose significant human and environmental health risks. In this study, a quantitative microbial risk assessment approach based on existing literature was conducted to evaluate and compare the quantitative health risks associated with different age groups using various drinking water supply systems. Results showed that both community-supply and self-supply modes exhibit similar levels of risk. However, the self-supply water source consistently showed higher risks compared to the community-supply one. Borehole water was found to be a more suitable option than well water, consistently showing between 5 and 8 lower health risks for E. coli and fecal coliform levels, respectively. The sensitivity analysis further showed the importance of prioritizing the reduction of E. coli concentration in well water and fecal coliform concentration in borehole water. This study offers a fresh perception on quantifying the impact of exposure concentration and age groups, shedding light on how they affect environmental health risks. These findings provide valuable insights for stakeholders involved in the management and protection of water sources.

The art of the deal: Deciphering the endowment effect from traders' eyes.

People are often reluctant to trade, a reticence attributed to the endowment effect. The prevailing account attributes the endowment effect to valuation-related bias, manifesting as sellers valuing goods more than buyers, whereas an alternative account attributes it to response-related bias, manifesting as both buyers and sellers tending to stick to the status quo. Here, by tracking and modeling eye activity of buyers and sellers during trading, we accommodate both views within an evidence-accumulation framework. We find that valuation-related bias is indexed by asymmetric attentional allocation between buyers and sellers, whereas response-related bias is indexed by arousal-linked pupillary reactivity. A deal emerges when both buyers and sellers attend to their potential gains and dilate their pupils. Our study provides preliminary evidence for our computational framework of the dynamic processes mediating the endowment effect and identifies physiological biomarkers of deal-making.

Corrigendum: Self-assembling and pH-Responsive protein nanoparticle as potential platform for targeted tumor therapy.

[This corrects the article DOI: 10.3389/fmolb.2023.1172100.].

Self-assembling and pH-responsive protein nanoparticle as potential platform for targeted tumor therapy.

Frequent injections at high concentrations are often required for many therapeutic proteins due to their short in vivo half-life, which usually leads to unsatisfactory therapeutic outcomes, adverse side effects, high cost, and poor patient compliance. Herein we report a supramolecular strategy, self-assembling and pH regulated fusion protein to extend the in vivo half-life and tumor targeting ability of a therapeutically important protein trichosanthin (TCS). TCS was genetically fused to the N-terminus of a self-assembling protein, Sup35p prion domain (Sup35), to form a fusion protein of TCS-Sup35 that self-assembled into uniform spherical TCS-Sup35 nanoparticles (TCS-Sup35 NP) rather than classic nanofibrils. Importantly, due to the pH response ability, TCS-Sup35 NP well retained the bioactivity of TCS and possessed a 21.5-fold longer in vivo half-life than native TCS in a mouse model. As a result, in a tumor-bearing mouse model, TCS-Sup35 NP exhibited significantly improved tumor accumulation and antitumor activity without detectable systemic toxicity as compared with native TCS. These findings suggest that self-assembling and pH responding protein fusion may provide a new, simple, general, and effective solution to remarkably improve the pharmacological performance of therapeutic proteins with short circulation half-lives.

Critical minority fractions causing membrane fouling in reclaimed water: Fouling characteristics, mechanisms and control strategies.

In regard to membrane-based technologies of wastewater reclamation, the reported key foulants were faced with dilemma that they could not be effectively separated and extracted from reclaimed water for thorough investigation. In this study, the crucial foulants were proposed as "critical minority fraction (FCM)", representing the fraction with molecular weight (MW) > 100 kDa which could be easily separated by physical filtration using MW cut-off membrane of 100 kDa with fairly high recovery ratio. FCM with low dissolved organic carbon (DOC) concentration (∼1 mg/L) accounted for less than 20% of the total DOC in reclaimed water, while contributed to more than 90% of the membrane fouling, and thus FCM could be considered as a "perfect criminal" causing membrane fouling. Furthermore, pivotal fouling mechanism was attributed to the significant attractive force between FCM and membranes, which led to severe fouling development due to the aggregation of FCM on membrane surface. Fluorescent chromophores of FCM were concentrated in regions of proteins and soluble microbial products, with proteins and polysaccharides accounted for 45.2% and 25.1% of the total DOC, specifically. FCM was further fractionated into six fractions, among which hydrophobic acids and hydrophobic neutrals were the dominant components in terms of DOC content (∼80%) as well as fouling contribution. Regarding to these pronounced properties of FCM, targeted fouling control strategies including ozonation and coagulation were applied and proved to achieve remarkable fouling control effect. High-performance size-exclusion chromatography results suggested that ozonation achieved distinct transformation of FCM into low MW fractions, while coagulation removed FCM directly, thus leading to effective fouling alleviation. Therefore, the investigation of the critical foulants was expected to help glean valuable insight into the fouling mechanism and develop targeted fouling control technologies in practical applications.

Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α.

OBJECTIVE: Mycobacterium tuberculosis /human immunodeficiency virus (MTB/HIV) coinfection has become an urgent problem in the field of prevention and control of infectious diseases in recent years. Adoptive cellular immunotherapy using antigen-specific T-cell receptor (TCR) engineered T cells which recognize the specific antigen artificially may have tremendous potential in anti-MTB/HIV coinfection. We have previously successfully identified a MTB Ag85B 199-207 and HIV-1 Env 120-128 peptide-bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A∗0201 + healthy individual and have further studied that how residues on the predicted complementarity determining region (CDR) 3 of the ß chain contribute to the bispecific TCR contact with the peptide-MHC. However, it is not clear which amino acids in the predicted CDR3α of the bispecific TCR play a crucial role in ligand recognition. METHODS: The variants in the CDR3α of the bispecific TCR were generated using alanine substitution. We then evaluated the immune effects of the five variants on T-cell recognition upon encounter with the MTB or HIV-1 antigen. RESULTS: Mutation of two amino acids (E112A, Y115A) in CDR3α of the bispecific TCR caused a markedly diminished T-cell response to antigen, whereas mutation of the other three amino acids (S113A, P114A, S116A) resulted in completely eliminated response. CONCLUSION: This study demonstrates that Ser 113 , Pro 114 and Ser 116 in CDR3α of the bispecific TCR are especially important for antigen recognition. These results will pave the way for the future development of an improved high-affinity bispecific TCR for use in adoptive cellular immunotherapy for MTB/HIV coinfected patients.

Corrigendum: The effects of empathy by caregivers on healthcare service satisfaction.

[This corrects the article DOI: 10.3389/fpsyg.2022.912076.].

Natural Compound 2,2',4'-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T.

Retinoid-related orphan receptor γt (RORγt), a vital transcription factor for the differentiation of the pro-inflammatory Th17 cells, is essential to the inflammatory response and pathological process mediated by Th17 cells. Pharmacological inhibition of the nuclear receptor RORγt provides novel immunomodulators for treating Th17-driven autoimmune diseases and organ transplant rejection. Here, we identified 2,2',4'-trihydroxychalcone (TDC), a natural chalcone derivant, binds directly to the ligand binding domain (LBD) of RORγt and inhibited its transcriptional activation activity. Using three mice models of Th17-related diseases, it was found that the administration of TDC effectively alleviated the disease development of experimental autoimmune encephalomyelitis (EAE), experimental colitis, and skin allograft rejection. Collectively, these results demonstrated TDC targeting RORγt to suppress Th17 cell polarization, as well as its activity, thus, indicating the potential of this compound in treating of Th17-related autoimmune disorders and organ transplant rejection disorders.

Patterned 2D Ferroelectric Perovskite Single-Crystal Arrays for Self-Powered UV Photodetector Boosted by Combining Ferro-Pyro-Phototronic and Piezo-Phototronic Effects.

Metal halide perovskite ferroelectrics possess various physical characteristics such as piezoelectric and pyroelectric effects, which could broaden the application of perovskite ferroelectrics and enhance the optoelectronic performance. Therefore, it is promising to combine multiple effects to optimize the performance of the self-powered PDs. Herein, patterned 2D ferroelectric perovskite (PMA)2PbCl4 microbelt arrays were demonstrated through a PDMS template-assisted antisolvent crystallization method. The perovskite arrays based flexible photodetectors exhibited fine self-powered photodetection performance under 320 nm illumination and much enhanced reproducibility compared with the randomly distributed single-crystal microbelts-based PDs. Furthermore, by introducing the piezo-phototronic effect, the performance of the flexible PD was greatly enhanced. Under an external tensile strain of 0.71%, the responsivity was enhanced by 185% from 84 to 155.5 mA/W. Our findings offer the advancement of comprehensively utilizing various physical characteristics of the ferroelectrics for novel ferroelectric optoelectronics.

The effects of empathy by caregivers on healthcare service satisfaction.

Healthcare service satisfaction focuses not only on the patients but also on the caregivers' perspectives. This study explored how caregivers' empathy toward patients affects their satisfaction with healthcare services through an electroencephalography (EEG) experiment. EEG mu rhythm was used as the neural indicator to reflect empathy. The results showed that empathy reduces caregivers' evaluation of healthcare service satisfaction because they share suffering with the patients. However, implementing physician-patient communication through a process-based informed consent (IC), compared to an event-based IC, can effectively alleviate such adverse effects.

Differentiation of Classical Swine Fever Virus Virulent and Vaccine Strains by CRISPR/Cas13a.

As a notifiable terrestrial and aquatic animal disease listed by World Organisation for Animal Health (formerly the Office International des Epizooties [OIE]), classical swine fever (CSF) has caused great economic losses to the swine industry worldwide during recent decades. Differentiation of infected and vaccinated animals (DIVA) is urgent for eradication of CSF. In this study, a diagnostic platform based on CRISPR/Cas13a was established with the ability to differentiate between classical swine fever virus (CSFV) virulent and vaccine strains. In combination with reverse transcription recombinase-aided amplification (RT-RAA), the detection limit for CSFV synthetic RNA templates reached 3.0 × 102 copies/µL. In addition, with boiling and chemical reduction, heating unextracted diagnostic samples to obliterate nucleases (HUDSON) treatment was introduced to inactivate nucleases and release viral genome, achieving robust pretreatment of tested sample before CRISPR/Cas13a detection without the need to extract viral nucleic acids. HUDSON-RT-RAA-CRISPR/Cas13a can directly detect cell cultures of virulent Shimen strain and vaccine hog cholera lapinized virus (HCLV) strain, with the detection limit of 3.5 × 102 copies/µL and 1.8 × 102 copies/µL, respectively, which was equally sensitive to nested PCR (nPCR) and 100 times more sensitive than antigen enzyme-linked immunosorbent assay (ELISA). Meanwhile, HUDSON-RT-RAA-CRISPR/Cas13a showed no cross-reactivity with bovine viral diarrhea virus (BVDV), atypical porcine pestivirus (APPV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV), African swine fever virus (ASFV), pseudorabies virus (PRV), and porcine circovirus 2 (PCV2), exhibiting good specificity. At last, a total of 50 pig spleen samples with suspected clinical signs were also assayed with HUDSON-RT-RAA-CRISPR/Cas13a, nPCR, and antigen ELISA in parallel. HUDSON-RT-RAA-CRISPR/Cas13a showed 100.0% with nPCR and 82.0% coincident rate with antigen ELISA, respectively. IMPORTANCE Classical swine fever (CSF) is a World Organisation for Animal Health (formerly the Office International des Epizooties [OIE]) notifiable terrestrial and aquatic animal disease, causing great economic losses to the swine industry worldwide during the past decades. Due to the use of the most effective and safe attenuated live vaccine for CSF prevention, differentiation of infected and vaccinated pigs is vital work, as well as a bottleneck for eradication of CSF. Methods with the ability to precisely differentiate classical swine fever virus (CSFV) virulent strains from vaccine strain hog cholera lapinized virus (HCLV) are urgently needed. Combining the high sensitivity of isothermal recombinase-aided amplification (RAA) with the accurate molecular sensing ability of Cas13a, we presented a novel method for CSFV detection without the need to extract viral nucleic acids, which showed great advantage to traditional detection methods for precise differentiation of CSFV virulent strains and vaccine strain, providing a novel powerful tool for CSF eradication.