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ObjectiveThis study aims to assess the effectiveness of the National Early Warning Score 2 (NEWS2) versus Glasgow Coma Scale (GCS) in predicting hospital mortality among patients with stroke and traumatic brain injury (TBI).LocationThis multicenter study was conducted at two anonymized tertiary care hospitals in distinct climatic regions of China, with a combined annual emergency admission exceeding 10,000 patients.PatientsThe study included 2,276 adult emergency admissions diagnosed with stroke (n = 1,088) or TBI (n = 1,188) from January 2021 to December 2023, excluding those with chronic pulmonary disease, severe cardiac conditions, or a history of brain surgery.Measuring and main outcomesThe receiver operating characteristic (ROC) curve and the area under the curve (AUC) were utilized to analyze the predictive accuracy of NEWS2 and GCS for hospital mortality at 24, 48, and 72 h post-admission and at discharge.ResultsOut of 2,276 patients (mean age 61.4, 65.6% male), 1855 survived while 421 succumbed. NEWS2 demonstrated superior predictive accuracy (AUC = 0.962) over GCS (AUC = 0.854) for overall hospital mortality. Specifically, NEWS2 outperformed GCS in predicting mortality at 24 h (0.917 vs. 0.843), 48 h (0.893 vs. 0.803), and 72 h (0.902 vs. 0.763). Notably, despite a higher AUC for NEWS2 at predicting 24-h hospital mortality, the sensitivity and specificity of GCS were considerably lower (12 and 31%, respectively) compared to NEWS2 (sensitivity of 95% and specificity of 81%). Subgroup analysis showed NEWS2 outperforming GCS in predicting in-hospital mortality for TBI and stroke patients. For TBI patients (n = 260), NEWS2 had an AUC of 0.960 (95% CI: 0.948–0.973) vs. GCS’s AUC of 0.811 (95% CI: 0.781–0.840). For stroke patients (n = 161), NEWS2 had an AUC of 0.930 (95% CI: 0.908–0.952) vs. GCS’s AUC of 0.858 (95% CI, 0.823–0.892). NEWS2 showed greater sensitivity in both groups, highlighting its effectiveness in identifying high-risk neurological patients.ConclusionNEWS2 scores are more precise and effective in predicting hospital mortality in stroke and TBI patients compared to GCS scores, although slightly less so within the first 24 h. Combining NEWS2 with GCS and clinical findings within the initial 24 h is recommended for a comprehensive prognosis evaluation.

Recently, herpesvirus of turkeys (HVT), which was initially employed as a vaccine against Marek’s disease (MD), has been shown to be a highly effective viral vector for producing recombinant vaccines that can simultaneously express the protective antigens of multiple poultry diseases. Prior to the development of commercial HVT-vectored dual-insert vaccines, the majority of HVT-vectored vaccines in use only contained a single foreign gene and were often generated using time-consuming and inefficient traditional recombination methods. The development of multivalent HVT-vectored vaccines that induce simultaneous protection against several avian diseases is of great value. In particular, efficacy interference between individual recombinant HVT vaccines can be avoided. Herein, we demonstrated the use of CRISPR/Cas9 gene editing technology for the insertion of an IBDV (G2d) VP2 expression cassette into the UL45/46 region of the recombinant rHVT-HA viral genome to generate the dual insert rHVT-VP2-HA recombinant vaccine. The efficacy of this recombinant virus was also evaluated in specific pathogen-free (SPF) chickens. PCR and sequencing results showed that the recombinant virus rHVT-VP2-HA was successfully constructed. Vaccination with rHVT-VP2-HA produced high levels of specific antibodies against IBDV (G2d) and H9N2/Y280. rHVT-VP2-HA can provide 100% protection against challenges with IBDV (G2d) and H9N2/Y280. These results demonstrate that rHVT-VP2-HA is a safe and highly efficacious vaccine for the simultaneous control of IBDV (G2d) and H9N2/Y280.

Parvoviruses are a group of non-enveloped DNA viruses that have a broad spectrum of natural infections, making them important in public health. NS1 is the largest and most complex non-structural protein in the parvovirus genome, which is indispensable in the life cycle of parvovirus and is closely related to viral replication, induction of host cell apoptosis, cycle arrest, DNA damage response (DDR), and other processes. Parvovirus activates and utilizes the DDR pathway to promote viral replication through NS1, thereby increasing pathogenicity to the host cells. Here, we review the latest progress of parvovirus in regulating host cell DDR during the parvovirus lifecycle and discuss the potential of cellular consequences of regulating the DDR pathway, targeting to provide the theoretical basis for further elucidation of the pathogenesis of parvovirus and development of new antiviral drugs.

BackgroundGrowing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear.MethodsMendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed.ResultsMR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04).ConclusionsThis study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.

Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating diseases of the central nervous system, have drawn the attention of many researchers due to the relapsing courses and cumulative disability. A first bibliometric analysis of NMOSD was conducted to identify the research hotspots and emerging trends. Articles relevant to NMOSD published in the core collection of Web of Science were retrieved and analyzed through visualized analysis using CiteSpace and VOSviewer, focusing on annual publication trends, countries, institutions, authors, journals, and keywords. The analysis showed that over the past 30 years, publications related to NMOSD had shown steady growth with slight fluctuations. The United States played an important part in this field, with the highest outputs and the greatest number of citations. Research hotspots of NMOSD had gradually shifted from the definition, biomarkers, and diagnostic criteria to diagnosis and treatment, particularly immunotherapy. This bibliometric analysis provides researchers with a theoretical basis for studying NMOSD and offers guidance for future research directions.

BackgroundRegulatory T cells (Treg) have been identified as a key modulator of neuroinflammation in stroke. However, little is known about the association of Treg subpopulations with clinical outcome in patients with acute ischemic stroke (AIS).MethodsPatients within 1 week from stroke onset were prospectively enrolled in this study. Healthy controls were sex-and age-matched 1:1 to AIS patients. The frequencies of Treg and Treg subsets were analyzed by flow cytometry and compared with nonstroke control. Univariate and multivariate logistic regression analysis was performed to investigate the prognostic value of Treg subsets in stroke outcomes.ResultsA total of 328 patients and 328 controls were included in the study. Compared with controls, patients with AIS had higher levels of Treg frequency and memory Treg (mTreg) frequency, but lower levels of naïve Treg (nTreg) frequency and nTreg/mTreg ratio. One hundred twenty-six (38.4%) patients experienced unfavorable outcome (modified Rankin score 2–6). Multivariate regression analysis showed that nTreg/mTreg ratio was negatively associated with unfavorable 90-day outcome (the highest tertile versus the lowest tertile: odds ratio 0.13, 95% confidential interval [CI] 0.05–0.35). The risk estimation of unfavorable 90 day outcome can be significantly improved by adding nTreg/mTreg ratio to the conventional clinical parameters (continuous net reclassification improvement 91.26, 95% CI 69.04–113.5%, p

Aging is a complex multifactorial process that greatly affects animal health. Multi-omics analysis is widely applied in evolutionary biology and biomedical research. However, whether multi-omics can provide sufficient information to reveal comprehensive changes in aged non-human primates remains unclear. Here, we explored changes in host–microbe interactions with aging in Chinese rhesus macaques (Macaca mulatta lasiota, CRs) using multi-omics analysis. Results showed marked changes in the oral and gut microbiomes between young and aged CRs, including significantly reduced probiotic abundance and increased pathogenic bacterial abundance in aged CRs. Notably, the abundance of Lactobacillus, which can metabolize tryptophan to produce aryl hydrocarbon receptor (AhR) ligands, was decreased in aged CRs. Consistently, metabolomics detected a decrease in the plasma levels of AhR ligands. In addition, free fatty acid, acyl carnitine, heparin, 2-(4-hydroxyphenyl) propionic acid, and docosahexaenoic acid ethyl ester levels were increased in aged CRs, which may contribute to abnormal fatty acid metabolism and cardiovascular disease. Transcriptome analysis identified changes in the expression of genes associated with tryptophan metabolism and inflammation. In conclusion, many potential links among different omics were found, suggesting that aged CRs face multiple metabolic problems, immunological disorders, and oral and gut diseases. We determined that tryptophan metabolism is critical for the physiological health of aged CRs. Our findings demonstrate the value of multi-omics analyses in revealing host–microbe interactions in non-human primates and suggest that similar approaches could be applied in evolutionary and ecological research of other species.

Avian reoviruses (ARVs) are ubiquitous in domestic poultry with 80% of them being non-pathogenic and they are frequently found in clinically healthy birds. ARVs have also been known to be the etiological agents of viral arthritis (VA), tenosynovitis, myocarditis, runting-stunting syndrome (RSS), and respiratory and enteric disease in chickens. Significant economic losses during the process of poultry husbandry are due, in part, to unmitigated ARV infections throughout the poultry industry. Recently, many isolates shared genetic similarities between those recovered from wild birds and those recovered from poultry. One explanation may be that there is a degree of spillover and spillback of ARVs between the two groups. However, studies on the role of wild birds in the epidemiology and pathogenicity of ARVs are insufficient. Here, we describe the pathogenicity in specific pathogen-free (SPF) chickens of ARV originating from wild birds. The challenge experiment was conducted in six groups including a negative control group, a positive control group (reference strain of S1133), and four groups (A15-157, A18-13, A18-205, A19-106) infected with ARVs from wild birds. The 7-day-old SPF chickens were inoculated with 106TCID50 ARV to evaluate the clinical signs, changes in weight gain, gross lesions, histological changes, virus replication, and serum antibody levels. The peak of clinical signs was from 3 to 5 days post infection (dpi). In addition, the death of one chicken was found in the group infected with the A18-13 isolate. Reduced body weight was also found in chickens infected with ARVs from wild birds compared to the negative control group. All the ARVs infection groups showed noticeable swelling of the footpad. In addition, ARVs were detected in the bursa, tendon, and hock joint by reverse transcription-polymerase chain reaction (RT-PCR) in all infected groups at 5 and 15 dpi. Histopathological observations revealed acute inflammatory responses on the synovium covering the joint surfaces (arthritis) and tendon sheaths (tenosynovitis), as well as bursa atrophy and lymphocyte depletion. The analysis of the humoral response was performed by ELISA assay, and chickens infected with ARVs showed seroconverted. In conclusion, this study described the typical severe disease of acute VA and tenosynovitis in SPF chickens infected with ARVs derived from wild birds. This study confirmed the pathogenicity of ARVs infection in SPF chickens for the first time, and these results enrich our understanding of the pathogenicity of ARVs derived from wild birds.

Avian reoviruses (ARVs) cause severe arthritis, tenosynovitis, pericarditis, and depressed growth in chickens, and these conditions have become increasingly frequent in recent years. Studies on the role of wild birds in the epidemiology of ARVs are insufficient. This study provides information about currently circulating ARVs in wild birds by gene detection using diagnostic RT-PCR, virus isolation, and genomic characterization. In this study, we isolated and identified 10 ARV isolates from 7,390 wild birds' fecal samples, including migratory bird species (bean goose, Eurasian teal, Indian spot-billed duck, and mallard duck) from 2015 to 2019 in South Korea. On comparing the amino acid sequences of the σC-encoding gene, most isolates, except A18-13, shared higher sequence similarity with the commercial vaccine isolate S1133 and Chinese isolates. However, the A18-13 isolate is similar to live attenuated vaccine av-S1133 and vaccine break isolates (SD09-1, LN09-1, and GX110116). For the p10- and p17-encoding genes, all isolates have identical fusion associated small transmembrane (FAST) protein and nuclear localization signal (SNL) motif to chicken-origin ARVs. Phylogenetic analysis of the amino acid sequences of the σC-encoding gene revealed that all isolates were belonged to genotypic cluster I. For the p10- and p17-encoding genes, the nucleotide sequences of all isolates indicated close relationship with commercial vaccine isolate S1133 and Chinese isolates. For the σNS-encoding gene, the nucleotide sequences of all isolates indicated close relationship with the Californian chicken-origin isolate K1600657 and belonged to chicken-origin ARV cluster. Our data indicates that wild birds ARVs were derived from the chicken farms. This finding suggests that wild birds serve as natural carriers of such viruses for domestic poultry.

BackgroundDemyelination diseases are complex puzzles that are not always straightforward to diagnose. Multiple sclerosis and neuromyelitis optica are two that are frequently encountered. Numerous autoantibodies newly discovered in recent years have significantly aided clinical reasoning and diagnosis in differentiating demyelination disorders. Here we report a case of demyelination disease with anti-flotillin autoantibodies positive, which is not common in past references.Case summaryThe patient presented with characteristic neuromyelitis optica symptoms and had remission and relapse. But his images exhibited characteristics of both neuromyelitis optica spectrum illness and multiple sclerosis.ConclusionThis is the first case report describing the clinical course and imaging characteristics of demyelination illness associated with anti-flotillin autoantibodies. Although so far it appears to be a subtype of multiple sclerosis, there is still a potential that it is separate from MS and NMOSD.

With an aim to develop a highly attenuated and strongly immunogenic distinguishable vaccine candidate, a waaJ (a gene involved in the synthesis of lipopolysaccharide) and spiC (a virulence gene) double deletion Korean epidemic strain of S. enterica ser. Gallinarum (SG005) was constructed. Our results showed that the growth and biochemical characteristics were not altered by this double deletion. The double deletion strain contained dual markers. One was a bacteriological marker (rough phenotype) and the other was a serological marker helping distinguish infected chickens from vaccinated chickens. The double deletion strain showed good genetic stability and reduced resistance to environmental stresses in vitro; furthermore, it was extremely safe and highly avirulent in broilers. Single intramuscular or oral immunization of 7-day-old broilers with the double deletion strain could stimulate the body to produce antibody levels similar to the conventional vaccine strain SG9R. In addition, against a lethal wild-type challenge, it conferred effective protection that was comparable to that seen in the group vaccinated with SG9R. In conclusion, this double deletion strain may be an effective vaccine candidate for controlling S. enterica ser. Gallinarum infection in broilers.

Sphingosine-1-phosphate (S1P) signaling is being increasingly recognized as a strong modulator of immune cell migration and endothelial function. Fingolimod and other S1P modulators in ischemic stroke treatment have shown promise in emerging experimental models and small-scale clinical trials. In this article, we will review the current knowledge of the role of S1P signaling in brain ischemia from the aspects of inflammation and immune interventions, sustaining endothelial functions, regulation of blood-brain barrier integrity, and functional recovery. We will then discuss the current and future therapeutic perspectives of targeting S1P for the treatment of ischemic stroke. Mechanism studies would help to bridge the gap between preclinical studies and clinical practice. Future success of bench-to-bedside translation shall be based on in depth understanding of S1P signaling during stroke and on the ability to have a fine temporal and spatial regulation of the signal pathway.

High-dose steroids, the first-line therapy for acute attacks in neuromyelitis optica spectrum disorder (NMOSD), were ineffective in a proportion of NMOSD attacks. This study aimed to explore possible predictors of high-dose steroid resistance. Demographics and disease characteristics of acute attacks were compared between those who responded to high-dose intravenous methylprednisolone (IVMP) and those resistant to IVMP. In total, 197 attacks in 160 patients were identified in our NMOSD registry. Compared with responders, attacks resistant to high-dose steroids tended to have a higher proportion of previous history of immunosuppressive use (25.5 vs. 15.5%, p = 0.080). Significantly higher levels of proteins in the cerebrospinal fluid (CSF) were found in non-responders than in responders [485.5 (388–656) vs. 387 (291.5–532) mg/L, p = 0.006]. More active lesions were found in the brain stem of non-responders (8 attacks in 55, 14.5%), especially in the pons (7.3%) and medulla (14.5%), as opposed to responders (7 patients in 142, 4.9%). Multivariable logistic regression showed that resistance to high-dose steroid treatment was associated with previous immunosuppressant use [odds ratio (OR), 2.31; 95% confidence interval (CI) 1.002–5.34, p = 0.049], CSF protein level above 450 mg/L (OR 3.42, 95% CI 1.72–6.82, p < 0.001), and active lesions in the brainstem (OR 3.80, 95% CI 1.17–12.32, p = 0.026). In conclusion, NMOSD patients with previous use of immunosuppressants, higher levels of CSF protein, and active lesions in the brainstem are more likely to respond poorly to high-dose IVMP alone during an acute attack.

The importance of employee green behavior (EGB) to an enterprise’s green development goal is increasingly emphasized in many industries. However, to date promoting EGB through interaction, namely between individuals and organizations, has not been a central concern. Therefore, from the perspective of the person-organization fit, this study considers the psychological distance between employees and the organization as a moderating variable, exploring the mechanisms of values fit, needs-supplies fit, and demands-abilities fit on green behaviors as within and outside the scope of employee responsibility. After collecting the results of questionnaires from 412 employees, our hypotheses were tested using the Structural Equation Model (SEM). The results show that (1) person-organization fit can effectively promote EGB in the workplace. However, different types of person-organization fit have different influencing paths and effect-strengths on employees’ task-related green behavior and proactive green behavior. (2) Values fit has the greatest incentive effect on EGB, followed by demands-abilities fit, while needs-supplies fit promotes only eco-helping behavior. (3) Psychological distance has a significant moderating effect on the relationship between the person-organization fit and EGB. The effect of person-organization fit on EGB is enhanced when employees are close with less emotional distance, while the effect is weakened in the case of close expectation distance. Finally, this study provides suggestions for enterprise managers providing ways to motivate EGB through the selection and allocation of human resources.

Interleukin-33 (IL-33), a member of the IL-1 superfamily, has been shown to play a critical role in many diseases through regulating the immune cell responses, including myeloid-derived suppressor cells (MDSCs). Our previous study demonstrated that IL-33 might play a protective role in kidney injury in gout patients by regulating the lipid metabolism. However, the role of IL-33in the development of MSU-induced inflammation remains elusive. In this study, an increased IL-33 expression was observed in gout patients, which was positively correlated with inflammatory marker CRP. To explore the effects and mechanisms of the increased IL-33 expression in the gout patients, the anti-ST2 antibody and exogenous recombinant IL-33 were used in MSU-induced peritonitis animal model that mimics human gout. Compared with control group, mice with exogenous recombinant IL-33 significantly ameliorated the inflammatory cells infiltration, while blockage of IL-33 signaling by anti-ST2 had no effect on the development of MSU-induced peritonitis. Furthermore, the crucial inflammatory cytokine IL-1β was markedly decreased in IL-33-treated mice. Besides that, a large number of anti-inflammatory MDSCs with CD11b+Gr1intF4/80+ phenotype was observed in the IL-33-treated mice, and adoptive transfer of IL-33-induced MDSCs (CD11b+Gr1intF4/80+) markedly inhibited the IL-1β production in MSU-induced peritonitis. In conclusion, our data provide clear evidences that the increased expression of IL-33 in the gout patients might be due to a cause of self-negative regulation, which inhibits the development of MSU-induced inflammation through expanding MDSCs. Thus, IL-33 might serve as a promising therapeutic target for gout.