Intranasal administration with recombinant vaccine PRVXJ-delgE/gI/TK-S induces strong intestinal mucosal immune responses against PDCoV.

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes enteric diseases in pigs leading to substantial financial losses within the industry. The absence of commercial vaccines and limited research on PDCoV vaccines presents significant challenges. Therefore, we evaluated the safety and immunogenicity of recombinant pseudorabies virus (PRV) rPRVXJ-delgE/gI/TK-S through intranasal mucosal immunization in weaned piglets and SPF mice. Results indicated that rPRVXJ-delgE/gI/TK-S safely induced PDCoV S-specific and PRV gB-specific antibodies in piglets, with levels increasing 7 days after immunization. Virus challenge tests demonstrated that rPRVXJ-delgE/gI/TK-S effectively improved piglet survival rates, reduced virus shedding, and alleviated clinical symptoms and pathological damage. Notably, the recombinant virus reduced anti-inflammatory and pro-inflammatory responses by regulating IFN-γ, TNF-α, and IL-1ß secretion after infection. Additionally, rPRVXJ-delgE/gI/TK-S colonized target intestinal segments infected with PDCoV, stimulated the secretion of cytokines by MLVS in mice, stimulated sIgA secretion in different intestinal segments of mice, and improved mucosal immune function. HE and AB/PAS staining confirmed a more complete intestinal mucosal barrier and a significant increase in goblet cell numbers after immunization. In conclusion, rPRVXJ-delgE/gI/TK-S exhibits good immunogenicity and safety in mice and piglets, making it a promising candidate vaccine for PDCoV.

Macrophage Polarization: An Important Candidate Regulator for Lung Diseases.

Macrophages are crucial components of the immune system and play a critical role in the initial defense against pathogens. They are highly heterogeneous and plastic and can be polarized into classically activated macrophages (M1) or selectively activated macrophages (M2) in response to local microenvironments. Macrophage polarization involves the regulation of multiple signaling pathways and transcription factors. Here, we focused on the origin of macrophages, the phenotype and polarization of macrophages, as well as the signaling pathways associated with macrophage polarization. We also highlighted the role of macrophage polarization in lung diseases. We intend to enhance the understanding of the functions and immunomodulatory features of macrophages. Based on our review, we believe that targeting macrophage phenotypes is a viable and promising strategy for treating lung diseases.

Serum marker and CT characteristics of coronary calcified nodule assessed by intravascular ultrasound.

BACKGROUND: Calcified nodule (CN) is a type of potentially vulnerable plaque. Its formation mechanism remains unknown. This study was to assess serum marker and computed tomography angiography (CTA) characteristics of CN validated by intravascular ultrasound (IVUS). METHODS: Patients who underwent coronary CTA followed by invasive coronary angiography and IVUS were retrospectively analyzed. Serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase, and calcium were collected. RESULTS: IVUS detected 128 de novo calcified lesions in 79 patients with coronary artery disease (CAD). CNs were identified in 11.4% (9/79) of patients and 9.4% (12/128) of lesions. Compared with patients with non-nodular calcified plaques, CN patients had higher serum level of ALP (82.00 vs 65.00 U/L, P = 0.022) and total plaque volume (673.00 vs 467.50 mm3, P = 0.021). Multivariable analyses revealed that serum ALP level and total plaque volume were independently associated with the prevalence of CN in CAD patients with calcified plaques. At lesion level, the CN group had a higher frequency of moderate to heavy calcification on angiography (75.00% vs 40.52%, P = 0.017). In terms of CTA characteristics, plaques with CN had a more severe diameter stenosis (79.00% vs 63.00%, P = 0.007), higher plaque burden (85.40% vs 77.05%, P = 0.005), total plaque density (398.00 vs 283.50 HU, P = 0.008), but lower lipid percentage (14.65% vs 19.75%, P = 0.010) and fiber percentage (17.90% vs 25.65%, P = 0.011). Mean plaque burden is an independent predictor of the prevalence of CN in calcified plaques (odds ratio = 1.102, 95% confidence interval: 1.025-1.185, P = 0.009). The AUC is 0.753 (95% confidence interval: 0.615-0.890, P = 0.004). When using 84.85% as the best cutoff value, the diagnostic sensitivity and specificity of mean plaque burden for predicting the presence of CN within calcified plaques were 66.7% and 80.2%, respectively. CONCLUSIONS: CN had different CTA imaging features from non-nodular coronary calcification. The presence of a CN was associated with a higher serum ALP level and plaque burden.

Characterization of B cell receptor H-CDR3 repertoire of spleen in PRV-infected mice.

Pseudorabies virus (PRV), also known as suid Alphaherpesvirus 1 (SuHV-1), which is one of the most devastating infectious pathogen of swine industry worldwide. Vaccination is the safest and most effective PRV prevention and control strategy. B cell receptor (BCR) is membrane-bound immunoglobulin located on the surface of B cells capable of specifically binding foreign antigens, which is one of the most important molecules regulating the proliferation and function of B cells. Here, to assess the molecular diversity of BCR H-CDR3 repertoire after different PRV strains infection, we detected the IGHV, IGHD, IGHJ genes usage and CDR3 sequence changes of mice spleen with PRV vaccine strain (Bartha-K61), variant strain (XJ) and mock infection by high-throughput sequencing. We found that PRV-infected groups shared partial BCR sequences, which are most likely to be PRV-specific BCR candidates. However, there were still differences in the IGHV genes usage as well as the combined usage of IGHV and IGHJ genes between the Bartha-K61 strain and XJ strain infection groups. In addition, the CDR3 sequences exhibited large differences in the types and lengths in PRV infection groups. Our study contributes to a better understanding of the host adaptive immune response to PRV infection and provides a theoretical basis for further research on novel and efficient PRV vaccines in the future.

Antiviral Activity of Porcine IFN-λ3 and IFN-α against Porcine Rotavirus In Vitro.

Interferons (IFNs) play a major role in the host's antiviral innate immunity. In response to viral infection, IFNs bind their receptors and initiate a signaling cascade, leading to the accurate transcriptional regulation of hundreds of IFN-stimulated genes (ISGs). Porcine rotavirus (PoRV) belongs to genus Rotavirus of the Reoviridae family; the infection is a global epidemic disease and a major threat to the pig industry. In this study, we found that IFN-λ3 inhibited the replication of PoRV in both MA104 cells and IPEC-J2 cells, and this inhibition was dose-dependent. Furthermore, the antiviral activity of IFN-λ3 was more potent in IPEC-J2 cells than in MA104 cells. Further research showed that IFN-λ3 and IFN-α might inhibit PoRV infection by activating ISGs, i.e., MxA, OASL and ISG15, in IPEC-J2 cells. However, the co-treatment of IFN-λ3 and IFN-α did not enhance the antiviral activity. Our data demonstrated that IFN-λ3 had antiviral activity against PoRV and may serve as a useful antiviral candidate against PoRV, as well as other viruses in swine.

TGF-ß1-induced EMT activation via both Smad-dependent and MAPK signaling pathways in Cu-induced pulmonary fibrosis.

Copper (Cu) is considered as an essential trace element for living organisms. However, over-exposure to Cu can lead to adverse health effects on human and animals. There are limited researches on pulmonary toxicity induced by Cu. Here, we found that copper sulfate (CuSO4)-treatment could induce pulmonary fibrosis with Masson staining and up-regulated protein and mRNA expression of Collagen I and α-Smooth Muscle Actin (α-SMA) in mice. Next, the mechanism underlying Cu-induced pulmonary fibrosis was explored, including transforming growth factor-ß1 (TGF-ß1)-mediated Smad pathway, mitogen-activated protein kinases (MAPKs) pathway and epithelial-mesenchymal transition (EMT). CuSO4 triggered pulmonary fibrosis by activation of the TGF-ß1/Smad pathway, which was accomplished by increasing TGF-ß1, p-Smad2 and p-Smad3 protein and mRNA expression levels. Also, up-regulated protein and mRNA expression of p-JNK, p-ERK, and p-p38 demonstrated that CuSO4 activated MAPKs pathways. Concurrently, EMT was activated by increasing vimentin and N-cadherin while decreasing E-cadherin protein and mRNA expression levels. Altogether, the abovementioned findings indicate that CuSO4 treatment may induce pulmonary fibrosis through the activation of EMT induced by TGF-ß1/Smad pathway and MAPKs pathways, revealing the mechanism Cu-caused pulmonary toxicity.

Copper induces hepatocyte autophagy via the mammalian targets of the rapamycin signaling pathway in mice.

Although copper is among the indispensable trace elements in animal physiological processes, it exerts toxicity upon over-exposure. The present study aimed to investigate hepatocyte autophagy induced by CuSO4 and its potential mechanism. A total of 240 ICR mice (four-week-old, 120 males and 120 females) were randomly divided into four groups, in which mice separately received 0, 4, 8, and 16 mg/kg of Cu (Cu2+-CuSO4) for 42 d. The results of increased autophagosomes and autophagy marker LC3B brown cell staining showed that excessive intake of Cu enhanced hepatocyte autophagy. Simultaneously, Cu inhibited the activity of mTOR through suppressing mRNA and protein expressions in mTOR, which in turn up-regulated expression levels of ULK1 and initiated autophagy. Also, over-exposure to Cu increased mRNA and protein expressions of Beclin1, Atg12, Atg5, Atg16L1, Atg7, Atg3, and LC3 and decreased mRNA and protein expressions of p62. These results indicate that excess Cu can enhance hepatocyte autophagy via inhibiting the mTOR signaling pathway and regulating mRNA and protein expressions of factors implicated to autophagy in mice.

Copper exposure induces hepatic G0/G1 cell-cycle arrest through suppressing the Ras/PI3K/Akt signaling pathway in mice.

Copper (Cu), as a common chemical contaminant in environment, is known to be toxic at high concentrations. The current research demonstrates the effects of copper upon hepatocyte cell-cycle progression (CCP) in mice. Institute of cancer research (ICR) mice (n = 240) at an age of four weeks were divided randomly into groups treated with different doses of Cu (0, 4, 8, and 16 mg/kg) for 21 and 42 days. Results showed that high Cu exposure caused hepatocellular G0/G1 cell-cycle arrest (CCA) and reduced cell proportion in the G2/M phase. G0/G1 CCA occurred with down-regulation (p < 0.05) of Ras, p-PI3K (Tyr458), p-Akt (Thr308), p-forkhead box O3 (FOXO3A) (Ser253), p-glycogen synthase kinase 3-ß (GSK3-ß) (Ser9), murine double minute 2 (MDM2) protein, and mRNA expression levels, and up-regulation (p < 0.05) of PTEN, p-p53 (Ser15), p27, p21 protein, and mRNA expression levels, which subsequently suppressed (p < 0.05) the protein and mRNA expression levels of CDK2/4 and cyclin E/D. These results indicate that Cu exposure suppresses the Ras/PI3K/Akt signaling pathway to reduce the level of CDK2/4 and cyclin E/D, which are essential for the G1-S transition, and finally causes hepatocytes G0/G1 CCA.

Immunotoxicity of nickel: Pathological and toxicological effects.

Nickel (Ni) is a widely distributed metal in the environment and an important pollutant because of its many industrial applications. With increasing incidences of Ni contamination, Ni toxicity has become a global public health concern and recent evidence suggests that Ni adversely affects the immune system. Hence, this paper reviews the literature on immune-related effects of Ni exposure, the immunotoxicological effects of Ni, and the underlying mechanism of Ni immunotoxicity. The main focus was on the effect of Ni on the development of organs of immune system, lymphocyte subpopulations, cytokines, immunoglobulins, natural killer (NK) cells, and macrophages. Moreover, Ni toxicity also induces inflammation and several studies demonstrated that Ni could induce immunotoxicity. Excessive Ni exposure can inhibit the development of immune organs by excessively inducing apoptosis and inhibiting proliferation. Furthermore, Ni can decrease T and B lymphocytes, the specific mechanism of which requires further research. The effects of Ni on immunoglobulin A (IgA), IgG, and IgM remain unknown and while Ni inhibited IgA, IgG, and IgM levels in an animal experiment, the opposite result was found in research on humans. Ni inhibits the production of cytokines in non-inflammatory responses. Cytokine levels increased in Ni-induced inflammation responses, and Ni activates inflammation through toll like (TL)4-mediated nuclear factor-κB (NF-κB) and signal transduction cascades mitogen-activated protein kinase (MAPK) pathways. Ni has been indicated to inactivate NK cells and macrophages both in vitro and in vivo. Identifying the mechanisms underlying the Ni-induced immunotoxicity may help to explain the growing risk of infections and cancers in human populations that have been exposed to Ni for a long time. Such knowledge may also help to prevent and treat Ni-related carcinogenicity and toxicology.

Association of white matter hyperintensities with migraine features and prognosis.

BACKGROUND: White matter hyperintensities (WMHs) are frequently detected in migraine patients. However, their significance and correlation to migraine disease burden remain unclear. This study aims to examine the correlation of WMHs with migraine features and explore the relationship between WMHs and migraine prognosis. METHODS: A total of 69 migraineurs underwent MRI scans to evaluate WMHs. Migraine features were compared between patients with and without WMHs. After an average follow-up period of 3 years, these patients were divided into two groups, according to the reduction of headache frequency: improved and non-improved groups. The percentage and degree of WMHs were compared between these two groups. RESULTS: A total of 24 patients (34.8%) had WMHs. Patients with WMHs were significantly older (39.0 ± 7.9 vs. 30.6 ± 10.4 years, P < 0.001) and had a longer disease duration (median: 180.0 vs. 84.0 months, P = 0.013). Furthermore, 33 patients completed the follow up period (15 patients improved and 18 patients did not improve). Patients in the non-improved group had a higher frequency of WMHs (55.6% vs. 13.3%, P = 0.027) and median WMHs score (1.0 vs. 0.0, P = 0.030). CONCLUSIONS: WMHs can predict unfavorable migraine prognosis. Furthermore, WMHs may have a closer association with age than migraine features.

Assessment of myelination progression in subcortical white matter of children aged 6-48 months using T2-weighted imaging.

PURPOSE: This study aims to provide a screening scoring method by assessing the age-related change of subcortical white matter (WM) myelination via T2-weighted imaging (T2WI). METHODS: This study retrospectively recruited 109 children aged 6-48 months without abnormalities on MRI. Based on Parazzini's study, we developed a modified T2WI-based method to assess subcortical WM myelination (frontal, temporal, parietal, occipital lobes, and insula) by scoring WM's signal changes. Inter- and intra-observer agreements were evaluated by Bland-Altman plot. Age-related changes of myelination score were explored by locally weighted scatterplot smoothing (LOESS), linear regression, and Spearman correlation coefficients (r). Relationships between diffusion tensor imaging (DTI) metrics and total myelination score were investigated to further validate practicability of the scoring method by tract-based spatial statistics (TBSS). RESULTS: This method showed good intra-observer (mean difference = 0.18, SD = 0.95) and inter-observer agreements (mean difference = - 0.06, SD = 1.01). The LOESS and linear regression results indicated that myelination proceeded in two phases: a period of rapid growth (6-20 months; slope = 0.561) and one of slower growth (21-48 months; slope = 0.097). Significant correlations between myelination score and age were observed in whole subcortical WM (r = 0.945; P < 0.001) and all regional subcortical WM (r_mean = 0.819, range, 0.664-0.928; P < 0.001). TBSS found significant correlations of WM-DTI metrics with myelination score during the range of 6-20 months, while no significant correlation was observed in 21-48 months. CONCLUSION: The modified T2WI-based screening scoring method is easily feasible to assess myelination progression of subcortical WM, especially suitable for children aged 6-20 months. It may show potential in identifying individual developmental abnormalities by scoring assessment in the future clinical practice.

Right-to-left shunt may be prone to affect the white matter integrity of posterior circulation in migraine without aura.

Numerous studies have indicated an association between migraine and right-to-left shunt. However, little is known about whether right-to-left shunt has an effect on the migraine brain. This observational study aims to explore the impact of right-to-left shunt on the brain of migraine without aura on microstructural level. Thirty-five patients with migraine without aura were enrolled in this study. Contrast-enhanced Transcranial Doppler was performed to evaluate the status of right-to-left shunt. Three-dimensional T1-weighted and diffusion tensor images were acquired for data analysis. We employed voxel-based morphometry and tract-based spatial statistical analyses to assess the differences of gray and white matter between migraineurs with and without right-to-left shunt, respectively. Among the 35 patients, 19 (54.3%) patients had right-to-left shunt. There were no significant differences in headache features between migraineurs with and without right-to-left shunt. There were significant increases of mean and radial diffusivity in migraineurs with right-to-left shunt compared with migraineurs without right-to-left shunt. The alterations were primarily located in the right posterior thalamic radiation, secondly in the body of corpus callosum and the right superior corona radiata. No significant differences were observed in values of fractional anisotropy and axial diffusivity. No significant between-group differences were found in gray matter volume. Right-to-left shunt may cause alterations of white matter integrity in migraine without aura, and the alterations are more likely to be located at the posterior circulation.

Infectivity and pathogenesis characterization of getah virus (GETV) strain via different inoculation routes in mice.

In recent years, the epidemiological profile of Getah virus (GETV) has become increasingly serious, posing a huge threat to animal and public health in China. GETV can cause multi-species infection, including horses, pigs, rats, cattle, kangaroos, reptiles and birds. However, there were few reports on the efficiency of the virus entering the host via routes of different systems. In the present study, a GETV strain (SC201807) was obtained from a piglet's blood in 2018 in Sichuan, China. First, we established a quantitative real-time polymerase chain reaction (qRT-PCR) SYBR assay specific to GETV. Then, we evaluated the infection efficiency of different routes using mouse animal model. 108 male mice were randomly divided into four groups as follows: intramuscular, intraoral and intranasal infection routes, and negative control. All mice in the experimental group were inoculated with 4 × 102.85 TCID50 GETV virus. Tissue tropism experiments show that GETV has a wide range of tissue distribution, and intramuscular infection is the first to infect all tissues of the body, and suggest that oral infection may be a new GETV transmission route. Histopathological examination results showed that intramuscular injection of GETV mainly caused different degrees of pathological damage to the tissues, and could rapidly induce a large amount of inflammatory regulatory factors such as IL-6 and TNF-α. Our data may help us to evaluate the risk of transmission of Porcine Getah virus and provide an experimental basis for the prevention and control of Porcine Getah virus.

Relationship between low relative muscle mass and aortic regional morphological changes in adults underwent contrast CT scans for cancer diagnostics.

OBJECTIVES: Low muscle mass is related to cardiovascular risk factors. This study aimed to investigate whether relative low muscle mass is related to the diameter and tortuosity of the aorta. METHODS: We performed a cross-sectional study of 208 adults without known cardiovascular disease who underwent Computed Tomography (CT) enhanced scan between 2020 and 2021. Skeletal muscle index (SMI) was estimated. The morphology of the aorta was measured by diameter and tortuosity using CT. We assessed the relationship between SMI and diameter and tortuosity of the aorta using Spearman correlation analysis and univariate and multivariate-adjusted regression models. RESULTS: Of all -individuals, 124 (59.6%) were male. The average age was 60.13 ± 16.33 years old. SMI was inversely associated with the diameter and tortuosity of the aorta (p < 0.05). Specifically, in a multivariable-adjusted model adjusting for potential confounders, a one-unit increase in the SMI was associated with a -13.56mm(95% confidence intervals (CI): -18.16 to -8.96, p < 0.001), -7.93 mm (95% CI: -10.85 to -5.02, p < 0.001), -8.01 mm (95% CI: -11.30 to -4.73, p < 0.001), -5.16 mm (95% CI: -7.57 to -2.75, p < 0.001) and -2.73 mm (95% CI: -5.18 to -0.27, p = 0.031) increase in L1-L5 diameter respectively, a -0.89 (95% CI: -1.14 to -0.64, p < 0.001) increase in the aorta tortuosity, a -0.48 (95% CI: -0.59 to -0.36, p < 0.001) increase in the descending thoracic aorta tortuosity, and a -0.44 (95% CI: -0.52 to -0.35, p < 0.001) increase in the abdominal aorta tortuosity. CONCLUSIONS: Relative muscle mass was negatively associated with the diameter and tortuosity of the aorta, suggesting muscle mass maintenance may play a role in preventing aortic morphological changes.

Isolation and pathogenicity comparison of two novel natural recombinant porcine reproductive and respiratory syndrome viruses with different recombination patterns in Southwest China.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the swine industry. Frequent mutations and recombinations account for PRRSV immune evasion and the emergence of novel strains. In this study, we isolated and characterized two novel PRRSV-2 strains from Southwest China exhibiting distinct recombination patterns. They were designated SCABTC-202305 and SCABTC-202309. Phylogenetic results indicated that SCABTC-202305 was classified as lineage 8, and SCABTC-202309 was classified as lineage 1.8. Amino acid mutation analysis identified unique amino acid substitutions and deletions in ORF5 and Nsp2 genes. The results of the recombination analysis revealed that SCABTC-202305 is a recombinant with JXA1 as the major parental strain and NADC30 as the minor parental strain. At the same time, SCABTC-202309 is identified as a recombinant with NADC30 as the major parental strain and JXA1 as the minor parental strain. In this study, we infected piglets with SCABTC-202305, SCABTC-202309, or mock inoculum (control) to study the pathogenicity of these isolates. Although both isolated strains were pathogenic, SCABTC-202305-infected piglets exhibited more severe clinical signs and higher mortality, viral load, and antibody response than SCABTC-202309-infected piglets. SCABTC-202305 also caused more extensive lung lesions based on histopathology. Our findings suggest that the divergent pathogenicity observed between the two novel PRRSV isolates may be attributed to variations in the genetic information encoded by specific genomic regions. Elucidating the genetic determinants governing PRRSV virulence and transmissibility will inform efforts to control this devastating swine pathogen.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the most critical pathogens impacting the global swine industry. Frequent mutations and recombinations have made the control of PRRSV increasingly difficult. Following the NADC30-like PRRSV pandemic, recombination events involving PRRSV strains have further increased. We isolated two novel field PRRSV recombinant strains, SCABTC-202305 and SCABTC-202309, exhibiting different recombination patterns and compared their pathogenicity in animal experiments. The isolates caused higher viral loads, persistent fever, marked weight loss, moderate respiratory clinical signs, and severe histopathologic lung lesions in piglets. Elucidating correlations between recombinant regions and pathogenicity in these isolates can inform epidemiologic tracking of emerging strains and investigations into viral adaptive mechanisms underlying PRRSV immunity evasion. Our findings underscore the importance of continued genomic surveillance to curb this economically damaging pathogen.

A time-course transcriptome analysis revealing the potential molecular mechanism of early gonadal differentiation in the Chinese giant salamander.

The Chinese giant salamander (CGS) Andrias davidianus is the largest extant amphibian and has recently become an important species for aquaculture with high economic value. Meanwhile, its wild populations and diversity are in urgent need of protection. Exploring the mechanism of its early gonadal differentiation will contribute to the development of CGS aquaculture and the recovery of its wild population. In this study, transcriptomic and phenotypic research was conducted on the critical time points of early gonadal differentiation of CGS. The results indicate that around 210 days post-hatching (dph) is the critical window for female CGS's gonadal differentiation, while 270 dph is that of male CGS. Besides, the TRPM1 gene may be the crucial gene among many candidates determining the sex of CGS. More importantly, in our study, key genes involved in CGS's gonadal differentiation and development are identified and their potential pathways and regulatory models at early stage are outlined. This is an initial exploration of the molecular mechanisms of CGS's early gonadal differentiation at multiple time points, providing essential theoretical foundations for its captive breeding and offering unique insights into the conservation of genetic diversity in wild populations from the perspective of sex development.

Multi-parametric Retinal Microvascular Functional Perfusion Imaging Based on Dynamic Fundus Fluorescence Angiography.

Retinal microvascular disease has caused serious visual impairment widely in the world, which can be hopefully prevented via early and precision microvascular hemodynamic diagnosis. Due to artifacts from choroidal microvessels and tiny movements, current fundus microvascular imaging techniques including fundus fluorescein angiography (FFA) precisely identify retinal microvascular microstructural damage and abnormal hemodynamic changes difficulty, especially in the early stage. Therefore, this study proposes an FFA-based multi-parametric retinal microvascular functional perfusion imaging (RM-FPI) scheme to assess the microstructural damage and quantify its hemodynamic distribution precisely. Herein, a spatiotemporal filter based on singular value decomposition combined with a lognormal fitting model was used to remove the above artifacts. Dynamic FFAs of patients (n = 7) were collected first. The retinal time fluorescence intensity curves were extracted and the corresponding perfusion parameters were estimated after decomposition filtering and model fitting. Compared with in vivo results without filtering and fitting, the signal-to-clutter ratio of retinal perfusion curves, average contrast, and resolution of RM-FPI were up to 7.32 ± 0.43 dB, 14.34 ± 0.24 dB, and 11.0 ± 2.0 µm, respectively. RM-FPI imaged retinal microvascular distribution and quantified its spatial hemodynamic changes, which further characterized the parabolic distribution of local blood flow within diameters ranging from 9 to 400 µm. Finally, RM-FPI was used to quantify, visualize, and diagnose the retinal hemodynamics of retinal vein occlusion from mild to severe. Therefore, this study provided a scheme for early and precision diagnosis of retinal microvascular disease, which might be beneficial in preventing its development.

Advances in the mechanism of inflammasomes activation in herpes virus infection.

Herpesviruses, prevalent DNA viruses with a double-stranded structure, establish enduring infections and play a part in various diseases. Despite their deployment of multiple tactics to evade the immune system, both localized and systemic inflammatory responses are triggered by the innate immune system's recognition of them. Recent progress has offered more profound understandings of the mechanisms behind the activation of the innate immune system by herpesviruses, specifically through inflammatory signaling. This process encompasses the initiation of an intracellular nucleoprotein complex, the inflammasome associated with inflammation.Following activation, proinflammatory cytokines such as IL-1ß and IL-18 are released by the inflammasome, concurrently instigating a programmed pathway for cell death. Despite the structural resemblances between herpesviruses, the distinctive methods of inflammatory activation and the ensuing outcomes in diseases linked to the virus exhibit variations.The objective of this review is to emphasize both the similarities and differences in the mechanisms of inflammatory activation among herpesviruses, elucidating their significance in diseases resulting from these viral infections.Additionally, it identifies areas requiring further research to comprehensively grasp the impact of this crucial innate immune signaling pathway on the pathogenesis of these prevalent viruses.

Transcriptome and metabolome analysis reveals PRV XJ delgE/gI/TK protects intracranially infected mice from death by regulating the inflammation.

Pseudorabies virus can cause inflammation in the central nervous system and neurological symptoms. To further investigate the protective mechanism of PRV XJ delgE/gI/TK in the central nervous system, an intracranial PRV-infection mice model was developed. The results demonstrated that immunization with PRV XJ delgE/gI/TK successfully prevented death caused by PRV-intracranial infection. Subsequently, the brains were collected for transcriptome and metabolome analysis. GO and KEGG enrichment analysis indicated that the differentially expressed genes were primarily enriched in pathways such as TNF, NOD-like receptor, JAK-STAT, MAPK, IL-17 and apoptosis signaling. Metabolomics analysis revealed that the differential metabolites were mainly associated with pathways such as fatty acid degradation, arachidonic acid metabolism, linoleic acid metabolism and unsaturated fatty acid biosynthesis. The combined analysis of metabolites and differentially expressed genes revealed a strong correlation between the differential metabolites and TNF, PI3K, and MAPK signaling pathways. Anti-inflammatory metabolites have been shown to inhibit the inflammatory response and prevent mouse death caused by PRV infection. Notably, when glutathione was injected intracranially and dihydroartemisinin was injected intraperitoneally, complete protection against PRV-induced death in mice was observed. Moreover, PRV activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrates that PRV XJ delgE/gI/TK can protects intracranially infected mice from death by regulating various metabolites with anti-inflammatory functions post-immunization.

Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption.

The low-carbohydrate ketogenic diet (KD) has long been practiced for weight loss, but the underlying mechanisms remain elusive. Gut microbiota and metabolites have been suggested to mediate the metabolic changes caused by KD consumption, although the particular gut microbes or metabolites involved are unclear. Here, we show that KD consumption enhances serum levels of taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA) in mice to decrease body weight and fasting glucose levels. Mechanistically, KD feeding decreases the abundance of a bile salt hydrolase (BSH)-coding gut bacterium, Lactobacillus murinus ASF361. The reduction of L. murinus ASF361 or inhibition of BSH activity increases the circulating levels of TDCA and TUDCA, thereby reducing energy absorption by inhibiting intestinal carbonic anhydrase 1 expression, which leads to weight loss. TDCA and TUDCA treatments have been found to protect against obesity and its complications in multiple mouse models. Additionally, the associations among the abovementioned bile acids, microbial BSH and metabolic traits were consistently observed both in an observational study of healthy human participants (n = 416) and in a low-carbohydrate KD interventional study of participants who were either overweight or with obesity (n = 25). In summary, we uncover a unique host-gut microbiota metabolic interaction mechanism for KD consumption to decrease body weight and fasting glucose levels. Our findings support TDCA and TUDCA as two promising drug candidates for obesity and its complications in addition to a KD.