Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases.

Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies. To determine the neurobiological underpinnings of GM atrophies in multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, and MOGAD, we conducted a virtual histology analysis that links T1-weighted image derived GM atrophy and gene expression using a multicenter cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD, and 2,169 healthy controls (HCs). First, interregional GM atrophy profiles across the cortical and subcortical regions were determined by Cohen's d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, MOGAD and HCs. Then, the GM atrophy profiles were spatially correlated with the gene expressions extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical feature relevant GM atrophy by subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden, and cognitive function. Multiple sclerosis showed severe widespread GM atrophy pattern, mainly involving subcortical nuclei and brainstem. AQP4+ NMOSD showed obvious widespread GM atrophy pattern, predominately located in occipital cortex as well as cerebellum. AQP4- NMOSD showed mild widespread GM atrophy pattern, mainly located in frontal and parietal cortices. MOGAD showed GM atrophy mainly involving the frontal and temporal cortices. High expression of genes specific to microglia, astrocytes, oligodendrocytes, and endothelial cells in multiple sclerosis, S1 pyramidal cells in AQP4+ NMOSD, as well as S1 and CA1 pyramidal cells in MOGAD had spatial correlations with GM atrophy profiles were observed, while no atrophy profile related gene expression was found in AQP4- NMOSD. Virtual histology of clinical feature relevant GM atrophy mainly pointed to the shared neuronal and endothelial cells among the four neuroinflammatory diseases. The unique underlying virtual histology patterns were microglia, astrocytes, and oligodendrocytes for multiple sclerosis; astrocytes for AQP4+ NMOSD; and oligodendrocytes for MOGAD. Neuronal and endothelial cells were shared potential targets across these neuroinflammatory diseases. These findings might help their differential diagnosis and optimal therapeutic strategies.

Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

Relationship between gut microbiota and nutritional status in patients on peritoneal dialysis.

Malnutrition is a common complication in the dialysis population, both hemodialysis and peritoneal dialysis (PD). We report our exploratory study on the characteristics of intestinal microbiota and nutritional status in PD patients. The nutritional status of our PD patients were evaluated, and their feces were collected for 16S rRNA gene V3-V4 regions amplification and high-throughput sequencing. The characteristics and differences of microbiota between the well-nourished (W) and malnourished (M) groups were compared. We studied the genera and the operational taxonomic units (OTUs) within the genus of our patients, initially comparing the malnourished and the well- nourished groups and later on reanalyzing the whole group using these OTUs. At the OTU level, 6 bacteria were significantly correlated with the serum albumin level. The abundances of 2 OTUs (OTU208 Lachnospiraceae_incertae_sedi and OTU4 Bacteroides) were more in W group. Meanwhile, 4 OTUs (OTU225 Akkermansia, OTU87 Megasphaera, OTU31 Peptostreptococcaceae_incertae_sedi and OTU168 Clostridium_sensu_strictu) displayed higher abundance among individuals in M group. Notably, the OTU168 Clostridium_sensu_stricto was the only bacteria that significantly correlated with serum albumin (r = - 0.356, P = 0.05), pre-albumin (r = - 0.399, P = 0.02), and SGA (r = 0.458, P = 0.01). The higher the OTU168 Clostridium_sensu_strictu, the lower serum albumin and pre-albumin and a higher score of SGA signifying a worse nutritional status. Our preliminary findings suggested a relationship between the nutrition status and microbiota in PD patients. Our results provide a basis for further exploration of the interactions between malnutrition and intestinal flora in PD patients with potential interventions using probiotics and prebiotics.

Gel-type emulsified muscle products: Mechanisms, affecting factors, and applications.

The gel-type emulsified muscle products improve fatty acid composition, maintain the oxidative stability, and achieve a better sensory acceptability. This review emphasizes the stabilization mechanisms of these emulsified muscle products. In particular, factors associated with the stability of the emulsified muscle systems are outlined, including the processing conditions (pH and heating), lipids, and emulsifiers. Besides, some novel systems are further introduced, including the Pickering emulsions and organogels, due to their great potential in stabilizing emulsified gels. Moreover, the promising prospects of emulsion muscle products such as improved gel properties, oxidative stability, freeze-thaw stability, fat replacement, and nutraceutical encapsulation were elaborated. This review comprehensively illustrates the considerations on developing gel-type emulsified products and provides inspiration for the rational design of emulsified muscle formulations with both oxidatively stable and organoleptically acceptable performance.

The Immunity Protection of Central Nervous System Induced by Pseudorabies Virus DelgI/gE/TK in Mice.

Based on a variant strain, we constructed a gE/gI/TK-deleted pseudorabies virus (PRV). A total of 18 female mice were randomized to a vaccination group to receive PRV XJ delgE/gI/TK, a vehicle group to receive Dulbecco's modified Eagle's medium, and a mock group to confirm the protection of PRV delgE/gI/TK on the central nervous system in mice. Subsequently, the vaccination and vehicle groups were infected with PRV XJ. The mice in the vehicle group showed more severe neurological symptoms and higher viral loads than those in the vaccination group. The exudation of Evans blue and the expression of tight junction protein showed no difference in all groups. HE staining showed vacuolar neuronal degeneration in the vehicle group brain, but no tissue lesions were observed in the vaccination group. TNF-α, IL-6, and synuclein were upregulated in the brain of mice in the vehicle group, while those were inhibited among mice in the vaccination group. IFN-ß, IFN-γ, ISG15, Mx1, and OAS1 showed no difference in the brain between the vaccination and vehicle groups. In addition, TNF-α and IL-6 were inhibited, and antiviral factors were increased in the intestine of the mice in the vaccination group compared to those in the vehicle group. Our study showed that PRV XJ delgE/gI/TK inhibited neurological damage and the inflammation of the intestine and brain induced by PRV and activated the innate immunity of the intestine.

mTORC1-Rps15 Axis Contributes to the Mechanisms Underlying Global Translation Reduction During Senescence of Mouse Embryonic Fibroblasts.

The reduction of protein translation is a common feature in senescent cells and aging organisms, yet the underlying mechanisms are not fully understood. Here we show that both global mRNA translation and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) kinase activity are declined in a senescent model of mouse embryonic fibroblasts (MEFs). Furthermore, RNA-seq analyses from polysomal versus total mRNA fractions identify TOP-like mRNA of Rps15 whose translation is regulated by mTORC1 during MEF senescence. Overexpression of Rps15 delays MEF senescence, possibly through regulating ribosome maturation. Together, these findings indicate that the activation of mTORC1-Rps15 axis ameliorate senescence by regulating ribosome biogenesis, which may provide further insights into aging research.

Is Overexpression of Ki-67 a Prognostic Biomarker of Upper Tract Urinary Carcinoma? A Retrospective Cohort Study and Meta-Analysis.

BACKGROUND: Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. The Ki-67 antigen is a classic marker of cellular proliferation, but there is still controversy regarding the significance and importance of Ki-67 in tumor progression. METHODS: In this study, we first detected Ki-67 expression in UTUC patients by immunohistochemistry (IHC). Subsequently, we quantitatively combined the results with those from the published literature in a meta-analysis after searching several databases. RESULTS: IHC results demonstrated that patients with muscle-invasive tumors (T2-T4) had higher Ki-67 expression than those with non-muscle-invasive tumors (Tis-T1), suggesting that high Ki-67 expression may be associated with the aggressive form of UTUC. Kaplan-Meier curves showed that patients with high Ki-67 expression had significantly poorer cancer-specific survival (CSS) and disease-free survival (DFS). Furthermore, multivariate analysis suggested that Ki-67 expression was an independent prognostic factor for CSS (hazard ratio, HR=3.196) and DFS (HR=3.517) in UTUC patients. Then, a meta-analysis of the published literature investigating Ki-67 expression and its effects on UTUC prognosis was conducted. After searching the PubMed, Medline, Embase, Cochrane Library and Scopus databases, 12 articles met the eligibility criteria for this analysis. The eligible studies included a total of 1740 patients with a mean number of 82 patients per study (range, 38-475). The combined results showed that increased Ki-67 levels were associated with poor survival and disease progression, with a pooled HR estimate of 2.081 and 2.791, respectively. In subgroup analysis, the pooled HR was statistically significant for cancer-specific survival (HR=2.276), metastasis-free survival (HR=3.008) and disease-free survival (HR=6.336). CONCLUSIONS: In conclusion, high Ki-67 expression was associated with poor survival in patients with UTUC, as well as a high risk of disease progression, although these findings need to be interpreted with caution. Large-scale, adequately designed, prospective trials are needed to further confirm the value of Ki-67 in prognosis of UTUC patients.