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Objective Mild cognitive impairment (MCI) is a pre-dementia state; 5-10% of cases per year will evolve into dementia. MCI can be amnestic (AMCI) or non-amnestic. AMCI is associated with a higher risk of progression.

Elimination of autoreactive CD4þ T cells through the death receptor Fas/CD95 is an important mechanism of immunological selftolerance. Fas deficiency results in systemic autoimmunity, yet does not affect the kinetics of T-cell responses to acute antigen exposure or infection. Here we show that Fas and TCR-induced apoptosis are largely restricted to CD4 þ T cells with an effector memory phenotype (effector memory T cells (T EM )), whereas central memory and activated naïve CD4 þ T cells are relatively resistant to both. Sensitivity of T EM to Fas-induced apoptosis depends on enrichment of Fas in lipid raft microdomains, and is linked to more efficient formation of the Fas death-inducing signaling complex. These results explain how Fas can cull T cells reactive against self-antigens without affecting acute immune responses. This work also identifies Fas-induced apoptosis as a possible immunotherapeutic strategy to eliminate T EM linked to the pathogenesis of a number of autoimmune diseases.

This study investigated the changes in brain-derived neurotrophic factor (BDNF) expression and the role of furin in BDNF maturation in reactive astrocytes from rats exposed to oxygen-glucose deprivation (OGD). Furin, a proprotein convertase, is upregulated and cleaves certain substrates during hypoxia in cancer cells. In addition, during hypoxia in the central nervous system, astrocytes become reactive and release BDNF to protect neurons. Maturation of BDNF in astrocytes requires furin-mediated endoproteolytic processing of the precursor protein pro-BDNF to BDNF. To expand our knowledge about the role of furin in BDNF maturation in astrocytes, these cells were exposed to OGD, and expression of furin and BDNF was detected by Western blot analysis. Changes in BDNF expression were observed when furin activity was inhibited by furin prosegment. We found that protein expression of BDNF and furin was upregulated, and this upregulation correlated with OGD stimulation. Furin inhibition reduced BDNF maturation and secretion. These results indicate that furin mediates the upregulation of BDNF in reactive astrocytes exposed to OGD and that furin may impact the biological effect of reactive astrocytes.

Background Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors with poor survival. Pyroptosis is a kind of programmed cell death that can regulate the proliferation, invasion, and metastasis of tumor cells. However, the expression levels of pyroptosis-related genes (PRGs) in HCC and their relationship with prognosis are still unclear. Methods Our study identified 35 PRGs through bioinformatics analysis that were differentially expressed between tumor samples and nontumor samples. According to these differentially expressed genes, HCC patients could be divided into two groups, cluster 1 and cluster 2. The least absolute shrinkage and selection operator (LASSO) Cox regression method was performed to construct a 10-gene signature that classified HCC patients in the cancer genome atlas (TCGA) database into low-risk and high-risk groups. Results The results showed that the survival rate of HCC patients in the low-risk group was significantly higher than that in the high-risk group (p < 0.001). The validation cohort, the Gene Expression Omnibus (GEO) cohort, was divided into two risk groups based on the median risk score calculated by the TCGA cohort. The overall survival (OS) of the low-risk group was significantly better than that of the high-risk group (p = 0.007). Univariate and multivariate Cox regression analyses revealed that the risk score was an independent factor in predicting OS in HCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that immune-related high-risk groups were rich in genes and had reduced immune status. Conclusions PRGs play a significant role in tumor immunity and have the potential capability to predict the prognosis of HCC patients.

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PURPOSE To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

This study evaluated the potential for using cowpeat, a composted dairy manure, as a component of container substrates for foliage plant propagation. Using a commercial formulation (20% perlite and 20% vermiculite with 60% Canadian or Florida peat based on volume) as controls, peat was replaced by cowpeat at 10% increments up to 60%, which resulted in a total of 14 substrates. Physical and chemical properties such as air space, bulk density, container capacity, total porosity, pH, carbon-to-nitrogen ratio, and cation exchange capacity of the cowpeat-substituted substrates were largely similar to those of the respective control. However, the electrical conductivity (EC) increased with the increased volume of cowpeat. The 14 substrates were used for rooting single-node cuttings of golden pothos (Epipremnum aureum) and heartleaf philodendron (Philodendron scandens ssp. oxycardium) and three-node cuttings of ‘Florida Spire’ fig (Ficus benjamina) and germinating seeds of sprenger asparagus (Asparagus densiflorus) in a shaded greenhouse. All cuttings rooted in the 14 substrates, and the resultant shoot and root dry weights of golden pothos and ‘Florida Spire’ fig 2 months after rooting did not significantly vary across seven Canadian peat- or Florida peat-based substrates. Shoot dry weights of heartleaf philodendron were also similar across substrates, but the root dry weight produced in the Canadian peat-based control substrate was much greater than that produced in the substrate containing 60% cowpeat. Root dry weight and root length produced in the Florida peat-based control substrate were also significantly greater than those produced in substrates substituted by 60% cowpeat. These results may indicate that cuttings of golden pothos and ‘Florida Spire’ fig are more tolerant of higher EC than those of heartleaf philodendron, as the substrate with 60% cowpeat had EC ≥ 4.16 dS·m−1. Seed germination rates of sprenger asparagus from cowpeat-substituted Canadian peat-based substrates were greater than or comparable to those of the control substrate. Seed germination rates were similar across the seven Florida peat-based substrates. The root-to-shoot ratios of seedlings germinated from both control substrates were significantly greater than those germinated from substrates substituted by cowpeat. This difference could be partially explained by the higher nutrient content in cowpeat-substituted substrates where shoot growth was favored over root growth. Propagation is a critical stage in commercial production of containerized plants. The success in using up to 60% cowpeat in rooting and seed germination substrates may suggest that cowpeat could be an alternative to peat for foliage plant propagation.