Cordyceps cicadae (Hypocreales: Cordycipitaceae) is a renowned entomopathogenic fungus used as herbal medicine in China. However, wild C. cicadae resources have been threatened by heavy harvesting. ...We hypothesised that Bombyx mori L. (Lepidoptera: Bombycidae) could be a new alternative to cultivate C. cicadae due to the low cost of rearing. Bacterial communities are crucial for the formation of Cordyceps and for promoting the production of metabolites. To better understand the bacterial community structure associated with Cordyceps, three Claviciptaceae fungi were used to explore the pathogenicity of the silkworms. Here, fifth-instar silkworms were infected with C. cicadae, Cordyceps cateniannulata (Hypocreales: Cordycipitaceae) and Beauveria bassiana (Hypocreales: Cordycipitaceae). Subsequently, we applied high-throughput sequencing to explore the composition of bacterial communities in silkworms. Our results showed that all three fungi were highly pathogenic to silkworms, which suggests that silkworms have the potential to cultivate Cordyceps. After fungal infection, the diversity of bacterial communities in silkworms decreased significantly, and the abundance of Staphylococcus increased in mummified larvae, which may play a role in the death process when the host suffers infection by entomopathogenic fungi. Furthermore, there were high similarities in the bacterial community composition and function in the C. cicadae and C. cateniannulata infected samples, and the phylogenetic analysis suggested that these similarities may be related to the fungal phylogenetic relationship. Our findings reveal that infection with different entomopathogenic fungi affects the composition and function of bacterial communities in silkworms and that the bacterial species associated with Cordyceps are primarily host dependent, while fungal infection affects bacterial abundance.
BACKGROUNDPrevious study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of ...3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis.METHODSHMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)2D3 supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)2D3-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)2D3 protecting against experimental colitis.RESULTSIntestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)2D3 supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)2D3 supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)2D3 in DSS-treated HT-29 cells.CONCLUSION1,25(OH)2D3 supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)2D3-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.
Aplastic anemia (AA) is a bone marrow failure disease caused by T cell hyperfunction. Although the overall response rate has been improved by immunosuppressive therapy (IST) plus Eltrombopag, 30% of ...patients have either no response or relapse. We therefore attempted to find other ways to improve the outcomes of AA patients. Traditional Chinese medicine has the advantages of low cost, reasonable effects, and few side effects. More and more clinical studies have confirmed that traditional Chinese medicine has a beneficial role in treating AA patients. This article reviews the potential mechanism of traditional Chinese medicine or its active ingredients in the treatment of AA. These include improving the bone marrow microenvironment, regulating immunity, and affecting the fate of hematopoietic stem cells. This provides useful information for further treatment of AA with integration of traditional Chinese and Western medicine and the development of new treatment strategies.
In order to improve the dielectric thermal stability of polyvinylidene fluoride (PVDF)-based film, nano silicon nitride (Si3N4) was introduced, and hence the energy storage performance was improved. ...The introduction of nano Si3N4 fillers will induce a phase transition of P(VDF-HFP) from polar β to nonpolar α, which leads to the improved energy storage property. As such, the discharging energy density of Si3N4/P(VDF-HFP) composite films increased with the amount of doped Si3N4. After incorporating 10wt% Si3N4 in Si3N4/P(VDF-HFP) films, the discharging density increased to 1.2 J/cm3 under a relatively low electric field of 100 MV/m. Compared with a pure P(VDF-HFP) film, both the discharging energy density and thermal dielectric relaxor temperature of Si3N4/P(VDF-HFP) increased. The working temperature increased from 80 °C to 120 °C, which is significant for ensuring its adaptability in high-temperature energy storage areas. Thus, this result indicates that Si3N4 is a key filler that can improve the thermal stability of PVDF-based energy storage polymer films and may provide a reference for high-temperature capacitor materials.
Lipid peroxidation due to oxidative stress (OS) may play an important role in the pathogenesis of chronic systemic inflammatory diseases such as multiple sclerosis (MS). Telomeres, repeated sequences ...that cap chromosome ends, undergo shortening with each cycle of cell division, resulting in cellular senescence. Research regarding telomere shortening has provided novel insight into the pathogenesis of various diseases. We hypothesized that OS damage leads to inflammatory reactions, which subsequently shortens the telomere length in MS. We enrolled 59 patients with MS, and age- and gender-matched 60 healthy controls. We divided MS subjects into three groups matched for age and gender according to the severity of disability: relatively benign course (BMS), secondary progressive MS, and primary progressive MS (PPMS). We analyzed the telomere length in peripheral blood mononuclear cells and the 8-iso-PGF2
α
concentration in urine, a reliable and stable marker of lipid peroxidation in vivo. The data showed significant higher levels of urinary 8-iso-PGF2
α
in MS subjects than in the controls. The lag-time, which represents the direct measurement of the resistance of low-density lipoprotein to oxidation, was shorter in the PPMS subjects than in the groups. Compared to that observed in the controls, the mean telomere length was significantly shorter in the PPMS group, whereas no significant telomere shortening was found between the controls and other subjects. Our data suggest that a decreased telomere length and enhanced lipid peroxidation reflects the severest stage of MS.
Abstract
Background
Stromal cells play an important role in the process of tumor progression, but the relationship between stromal cells and metabolic reprogramming is not very clear in gastric ...cancer (GC).
Methods
Metabolism-related genes associated with stromal cells were identified in The Cancer Genome Atlas (TCGA) and GSE84437 datasets, and the two datasets with 804 GC patients were integrated into a training cohort to establish the prognostic signature. Univariate Cox regression analysis was used to screen for prognosis-related genes. A risk score was constructed by LASSO regression analysis combined with multivariate Cox regression analysis. The patients were classified into groups with high and low risk according to the median value. Two independent cohorts, GSE62254 (n = 300) and GSE15459 (n = 191), were used to externally verify the risk score performance. The CIBERSORT method was applied to quantify the immune cell infiltration of all included samples.
Results
A risk score consisting of 24 metabolic genes showed good performance in predicting the overall survival (OS) of GC patients in both the training (TCGA and GSE84437) and testing cohorts (GSE62254 and GSE15459). As the risk score increased, the patients’ risk of death increased. The risk score was an independent prognostic indicator in both the training and testing cohorts suggested by the univariate and multivariate Cox regression analyses. The patients were clustered into four subtypes according to the quantification of 22 kinds of immune cell infiltration (ICI). The proportion of ICI Cluster C with the best prognosis in the low-risk group was approximately twice as high as that in the high-risk group, and the risk score of ICI Cluster C was significantly lower than that of the other three subtypes.
Conclusion
Our study proposed the first scheme for prognostic risk classification of GC from the perspective of tumor stromal cells and metabolic reprogramming, which may contribute to the development of therapeutic strategies for GC.
Estimating the causal impact of sport or physical activity on health and well-being is an issue of great relevance in the sport and health literature. The increasing availability of individual level ...data has encouraged this interest. However, this analysis requires dealing with two types of simultaneity problem: (1) between exercise and response variables; and (2) across the different response variables. This note discusses how the previous literature has dealt with these two questions with particular attention paid to the use of seemingly aseptic econometric models proposed by some recent empirical papers. Regardless of the approach, identification necessarily requires the use of untestable hypotheses. We provide some recommendations based on analyzing the robustness of the estimation results to changes in the adopted identification assumptions.
BackgroundRecent studies suggest machine learning represents a promising predictive option for patients in intensive care units (ICU). However, the machine learning performance regarding its actual ...predictive value for early detection in acute kidney injury (AKI) patients remains uncertain.ObjectiveThis study represents the inaugural meta-analysis aiming to investigate the predictive value of machine learning for assessing the risk of AKI among ICU patients.MethodsPubMed, Web of Science, Embase, and the Cochrane Library were all thoroughly searched from inception to June 25, 2022. Eligible studies for inclusion were those concentrating on the predictive value and the development, validation, or enhancement of a prediction model for AKI patients in the ICU. Measures of effects, including c-index, sensitivity, specificity, and their corresponding 95% confidence intervals (CIs), were employed for analysis. The risk of bias in the included original studies was assessed using Probst. The meta-analysis in our study was carried out using R version 4.2.0.ResultsThe systematic search yielded 29 articles describing 13 machine-learning models, including 86 models in the training set and 57 in the validation set. The overall c-index was 0.767 (95% CI 0.746, 0.788) in the training set and 0.773 (95% CI 0.741, 0.804) in the validation set. The sensitivity and specificity of included studies are as follows: sensitivity train: 0.66 (95% CI 0.59, 0.73), validation: 0.73 (95% CI 0.68, 0.77); and specificity train: 0.83 (95% CI 0.78, 0.87), validation: 0.75 (95% CI 0.71, 0.79).ConclusionThe machine learning-based method for predicting the risk of AKI in hospital ICU patients has excellent predictive value and could potentially serve as a prospective application strategy for early identification. PROSPERO Registration number ID: CRD42022362838.
Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause ...serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity.
The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain.
We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 μM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 μM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in "ribosome biogenesis (GO:0042254)" and "ribosome (GO:0005840)" were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis.
Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis.
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