Oncogenic magnesium transporter 1 upregulates programmed death-1-ligand 1 expression and contributes to growth and radioresistance of glioma cells through the ERK/MAPK signaling pathway

Radiotherapy has been established as a major therapeutic modality for glioma, whereas new therapeutic targets are needed to prevent tumor recurrence. This study intends to explore the regulatory role of magnesium transporter 1 (MAGT1) in radiotherapy resistance of glioma through modulating ERK and programmed death-1-ligand 1 (PD-L1). Our bioinformatics analysis identified differentially expressed MAGT1 in glioma, expression of which was subsequently determined in cohort data of TCGA database and microarray dataset as well as glioma cell lines. Artificial modulation of MAGT1, ERK, and PD-L1 expression was performed to examine their effects on glioma cell proliferation and radioresistance, as reflected by MTT and colony formation assays under irradiation. Mouse glioma cells with manipulated MAGT1 and ERK inhibitors were further injected into mice to assess the in vivo tumor formation ability of glioma cells. It was noted that MAGT1 expression was highly expressed in glioma tissues of TCGA data and microarray dataset, which was then validated in glioma cell lines. Ectopic expression of MAGT1 was revealed to promote the proliferation and radioresistance of glioma cells, which was attributed to the MAGT1-mediated activation of the ERK/MAPK signaling pathway. It was illuminated that MAGT1 stimulated PD-L1 expression through the ERK/MAPK pathway and thus facilitated glioma cell growth. Additionally, MAGT1 overexpression accelerated the in vivo tumor formation of glioma cells, while the ERK inhibitor negated its effect. In conclusion, MAGT1 enhances the growth and radioresistance of glioma cells through the ERK/MAPK signaling pathway-mediated upregulation of PD-L1 expression.</p

Table_1_Chemoselectivity in Gold(I)-Catalyzed Propargyl Ester Reactions: Insights From DFT Calculations.DOCX

Au-catalyzed propargyl ester reactions have been investigated by a comprehensive density functional theory (DFT) study. Our calculations explain the experimental observed chemoselectivity of Au-catalyzed propargyl ester reactions very well by considering all possible pathways both in the absence and presence of 1,2,3-triazole (TA). The “X-factor” of TA is disclosed to have triple effects on this reaction. First of all, it can stabilize and prevent rapid decomposition of the Au catalyst. Secondly, the existence of TA promotes the nucleophilic attack and alters the chemoselectivity of this reaction. Moreover, TA acts as a “relay” to promote the proton transfer.</p

Data_Sheet_1_Causal relationship between tea intake and cardiovascular diseases: A Mendelian randomization study.docx

BackgroundAlthough studies suggest that tea consumption is associated with a reduced risk of cardiovascular disease (CVD). There is no unified conclusion about the potential relationship between tea drinking and CVD. We used a two-sample Mendelian randomized (MR) analysis to systematically explore the causal relationship between tea intake and CVD subtypes for the first time. Furthermore the mediating effect of hypertension was also explored by a two-step MR.MethodsGenetic instruments for tea intake were identified from a genome-wide association studies (GWAS) involving 447,485 people. Summary data on cardio-vascular disease came from different GWAS meta-analysis studies. In the first step we explored the causal effect of tea intake and CVD. In the second step, we examined the association of hypertension with heart failure and ischemic stroke and estimated the mediating effect of hypertension. Inverse variance weighted MR analysis was used as the primary method for causal analysis. A further sensitivity analysis was performed to ensure robustness of the results.ResultsOne standard deviation increase in tea intake was associated with a 25% (OR = 0.75, 95%CI = 0.61–0.91, p = 0.003) lower risk of hypertension, a 28% (OR = 0.72, 95%CI = 0.58–0.89, p = 0.002) lower risk of heart failure, and a 29% (OR = 0.71, 95%CI = 0.55–0.92, p = 0.008) lower risk of ischemic stroke, respectively. And the association between tea drinking and the risk of heart failure and ischemic stroke may be mediated by hypertension. Sensitivity analyses found little evidence of pleiotropy.ConclusionOur two-sample MR analysis provided genetic evidence that tea intake was significantly associated with a reduced risk of hypertension, heart failure, and ischemic stroke, and that hypertension may be a potential mediator. Further large randomized controlled trials should be conducted to confirm the causal effect of tea consumption on cardiovascular disease risk.</p

Image_2_Abundant and Rare Microbial Communities Respectively Contribute to an Aquaculture Pond Ecosystem.tif

Unraveling the assembly mechanism is a core research topic of microbial ecology. Abundant and rare microbial communities are crucial for diversity, function and host health in a given ecosystem, but few studies focused on their assembly strategies. Here, we explored the microbial diversity of abundant and rare communities of water, shrimp intestine and sediment habitats in the shrimp cultural ponds. Our results found that the numbers of rare operational taxonomic units (OTUs) (6,003, 4,566 and 8,237 OTUs of water, intestine and sediment) was dozens of times more than abundant ones (only 199, 157 and 122 OTUs of water, intestine and sediment). The community diversity of abundant and rare microbial taxa was markedly different, as well as their taxonomic composition. Despite different diversity, similar abundance-occupancy relationship and biogeographic patterns between the abundant and rare microbial communities were observed, with much stronger obvious distance-decay relationships for rare community than abundant community. Furthermore, stochastic processes dominated the community assemblies of both abundant and rare microbial taxa, and deterministic process contributed more microbial community variation to rare taxa than abundant taxa. All the findings advance our understanding on the community assembly strategies of abundant and rare microbial taxa and prompt the contributions of abundant and rare microbial community to the aquatic ecosystems, which will improve aquaculture management strategy.</p

Image_4_Abundant and Rare Microbial Communities Respectively Contribute to an Aquaculture Pond Ecosystem.tif

Unraveling the assembly mechanism is a core research topic of microbial ecology. Abundant and rare microbial communities are crucial for diversity, function and host health in a given ecosystem, but few studies focused on their assembly strategies. Here, we explored the microbial diversity of abundant and rare communities of water, shrimp intestine and sediment habitats in the shrimp cultural ponds. Our results found that the numbers of rare operational taxonomic units (OTUs) (6,003, 4,566 and 8,237 OTUs of water, intestine and sediment) was dozens of times more than abundant ones (only 199, 157 and 122 OTUs of water, intestine and sediment). The community diversity of abundant and rare microbial taxa was markedly different, as well as their taxonomic composition. Despite different diversity, similar abundance-occupancy relationship and biogeographic patterns between the abundant and rare microbial communities were observed, with much stronger obvious distance-decay relationships for rare community than abundant community. Furthermore, stochastic processes dominated the community assemblies of both abundant and rare microbial taxa, and deterministic process contributed more microbial community variation to rare taxa than abundant taxa. All the findings advance our understanding on the community assembly strategies of abundant and rare microbial taxa and prompt the contributions of abundant and rare microbial community to the aquatic ecosystems, which will improve aquaculture management strategy.</p

DataSheet_1_Abundant and Rare Microbial Communities Respectively Contribute to an Aquaculture Pond Ecosystem.docx

Unraveling the assembly mechanism is a core research topic of microbial ecology. Abundant and rare microbial communities are crucial for diversity, function and host health in a given ecosystem, but few studies focused on their assembly strategies. Here, we explored the microbial diversity of abundant and rare communities of water, shrimp intestine and sediment habitats in the shrimp cultural ponds. Our results found that the numbers of rare operational taxonomic units (OTUs) (6,003, 4,566 and 8,237 OTUs of water, intestine and sediment) was dozens of times more than abundant ones (only 199, 157 and 122 OTUs of water, intestine and sediment). The community diversity of abundant and rare microbial taxa was markedly different, as well as their taxonomic composition. Despite different diversity, similar abundance-occupancy relationship and biogeographic patterns between the abundant and rare microbial communities were observed, with much stronger obvious distance-decay relationships for rare community than abundant community. Furthermore, stochastic processes dominated the community assemblies of both abundant and rare microbial taxa, and deterministic process contributed more microbial community variation to rare taxa than abundant taxa. All the findings advance our understanding on the community assembly strategies of abundant and rare microbial taxa and prompt the contributions of abundant and rare microbial community to the aquatic ecosystems, which will improve aquaculture management strategy.</p

Image_3_Abundant and Rare Microbial Communities Respectively Contribute to an Aquaculture Pond Ecosystem.tif

Unraveling the assembly mechanism is a core research topic of microbial ecology. Abundant and rare microbial communities are crucial for diversity, function and host health in a given ecosystem, but few studies focused on their assembly strategies. Here, we explored the microbial diversity of abundant and rare communities of water, shrimp intestine and sediment habitats in the shrimp cultural ponds. Our results found that the numbers of rare operational taxonomic units (OTUs) (6,003, 4,566 and 8,237 OTUs of water, intestine and sediment) was dozens of times more than abundant ones (only 199, 157 and 122 OTUs of water, intestine and sediment). The community diversity of abundant and rare microbial taxa was markedly different, as well as their taxonomic composition. Despite different diversity, similar abundance-occupancy relationship and biogeographic patterns between the abundant and rare microbial communities were observed, with much stronger obvious distance-decay relationships for rare community than abundant community. Furthermore, stochastic processes dominated the community assemblies of both abundant and rare microbial taxa, and deterministic process contributed more microbial community variation to rare taxa than abundant taxa. All the findings advance our understanding on the community assembly strategies of abundant and rare microbial taxa and prompt the contributions of abundant and rare microbial community to the aquatic ecosystems, which will improve aquaculture management strategy.</p

Image_1_Abundant and Rare Microbial Communities Respectively Contribute to an Aquaculture Pond Ecosystem.tif

Unraveling the assembly mechanism is a core research topic of microbial ecology. Abundant and rare microbial communities are crucial for diversity, function and host health in a given ecosystem, but few studies focused on their assembly strategies. Here, we explored the microbial diversity of abundant and rare communities of water, shrimp intestine and sediment habitats in the shrimp cultural ponds. Our results found that the numbers of rare operational taxonomic units (OTUs) (6,003, 4,566 and 8,237 OTUs of water, intestine and sediment) was dozens of times more than abundant ones (only 199, 157 and 122 OTUs of water, intestine and sediment). The community diversity of abundant and rare microbial taxa was markedly different, as well as their taxonomic composition. Despite different diversity, similar abundance-occupancy relationship and biogeographic patterns between the abundant and rare microbial communities were observed, with much stronger obvious distance-decay relationships for rare community than abundant community. Furthermore, stochastic processes dominated the community assemblies of both abundant and rare microbial taxa, and deterministic process contributed more microbial community variation to rare taxa than abundant taxa. All the findings advance our understanding on the community assembly strategies of abundant and rare microbial taxa and prompt the contributions of abundant and rare microbial community to the aquatic ecosystems, which will improve aquaculture management strategy.</p

DataSheet_1_The Association Between Psoriasis and Risk of Cardiovascular Disease: A Mendelian Randomization Analysis.docx

BackgroundA large number of observational studies showed that patients with psoriasis have a higher risk of cardiovascular disease (CVD), but most studies did not fully adjust for confounding factors, so it is not clear whether the risk of CVD is directly attributed to psoriasis. We used Mendelian randomization (MR) to evaluate the potential causal relationship between psoriasis and CVD.MethodsWe used genetic instruments from the genome-wide association study (GWAS) of European descent for psoriasis to investigate its relationship with CVD. Inverse variance-weighted (IVW) MR analyses were used for the primary analysis. In addition, a variety of other methods were used to replicate the analysis.ResultsThe fixed-effects IVW method indicated that genetic susceptibility to psoriasis was associated with a higher risk of heart failure (HF) [odds ratio (OR) = 1.04; 95% CI, 1.01–1.06, P = 2.72E-03], atrial fibrillation (AF) (OR = 1.04; 95% CI, 1.02–1.07, P = 3.27E-04), myocardial infarction (MI) (OR = 1.07; 95% CI, 1.01–1.12, P = 0.01), valvular heart disease (VHD) (OR = 1.001; 95% CI, 1.000–1.002, P = 1.85E-03), and large artery stroke (LAS) (OR = 1.11; 95% CI, 1.05–1.18, P = 5.37E-04) but not with the other two subtypes of ischemic stroke (IS) [cardioembolic stroke (CES) (OR = 1.03; 95% CI, 0.98–1.07, P = 0.27) and small vessel stroke (SVS) (OR = 1.00; 95% CI, 0.95–1.07), P = 0.88)]. Sensitivity analysis found weak evidence of horizontal diversity and heterogeneity to ensure the stability of the results.ConclusionOur study provided evidence for a potential causal link between psoriasis and CVD. These findings partly suggest that early monitoring of cardiovascular risk in patients with psoriasis is intentional.</p

Image_4_Sedimentary Nitrogen and Sulfur Reduction Functional-Couplings Interplay With the Microbial Community of Anthropogenic Shrimp Culture Pond Ecosystem.TIFF

Sediment nitrogen and sulfur cycles are essential biogeochemical processes that regulate the microbial communities of environmental ecosystems, which have closely linked to environment ecological health. However, their functional couplings in anthropogenic aquaculture sedimentary ecosystems remain poorly understood. Here, we explored the sediment functional genes in shrimp culture pond ecosystems (SCPEs) at different culture stages using the GeoChip gene array approach with 16S amplicon sequencing. Dissimilarity analysis showed that the compositions of both functional genes and bacterial communities differed at different phases of shrimp culture with the appearance of temporal distance decay (p < 0.05). During shrimp culture, the abundances of nitrite and sulfite reduction functional genes decreased (p < 0.05), while those of nitrate and sulfate reduction genes were enriched (p < 0.05) in sediments, implying the enrichment of nitrites and sulfites from microbial metabolism. Meanwhile, nitrogen and sulfur reduction genes were found to be linked with carbon degradation and phosphorous metabolism (p < 0.05). The influence pathways of nutrients were demonstrated by structural equation modeling through environmental factors and the bacterial community on the nitrogen and sulfur reduction functions, indicating that the bacterial community response to environmental factors was facilitated by nutrients, and led to the shifts of functional genes (p < 0.05). These results indicate that sediment nitrogen and sulfur reduction functions in SCPEs were coupled, which are interconnected with the SCPEs bacterial community. Our findings will be helpful for understanding biogeochemical cycles in anthropogenic aquaculture ecosystems and promoting sustainable management of sediment environments through the framework of an ecological perspective.</p