Microstructural evolution of the coexistence for spinodal decomposition and ordering in Fe-23Al alloy during aging

The microstructural evolution of the coexistence ofspinodal decomposition and ordering ischaracterized by metallographic microscopy andtransmission electron microscopy in aged Fe-23Al(i.e. Fe-23at%Al) alloy. This paper discusses aphase transition mechanism of the microstructureevolution. The obtained results indicate that the asquenchedFe-23Al alloys with equiaxed grain sizeof about 500μm comprise two kinds of the orderedphase in nano-scale, i.e., B2-FeAl and DO3-Fe 3Alphases. The average size of B2-FeAl orderingphases is about 15nm, while the size of DO3-Fe 3Alordering phases is extreme fine in the as- quenchedFe-23Al alloys. The as-quenched Fe-23Al alloypresents characteristics of the coexistence ofspinodal decomposition and ordering during thesubsequent age ing at 565°C and 520°C. Thedomain size of B2-FeAl ordered phase rapidlyincreases while the one of DO3-Fe 3Al orderedphase slowly develops with the increase in agingtime/with increased ageing time. A conclusion isreached that the coarsening process of both B2-FeAl and DO3-Fe 3Al ordered phase is controlledby the spinodal decomposition mechanism

Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury

Objective: The PRAS40 is an essential inhibitory subunit of the mTORC1 complex, which regulates autophagy. It has been suggested that Erxian Decoction (EXD) could treat spinal cord injury (SCI) via the autophagy pathway. However, the mechanism of whether EXD acts through PRAS40 remains unclear.Methods: With the help of immobilized PRAS40, isothermal titration calorimetry (ITC) and molecular docking, the bioactive metabolites in the EXD were screened. To establish in vitro SCI models, PC12 cells were exposed to hydrogen peroxide (H2O2) and then treated with the identified EXD substances. Furthermore, Western blot assay was carried out to identify potential molecular mechanisms involved. For assessing the effect of metabolites in vivo, the SCI model rats were first pretreated with or without the metabolite and then subjected to the immunohistochemistry (IHC) staining, Basso, Beattie & Bresnahan (BBB) locomotor rating scale, and H&E staining.Results: The immobilized PRAS40 isolated indole, 4-nitrophenol, terephthalic acid, palmatine, sinapinaldehyde, and 3-chloroaniline as the potential ligands binding to PRAS40. Furthermore, the association constants of palmatine and indole as 2.84 × 106 M-1 and 3.82 × 105 M-1 were elucidated via ITC due to the drug-like properties of these two metabolites. Molecular docking results also further demonstrated the mechanism of palmatine binding to PRAS40. Western blot analysis of PC12 cells demonstrated that palmatine inhibited the expression of p-mTOR by binding to PRAS40, activating the autophagic flux by markedly increasing LC3. The injection of palmatine (10μM and 20 μM) indicated notably increased BBB scores in the SCI rat model. Additionally, a dose-dependent increase in LC3 was observed by IHC staining.Conclusion: This research proved that EXD comprises PRAS40 antagonists, and the identified metabolite, palmatine, could potentially treat SCI by activating the autophagic flux

The difference of affect improvement effect of music intervention in aerobic exercise at different time periods

Objectives: A randomized controlled experimental design that combines exercise and music intervention was adopted in this study to verify whether this approach could help improve human affect. The differences in the effect of music listening on affective improvement were compared in four different periods: before, during, and after aerobic power cycling exercise and the whole exercise course.Method: A total of 140 subjects aged 19–30 years (average age: 23.6 years) were recruited and randomly divided into four music intervention groups, namely, the pre-exercise, during-exercise, post-exercise, and the whole-course groups. The subjects’ demographic and sociological variables and daily physical activities were collected using questionnaires. Individual factors, such as the subjects’ noise sensitivity, personality traits, and degree of learning burnout, were collected via scale scoring. A laboratory in Zhejiang Normal University was selected as the experimental site. The testing procedure can be summarized as follows. In a quiet environment, the subjects were asked to sit quietly for 5 min after completing a preparation work, and then they were informed to take a pre-test. The four subject groups wore headphones and completed 20 min of aerobic cycling (i.e., 7 min of moderate-intensity cycling [50%*HRR + RHR] + 6 min of low-intensity interval cycling [30%*HRR + RHR] + 7 min of moderate-intensity cycling [50%*HRR + RHR] after returning to a calm state (no less than 20 min) for post-testing. The affect improvement indicators (dependent variables) collected in the field included blood pressure (BP), positive/negative affect, and heart rate variability indicators (RMSSD, SDNN, and LF/HF).Results: 1) Significant differences were found in the participants’ systolic BP (SBP) indices and the effect of improvement of the positive affect during the exercise–music intervention among the four groups at different durations for the same exercise intensity (F = 2.379, p = 0.030, ɳp2 = 0.058; F = 2.451, p = 0.043, ɳp2 = 0.091). 2) Music intervention for individuals during exercise contribute more to the reduction of SBP than the other three time periods (F = 3.170, p = 0.047, ɳp2 = 0.068). Improvement in the participants’ negativity affective score was also better during exercise, and it was significantly different than the other three time periods (F = 5.516, p = 0.006, ɳp2 = 0.113). No significant differences were found in the improvement effects of the other effective indicators for the four periods.Conclusion: Exercise combined with music intervention has a facilitative effect on human affect improvement, and listening to music during exercise has a better impact on affective improvement than music interventions at the other periods. When people perform physical activities, listening to music during exercise positively affects the progress effect among them

Dietary Stress From Plant Secondary Metabolites Contributes to Grasshopper (Oedaleus asiaticus) Migration or Plague by Regulating Insect Insulin-Like Signaling Pathway

Diets essentially affect the ecological distribution of insects, and may contribute to or even accelerate pest plague outbreaks. The grasshopper, Oedaleus asiaticus B-Bienko (OA), is a persistent pest occurring in northern Asian grasslands. Migration and plague of this grasshopper is tightly related to two specific food plants, Stipa krylovii Roshev and Leymus chinensis (Trin.) Tzvel. However, how these diets regulate and contribute to plague is not clearly understood. Ecological studies have shown that L. chinensis is detrimental to OA growth due to the presence of high secondary metabolites, and that S. krylovii is beneficial because of the low levels of secondary metabolites. Moreover, in field habitats consisting mainly of these two grasses, OA density has negative correlation to high secondary metabolites and a positive correlation to nutrition content for high energy demand. These two grasses act as a ‘push-pull,’ thus enabling the grasshopper plague. Molecular analysis showed that gene expression and protein phosphorylation level of the IGF → FOXO cascade in the insulin-like signaling pathway (ILP) of OA negatively correlated to dietary secondary metabolites. High secondary metabolites in L. chinensis down-regulates the ILP pathway that generally is detrimental to insect survival and growth, and benefits insect detoxification with high energy cost. The changed ILP could explain the poor growth of grasshoppers and fewer distributions in the presence of L. chinensis. Plants can substantially affect grasshopper gene expression, protein function, growth, and ecological distribution. Down-regulation of grasshopper ILP due to diet stress caused by high secondary metabolites containing plants, such as L. chinensis, results in poor grasshopper growth and consequently drives grasshopper migration to preferable diet, such as S. krylovii, thus contributing to grasshopper plague outbreaks

Large manipulative experiments revealed variations of insect abundance and trophic levels in response to the cumulative effects of sheep grazing

This study was supported by the National Natural Science Foundation of China, 31672485, the Earmarked Fund for China Agriculture Research System, CARS-34-07, and the Innovation Project of Chinese Academy of Agricultural Sciences.Livestock grazing can affect insects by altering habitat quality; however, the effects of grazing years and intensities on insect abundance and trophic level during manipulative sheep grazing are not well understood. Therefore, we investigated these effects in a large manipulative experiment from 2014 to 2016 in the eastern Eurasian steppe, China. Insect abundance decreased as sheep grazing intensities increased, with a significant cumulative effect occurring during grazing years. The largest families, Acrididae and Cicadellidae, were susceptible to sheep grazing, but Formicidae was tolerant. Trophic primary and secondary consumer insects were negatively impacted by increased grazing intensities, while secondary consumers were limited by the decreased primary consumers. Poor vegetation conditions caused by heavy sheep grazing were detrimental to the existence of Acrididae, Cicadellidae, primary and secondary consumer insects, but were beneficial to Formicidae. This study revealed variations in insect abundance and trophic level in response to continuous sheep grazing in steppe grasslands. Overall, our results indicate that continuous years of heavy- and over- sheep grazing should be eliminated. Moreover, our findings highlight the importance of more flexible sheep grazing management and will be useful for developing guidelines to optimize livestock production while maintaining species diversity and ecosystem health.Publisher PDFPeer reviewe

KIAA1199 Correlates With Tumor Microenvironment and Immune Infiltration in Lung Adenocarcinoma as a Potential Prognostic Biomarker

Background: KIAA1199 has been considered a key regulator of carcinogenesis. However, the relationship between KIAA1199 and immune infiltrates, as well as its prognostic value in lung adenocarcinoma (LUAD) remains unclear.Methods: The expression of KIAA1199 and its influence on tumor prognosis were analyzed using a series of databases, comprising TIMER, GEPIA, UALCAN, LCE, Prognoscan and Kaplan-Meier Plotter. Further, immunohistochemistry (IHC), western blot (WB) and receiver operating characteristic (ROC) curve analyses were performed to verify our findings. The cBioPortal was used to investigate the genomic alterations of KIAA1199. Prediction of candidate microRNA (miRNAs) and transcription factor (TF) targeting KIAA1199, as well as GO and KEGG analyses, were performed based on LinkedOmics. TIMER and TISIDB databases were used to explore the relationship between KIAA1199 and tumor immune infiltration.Results: High expression of KIAA1199 was identified in LUAD and Lung squamous cell carcinoma (LUSC) patients. High expression of KIAA1199 indicated a worse prognosis in LUAD patients. The results of IHC and WB analyses showed that the expression level of KIAA1199 in tumor tissues was higher than that in adjacent tissues. GO and KEGG analyses indicated KIAA1199 was mainly involved in extracellular matrix (ECM)-receptor interaction and extracellular matrix structure constituent. KIAA1199 was positively correlated with infiltrating levels of CD4+ T cells, macrophages, neutrophil cells, dendritic cells, and showed positive relationship with immune marker subsets expression of a variety of immunosuppressive cells.Conclusion: High expression of KIAA1199 predicts a poor prognosis of LUAD patients. KIAA1199 might exert its carcinogenic role in the tumor microenvironment via participating in the extracellular matrix formation and regulating the infiltration of immune cells in LUAD. The results indicate that KIAA1199 might be a novel biomarker for evaluating prognosis and immune cell infiltration in LUAD

Sodium-glucose cotransporter-2 inhibitors and incidence of atrial fibrillation in older adults with type 2 diabetes: a retrospective cohort analysis

ObjectivesTo investigate the risk of atrial fibrillation (AF) with sodium-glucose cotransporter-2 inhibitors (SGLT2is) compared to dipeptidyl peptidase-4 inhibitor (DPP4i) use in older US adults and across diverse subgroups.MethodsWe conducted a retrospective cohort analysis using claims data from 15% random samples of Medicare fee-for-service beneficiaries. Patients were adults with type 2 diabetes (T2D), no preexisting AF, and were newly initiated on SGLT2i or DPP4i. The outcome was the first incident AF. Inverse probability treatment weighting (IPTW) was used to balance the baseline covariates between the treatment groups including sociodemographics, comorbidities, and co-medications. Cox regression models were used to assess the effect of SGLT2i compared to DPP4i on incident AF.ResultsOf the 97,436 eligible individuals (mean age 71.2 ± 9.8 years, 54.6% women), 1.01% (n = 983) had incident AF over a median follow-up of 361 days. The adjusted incidence rate was 8.39 (95% CI: 6.67–9.99) and 11.70 (95% CI: 10.9–12.55) per 1,000 person-years in the SGLT2i and DPP4i groups, respectively. SGLT2is were associated with a significantly lower risk of incident AF (HR 0.73; 95% CI, 0.57 to 0.91; p = 0.01) than DPP4is. The risk reduction of incident AF was significant in non-Hispanic White individuals and subgroups with existing atherosclerotic cardiovascular diseases and chronic kidney disease.ConclusionCompared to the use of DPP4i, that of SGLT2i was associated with a lower risk of AF in patients with T2D. Our findings contribute to the real-world evidence regarding the effectiveness of SGLT2i in preventing AF and support a tailored therapeutic approach to optimize treatment selection based on individual characteristics

Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action