Search

Abstract Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen–glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

The Lawson's Classroom Test of Scientific Reasoning (LCTSR) is a popular instrument that measures the development of students' scientific reasoning skills. The instrument has a two-tier question design, which has led to multiple ways of scoring and interpretation. In this research, a method of pattern analysis was proposed and applied to analyze two-tier item pairs on the subskill of Control-of-Variable (COV) of LCTSR. The data were collected from students in grade 4 through college in both the United States and China. Students' response patterns to two combined item pairs were analyzed and compared against students at different grade levels and reasoning development levels. Six performance levels were established based on students' response patterns, serving as indicators of COV reasoning development levels. With the new method, a relation was obtained between students' level of COV skills and grade level, as well as their level of overall reasoning development. It can provide useful information on the possible developmental levels of students' reasoning skills.

Most studies have concentrated in assessing students' overall attitudes towards science, mathematics, and engineering/technology or the attitude towards individual STEM domain. The present research aims to explore primary students' gender and grade differences of their STEM domain-specific attitudes including self-efficacy and expectancy-value beliefs, as well as their correlations. The results showed no detected significant effects among these different STEM domains in the overall attitudes, the overall self-efficacy beliefs, and the overall expectancy-value beliefs for primary students. The correlations between self-efficacy and expectancy-value were much stronger for the science domain and engineering/technology domain than the mathematics domain. No gender difference of the self-efficacy beliefs was detected except in the mathematics domain, and the result that lower primary students performed significantly better than upper primary students in the self-efficacy was also mainly contributed by the grade difference in the mathematics domain. Whereas no different expectancy-value beliefs existed across genders and grade levels in various STEM domains. The present results reported some unique performances by the primary school students compared to the elder group.

In recent years, game-based learning has attracted much attention in education; however, the effectiveness of game-based learning is still not solidly confirmed. In the present research, a game-based learning in the physics domain with guides provided direct and immediate feedback. The research was conducted among three different groups: the traditional group, the educational video group, and the game-based learning group. The result showed that the game-based learning group performed the best among the three groups, followed by the educational video group, and the traditional group performed the worst. Students in the game-based learning group were enrolled into an interview to study which types of guides enhanced students' game-based learning. From the interview, the prompts and the interactive characteristic of the game-based learning environment took the first two places. In addition, students benefited from the features of game-based learning including task requirements for execution, the tip prompt function, the feedback mechanism, and the story settings. Therefore, it is necessary to integrate applicable guides into the design of game-based learning according to students' perspectives for providing engaging learning experience.

Abstract Scutellarin is used to treat brain ischaemia. However, its underlying mechanism of action remains unclear. This study aimed to elucidate the potential mechanism of action of scutellarin in brain ischaemia through network pharmacology and experimental verification. The JAK2/STAT3 signalling pathway was identified and experimentally verified. Expression of JAK2/STAT3 signalling related proteins in TNC-1 astrocytes with BV-2 microglia-conditioned medium (CM), CM + lipopolysaccharide (LPS) (CM + L), and CM pretreated with scutellarin + LPS (CM + SL) was analysed by Western Blot and immunofluorescence staining. Expression levels of JAK2, p-JAK2, STAT3, and p-STAT3 were evaluated in astrocytes pre-treated with AG490. Middle cerebral artery occlusion (MCAO) in rats was performed in different experimental groups to detect expression of the above biomarkers. Network pharmacology suggested that the JAK2/STAT3 signalling pathway is one of the mechanisms by which scutellarin mitigates cerebral ischaemic damage. In TNC-1 astrocytes, p-JAK2 and p-STAT3 expression were significantly up-regulated in the CM + L group. Scutellarin promoted the up-regulation of various markers and AG490 neutralised the effect of scutellarin. In vivo, up-regulation of p-JAK2 and p-STAT3 after ischaemia is known. These results are consistent with previous reports. Scutellarin further enhanced this upregulation at 1, 3, and 7 d after MCAO. Scutellarin exerts its therapeutic effects on cerebral ischaemia by activating the astrocyte JAK2/STAT3 signalling, which provides a firm experimental basis for its clinical application.

Bisphenol A (BPA) is a widespread environmental pollutant linked to detrimental effects on human health and reduced life expectancy following chronic exposure. This prospective cohort study aimed to examine the association between BPA exposure and mortality in American adults and to explore the potential mitigating effects of dietary quality on BPA-related mortality. This study utilized data from 8761 American adults in the 2003–2016 National Health and Nutrition Examination Survey (NHANES). Urinary BPA levels were employed to assess BPA exposure, and dietary quality was evaluated using the Healthy Eating Index-2015 (HEI-2015). All-cause, cardiovascular disease (CVD), and cancer mortality statuses were determined until December 31, 2019, resulting in a cumulative follow-up of 80,564 person-years. The results showed that the highest tertile of urinary BPA levels corresponded to a 36% increase in all-cause mortality and a 62% increase in CVD mortality compared to the lowest tertile. In contrast, the highest tertile of HEI-2015 scores was associated with a 29% reduction in all-cause mortality relative to the lowest tertile. Although no significant interaction was found between HEI-2015 scores and urinary BPA levels concerning mortality, the association between HEI-2015 scores and both all-cause and CVD mortality was statistically significant at low urinary BPA levels. Continuous monitoring of BPA exposure is crucial for evaluating its long-term adverse health effects. Improving dietary quality can lower all-cause mortality and decrease the risk of all-cause and CVD mortality at low BPA exposure levels. However, due to the limited protective effect of dietary quality against BPA exposure, minimizing BPA exposure remains a vital goal.

为提升燃料的综合燃烧品质和性能，进一步降低有害物质排放和缓解温室效应，以燃烧动力学和化学反应机制作为理论基础，采用Chemkin软件将生物柴油替代物和氨气充分融合，模拟并计算氨气掺混比例分别为0、5%、10%、15%、20%的5组燃料在均质压燃发动机模式下燃烧和排放指标的数值，对比分析得到不同掺混比例对发动机燃烧和排放的影响和变化规律。结果表明：随着氨气掺混比例增加，燃料的点火滞燃期有所缩短，缸内燃烧最高温度升高，排温降低；排放方面，NOx的排放升高，CO2、CO和总碳氢化合物（THC）的排放均明显降低；生物柴油掺混氨气的最佳比例为20%，此时发动机功率下降12百分点，NO的单位功率排放升高了0.003 kW-1，而CO2和THC的单位功率排放分别降低了0.01 kW-1和0.001 3 kW-1。综上，生物柴油掺混氨气后改善了燃烧性能，降低了排放量，具有良好的应用前景 In order to improve the comprehensive combustion quality and performance of the fuel, further reduce the emission of harmful substances and mitigate the greenhouse effect, based on the theoretical basis of combustion kinetics and chemical reaction mechanism, the Chemkin software was used to fully integrate the mechanism of biodiesel substitute and ammonia gas, simulate and calculate the combustion and emission values of 5 groups of fuels with the ammonia gas molar ratio of 0, 5%, 10%, 15% and 20% respectively in homogeneous charge compression ignition engine mode. The effects and change rule of different mixing ratio on engine combustion and emission were compared and analysed. The results showed that with the increase of ammonia gas ratio, the ignition delay period of fuel was shortened, the maximum combustion temperature in the cylinder increased, and the exhaust temperature decreased. In terms of emission, NOx emission increased, while CO2, CO and total hydrocarbon (THC) emissions decreased significantly. The optimal ratio of biodiesel blended with ammonia gas was 20%, and under this condition, the engine power decreased by 12 percentage, and the unit power emission ratio of NO increased by 0.003 kW-1, while the unit power emission ratios of CO2 and THC decreased significantly, which were 0.01 kW-1 and 0.001 3 kW-1 respectively. In conclusion, biodiesel blended with ammonia gas significantly improves combustion and reduces emissions, and has good application prospect.

Accumulating evidence linked bisphenol A (BPA) exposure with several diseases and even premature death. We aimed to evaluate the association between BPA exposure and mortality in US adults from the National Health and Nutrition Examination Survey (NHANES, 2003–2016), and to explore whether an anti-inflammatory diet can mitigate the deleterious effect of BPA on mortality. A cohort study including 8142 adults was conducted. Of these, 4143 (50.2%) were men, with a weighted average age of 55.9 years. Urinary BPA was measured by the on-line solid phase extraction, coupled to high performance liquid chromatography and tandem mass spectrometry. Dietary Inflammatory Index (DII) score was calculated based on 28 available kinds of food parameters in NHANES. Cox proportional hazards regression models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD), and cancer mortality. After 75927 person-years of follow-up (median, 9.3 years; maximum, 17.1 years), BPA exposure and DII score were independently associated with all-cause mortality. The fully-adjusted HR (95% CI) in the high versus low levels of BPA was 1.33 (1.05–1.70) for all-cause mortality, and the anti-inflammatory versus pro-inflammatory category of DII was 0.70 (0.56–0.87). There was no significant interaction between BPA and DII (p = 0.200). However, an indication of combined effect was found that, participants in subgroups with low BPA exposure and concurrently with anti-inflammatory category of DII score had 53% significantly lower all-cause mortality. Our findings highlight the importance of another monitoring cycles of BPA exposure, and its long-term adverse effects on health, even though the US government had restricted its use nowadays. Besides, we provided a new perspective against the adverse health effect induced by BPA exposure, that future studies could explore the offset impact of other healthy dietary patterns on the deleterious effect of BPA on health outcomes.

Purpose Many investigations on prognostic factors in lung cancer have been conducted; however, little is known regarding the outcomes of lung cancer cases complicated by deep vein thrombosis (DVT). This study aimed to determine the risk factors and impact on outcomes of lung cancer patients concurrent with DVT. Methods Lung cancer patients who underwent lower-extremity venous ultrasound were enrolled in this study. The patients were divided into a DVT group and a non-DVT group. Demographic information, clinical characteristics, and survival were analyzed by t-test, Wilcoxon test, chi-squared test, and logistic regression analysis. Results Of the 160 enrolled lung cancer patients, DVT was detected in 30 patients. Among the DVT group, adenocarcinoma was the most common histological type (27/30, 90.00%). Lung cancer complicated with DVT was associated with advanced stage, more severe myocardial injury, and a hypercoagulable state (P < .05). Differences in driver genes between the two groups were not significant. Radiologically, lung cancer patients with DVT were more likely to present with pericardial effusion and pleural effusion than patients without DVT (P < .05). Following multivariable logistic regression analysis, advanced stage (OR 5.368, [95%CI 1.871-18.165], P = .021), NT-proBNP >300 pg/ml (OR 5.575, [95%CI 1.733-3.722], P = .018), D-dimer >5 mg/L (OR 8.449, [95%CI 4.323-18.536], P = .004), CRP >12 mg/L (OR 6.687, [95%CI 1.967-13.617], P = .010), and serum CEA >25 ng/ml (OR 4.755, [95%CI 1.358-3.123], P = .029) were independent risk factors for adenocarcinoma complicated with DVT. Finally, survival analysis revealed that the occurrence of DVT resulted in a poorer prognosis despite anticoagulant therapy (P < .05). Conclusion DVT is a potential complication in patients with lung adenocarcinoma and could represent a prognostic marker for unfavorable outcome. It is essential to screen for DVT in high-risk adenocarcinoma patients.

To realize nanoscale manufacturing based on laser direct writing technology, objective lenses with high numerical apertures immersed in water or oil are necessary. The use of liquid medium restricts its application in semiconductors. Achieving nanoscale features on silicon by laser direct writing in a low refractive index medium has been a challenge. In this work, a microsphere assisted femtosecond laser far-field induced dewetting approach is proposed. A reduction in the full-width at half-maximum of the focused light spot is realized by modulating tightly focused light through microspheres and achieving a minimum feature size of 9 nm on silicon in ambient air with energy smaller than the ablation threshold. Theoretical analysis and numerical simulation of laser processing are performed based on a two-temperature model. Furthermore, we explored the potential of femtosecond laser-induced dewetting in nanolithography and demonstrated its ability to achieve an arbitrary structure on silicon. Our work enables laser-based far-field sub-10-nm feature etching on a large-scale, providing a novel avenue for nanoscale silicon manufacturing. [ABSTRACT FROM AUTHOR]

Coronaviruses (CoVs), the largest positive-sense RNA viruses, have caused infections in both humans and animals. The cross-species transmission of CoVs poses a serious threat to public health. Rodents and bats, the two largest orders of mammals, serve as significant natural reservoirs for CoVs. It is important to monitor the CoVs carried by bats and rodents. In this study, we collected 410 fecal samples from bats and 74 intestinal samples from rats in Yunnan Province, China. Using RT-PCR, we identified one positive sample for alphacoronavirus (TC-14) from Rhinolophus sinicus (Chinese rufous horseshoe bat) and two positive samples for betacoronavirus (GS-53, GS-56) from Apodemus ilex (Rodentia: Muridae). We successfully characterized the complete genomes of TC-14 and GS-56. Phylogenetic analysis revealed that TC-14 clustered with bat CoV HKU2 and SADS-CoV, while GS-56 was closely related to rat CoV HKU24. The identification of positive selection sites and estimation of divergence dates further helped characterize the genetic evolution of TC-14 and GS-56. In summary, this research reveals the genetic evolution characteristics of TC-14 and GS-56, providing valuable references for the study of CoVs carried by bats and rodents in Yunnan Province. [ABSTRACT FROM AUTHOR]

Merchants need not fear platform entry because that can raise merchants' profits by resolving quality uncertainty for consumers. Merchants are wary of a platform's competitive entry reducing sales and margins. Profit-maximizing platforms seek to provide credible quality information to gain consumer trust and confidence. Can a platform enter so that resulting multisender prices alleviate consumers' uncertainty by signaling quality? Can merchants also benefit from platform entry? We provide answers by analyzing strategic platform and merchant pricing under quality uncertainty. A modeling innovation is a leader-follower framework for platform-merchant competition. Consumers resolve uncertainty using both platform and merchant prices. Using what we label perfect Bayes-consistent beliefs, we identify perfect Bayesian equilibrium that satisfies the intuitive criterion, and also out-of-equilibrium beliefs that are unprejudiced. A substantive finding is that platform entry can raise merchant profits when the quality is high by moving the equilibrium from pooling to separating, and supporting higher prices. Another strategic consequence of platform entry could be a separating equilibrium with incomplete market coverage due to price distortion moving to one of complete market coverage due to seller competition. Indeed, conditions exist in our model for an equilibrium outcome identical to complete information. Finally, facing entry cost, a platform may choose to enter only with high quality but quality revelation remains price dependent and not based on mere entry. History: Yuxin Chen served as the senior editor for this article. Funding: Y. Qiu was supported by the Natural Science Foundation of China [Grant 71902142] toward completion of this paper. Supplemental Material: The online appendix is available at https://doi.org/10.1287/mksc.2021.0227. [ABSTRACT FROM AUTHOR]

Objective: Sepsis is a common disease in internal medicine, with a high incidence and dangerous condition. Due to the limited understanding of its pathogenesis, the prognosis is poor. The goal of this project is to screen potential biomarkers for the diagnosis of sepsis and to identify competitive endogenous RNA (ceRNA) networks associated with sepsis.Methods: The expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) were derived from the Gene Expression Omnibus (GEO) dataset. The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were screened by bioinformatics analysis. DEmRNAs were analyzed by protein-protein interaction (PPI) network analysis, transcription factor enrichment analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Set Enrichment Analysis (GSEA). After the prediction of the relevant database, the competitive ceRNA network is built in Cytoscape. The gene-drug interaction was predicted by DGIgb. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm five lncRNAs from the ceRNA network.Results: Through Venn diagram analysis, we found that 57 DElncRNAs, 6 DEmiRNAs and 317 DEmRNAs expressed abnormally in patients with sepsis. GO analysis and KEGG pathway analysis showed that 789 GO terms and 36 KEGG pathways were enriched. Through intersection analysis and data mining, 5 key KEGG pathways and related core genes were revealed by GSEA. The PPI network consists of 247 nodes and 1,163 edges, and 50 hub genes are screened by the MCODE plug-in. In addition, there are 5 DElncRNAs, 6 DEmiRNAs and 28 DEmRNAs in the ceRNA network. Drug action analysis showed that 7 genes were predicted to be molecular targets of drugs. Five lncRNAs in ceRNA network are verified by qRT-PCR, and the results showed that the relative expression of five lncRNAs was significantly different between sepsis patients and healthy control subjects.Conclusion: A sepsis-specific ceRNA network has been effectively created, which is helpful to understand the interaction between lncRNAs, miRNAs and mRNAs. We discovered prospective sepsis peripheral blood indicators and proposed potential treatment medicines, providing new insights into the progression and development of sepsis.

The effects of oxytetracycline on anaerobic ammonium oxidation (ANAMMOX) were analyzed in this study. Meanwhile, the change of specific ANAMMOX activity (SAA) and the content of heme c were also revealed. The performance of ANAMMOX reactor decreased gradually when the increase of OTC concentration from 2mg/L to 10mg/L under 10‰ salinity. The nitrogen removal performance almost collapsed until the elevation to 10 mg/L OTC, observed with a huge decrease of SAA of 77.71% and heme c content of 88.04%. After no addition of OTC into the ANAMMOX reactor, the system performance recovered within 20 days. At the end of this phase, NH4+-N was completely removed, NO2--N was removed above 99%, and total nitrogen removal efficiency recovered to 85.33%.

In addition to the common blood and urine, fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body's state. Wearable sweat sensors are crucial for understanding human physiological health; however, real-time in situ measurement of multiple biomarkers in sweat remains a significant challenge. Here, we propose a wearable microfluidic patch featuring an integrated microfluidic channel and evaporation pump for accelerated and continuous sweat collection, eliminating the need for additional sweat storage cavities that typically impede real-time detection. Capillary forces are harnessed to facilitate the rapid flow of sweat through the detection area, while an evaporation pump based on porous laser-induced graphene enhances sweat evaporation. The synergistic integration of these two components enables an uninterrupted flow of fresh sweat within the patch, ensuring real-time monitoring. The influence of channel size parameters on sweat flow velocity is analyzed, and the optimal width-to-height ratio for achieving the desired flow velocity is determined. By implementing a multi-channel parallel design with chamfering, liquid flow resistance is effectively reduced. Furthermore, the patch integrates sensor modules for sodium ion, chloride ion, glucose, and pH value measurements, ensuring excellent sealing and stability of the assembled system. This work presents a simplified approach to developing wearable sweat sensors that hold the potential for health monitoring and disease diagnosis. [ABSTRACT FROM AUTHOR]

(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated the therapeutic effects of the active ingredient Eleutheroside B (EB) from the traditional Chinese medicine Eleutheroside on diabetes mellitus in a zebrafish model. Concomitant hepatic injury was also analysed, along with the study of possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies. (2) Methods: A zebrafish diabetes model was constructed by soaking in a 1.75% glucose solution and feeding a high-fat diet. The intervention drug groups were metformin (100 μg∙mL−1) and EB (50, 100, and 150 μg∙mL−1) via water-soluble exposure for 30 days. Glucose, TG, TC, LDL-C, and HDL-C were evaluated in different treatment groups. GLUT4 protein expression was also evaluated in each group, and liver injury was observed by HE staining. Metabolomics techniques were used to investigate the mechanism by which EB regulates endogenous markers and metabolic pathways during the development of diabetes. (3) Results: All EB treatment groups in diabetic zebrafish showed significantly reduced body mass index (BMI) and improved blood glucose and lipid profiles. EB was found to upregulate GLUT4 protein expression and ameliorate the liver injury caused by diabetes. Metabolomics studies showed that EB causes changes in the metabolic profile of diabetic zebrafish. These were related to the regulation of purine metabolism, cytochrome P450, caffeine metabolism, arginine and proline metabolism, the mTOR signalling pathway, insulin resistance, and glycerophospholipid metabolism. (4) Conclusions: EB has a hypoglycaemic effect in diabetic zebrafish as well as significantly improving disorders of glycolipid metabolism. The mechanism of action of EB may involve regulation of the mTOR signalling pathway, purine metabolism, caffeine metabolism, and glycerophospholipid metabolism. [ABSTRACT FROM AUTHOR]

It is well known that the storage of the valuable helium and other natural gases needs thick well-confined aquitards. Meanwhile, the assumption that deep aquifers are confined is most evident from the wide practices of targeting deep aquifers as the storage of toxic wastes and CO2. With the negative phase shifts of the M2 tidal wave, previously, deep Gaocun well (~3500 m) in the North China Platform is assumed to be confined fairly well. However, water level of the Gaocun well has been continuously decreasing for ~40 years without coseismic variations and without explainable mechanism. In this study, innovatively, we find that even buried in ~3500 meters deep, and covered by thick compact mudstones, the aquifer of well Gaocun is calculated to be continuously leaking for ~40 years probably induced by the vertical leakage incurred by aquitard fractures, which is under the assumptions of the none-leaking bottom layer and none direct pumping or exploiting in the observation aquifer layer. Meanwhile, for the first time, we did a detailed systematic comparison between the leaky models of the tidal response and the barometric response of water level, which indicate a consistency leaky result, and the minor difference mainly induced by the frequency differences. Merits and demerits of both models are also analyzed. Last but not least, underground fluid leakages might frequently occur, which are becoming increasingly worldwide urgent since that might also be related with surface sourced contaminations, toxic waste burials, and burial and exploration of the natural gas reservoirs.