The pharmaceutical industry has been desperately searching for efficient drug discovery methods. Organ-on-a-Chip, a cutting-edge technology that can emulate the physiological environment and ...functionality of human organs on a chip for disease modeling and drug testing, shows great potential for revolutionizing the drug development pipeline. However, successful translation of this novel engineering platform into routine pharmacological and medical scenarios remains to be realized. In this review, we discuss how the Organ-on-a-Chip technology can have critical roles in different preclinical stages of drug development and highlight the current challenges in translation and commercialization of this technology for the pharmacological and medical end-users. Moreover, this review sheds light on the future developmental trends and need for a next-generation Organ-on-a-Chip platform to bridge the gap between animal studies and clinical trials for the pharmaceutical industry.
Organ-on-a-Chip is a promising interdisciplinary technique emulating in vivo physiology and pathology for in vitro disease modeling, drug screening, and precision medicine.The Organ-on-a-Chip technology can be organically incorporated into the drug development pipeline from early drug discovery to preclinical screening, testing, and translation of new drugs, which bridges the gap between animal studies and clinical trials involving human subjects.The future development of personalized Organ-on-a-Chip and continuous integration of novel engineering tools (e.g., automation handling, 3D printing. and in situ multisensors) and biological concepts (e.g., patient-specific induced pluripotent stem cells and organoids) into Organ-on-a-Chip platform will unprecedentedly promote its biomedical applications.
The optimal planning of electric vehicle (EV) charging stations (ECSs) with advanced control algorithms is very important to accelerate the development of EVs, which is a promising solution to reduce ...carbon emissions of conventional internal combustion engine vehicles (ICEVs). The large and fluctuant load currents of ECSs can bring negative impacts to both EV-related power converters and power distribution systems if the energy flow is not regulated properly. Recent review papers related to EVs found in open literature have mainly focused on the design of power converter-based chargers and power interfaces, analyses of power quality (PQ) issues, the development of wireless charging techniques, etc. There is currently no review paper that focuses on key technologies in various system configurations, optimal energy management and advanced control issues in practical applications. To compensate for this insufficiency and provide timely research directions, this paper reviews 143 previously published papers related to the aforementioned topics in recent literature including 17 EV-related review papers found in Institute of Electrical and Electronics Engineers (IEEE)/Institution of Engineering and Technology (IET) (IEEE/IET) Electronic Library (IEL) and ScienceDirect OnSite (SDOS) databases. In this paper, existing system configurations, related design methods, algorithms and key technologies for ECSs are systematically reviewed. Based on discussions given in the reviewed papers, the most popular ECS configuration is a hybrid system design that integrates renewable energy (RE)-based power generation (REBPG), various energy storage systems (ESSs), and utility grids. It is noteworthy that the addition of an ESS with properly designed control algorithms can simultaneously buffer the fast, fluctuant power demand during charging, smooth the intermittent power generation of REBPG, and increase the overall efficiency and operating flexibility of ECSs. In addition, verifying the significance of the flexibility and possible profits that portable ESSs provide in ECS networks is a potential research theme in ECS fields, in which the potential applications of portable ESSs in the grid-tied ECSs are numerous and could cover a full technical spectrum.
Environmental innovation has been recognized as an efficient way of addressing environmental problems. However, how environmental innovation may affect carbon emissions in China and whether the ...effect may differ among various environmental innovation variables remain to be investigated. Therefore, based on the panel data of China’s 30 provinces during 2000–2013, we use a system generalized method of moments (SGMM) technique to estimate the effect of environmental innovation on carbon emissions in China. Also, we evaluate the effect on carbon emission reduction of China’s initial carbon emissions trading (CET) scheme. Empirical results indicate that, most environmental innovation measures in China reduce carbon emissions effectively. Among the various environmental innovation factors, energy efficiency exerts the most evident effect on carbon emissions abatement in China; meanwhile, resources for innovation and knowledge innovation also play prominent roles in this regard. However, the impact of governmental environmental policies on curbing carbon emissions reduction suffers from a lag effect, which mainly occurred during 2006–2013. Finally, despite the short time of operation and incomplete market mechanism, the pilot CET in China has appeared relatively promising with regard to carbon emissions reduction.
•The SGMM is used for the effect of environmental innovation on carbon emissions.•Energy efficiency proves the most effective way to reduce China’s carbon emissions.•Innovation resources and knowledge innovation are conducive for carbon reduction.•The governmental environmental policies have lag effect on carbon reduction.•The effect of China’s initial CET on carbon emissions reduction has appeared.
In order to reduce carbon emissions and urban smog, the Chinese government has instituted a number of policies to promote the diffusion of new energy vehicles (NEVs), achieving remarkable results. ...This paper aims to quantify the effectiveness of various policies. After reviewing and quantifying the policies directly related to the sales and driving of NEVs in the past five years, we established a multivariate co-integration model and an error correction model to analyse the long- and short-term effects of these policies. The results demonstrate positive co-integration for the relationship between the NEV market share and the NEV purchase subsidy, tax exemption, the policy of restricting internal combustion engine vehicle (ICEV) purchase, and the abolishment of traffic restrictions for NEVs. China's unique policy of restricting ICEVs has in fact promoted NEV sales by adjusting the supply and demand to influence the consumers' choices. Finally, we found technology to still be a bottleneck factor in the NEV industry, and technological progress's effect on NEV diffusion is greater than the economic subsidy policy. Therefore, this study suggests that the funds being made available from the gradual reduction of the purchase subsidy should be transferred to research and development.
•China's recent incentive policies to promote the NEV industry have been effective.•China's unique restrictions on vehicle purchases have a significantly positive impact on NEV diffusion.•The impact of different method for vehicle purchasing restriction on NEV sales is different.•The resources gained from reducing subsidies should be used to encourage the R&D of technologies.
For seeking high enantiopurity, the previously reported thermal asymmetric catalysis is usually carried out at low temperature sometimes with limited yield, that is, the high enantiomeric excess (ee) ...usually at the cost of high yield. Thus, the achieving both high stereoselectivity and yield is an enormous challenge. We report herein two metal nanoparticle (M NP)-loaded and porphyrin-containing homochiral covalent organic framework (CCOF)-based composite catalysts, and their application in the thermally-driven asymmetric one-pot Henry and A
-coupling reactions. All the reactions are conducted at elevated temperatures with both excellent stereoselectivity and yield which resulted from the synergy of CCOF confinement effect and M NP catalytic activation. Notably, the needed thermal energy for the asymmetric reactions herein is derived from the photothermal conversion via porphyrin-based CCOF upon irradiation with visible light. Remarkably, the CCOF confinement effect can be effectively maintained up to 100 °C for the asymmetric one-pot Henry and A
-coupling reactions herein.
A physical education and fitness course is a course with physical practice as the main means. Teachers often pay more attention to students’ physical practice in teaching but neglect the development ...of moral education, aesthetic education, intellectual education, and labor education. Aiming at this kind of teaching problem, this paper combines the concept of “five education” and the characteristics of physical education teaching. It puts forward the physical education teaching mode and practice path that permeates the idea of “five education.” Selection of research subjects, design, and distribution of a humanistic literacy questionnaire to obtain data, reliability test processing to ensure accuracy of research, and analysis of this paper. SPSS software is used to analyze an example of sports education work that integrates the concept of five education. Data presentation: the mean values of the post-test students’ humanistic literacy in the experimental group and the control group are 9.45 and 9.36, respectively, and the P value is 0.009, which indicates that the integration of the concept of five education in college physical education teaching is more advantageous in the cultivation of students’ humanistic literacy in comparison with the traditional physical education teaching mode. This study makes physical education classroom teaching more dynamic and versatile, gives a new meaning to physical education classroom teaching, and improves the effectiveness of physical education teaching.
Summary
MicroRNAs (miRNAs) are small RNAs that regulate the expression of target genes post‐transcriptionally; they are known to play major roles in development and responses to abiotic stress. ...miR408 is a highly conserved miRNA in plants that responds to the availability of copper and targets genes encoding copper‐containing proteins. It was recently recognized to be an important component of the HY5–SPL7 gene network that mediates a coordinated response to light and copper, illustrating its central role in the response of plants to the environment. Expression of miR408 is significantly affected by a variety of developmental and environmental conditions; however, its biological function is unknown. Involvement of miR408 in the abiotic stress response was investigated in Arabidopsis. Expression of miR408, as well as its target genes, was investigated in response to salinity, cold, oxidative stress, drought and osmotic stress. Analyses of transgenic plants with modulated miR408 expression revealed that higher miR408 expression leads to improved tolerance to salinity, cold and oxidative stress, but enhanced sensitivity to drought and osmotic stress. Cellular antioxidant capacity was enhanced in plants with elevated miR408 expression, as manifested by reduced levels of reactive oxygen species and induced expression of genes associated with antioxidative functions, including Cu/Zn superoxide dismutases (CSD1 and CSD2) and glutathione‐S‐transferase (GST‐U25), as well as auxiliary genes: the copper chaperone CCS1 and the redox stress‐associated gene SAP12. Overall, the results demonstrate significant involvement of miR408 in abiotic stress responses, emphasizing the central function of miR408 in plant survival.
Significance Statement
Plant microRNAs (miRNAs) are key post‐transcriptional regulators of gene expression. Here we show that expression of miR408 and its target genes contribute to abiotic stress tolerance.
High-entropy thin films of Mn
0.6
Co
0.6
Ni
0.6
Mg
0.6
Cu
0.6
O
4
, Mn
0.6
Co
0.6
Ni
0.6
Mg
0.6
Zn
0.6
O
4
, and Mn
0.6
Co
0.6
Ni
0.6
Cu
0.6
Zn
0.6
O
4
(MCNMC, MCNMZ, and MCNCZ) with equiatomic ...proportions were synthesized using chemical solution deposition on silicon substrates. Structural analysis confirmed a consistent face-centered cubic spinel structure, while significant differences in surface morphology were observed. Quantification of the valence states of Mn ions revealed an inverse variation in the concentrations of Mn
4+
and Mn
2+
ions. The heightened infrared light absorption of the MCNMC thin film was assigned to Cu-induced Jahn-Teller distortion and highly polarized Mg-O bonds. All samples exhibited negative temperature coefficient behaviors in their electrical properties. Additionally, the MCNMC thin film demonstrated the lowest resistance due to its denser microstructure, close proximity of Mn
3+
/Mn
4+
ion concentrations, and additional Cu
+
/Cu
2+
ion pairs, enhancing small polaron hopping conductivity. In contrast, the MCNMZ thin film showed moderate resistance but boasted the highest thermal constant (
B
25/50
) of 3768 K, attributed to its distinctive grain chain structure, facilitating carrier transport while introducing migration barriers.
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Many previous studies have demonstrated that the infiltrating of immune and stromal cells in the tumor ...microenvironment contributes significantly to prognosis.
Dataset TCGA-UVM, download from TCGA portal, was taken as the training cohort, and GSE22138, obtained from GEO database, was set as the validation cohort. ESTIMATE algorithm was applied to find intersection differentially expressed genes (DEGs) among tumor microenvironment. Kaplan-Meier analysis and univariate Cox regression model were performed on intersection DEGs to initial screen for potential prognostic genes. Then these genes entered into the validation cohort for validation using the same methods as that in the training cohort. Moreover, we conducted correlation analyses between the genes obtained in the validation cohort and the status of chromosome 3, chromosome 8q, and tumor metastasis to get prognosis genes. At last, the immune infiltration analysis was performed between the prognostic genes and 6 main kinds of tumor-infiltrating immune cells (TICs) for understanding the role of the genes in the tumor microenvironment.
959 intersection DEGs were found in the UM microenvironment. Kaplan-Meier and Cox analysis was then performed in the training and validation cohorts on these DEGs, and 52 genes were identified with potential prognostic value. After comparing the 52 genes to chromosome 3, chromosome 8q, and metastasis, we obtained 21 genes as the prognostic genes. The immune infiltration analysis showed that Neutrophil had the potential prognostic ability, and almost every prognostic gene we had identified was correlated with abundances of Neutrophil and CD8+ T Cell.
Identifying 21 prognosis genes (SERPINB9, EDNRB, RAPGEF3, HFE, RNF43, ZNF415, IL12RB2, MTUS1, NEDD9, ZNF667, AZGP1, WARS, GEM, RAB31, CALHM2, CA12, MYEOV, CELF2, SLCO5A1, ISM1, and PAPSS2) could accurately identify patients' prognosis and had close interactions with Neutrophil in the tumor environment, which may provide UM patients with personalized prognosis prediction and new treatment insights.