Using a light-emitting diode (LED) as the light source, the effects of eight different light treatments white light (control, W), purple light (P), blue light (B), red light (R), green light (G), ...yellow light (Y), red–blue light in a 9:1 ratio (9R/1B), and red–blue light in a 4:1 ratio (4R/1B) on the growth, quality and nitrogen metabolism of lettuce were studied. The results showed that compared with the white light, the purple light, blue light, red light, and the red-blue light combination could all increase the biomass of the aboveground part of lettuce to various degrees, while green light and yellow light inhibited lettuce growth. Under blue light, the contents of soluble protein and flavonoid in lettuce were the highest; under red light, the soluble sugar content was the highest, while the contents of soluble protein, free amino acids, and vitamin C (VC) were relatively higher under the 4R/1B light condition. Compared with white light, the sources of purple, blue, and red lights as well as the red–blue light combination all significantly reduced nitrate accumulation in lettuce, and the activities of the nitrogen (N) metabolism-related enzymes such as nitrate reductase, nitrite reductase, glutamine synthetase, glutamate synthase, and glutamate dehydrogenase were increased to varying degrees. In contrast, the contents of nitrate and ammonium N were significantly accumulated in lettuce under green light, and the activities of relative enzymes were significantly reduced. Therefore, the purple light, blue light, and red–blue combination light sources could promote N assimilation and improve the aboveground biomass accumulation in lettuce by improving the activity of the N metabolism-related enzymes in lettuce. Particularly under the 4R/1B light source, the biomass, soluble protein, VC, and total amino acid content were rather high in lettuce, which indicated that the 4R/1B light source could better effectively improve the nutritional quality and promote the growth of lettuce, while yellow light and green light are not suitable to serve as direct sources in a plant factory. These results provide a certain theoretical basis for the regulation of the light environment in cultivation facilities.
Emerging evidence suggests that microRNAs (miRs) are associated with the progression of osteoarthritis (OA). In this study, the role of exosomal miR-136-5p derived from mesenchymal stem cells (MSCs) ...in OA progression is investigated and the potential therapeutic mechanism explored.
Bone marrow mesenchymal stem cells (BMMSCs) and their exosomes were isolated from patients and identified. The endocytosis of chondrocytes and the effects of exosome miR-136-5p on cartilage degradation were observed and examined by immunofluorescence and cartilage staining. Then, the targeting relationship between miR-136-5p and E74-like factor 3 (ELF3) was analyzed by dual-luciferase report assay. Based on gain- or loss-of-function experiments, the effects of exosomes and exosomal miR-136-5p on chondrocyte migration were examined by EdU and Transwell assay. Finally, a mouse model of post-traumatic OA was developed to evaluate effects of miR-136-5p on chondrocyte degeneration in vivo.
In the clinical samples of traumatic OA cartilage tissues, we detected increased ELF3 expression, and reduced miR-136-5p expression was determined. The BMMSC-derived exosomes showed an enriched level of miR-136-5p, which could be internalized by chondrocytes. The migration of chondrocyte was promoted by miR-136-5p, while collagen II, aggrecan, and SOX9 expression was increased and MMP-13 expression was reduced. miR-136-5p was verified to target ELF3 and could downregulate its expression. Moreover, the expression of ELF3 was reduced in chondrocytes after internalization of exosomes. In the mouse model of post-traumatic OA, exosomal miR-136-5p was found to reduce the degeneration of cartilage extracellular matrix.
These data provide evidence that BMMSC-derived exosomal miR-136-5p could promote chondrocyte migration in vitro and inhibit cartilage degeneration in vivo, thereby inhibiting OA pathology, which highlighted the transfer of exosomal miR-136-5p as a promising therapeutic strategy for patients with OA.
Time‐varying electricity tariffs provide consumers the flexibility to adjust their consumption patterns in response to price variations to reduce the cost of electricity while at the same time ...contributing to grid operation. As more homes and buildings utilize time‐varying tariffs, utilities and regulators must seek ways to model demand‐side flexibilities to predict future demands and design new incentives. This paper proposes a novel end‐to‐end deep learning framework that simultaneously identifies demand baselines and the price‐response model from the net demand measurements and price signals. A gradient‐descent approach is then proposed that backpropagates the net demand forecast errors to update the weights of the price‐response model and the weights of the baseline demand forecast jointly. The effectiveness of the approach is demonstrated through computation experiments with synthetic demand response traces and a large‐scale real‐world DR dataset. The results show that the approach accurately identifies the DR model, even without prior knowledge about the baseline demand.
This paper proposes a novel end‐to‐end deep learning framework that simultaneously identifies demand baselines and the price‐response model from the net demand measurements and price signals. We demonstrate the effectiveness of our approach through computation experiments with synthetic demand response traces and a large‐scale real‐world demand response dataset. Our results show that the approach accurately identifies the demand response model, even without prior knowledge about the baseline demand.
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•Analyzing intellectual property cooperation mechanism among heterogeneous entities.•GIUR intellectual property cooperation under two types of scenarios is introduced.•Evolutionary ...game modeling of GIUR intellectual property cooperation is proposed.•Giving the simulation results of GIUR intellectual property cooperation behavior.
Intellectual property cooperation is vital to integrating innovation resources, improving innovation energy. It involves many factors including behavioral agents and national economy-macro-management scenarios, should be seriously considered by multi-stakeholders during the process of intellectual property cooperation. Based on the evolutionary game theory, this paper analyzes the Government-Industry-University-Research (GIUR) intellectual property cooperation behavior and its influencing factors from market mechanism and administrative supervision mechanism. Firstly, the newly proposed game models are developed to observe the cooperation behavior which can be realized as strategies and payoff functions of the multi-stakeholders, then, the evolutionary replication dynamics equations are formulated to study evolutionarily stable strategies of multi-stakeholders. Finally, to verify the theoretical results, simulation experiments are conducted with meaningful results: under the market mechanism, the reasonable government subsidy incentive, and the liquidated damages can make GIUR practice an active intellectual property cooperation behavior to each other; under the administrative supervision mechanism, reasonable tax rate and administrative penalties are conducive to promoting and stabilizing GIUR intellectual property cooperation. In addition, the government will have the “interest appeal” to maximize additional social benefits in the game with enterprises, universities or research institutes. The results can guide GIUR to make better decisions in the future.
China has witnessed accelerating urbanization in many cities bringing both economic benefits and hardships for citizens. Often children bear the heaviest burden in the high-density cities. The value ...of outdoor play has been emphasized in many research fields with its physical, psychological and social benefits for children's development. However, by a range of measures, there is growing evidence that children in China spend less time enjoying outdoor play currently. This study research aims to explore the children's experience of outdoor play in their community areas by taking Wuhan as an example. Questionnaires designed for both children and their parents had been collected and analyzed to find out the relationship between play value and outdoor play spaces.
Degradation of extracellular matrix (ECM) underlies loss of cartilage tissue in osteoarthritis, a common disease for which no effective disease-modifying therapy currently exists. Here we describe ...BNTA, a small molecule with ECM modulatory properties. BNTA promotes generation of ECM components in cultured chondrocytes isolated from individuals with osteoarthritis. In human osteoarthritic cartilage explants, BNTA treatment stimulates expression of ECM components while suppressing inflammatory mediators. Intra-articular injection of BNTA delays the disease progression in a trauma-induced rat model of osteoarthritis. Furthermore, we identify superoxide dismutase 3 (SOD3) as a mediator of BNTA activity. BNTA induces SOD3 expression and superoxide anion elimination in osteoarthritic chondrocyte culture, and ectopic SOD3 expression recapitulates the effect of BNTA on ECM biosynthesis. These observations identify SOD3 as a relevant drug target, and BNTA as a potential therapeutic agent in osteoarthritis.
Injury induces profound transcriptional remodeling events, which could lead to only wound healing, partial tissue repair, or perfect regeneration in different species. Injury-responsive enhancers ...(IREs) are cis-regulatory elements activated in response to injury signals, and have been demonstrated to promote tissue regeneration in some organisms such as zebrafish and flies. However, the functional significances of IREs in mammals remain elusive. Moreover, whether the transcriptional responses elicited by IREs upon injury are conserved or specialized in different species, and what sequence features may underlie the functional variations of IREs have not been elucidated.
We identified a set of IREs that are activated in both regenerative and non-regenerative neonatal mouse hearts upon myocardial ischemia-induced damage by integrative epigenomic and transcriptomic analyses. Motif enrichment analysis showed that AP-1 and ETS transcription factor binding motifs are significantly enriched in both zebrafish and mouse IREs. However, the IRE-associated genes vary considerably between the two species. We further found that the IRE-related sequences in zebrafish and mice diverge greatly, with the loss of IRE inducibility accompanied by a reduction in AP-1 and ETS motif frequencies. The functional turnover of IREs between zebrafish and mice is correlated with changes in transcriptional responses of the IRE-associated genes upon injury. Using mouse cardiomyocytes as a model, we demonstrated that the reduction in AP-1 or ETS motif frequency attenuates the activation of IREs in response to hypoxia-induced damage.
By performing comparative genomics analyses on IREs, we demonstrated that inter-species variations in AP-1 and ETS motifs may play an important role in defining the functions of enhancers during injury response. Our findings provide important insights for understanding the molecular mechanisms of transcriptional remodeling in response to injury across species.
Breast cancer is the most commonly diagnosed cancer (estimated 2.3 million new cases in 2020) and the leading cause of cancer death (estimated 685,000 deaths in 2020) in women globally. Breast ...cancers have been categorized into four major molecular subtypes based on the immunohistochemistry (IHC) expression of classic hormone and growth factor receptors including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as a proliferation marker Ki-67 protein expression. Triple-negative breast cancer (TNBC), a breast cancer subtype lacking ER, PR, and HER2 expression, is associated with a high metastatic potential and poor prognosis. TNBC accounts for approximately only 15%–20% of new breast cancer diagnoses; it is responsible for most breast cancer–related deaths due to the lack of targeted treatment options for this patient population, and currently, systemic chemotherapy, radiation, and surgical excision remain the major treatment modalities for these patients with TNBC. Although breast cancer patients in general do not have a robust response to the immunotherapy, a subset of TNBC has been demonstrated to have high tumor mutation burden and high tumor-infiltrating lymphocytes, resembling the features observed on melanoma or lung cancers, which can benefit from the treatment of immune checkpoint inhibitors (ICIs). Therefore, the immunogenic nature of this aggressive disease has presented an opportunity for the development of TNBC-targeting immunotherapies. The recent US Food and Drug Administration approval of atezolizumab in combination with the chemotherapeutic agent nab-paclitaxel for the treatment of PD-L1-positive unresectable, locally advanced, or metastatic TNBC has led to a new era of immunotherapy in TNBC treatment. In addition, immunotherapy becomes an active research area, both in the cancer biology field and in the oncology field. In this review, we will extend our coverage on recent discoveries in preclinical research and early results in clinical trials from immune molecule-based therapy including cytokines, monoclonal antibodies, antibody–drug conjugates, bi-specific or tri-specific antibodies, ICIs, and neoantigen cancer vaccines; oncolytic virus-based therapies and adoptive immune cell transfer–based therapies including TIL, chimeric antigen receptor-T (CAR-T), CAR-NK, CAR-M, and T-cell receptor-T. In the end, we will list a series of the challenges and opportunities in immunotherapy prospectively and reveal novel technologies such as high-throughput single-cell sequencing and CRISPR gene editing-based screening to generate new knowledges of immunotherapy.
Carthamus tinctorius L. is widely used in traditional Chinese medicines for the treatment of cardiovascular disease. However, our current understanding of the molecular mechanisms supporting its ...clinical application still lags behind. In this study, a systems pharmacology approach integrating drug-likeness evaluation, oral bioavailability prediction, target exploration, GO enrichment analysis, KEGG pathway performance and network construction was adopted to explore its therapeutic mechanism. A total of 21 active ingredients contained in Carthamus tinctorius L. and 113 major proteins were screened out as effective players in the treatment of cardiovascular disease through some related pathways. And the association among the active ingredients, major hubs and main pathways was investigated, implying the potential biological progression of Carthamus tinctorius L. acting on cardiovascular disease. Importantly, the majority of hubs and pathways were found to be highly related with platelet activation process. Core genes that can be regulated by Carthamus tinctorius L. in platelet activation pathway were PRKACA, PIK3R1, MAPK1, PPP1CC, PIK3CA and SYK, and they may play a central role in suppressing platelet aggregation. The systems pharmacology approach used in this study may provide a feasible tool to clarify the mechanism of traditional Chinese medicines and further develop their therapeutic potentials.
Recent advances in materials science allowed the incorporation of advanced two dimensional (2D) materials in electronic devices. For example, field effect transistors (FETs) using graphene channels ...have shown unprecedented carrier mobility at room temperature, which is further complemented by its intrinsic flexibility, transparency, chemical stability and even thermal heat dissipation. Other 2D materials such as transition metal dichalcogenides (TMDs) can provide additional functionalities to the devices, such as band gap induced high ON/OFF ratios in FETs. Interestingly, these 2D metallic (graphene) and 2D semiconducting materials (2D/TMDs) have been mainly implemented in devices using traditional three dimensional (3D) insulators, such as HfO2, Al2O3 and SiO2, which may not be the best solution given the complex and defective interface bonding. For this reason recently 2D insulators have been started to be used as dielectric in different electronic devices, showing interesting phenomena. A 2D insulator differs from traditional 3D insulators in that it holds a layered structure, in which the bonding in plane is covalent while the plane-to-plane interaction is governed by van der Waals interactions. This genuine structure has been demonstrated to remarkably alter some reliability phenomena like, for example, the entire dielectric breakdown process. In this review, we analyze the performance of 2D layered dielectrics, focusing on hexagonal boron nitride. Different synthesis methods, electrical characterization, reliability and variability analyses, as well as dielectric breakdown process are discussed. Moreover, it should be highlighted that, in many device applications (like capacitors or resistive switching memories), 2D dielectrics may not require the annoying transfer process usually required for graphene and 2D/TMDs, which further facilitates its introduction in the industry.
In this manuscript, we review the use of hexagonal boron nitride as dielectric, paying special attention to the synthesis methods, nanoscale homogeneity, reliability and dielectric breakdown process. In summary, hexagonal boron nitride is much more homogeneous and stable against electrical fields than other 3D dielectrics (such as HfO2) which can provide some advantages like reduced scattering effects and predictable dielectric breakdown process. Display omitted
•The synthesis, homogeneity, reliability and dielectric breakdown process of hexagonal boron nitride (h-BN) is reviewed.•BN is more homogeneous and stable vs. electrical fields than HfO2.•The layer-by-layer dielectric breakdown behavior of h-BN may have deep influence in the reliability of electronic devices.
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