Search

It is of great significance to explore the molecular mechanism of gametophytic sexual reproduction in the genetic improvement and breeding of tea plants [Camellia sinensis (L.) O. Kuntze]. Imported beta family members (IMBs) are a class of widely distributed nucleoplasmic transport receptor proteins in eukaryotes, affecting plant development and reproduction, and participating in flowering time and sexual reproduction. Still missing, though, is a thorough examination of IMB members in tea plants. Here, seven members of the IMB gene family were screened by a genome-wide investigation in tea plants. These members were scattered unevenly throughout five chromosomes. All of them contained the conserved KAP95 and HEAT Repeat domains. Additionally, the promoter regions of CsIMBs harbored cis-acting elements associated with plant hormones, light, and abiotic stress responses. In order to further confirm the function of CsIMBs in the sexual reproduction of tea plants, the expression patterns of CsIMBs in different flower development stages and the ovary (before and after pollination) were analyzed. The expression results highlighted that CsIMBs were related to the fertility and fruiting of tea plants. Furthermore, five of the seven CsIMBs (CsIMB1a, CsIMB1b, CsIMB2, CsIMB3a, and CsIMB3b) were found to be localized in the nucleus revealed by subcellular localization analysis. These results offer a comprehensive characterization of IMB genes as well as insights into the potential roles of CsIMBs participating in the gametophytic sexual reproduction of C. sinensis. [ABSTRACT FROM AUTHOR]

As a novel histone deacetylase inhibitor (HDACi), LAQ824 (LAQ) effectively inhibits the proliferation of hematological malignancies and solid tumors. However, phase II trials of LAQ in solid tumors were terminated due to dose-dependent toxicity. Furthermore, LAQ has been shown to induce the activation of the Notch signaling pathway in hematopoietic stem cells, which is associated with tumor progression and drug resistance in colon and breast cancers. Therefore, in this study, we investigated the strategy of LAQ combined with a Notch signaling pathway inhibitor to treat solid tumors. We used RT-PCR and Western blot methods to demonstrate that LAQ upregulated the Notch signaling pathway in solid tumor cell lines at the molecular level. The combination of LAQ and a Notch signaling pathway inhibitor was shown by a Chou–Talalay assay to have a synergistic effect in inhibiting solid tumor cell line proliferation in vitro. We also demonstrated that the combination of LAQ and a Notch signaling pathway inhibitor significantly inhibited the growth of tumor cells in vivo using an allograft tumor model. This study indicates that inhibition of the Notch signaling pathway provides a valuable strategy for enhancing solid tumor sensitivity to LAQ. [ABSTRACT FROM AUTHOR]

The high vascularization of glioma highlights the potential value of anti-angiogenic therapeutics for glioma treatment. Previously, we designed a novel vascular-targeting and blood–brain barrier (BBB)-penetrating peptide, TAT-AT7, by attaching the cell-penetrating peptide TAT to a vascular-targeting peptide AT7, and we demonstrated that TAT-AT7 could target binding to the vascular endothelial growth factor receptor 2 (VEGFR-2) and Neuropilin-1 (NRP-1), which are both highly expressed in endothelial cells. TAT-AT7 has been proven to be a good targeting peptide which could effectively deliver the secretory endostatin gene to treat glioma via the TAT-AT7-modified polyethyleneimine (PEI) nanocomplex. In the current study, we further explored the molecular binding mechanisms of TAT-AT7 to VEGFR-2 and NRP-1 and its anti-glioma effects. Accordingly, TAT-AT7 was proven to competitively bind to VEGFR-2 and NRP-1 and prevent VEGF-A165 binding to the receptors by the surface plasmon resonance (SPR) assay. TAT-AT7 inhibited endothelial cells' proliferation, migration, invasion, and tubule formation, as well as promoted endothelial cells' apoptosis in vitro. Further research revealed that TAT-AT7 inhibited the phosphorylation of VEGFR-2 and its downstream PLC-γ, ERK1/2, SRC, AKT, and FAK kinases. Additionally, TAT-AT7 significantly inhibited angiogenesis of zebrafish embryo. Moreover, TAT-AT7 had a better penetrating ability and could penetrate the BBB into glioma tissue and target glioma neovascularization in an orthotopic U87-glioma-bearing nude mice model, and exhibited the effect of inhibiting glioma growth and angiogenesis. Taken together, the binding and function mechanisms of TAT-AT7 were firstly revealed, and TAT-AT7 was proven to be an effective and promising peptide for the development of anti-angiogenic drugs for targeted treatment of glioma. [ABSTRACT FROM AUTHOR]

The human tibiofibular complex has undergone a long evolutionary process, giving its structure a high bearing-capacity. The distinct tibiofibular shape can be used in engineering to acquire excellent mechanical properties. In this paper, four types of bionic tubes were designed by extracting the dimensions of different cross-sections of human tibia–fibula. They had the same outer profiles, but different inner shapes. The concept of specific stiffness was introduced to evaluate the mechanical properties of the four tubes. Finite-element simulations and physical bending-tests using a universal testing machine were conducted, to compare their mechanical properties. The simulations showed that the type 2 bionic tube, i.e., the one closest to the human counterpart, obtained the largest specific-stiffness (ε = 6.46 × 104), followed by the type 4 (ε = 6.40 × 104) and the type 1 (ε = 6.39 × 104). The type 3 had the largest mass but the least stiffness (ε = 6.07 × 104). The specific stiffness of the type 2 bionic tube increased by approximately 25.8%, compared with that of the type 3. The physical tests depicted similar findings. This demonstrates that the bionic tube inspired by the human tibiofibular shape has excellent effectiveness and bending properties, and could be used in the fields of healthcare engineering, such as robotics and prosthetics. [ABSTRACT FROM AUTHOR]

Aerodynamic compressor designs require considerable prior knowledge and a deep understanding of complex flow fields. With the development of computer science, artificial intelligence (AI) has been widely applied to compressors design. Among the various AI models, deep reinforcement learning (RL) methods have successfully addressed complex problems in different domains. This paper proposes a modified deep deterministic policy gradient algorithm for compressor design and trains several agents, improving the performance of a 3D transonic rotor for the first time. An error reduction process was applied to improve the capability of the surrogate models, and then RL environments were established based on the surrogate models. The rotors generated by the agent were evaluated by computational fluid dynamic methods, and the flow field analysis indicated that the combination of the sweep, lean, and segment angle modifications reduced the loss near the tip, while improving the pressure ratio in the middle section. Different policy combinations were explored, confirming that the combined policy improved the rotor performance more than single policies. The results demonstrate that the proposed RL method can guide future compressor designs. [ABSTRACT FROM AUTHOR]

An aircraft engine's performance depends largely on the compressors' aerodynamic design, which aims to achieve higher stage pressure, efficiency, and an acceptable stall margin. Existing design methods require substantial prior knowledge and different optimization algorithms to determine the 2D and 3D features of the blades, in which the design policy needs to be more readily systematized. With the development of artificial intelligence (AI), deep reinforcement learning (RL) has been successfully applied to complex design problems in different domains and provides a feasible method for compressor design. In addition, the applications of AI methods in compressor research have progressively developed. This paper described a combined artificial-intelligence aerodynamic design method based on a modified deep deterministic policy gradient algorithm and a genetic algorithm (GA) and integrated the GA into the RL framework. The trained agent learned the design policy and used it to improve the GA optimization result of a single-stage transonic compressor rotor. Consequently, the rotor exhibited a higher pressure ratio and efficiency owing to the sweep feature, lean feature, and 2D airfoil angle changes. The separation near the tip and the secondary flow decreased after the GA process, and at the same time, the shockwave was weakened, providing improved efficiency. Most of these beneficial flow field features remained after agent modification to improve the pressure ratio, showing that the policy learned by the agent was generally universal. The combination of RL and other design optimization methods is expected to benefit the future development of compressor designs by merging the advantages of different methods. [ABSTRACT FROM AUTHOR]

In the existing research on prosthetic footplates, rehabilitation insoles, and robot feet, the cushioning parts are basically based on simple mechanisms and elastic pads. Most of them are unable to provide adequate impact resistance especially during contact with the ground. This paper developed a bioinspired heel pad by optimizing the inner structures inspired from human heel pad which has great cushioning performance. The distinct structures of the human heel pad were determined through magnetic resonance imaging (MRI) technology and related literatures. Five-layer pads with and without inner structures by using two materials (soft rubber and resin) were obtained, resulting in four bionic heel pads. Three finite element simulations (static, impact, and walking) were conducted to compare the cushioning effects in terms of deformations, ground reactions, and principal stress. The optimal pad with bionic structures and soft rubber material reduced 28.0% peak vertical ground reaction force (GRF) during walking compared with the unstructured resin pad. Human walking tests by a healthy subject wearing the 3D printed bionic pads also showed similar findings, with an almost 20% decrease in peak vertical GRF at normal speed. The soft rubber heel pad with bionic structures has the best cushioning performance, while the unstructured resin pad depicts the poorest. This study proves that with proper design of the inner structures and materials, the bionic pads will demonstrate distinct cushioning properties, which could be applied to the engineering fields, including lower limb prosthesis, robotics, and rehabilitations. [ABSTRACT FROM AUTHOR]

(1) Background: We aimed to compare gender differences in knee biomechanics and neuromuscular characteristics, and to determine the relationships between lower limb muscle pre-activations and knee biomechanics during a single leg drop landing, in order to identify riskier landing patterns to prevent injury and intervene properly. (2) Methods: Descriptive laboratory cross-sectional study on 38 healthy untrained subjects with low to moderate physical activity status. (3) Results: During the initial-contact phase of landing, females demonstrated greater peak vertical ground reaction force (GRF) normalized to body weight (49.12 ± 7.53 vs. 39.88 ± 5.69 N/kg; p < 0.001; Hedge's g = 1.37), peak knee anterior reaction force normalized to body weight (0.23 ± 0.04 vs. 0.17 ± 0.05 N/kg; p < 0.001; Hedge's g = 1.33), and decreased pre-activation of the semitendinosus (45.10 ± 20.05% vs. 34.03 ± 12.05%; p = 0.04; Hedge's g = 0.67). The final regression equation was peak knee anterior reaction force = 0.024 + 0.025 (peak knee flexion moment) − 0.02 (semitendinosus-to-vastus lateralis pre-activation ratio) + 0.003 (peak vertical GRF) (R2 = 0.576, p < 0.001). (4) Conclusions: Overall, the data provided in this study support that a reduced semitendinosus-to-vastus lateralis pre-activation ratio predicted an increase in knee anterior reaction force and potentially an increase in ACL forces. Female non-athletes had gender-specific landing characteristics that may contribute to ACL injury. Future studies are warranted to consider more possible predictors of non-contact ACL injury. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) infection causes huge economic losses to the pig industry worldwide. DNAJA3, a member of the Hsp40 family proteins, is known to play an important role in the replication of several viruses. However, it remains unknown if it interacts with PEDV. We found that DNAJA3 interacted with PEDV S1, initially with yeast two-hybrid screening and later with Co-IP, GST pull-down, and confocal imaging. Further experiments showed the functional relationship between DNAJA3 and PEDV in the infected IPEC-J2 cells. DNAJA3 overexpression significantly inhibited PEDV replication while its knockdown had the opposite effect, suggesting that it is a negative regulator of PEDV replication. In addition, DNAJA3 expression could be downregulated by PEDV infection possibly as the viral strategy to evade the suppressive role of DNAJA3. By gene silencing and overexpression, we were able to show that DNAJA3 inhibited PEDV adsorption to IPEC-J2 cells but did not affect virus invasion. In conclusion, our study provides clear evidence that DNAJA3 mediates PEDV adsorption to host cells and plays an antiviral role in IPEC-J2 cells. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, the involvement of IDH1 in atherosclerotic foam cells was explored. Inhibiting macrophage ferroptosis and foam cell formation by knocking down IDH1 is a promising study direction for better understanding the occurrence and progression of atherosclerosis, as well as the treatment targets for atherosclerosis. A distinctive feature of ferroptosis is intracellular iron accumulation and the impairment of antioxidant capacity, resulting in a lethal accumulation of lipid peroxides leading to cell death. This study was conducted to determine whether inhibiting isocitrate dehydrogenase 1 (IDH1) may help to prevent foam cell formation by reducing oxidized low-density lipoprotein (ox-LDL)-induced ferroptosis in macrophages and activating nuclear factor erythroid 2-related factor 2 (NRF2). Gene expression profiling (GSE70126 and GSE70619) revealed 21 significantly different genes, and subsequent bioinformatics research revealed that ferroptosis and IDH1 play essential roles in foam cell production. We also confirmed that ox-LDL elevates macrophage ferroptosis and IDH1 protein levels considerably as compared with controls. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, reduced ox-LDL-induced elevated Fe2+ levels, lipid peroxidation (LPO) buildup, lactate dehydrogenase (LDH) buildup, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4), ferritin heavy polypeptide 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) protein downregulation. More crucially, inhibiting IDH1 reduced Fe2+ overload, lipid peroxidation, LDH, and glutathione depletion, and elevated GPX4, FTH1, and SLC7A11 protein expression, resulting in a reduction in ox-LDL-induced macrophage ferroptosis. IDH1 inhibition suppressed ox-LDL-induced macrophage damage and apoptosis while raising NRF2 protein levels. We have demonstrated that inhibiting IDH1 reduces ox-LDL-induced ferroptosis and foam cell formation in macrophages, implying that IDH1 may be an important molecule regulating foam cell formation and may be a promising molecular target for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO), as a signal molecule, is involved in the mediation of heavy-metal-stress-induced physiological responses in plants. In this study, we investigated the effect of NO on Camellia sinensis pollen tubes exposed to aluminum (Al) stress. Exogenous application of the NO donor decreased the pollen germination rate and pollen tube length and increased the malondialdehyde (MDA) content and antioxidant enzyme activities under Al stress. Simultaneously, the NO donor effectively increased NO content in pollen tube of C. sinensis under Al stress and could aggravate the damage of Al3+ to C. sinensis pollen tubes by promoting the uptake of Al3+. In addition, application of the NO-specific scavenger significantly alleviated stress damage in C. sinensis pollen tube under Al stress. Moreover, 18 CsALMT members from a key Al-transporting gene family were identified, which could be divided into four subclasses. Pearson correlation analysis showed the expression level of CsALMT8 showed significant positive correlation with the Al3+ concentration gradient and NO levels, but a significant negative correlation with pollen germination rate and pollen tube length. The expression level of CsALMT5 was negatively correlated with the Al3+ concentration gradient and NO level, and positively correlated with pollen germination rate and pollen tube length. The expression level of CsALMT17 showed a significant negative correlation with Al3+ concentration and NO content in pollen tubes, but significant positive correlation with pollen germination rate and pollen tube length. In conclusion, a complex signal network regulated by NO-mediated CsALMTs revealed that CsALMT8 was regulated by environmental Al3+ and NO to assist Al3+ entry into pollen tubes; CsALMT5 might be influenced by the Al3+ signal, stimulate malate efflux in vacuoles and chelate with Al3+ to detoxify Al in C. sinensis pollen tube. [ABSTRACT FROM AUTHOR]

Background and aims: although an association between metabolic syndrome (MS) and cardiovascular disease risk has been documented, the relationship in patients with complex calcified coronary lesions undergoing rotational atherectomy (RA) and drug-eluting stent(DES) insertion remains controversial. Here, the influence of MS on outcomes was assessed. Methods and results: we retrospectively included 398 patients who underwent RA and DES insertion for complex calcified coronary lesions in our institution between June 2015 and January 2019. The modified Adult Treatment Plan III was used to diagnose MS. The endpoint was major adverse cardiovascular events (MACEs), comprising mortality from all causes, myocardial infarction, and target vessel revascularization (TVR). In all, 173 (43.5%) patients had MS. MS was significantly associated with MACE over the 28.32 ± 6.79-month follow-up period (HR 1.783, 95% CI from 1.122 to 2.833) even after adjustment for other possible confounders. Conclusion: MS was frequently observed in patients treated with RA with DES insertion for complex calcified coronary lesions. MS independently predicted MACE in these patients. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis. [ABSTRACT FROM AUTHOR]

Parameter sensitivity analysis is usually required to select the key parameters with high sensitivity to the optimal goal before the optimization is carried out, especially for flux-switching permanent magnet (FSPM) machines where lot of design parameters should be considered. Unlike the traditional studies on parameter sensitivity, which are generally experience- or statistics-based, and are time-consuming, this paper proposes a parameter sensitivity analysis method of a FSPM machine based on a magnetic equivalent circuit (MEC), which enables the parameters' sensitivities to be evaluated by their exponential in the nondimensionalized equations, thus providing a fast and accurate way to obtain the parameter sensitivities. Thereafter, the influences of modular manufacturing methods on magnetic performances are discussed, and the robust design approach for the FSPM machine is introduced, which aims to achieve the best machine stability and robustness by setting boundaries on design dimensions when taking into account the manufacturing tolerances. Experimental validations are also presented. [ABSTRACT FROM AUTHOR]

In this paper, the 12-slot/4-pole (12/4) synchronous reluctance motor (SynRM) with concentrated windings is proposed for low-cost hybrid vehicles. The non-linear magnetic equivalent circuit (MEC) model of the 12/4 SynRM is built to obtain the main electromagnetic characteristics such as coil flux, inductances, torque, etc. The magnetic saturation is also counted in by the MEC. Results calculated by MEC are validated by 2D finite element analysis (FEA). Then, aiming at larger average torque, lower torque ripple and lower total harmonic distortion (THD) in phase voltage, the parameter optimization method of the SynRM is proposed based on the Taguchi method and the MEC model. The proposed Taguchi-MEC method enables a fast optimization with satisfactory accuracy. Finally, the motor prototype is manufactured, and experimental validations are carried out. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) as a momentous signal molecule participates in plant reproductive development and responds to various abiotic stresses. Here, the inhibitory effects of the NO-dominated signal network on the pollen tube growth of Camellia sinensis under low temperature (LT) were studied by microRNA (miRNA) omics analysis. The results showed that 77 and 71 differentially expressed miRNAs (DEMs) were induced by LT and NO treatment, respectively. Gene ontology (GO) analysis showed that DEM target genes related to microtubules and actin were enriched uniquely under LT treatment, while DEM target genes related to redox process were enriched uniquely under NO treatment. In addition, the target genes of miRNA co-regulated by LT and NO are only located on the cell membrane and cell wall, and most of them are enriched in metal ion binding and/or transport and cell wall organization. Furthermore, DEM and its target genes related to metal ion binding/transport, redox process, actin, cell wall organization and carbohydrate metabolism were identified and quantified by functional analysis and qRT-PCR. In conclusion, miRNA omics analysis provides a complex signal network regulated by NO-mediated miRNA, which changes cell structure and component distribution by adjusting Ca2+ gradient, thus affecting the polar growth of the C. sinensis pollen tube tip under LT. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS),which is inflammatory disorder of the lung, which is caused by pneumonia, aspiration of gastric contents, trauma and sepsis, results in widespread lung inflammation and increased pulmonary vascular permeability. Its pathogenesis is complicated and the mortality is high. Thus, there is a tremendous need for new therapies. We have reported that HJB-1, a 17-hydroxy-jolkinolide B derivative, exhibited strong anti-inflammatory effects in vitro. In this study, we investigated its impacts on LPS-induced ARDS mice. We found that HJB-1 significantly alleviated LPS-induced pulmonary histological alterations, inflammatory cells infiltration, lung edema, as well as the generation of inflammatory cytokines TNF-α, IL-1β and IL-6 in BALF. In addition, HJB-1 markedly suppressed LPS-induced IκB-α degradation, nuclear accumulation of NF-κB p65 subunit and MAPK phosphorylation. These results suggested that HJB-1 improved LPS-induced ARDS by suppressing LPS-induced NF-κB and MAPK activation.