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Abstract The mitochondrial malic enzyme 2 (ME2), which is frequently elevated during carcinogenesis and may be a target for cancer therapy, catalyzes the conversion of malate to pyruvate. The processes controlling ME2 activity, however, remain largely unclear. In this work, we show that human hepatocellular carcinoma (HCC) tissues contain high levels of ME2 and that the methylation of ME2 stimulates the growth and migration of HCC cells. Furthermore, we observed that ME2 interacts with protein arginine methyltransferase 1 (PRMT1) and that ME2 enzymatic activity is activated by mutation of ME2 at lysine 67. Mitochondrial respiration was markedly increased by activated ME2, which promoted cell division and carcinogenesis. Furthermore, a negative prognosis for patients was strongly linked with the expression levels of PRMT1 and ME2 R67K in HCC tissues. These findings imply that hepatocellular carcinoma growth is aided by PRMT1-mediated ME2 methylation, that is an essential signaling event that cancer cells need to continue mitochondrial respiration.

Abstract This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433–0.973) and 0.682 (95% CI: 0.464–0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511–1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14–3.4) and PFS 2.13 (95% CI: 1.28–3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

Introduction: This study aimed to assess the impact of prophylactic use of PEG-rhG-CSF on first-line immunochemotherapy in advanced NSCLC. Methods: A cohort of patients with advanced NSCLC who received first-line immunochemotherapy at Shengjing Hospital of China Medical University between January 2019 and July 2024 was selected for this study. Patients were divided into the following two groups: a treatment group that received prophylactic PEG-rhG-CSF (≥1 cycle) 48 hours after immunochemotherapy and a control group that did not receive PEG-rhG-CSF. The primary end points were progression-free survival (PFS), overall survival (OS), overall response rate, and safety. A propensity score-matched analysis was performed to reduce potential confounders. Results: A total of 220 patients were enrolled, with 87 in the treatment group and 133 in the control group. Median PFS was 10.5 months in both the treatment and control groups (p = 0.86), and median OS was 33.9 months in the treatment group versus not reached in the control group (p = 0.71). The overall response rate was 64.4% in the treatment group and 58.6% in the control group (p = 0.40). After propensity score-matched analysis (each group included 78 patients), median PFS was 12.6 months in the treatment group versus 10.5 months in the control group (p = 0.99), and median OS remained 30.3 months in the treatment group versus not reached in the control group (p = 0.85). The treatment group had a reduced incidence of chemotherapy interruptions, any grade of leukopenia, any grade of neutropenia, and grades 3 to 5 neutropenia, without an increase in immune-related adverse events. Conclusions: The prophylactic use of PEG-rhG-CSF in patients with advanced NSCLC undergoing first-line immunochemotherapy did not compromise efficacy and safety. It reduced chemotherapy interruptions and neutropenia, without increasing immune-related adverse events, thus supporting safe and uninterrupted treatment.

ABSTRACT Introduction Lung cancer thoracoscopic postoperative wound complications bring great pain and inconvenience to patients. Methods To provide clinical nurses with a more scientific and effective nursing plan, this study evaluated the effect of refined nursing on wound complications after thoracoscopic surgery for lung cancer. Two‐hundred thirty patients undergoing thoracoscopic radical resection for lung cancer were randomly divided into two groups according to the random number table method. The study group received refined nursing intervention (115 cases), and the control group received routine nursing intervention (115 cases). The effects of the two groups' nursing modes on the wound complications (pleural effusion, incision infection, lung leakage, and wound bleeding) after thoracoscopic surgery for lung cancer were compared. Results According to the study results, the study group experienced a shorter intraoperative blood loss, lower extubation time, shorter hospital stay, and lower wound complication rate than the control group (p

Dendritic mesoporous silica nanoparticles (DMSNs) are a new class of solid porous materials used for enzyme immobilization support due to their intrinsic characteristics, including their unique open central–radial structures with large pore channels and their excellent biocompatibility. In this review, we review the recent progress in research on enzyme immobilization using DMSNs with different structures, namely, flower-like DMSNs and tree-branch-like DMSNs. Three DMSN synthesis methods are briefly compared, and the distinct characteristics of the two DMSN types and their effects on the catalytic performance of immobilized enzymes are comprehensively discussed. Possible directions for future research on enzyme immobilization using DMSNs are also proposed.

Purpose: This study aimed to analyze the efficacy and safety of neoadjuvant and adjuvant immunotherapies for non-small cell lung cancer (NSCLC). Methods: Electronic literature searches were conducted in PubMed, OVID, Web of SCI, Embase, Cochrane Library, and the Chinese National Knowledge Infrastructure databases. The deadline for literature update and retrieval is February 16, 2024. Studies presented at meetings were also screened. Randomized controlled trials (RCTs) and single-arm trials were included, and the data were extracted according to the inclusion and exclusion criteria. Data analysis was performed using Stata (16.0) software. Results: A total of 5850 patients in 11 RCTs and 6 single-arm trial studies involving neoadjuvant and/or adjuvant immune checkpoint inhibitor (ICI)-based therapies were included. Regarding neoadjuvant therapy, the overall complication rate after surgery reached 35% (95% CI, 0.21-0.49). Higher rates of pathological complete response (OR = 7.83; 95% CI, 5.95-10.31; P

Nonalcoholic fatty liver disease (NAFLD) is a prevalent medical condition with an ever-growing trend. Although multiple intracellular mechanisms are involved, endoplasmic reticulum (ER) stress has been demonstrated to play a significant role in the genesis and progression. Most of the research supports the advantages of exercise for NAFLD. However, little is known about the molecular mechanism(s) that underpin the effectiveness of exercise training in NAFLD. This study aimed to identify how aerobic exercise affected hepatic ER stress in a mouse NAFLD model. In this study, the mice were fed either a standard diet (SD) or a high-fat diet (HFD) for 17 weeks. HFD mice were trained on a treadmill during the last eight weeks. All animals were tested for serum levels of biochemical assays, protein expression, and gene expression. The hematoxylin and eosin, Oil red O, and immunohistochemistry staining were also performed. The results indicated that a high-fat diet generated NAFLD, with serum lipid disruption and hepatic function impairment, and increased GRP78 and ATF6 expressions. However, aerobic training reversed the majority of these alterations. It is concluded that NAFLD appears to be associated with hepatic ER stress response, and aerobic exercise mitigates NAFLD via lowering ER stress proteins GRP78 and ATF6.

This study investigates the factors influencing undergraduate students’ self-directed learning (SDL) abilities in generative Artificial Intelligence (AI)-driven interactive learning environments. The advent of generative AI has revolutionized interactive learning environments, offering unprecedented opportunities for personalized and adaptive education. Generative AI supports teachers in delivering smart education, enhancing students’ acceptance of technology, and providing personalized, adaptive learning experiences. Nevertheless, the application of generative AI in higher education is underexplored. This study explores how these AI-driven platforms impact undergraduate students’ self-directed learning (SDL) abilities, focusing on the key factors of teacher support, learning strategies, and technology acceptance. Through a quantitative approach involving surveys of 306 undergraduates, we identified the key factors of motivation, technological familiarity, and the quality of AI interaction. The findings reveal the mediating roles of self-efficacy and learning motivation. Also, the findings confirmed that improvements in teacher support and learning strategies within generative AI-enhanced learning environments contribute to increasing students’ self-efficacy, technology acceptance, and learning motivation. This study contributes to uncovering the influencing factors that can inform the design of more effective educational technologies and strategies to enhance student autonomy and learning outcomes. Our theoretical model and research findings deepen the understanding of applying generative AI in higher education while offering important research contributions and managerial implications.

Abstract Background The WRKY transcription factors play significant roles in plant growth, development, and defense responses. However, in cotton, the molecular mechanism of most WRKY proteins and their involvement in Verticillium wilt tolerance are not well understood. Results GhWRKY70 is greatly up-regulated in cotton by Verticillium dahliae. Subcellular localization suggests that GhWRKY70 is only located in the nucleus. Transcriptional activation of GhWRKY70 further demonstrates that GhWRKY70 function as a transcriptional activator. Transgenic Arabidopsis plants overexpressing GhWRKY70 exhibited better growth performance and higher lignin content, antioxidant enzyme activities and jasmonic acid (JA) levels than wild-type plants after infection with V. dahliae. In addition, the transgenic Arabidopsis resulted in an enhanced expression level of AtAOS1, a gene related to JA synthesis, further leading to a higher JA accumulation compared to the wild type. However, the disease index (DI) values of the VIGS-treated cotton plants with TRV:WRKY70 were also significantly higher than those of the VIGS-treated cotton plants with TRV:00. The chlorophyll and lignin contents of TRV:WRKY70 plants were significantly lower than those of TRV:00 plants. GhAOS1 expression and JA abundance in TRV:WRKY70 plants were decreased. The GhWRKY70 protein was confirmed to bind to the W-box element in the promoter region of GhAOS by yeast one-hybrid assay and transient expression. Conclusion These results indicate that the GhWRKY70 transcription factor is a positive regulator in Verticillium wilt tolerance of cotton, and may promote the production of JA via regulation of GhAOS1 expression.

AbstractCotton (Gossypium hirsutum) is an important economic crop, so it is of great significance to analyze its molecular mechanisms of resistance to Verticillium Wilt. The WRKY gene family encodes transcription factors (TFs) involved in plant resistance to biotic and abiotic stress. Here, we identified 17 group III WRKY genes in cotton based on the cotton genome project. The phylogenetic relationship and evolutionary of WRKY Group III TFs in Arabidopsis thaliana and G. hirsutum showed that all the WRKY Group III TFs were divided into two clades. Overall, Group III WRKYs with similar motif patterns showed a tendency to cluster into the same group in the phylogenetic tree. Elements related to jasmonic acid (JA) and salicylic acid (SA) regulation were identified in the promoter region of most WRKY Group III genes. The expression levels of five Group III genes were up-regulated more than two-fold and three genes were down-regulated after Verticillium dahliae Kleb. infection. Moreover, three group III GhWRKY genes with JA or SA regulatory element in the promoter region could be significantly induced by JA or SA, respectively. Subcellular localization and transcriptional activation analysis in yeast showed that Cot_14615 protein localized to the nucleus of mesophyll cells in Nicotiana tabacum and had transcription activation function. Our data on cotton group III WRKY genes can serve as a basis for further studies into their potential function in cotton resistant to Verticillium Wilt.

We aimed to explore the role of antithrombin III (AT-III) activity in diagnosing patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and chronic bronchitis, and its relationship with all-cause mortality of AECOPD patients. We performed univariate and multivariate Cox regression analyses of the factors determining all-cause mortality. We recruited 279 patients with AECOPD and 91 with chronic bronchitis. On admission, patients with AECOPD had lower AT-III activity (80.7 vs. 86.35%, p = 0.002) and higher neutrophil percentages (70.12 vs. 66.40%, p = 0.02) than those with chronic bronchitis. The patients who died were older (78 vs. 73 years, p 79.75%. AT-III activity was lower in patients with AECOPD than in those with chronic bronchitis and is potentially useful as an independent predictor of all-cause mortality in patients with AECOPD: reduced AT-III activity and increased CRP and D-dimer levels indicate a higher risk of all-cause mortality.

With the rapid increase in the use of renewable energy sources, the strength of the power grid is reduced, which may lead to many weak distribution networks. The inertia of the weak distribution network decreases significantly, which leads to poor voltage quality. It means that the voltage and frequency are distorted and deviated. Battery storage can balance the frequent power disturbance and improve the frequency quality. However, it usually requires a central controller to dispatch the power in the current-controlled mode or respond natively with a fixed linear curve in voltage-controlled mode. The performance is poor when the power demand is in a wide range, which further deteriorates the frequency quality. To solve this problem, this paper proposes an adaptive frequency deviation improvement method for energy storage in the voltage-controlled mode. This method can change the power output characteristics of the storage inverter according to the magnitude and trend of power demand, where both frequency deviation and changing rate are used to shape the output power curve. A transfer function model for a voltage-controlled storage inverter is set up for theoretical analysis. Then, with the model, an adaptive frequency deviation improvement method is proposed with a fast response to power demand in a wide range. Finally, the results verify the effectiveness of the proposed method for frequency quality improvement with a high penetration level of stochastic photovoltaic power.

PurposeTo evaluate the correlation between microvascular density (MVD) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) parameters and the effect of glycolytic flux after transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor.Materials and methodsVX2 liver tumor allografts in 15 New Zealand white rabbits were treated with sterile saline (control group, n = 5) or lipiodol-doxorubicin emulsion (experimental group, n = 10). MRI was performed 2 weeks after the procedure to evaluate IVIM parameters, including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF). All animal samples were taken of the tumor and surrounding liver. Immunostaining for CD31, CD34, CD105, and VEGF was used to evaluate MVD. The protein expression of Glut4, HK2, PKM2, LDHA, and MCT1 was determined using western blotting. Pearson correlation tests were used to analyze the relationship between MVD and IVIM parameters.ResultsD* value in the peritumoral region was negatively correlated with CD34 (r = –0.71, P = 0.01). PF value positively correlated with CD34 (r = 0.68, P = 0.015), CD105 (r = 0.76, P = 0.004) and VEGF (r = 0.72, P = 0.008) in the peritumoral region. Glut4, HK2, PKM2, and MCT1 in the peritumoral regions were higher in the experimental group than in the control group (all P < 0.05).ConclusionIVIM parameters were correlated with MVD in the intratumoral and peritumoral regions after TACE in a rabbit liver tumor model. The angiogenesis reflected by MVD may be related to changes of glycolytic flux.

Polyetheretherketone (PEEK) has gradually become the mainstream material for preparing orthopedic implants due to its similar elastic modulus to human bone, high strength, excellent wear resistance, radiolucency, and biocompatibility. Since the 1990s, PEEK has increasingly been used in orthopedics. Yet, the widespread application of PEEK is limited by its bio-inertness, hydrophobicity, and susceptibility to microbial infections. Further enhancing the osteogenic properties of PEEK-based implants remains a difficult task. This article reviews some modification methods of PEEK in the last five years, including surface modification of PEEK or incorporating materials into the PEEK matrix. For surface modification, PEEK can be modified by chemical treatment, physical treatment, or surface coating with bioactive substances. For PEEK composite material, adding bioactive filler into PEEK through the melting blending method or 3D printing technology can increase the biological activity of PEEK. In addition, some modification methods such as sulfonation treatment of PEEK or grafting antibacterial substances on PEEK can enhance the antibacterial performance of PEEK. These strategies aim to improve the bioactive and antibacterial properties of the modified PEEK. The researchers believe that these modifications could provide valuable guidance on the future design of PEEK orthopedic implants.

CuO-added 0.96(Na0.5K0.5)(Nb1-xSbx)-0.04BaTiO3 ceramics with 0.0 ≤ x ≤ 0.1 were sintered at 980°C for 6 hours and the effects of antimony on the successive phase transition and the corresponding piezoelectric properties were carefully studied. It was found that with the increasing of x values, the crystal structures varied from orthorhombic-tetragonal polymorphic phase boundary (PPB), orthorhombic-tetragonal-cubic PPB, and finally to the tetragonal-cubic PPB structure. Accordingly, the piezoelectric properties of the specimens were influenced by the varied crystal structures. In particular, the specimen with a tetragonal (88.01%)-cubic (11.99%) PPB structure (x = 0.06) showed a large d33 of 302 pC/N and a high strain of 0.17% at 4.5kV/mm, revealing its promising potential as the Pb-free piezoelectric actuators.

With the rapid development of 5G technology, people have put forward many new requirements for low-dielectric materials. The newest version of 5G communication technology requires frequency ranges become higher. This means that the wavelength of waves used in the 5G communication technology become shorter. The shorter the wavelength of the electromagnetic wave is, the poorer the diffraction ability it has, and the stronger the attenuation that occurs during its propagation. The existing materials are far from meeting the new requirements of 5G technology. Therefore, the research of new low-dielectric materials has become a hot spot. This article summarizes the related researches on some new types of poly aryl ether materials with low dielectric constant and low dielectric loss to provide experience for follow-up work.

In recent years, various breakthroughs have been made in tumor immunotherapy that have contributed to prolonging the survival of tumor patients. However, only a subset of patients respond to immunotherapy, which limits its use. One reason for this is that the tumor microenvironment (TME) hinders the migration and infiltration of T cells and affects their continuous functioning, resulting in an exhausted phenotype. Therefore, clarifying the mechanism by which T cells become exhausted is of significance for improving the efficacy of immunotherapy. Several recent studies have shown that mitochondrial dynamics play an important role in the immune surveillance function of T cells. Dynamin-related protein 1 (Drp1) is a key protein that mediates mitochondrial fission and maintains the mitochondrial dynamic network. Drp1 regulates various activities of T cells in vivo by mediating the activation of a series of pathways. In addition, abnormal mitochondrial dynamics were observed in exhausted T cells in the TME. As a potential target for immunotherapy, in this review, we describe in detail how Drp1 regulates various physiological functions of T cells and induces changes in mitochondrial dynamics in the TME, providing a theoretical basis for further research.

The effect of an innovative two-step heat-treatment process on the microstructure and mechanical properties of a Ti-TiAl laminate composite fabricated by hot-pack rolling was studied in this paper. After heat treatment, the fracture toughness of the composite was enhanced and the elongation of the composite was almost twice that of the initial one. These changes were due to the dislocations and substructures stored in the Ti-43Al-9V alloy being decreased, the microstructure of the DsTi700 alloy turning to a duplex structure, the acicular α2 phase being precipitated at the interfacial region and the residual stresses stored in interfacial region being eliminated. The precipitation of dual-scale silicides was the main reason for the slightly reduced strength. Compared with the initial composite, the tensile strength of the heat-treated composite at 25° and 700° only reduced by 2.7% and 4%, respectively. The primary annealing temperature had a huge impact on the mechanical properties of the composite. However, with the change in secondary annealing temperature, the mechanical properties of the composite were not changed significantly. After heat treatment at 940–960 °C/2 h/AC + 725–750 °C/6 h/AC, the composite might possess high, comprehensive mechanical properties.

The giant magneto-impedance (GMI) effect of Co83.2Fe5.2Si8.8B2.8 ribbons at frequencies of

The purpose of this study is to understand the mechanism of sodium arsenite (NaAsO2)-induced apoptosis of L-02 human hepatic cells, and how Dictyophora polysaccharide (DIP) protects L-02 cells from arsenic-induced apoptosis. The results revealed that DIP pretreatment inhibited NaAsO2 induced L-02 cells apoptosis by increasing anti-apoptotic Bcl-2 expression and decreasing pro-apoptotic Bax expression. Proteomic analysis showed that arsenic treatment disrupted the expression of metabolism and apoptosis associated proteins, including ribosomal proteins (RPs). After pretreatment with DIP, the expression levels of these proteins were reversed or restored. For the first time, it was observed that the significant decrease of cytoplasmic RPs and the increase of mitochondrial RPs were related to human normal cell apoptosis induced by arsenic. This is also the first report that the protective effect of DIP on cells was related to RPs. The results highlight the relationship between RPs and apoptosis, as well as the relationship between RPs and DIP attenuating arsenic-induced apoptosis.

Titanium alloys are widely used in marine engineering and other industries. To broaden their application, a novel (α + β) titanium alloy Ti−6Al−3Mo−2Zr−2Fe was studied in this work. A tube with an outer diameter of 60mm, inner diameter of 38 mm, and length of 500 mm was produced by ingot metallurgy and hot extrusion. The microstructure, mechanical properties, and corrosion resistance of the tube were systematically analyzed. The as−extruded Ti−6Al−3Mo−2Zr−2Fe alloy exhibited a typical duplex microstructure. EBSD observation showed that a strong <10 1¯0>//RD fiber texture of an α phase with a close−packed hexagonal structure was formed in the radial direction. The transformation temperature Tβ was determined to be 880–890 °C. A duplex microstructure with fine α platelets was obtained when the alloy was solution−treated at 850 °C for 1 h and underwent an aging treatment at 550 °C for 6 h. The room−temperature tensile strength and elongation of the aged alloy reached 1081.5 MPa and 6.5%, respectively. The corrosion resistance was tested by open circuit potential and a potentiodynamic polarization curve. The results show that the corrosion resistance of the Ti−6Al−3Mo−2Zr−2Fe alloy was better than that of the commonly used TC4 alloy in both a 3.5% NaCl solution and an acidic solution.

It is known that chronic stress modulates multiple processes in a complex microenvironment, such as angiogenesis and immune function. However, the role of chronic stress inducing tumor angiogenesis and how it contributes to tumor progression are not quite clear. The following study assess psychological state from numerous ambulatory cancer cases (n=332), and chronic stress-related hormone levels were further measured. Here, we show that chronic stress not only causes behavioral changes in human, most importantly attributed to an elevated level of stress-related hormones. To address this, isoprenaline, the agonist of β2-adrenergic receptor (β2-AR), was utilized for simulating chronic stress and demonstrating the mechanism of stress in tumor angiogenesis at molecular level both in vivo and in vitro. As suggested by this study, isoprenaline promote VEGF autocrine of HUVECs, which can induce plexinA1 and VEGFR2 expression. Moreover, we show that isoprenaline promoted the expression of p-JAK2 and p-STAT3 in vitro. The results reveal that, isoprenaline enhances the autocrine of VEGF in HUVECs and up-regulating plexinA1 and VEGFR2 levels, thus activating the phosphorylation of JAK2-STAT3 pathway, the two essential parts during angiogenesis. The present work indicates that, the mechanism of chronic stress in enhancing angiogenesis is probably achieved through activating the plexinA1/VEGFR2-JAK2-STAT3 signal transduction pathway within HUVECs, and this is probably a candidate target for developing a strategy against angiogenesis in cancer.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) greatly improve the survival and quality of life of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, many patients exhibit de novo or primary/early resistance. In addition, patients who initially respond to EGFR-TKIs exhibit marked diversity in clinical outcomes. With the development of comprehensive genomic profiling, various mutations and concurrent (i.e., coexisting) genetic alterations have been discovered. Many studies have revealed that concurrent genetic alterations play an important role in the response and resistance of EGFR-mutant NSCLC to EGFR-TKIs. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on EGFR-TKI treatment efficacy is necessary. Further exploration of other biomarkers that can predict EGFR-TKI efficacy will help clinicians identify patients who may not respond to TKIs and allow them to choose appropriate treatment strategies. Here, we review the literature on specific gene alterations that coexist with EGFR mutations, including common alterations (intra-EGFR [on target] co-mutation, TP53, PIK3CA, and PTEN) and driver gene alterations (ALK, KRAS, ROS1, and MET). We also summarize data for other biomarkers (e.g., PD-L1 expression and BIM polymorphisms) associated with EGFR-TKI efficacy.

WRKY transcription factors are involved in complex signalling processes that occur during stress responses. However, in contrast to the exploration of such mechanisms in model plants, far less research has focussed on the WRKY family in cotton. We previously identified GbWRKY1 in cotton (Gossypium barbadense), the expression of which is induced upon infection by Verticillium dahliae. Our current results indicate that this gene with three introns, has a group of cis-acting elements in its promoter that are associated with plant growth and development as well as responses to environmental stresses. Here, we used virus-induced gene silencing to characterize the role of GbWRKY1. Silencing in cotton simultaneously up-regulated salicylic acid (SA)-mediated responses and inhibited jasmonate (JA)-inducible and ethylene (ET)-inducible defences, resulting in an increased susceptibility to V. dahliae. However, when compared with wild-type Arabidopsis, transgenic plants exhibited more resistance to infection with V. dahliae. In the latter genotype, expression was increased for pathogen-related PR4 and ACS2, two genes involved in the JA pathway and ET biosynthesis, while expression of PR5, involved in the SA pathway, decreased after V. dahliae infection. Moreover, POD activity and lignin content related to ethylene synthesis in transgenic Arabidopsis were higher than those in wild-type Arabidopsis after V. dahliae infection. Collectively, these findings suggest that GbWRKY1 is regulated by signalling pathways for SA, JA and ET, and mainly involved in resistance to V. dahliae attack by ET signalling pathway the response. This highlights the importance of WRKYs in regulating pathogen-induced responses and plant development.

Targeting noncoding nucleic acids with small molecules represents an important and significant challenge in chemical biology and drug discovery. Here the authors characterize DC-34, a small molecule that exhibits selective binding to specific G4 structures, and provide a structural basis for its selectivity

Marginal zone B cells differentiate into plasma cells rapidly in response to T-cell-independent antigens, but how they do so is not clear. Here the authors show TACI cooperates with TLR signalling to drive mTOR activity and subsequent class switching and plasmablast differentiation.

A time-delayed feedback control is applied to a nonlinear piezoelectric energy harvesting system excited by additive and multiplicative Gaussian white noises to improve its energy harvesting performance. An equivalent decoupling system can be obtained by using a variable transformation. Based on the standard stochastic averaging method, the Fokker–Plank–Kolmogorov equation and the stationary probability density functions of the amplitude, displacement, and velocity of the harvester are obtained, respectively. In addition, the approximate expressions of mean square electric voltage and the mean extracted output power are derived. Finally, the paper explores the influences of parameters on the mean square electric voltage. The results show that noise intensity, time delay, feedback strength, time constant ratio, and coupling coefficients have great influences on the mean square electric voltage. The accuracy of the theoretical method is verified by the Monte Carlo simulation.

Naked Co68.25Fe4.5Si12.25B15 metal fibers with diameter from 25 µm to 100 µm are produced by melt extraction method. Significant diameter dependence of magnetic properties is studied. Their microstructure and magnetic properties of hysteresis loops and giant magneto impedance (GMI) effect at frequencies from 0.1MHz to13MHz are investigated. The results show that the coercivity increases with the diameter of fibers and the GMI effect is best in fiber with a diameter of 35µm. It is found that the cooling rate of solidification decreases with the increase of fiber diameter. And fibers are amorphous with the diameter of 50µm and there are nanocrystallines in fibers with a diameter of 85µm. The grain boundary blocks the magnetization process which makes lower circular permeability, larger coercivity and lower field sensitivity of GMI effect. The original microstructure of Co-based fibers decides their magnetic properties. Therefore, material design is important to improve the GMI effect in magnetic field sensor making.

The giant magneto impedance, GMI, effect of Co-based metallic fibers prepared by melt-extracted technology is investigated under different bias direct electrical current Ib. The GMI curves have single peaks which are symmetric about zero field at and below 1MHz. However, the bimodal GMI curves which have asymmetric peaks are observed when Ib is over 2mA at 0.1MHz. And asymmetric GMI, AGMI, effect is also appeared at 1MHz when Ib just is 1mA and the field sensitivity of GMI effect is increased 5.6 times. The GMI effect and magnetization process is affected by the bias magnetic field profoundly induced by Ib, which is correlated with the outer shell domain structures with circumferentially magnetization easy axis existed in the outer shell of Co-rich magnetic wires with low and negative magnetostriction. Below 1 MHz, only if the bias current is over 1.5mA which induces a magnetic circumferential magnetic field is above the coercivity of 14.4A/m, the circumferential magnetization and GMI effect can experience the bias magnetic field effect. Above 1MHz, the skin effect gets stronger and significantly decreases the total participants of circular magnetization process in the fibers and consequently, the circular outer shell magnetization process gets much sensitive to circular bias magnetic field. AGMI effect with high field sensitivity is realized due to the bias current.

Novel β-solidifying TiAl alloys have great potential for engineering applications in the aerospace and automotive industries. The introduction of the β0 phase will inevitably affect crack propagation. However, the related mechanism is unclear. In this study, the crack propagation behavior of different β0-containing microstructures was systematically investigated by three-point bending tests. The results show that the coarse γ/α2 lamellar microstructure exhibits better fracture toughness than the fine-grain microstructure because large numbers of γ/α2 lamellar boundaries can effectively hinder crack propagation. The propagation direction depends largely on the orientation of the γ/α2 lamellae. When the angle between the crack propagation direction and the γ/α2 lamellar boundary is small, the crack tends to propagate along γ/α2 lamellae. When the angle is close to 90°, the crack generally propagates by the trans-lamellar mode. Moreover, the crack tends to traverse across the fine β0/γ duplex region due to the low resistance of fine grains in the crack propagation. The transgranular and intergranular modes are the main fracture mechanisms in the microstructure of the fine β0/γ grains. Some shear ligaments can also be identified in the lamellar microstructure and these can consume propagation energy. The enlarged image shows that the crack propagation direction can be changed by the β0 phase, owing to its high hardness. The crack tends to stop at the β0 phase region.

Cotton is one of the most important economic crops in the world. Gossypium barbadense L. has higher resistance to Verticillium wilt than Gossypium hirsutum L. In the present study, seedlings of Pima90-53 (G. barbadense) had better growth performance than those of CRI8 (G. hirsutum) inoculated with Verticillium dahliae. WRKY1 genomic DNA of Pima90-53 and CRI8 were isolated (GbWRKY1 and GhWRKY1) and predicted to include three introns which were 289, 92, 87 bp and 286, 92, 87 bp in length, respectively. Compared with the DNA sequence of GbWRKY1, GhWRKY1 had a 13-base deletion in exon 4, which resulted in premature termination of translation. It was predicted that the GbWRKY1 and GhWRKY1 proteins contain two WRKY domains and zinc-finger motifs belonging to group I WRKY proteins. Two promoters, located 1745 bp and 1738 bp upstream of GbWRKY1 and GhWRKY1, were cloned and predicted to contain important regulatory elements (TATA-box, CAAT-box and pathogen/elicitor-related elements). Interestingly, compared with GbWRKY1, the GhWRKY1 promoter lacked an ethylene-responsive element (ERE) component. The relative expression of GbWRKY1, too, was higher than that of GhWRKY1 after V. dahliae and ACC (1-aminocyclopropane-1-carboxylic acid) induction. The results suggest that the difference in the promoter sequence could probably be one of the reasons that lead to different expression patterns and resistance to Verticillium wilt in Pima90-53 and CRI8.

This study was designed to investigate beneficial effects of swimming exercise training on learning/memory, synaptic plasticity and CREB (cAMP response element binding protein) expression in hippocampus in a rat model of d-galactose-induced aging (DGA). Eighty adult male rats were randomly divided into four groups: Saline Control (group C), DGA (group A), Swimming exercise before DGA (group S1), and Swimming during DGA (group S2). These four groups of animals were further divided into Morris water maze training group (M subgroup) and sedentary control group (N subgroup). Spatial learning/memory was tested using Morris water maze training. The number and density of synaptophysin (Syp) and metabotropic glutamate receptor 1 (mGluR1) in hippocampal dentate gyrus area, CREB mRNA and protein expression and DNA methylation levels were determined respectively with immunohistochemistry, western blot, real-time PCR, and MassArray methylation detection platform. We found that compared with group C, DGA rats showed aging-like poor health and weight loss as well as hippocampal neurodegenerative characteristics. Exercise training led to a time-dependent decrease in average escape latency and improved spatial memory. Exercise training group (S2M) had significantly increased swim distance as compared with controls. These functional improvements in S2M group were associated with higher Syp and mGluR1 values in hippocampus (p < 0.01) as well as higher levels of hippocampal CREB protein/mRNA expression and gene methylation. In conclusion, swimming exercise training selectively during drug-induced aging process protected hippocampal neurons against DGA-elicited degenerative changes and in turn maintained neuronal synaptic plasticity and learning/memory function, possibly through upregulation of hippocampal CREB protein/mRNA and reduction of DGA-induced methylation of CREB.

We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTORΔ/Δ) alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival. While mTORΔ/Δ mice are smaller than wild-type mice, these animals do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, mTORΔ/Δ mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTORΔ/Δ mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.

Notch signaling is essential to the regulation of cell differentiation, and aberrant activation of this pathway is implicated in human fibrotic diseases, such as pulmonary, renal, and peritoneal fibrosis. However, the role of Notch signaling in hepatic fibrosis has not been fully investigated. In the present study, we show Notch signaling to be highly activated in a rat model of liver fibrosis induced by carbon tetrachloride (CCl(4)), as indicated by increased expression of Jagged1, Notch3, and Hes1. Blocking Notch signaling activation by a γ-secretase inhibitor, DAPT, significantly attenuated liver fibrosis and decreased the expression of snail, vimentin, and TGF-β1 in association with the enhanced expression of E-cadherin. The study in vitro revealed that DAPT treatment could suppress the EMT process of rat hepatic stellate cell line (HSC-T6). Interestingly, DAPT treatment was found not to affect hepatocyte proliferation in vivo. In contrast, DAPT can inhibit hepatocyte apoptosis to some degree. Our study provides the first evidence that Notch signaling is implicated in hepatic fibrogenesis and DAPT treatment has a protective effect on hepatocytes and ameliorates liver fibrosis. These findings suggest that the inhibition of Notch signaling might present a novel therapeutic approach for hepatic fibrosis.

ABSTRACT Objective: To investigate the predictive value of transcranial Doppler (TCD) ultrasound for cerebral small vessel disease in elderly patients. Methods: Transcranial Doppler ultrasound and magnetic resonance imaging (MRI) were performed on 184 elderly patients with cerebral small vessel disease. The relationship of clinical characteristics and TCD ultrasound parameters with severe white matter lesions (WMLs) in MRI were investigated by univariate analysis and multivariate analysis. Results: The univariate analysis showed that age, left middle cerebral artery (MCA) mean flow velocity, right MCA mean flow velocity and mean MCA pulsatility index were significantly correlated with severe WMLs (p < 0.05). The multivariate logistic regression analysis showed that only age (odds ratio: 1.21; 95%CI: 1.10–1.36; p < 0.01) and MCA pulsatility index (dominance ratio: 1.13; 95%CI: 1.06–1.80; p = 0.02) were significantly correlated with severe WMLs. The analysis of TCD ultrasound parameters showed that when the cut-off for MCA pulsatility index was 1.04, it could identify severe WMLs. The area under the curve was 0.70 (95%CI: 0.60–0.80). The sensitivity and specificity were 63.0% and 72.0%, respectively. The positive and negative predictive values were 35.4% and 86.6%, respectively. Conclusion: The MCA pulsatility index in TCD ultrasound is significantly correlated with severe WMLs; and TCD ultrasound can guide selective MRI for the detection of WMLs.

Background. Prostate cancer (PC) prevention is effectively achieved through its inhibition. Oridonin (ORD), an active diterpenoid isolated from Rabdosia rubescens, has been shown to have an inhibitory effect on PC cells, although its impact on PC is unknown. Objectives. The present work investigated the actions and probable mechanisms of ORD on cellular proliferation, apoptosis, PC, and the wingless-type MMTV integration site family member 2 (Wnt)/β-catenin signaling pathway using the androgen-independent PC-3 cell line. Materials and methods. In this study, cell viability was analyzed with MTT assay method, apoptotic morphology determined using DAPI dye method, while protein (CD1333, OCT-4, Nanog, SOX-2 & Aldh1A1) and mRNA expressions were analyzed with western blotting and real time polymerase chain reaction (PCR). Results. We demonstrated a concentration-dependent ORD inhibition of PC-3 cell proliferation and inhibition of induction apoptosis. Furthermore, ORD decreased PC-3 Wnt-2, phosphorylated glycogen synthase kinase-3 (p-GSK3), and β-catenin protein levels and downregulated cyclin-D1 and c-myc messenger ribonucleic acid (mRNA). Conclusions. Oridonin inhibited proliferation and induced apoptosis in PC-3 cells, with the findings suggesting that it acted via the Wnt/β-catenin pathway to exert its effects. This study demonstrates that ORD may impact PC. [ABSTRACT FROM AUTHOR]