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The mechanical properties of local materials subjected to various stress triaxialities were investigated via self-designed small punch tests and corresponding simulations, which were tailored to the geometry and notch forms of the samples. The finite element model was developed on the basis of the actual test method. After verifying the accuracy of the simulation, the stress, strain, and void volume fraction distributions of the Ti6Al4V titanium alloy under different stress states were compared and analyzed. The results indicate that the mechanical properties of the local material significantly differ during downward pressing depending on the geometric shape. A three-dimensional tensile stress state was observed in the center area, where the void volume fraction was greater than the fracture void volume fraction. The fracture morphology of the samples further confirmed the presence of different stress states. Specifically, the fracture morphology of the globular head samples (with or without U-shaped notches) predominantly featured dimples. Modifying the specimen's geometry effectively increased stress triaxiality, facilitating the determination of the material's constitutive relationship under varying stress states. [ABSTRACT FROM AUTHOR]

With the rapid progress in deciphering the pathogenesis of Alzheimer's disease (AD), it has been widely accepted that the accumulation of misfolded amyloid β (Aβ) in the brain could cause the neurodegeneration in AD. Although much evidence demonstrates the neurotoxicity of Aβ, the role of Aβ in the nervous system are complex. However, more comprehensive studies are needed to understand the physiological effect of Aβ40 monomers in depth. To explore the physiological mechanism of Aβ, we employed mass spectrometry to investigate the altered proteomic events induced by a lower submicromolar concentration of Aβ. Human neuroblastoma SH-SY5Y cells were exposed to five different concentrations of Aβ1-40 monomers and collected at four time points. The proteomic analysis revealed the time–course behavior of proteins involved in biological processes, such as RNA splicing, nuclear transport and protein localization. Further biological studies indicated that Aβ40 monomers may activate PI3K/AKT signaling to regulate p-Tau, Ezrin and MAP2. These three proteins are associated with dendritic morphogenesis, neuronal polarity, synaptogenesis, axon establishment and axon elongation. Moreover, Aβ40 monomers may regulate their physiological forms by inhibiting the expression of BACE1 and APP via activation of the ERK1/2 pathway. A comprehensive exploration of pathological and physiological mechanisms of Aβ is beneficial for exploring novel treatment. [ABSTRACT FROM AUTHOR]

The robust carbon storage (CS) capacity of terrestrial ecosystems is crucial in mitigating climate change and holds indispensable significance for global sustainable development. The diverse topography of Central Asia (CA), comprising oases, grasslands, forests, deserts, and glaciers, has fostered industries like animal husbandry, irrigation agriculture, and mining. However, the fragile arid ecosystems of CA render it highly sensitive to climate change and human activities, with their impact on the sustainable development of multifunctional landscapes in this region remaining ambiguous in the future. This study linked land use changes with multiple socio-economic and ecological indicators to predict the dynamics of land use and changes in CS in CA. The findings reveal a significant spatial heterogeneity in CS, with considerable variations among five countries driven by differences in landscape composition. Kyrgyzstan and Kazakhstan, characterized by grasslands, demonstrate higher CS per unit area, whereas Turkmenistan, dominated by barren land, exhibits the lowest CS per unit area. Strategies involving innovative development and improved biodiversity conservation have proven effective in augmenting CS. Meanwhile, high economic and population growth stimulates the expansion of cropland and urban land, reducing the CS capacity of ecosystems. This study contributes to a more precise assessment of CS dynamics in CA. Furthermore, by elucidating the interrelationships between future socio-economic development and environmental conservation in CA, it offers solutions for enhancing the conservation of multifunctional landscapes in CA. [ABSTRACT FROM AUTHOR]

In order to enhance the transient stability of offshore wind turbines (OWTs) in marine energy systems, the grid codes stipulate that OWTs should possess the low-voltage ride-through (LVRT) ability of being grid-tied and injecting reactive current during grid fault. However, the grid-side converter (GSC) of OWTs may lose stability under weak grid or severe fault conditions due to inaccurate current references. To address this issue, a novel transient current control method is proposed to improve the transient stability of permanent-magnet-synchronous-generator (PMSG)-based OWTs. The feature of DC-link overvoltage is investigated and is alleviated by utilizing the GSC's overcurrent capacity and chopper. Additionally, the equivalent circuit of the PMSG-based OWT connected to the onshore grid is derived based on Thevenin's theorem. The feasible current region (FCR) is then determined, taking into account the GSC capacity, pre-fault power ability, LVRT requirement, and synchronization stability. Furthermore, a grid-impedance-based transient current control method is designed to enhance the fault ride-through performance and mitigate power oscillation of the OWT under various transient grid impedance and fault conditions. Finally, a simulation model is conducted using PSCAD v4.6.3 software to validate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Predicting energy consumption in large exposition centers presents a significant challenge, primarily due to the limited datasets and fluctuating electricity usage patterns. This study introduces a cutting-edge algorithm, the contrastive transformer network (CTN), to address these issues. By leveraging self-supervised learning, the CTN employs contrastive learning techniques across both temporal and contextual dimensions. Its transformer-based architecture, tailored for efficient feature extraction, allows the CTN to excel in predicting energy consumption in expansive structures, especially when data samples are scarce. Rigorous experiments on a proprietary dataset underscore the potency of the CTN in this domain. [ABSTRACT FROM AUTHOR]

Improving the accuracy of the forecasting of building power consumption is helpful in reducing commercial expenses and carbon emissions. However, challenges such as the shortage of training data and the absence of efficient models are the main obstacles in this field. To address these issues, this work introduces a model named MTLTFT, combining multi-task learning (MTL) with the temporal fusion transformer (TFT). The MTL approach is utilized to maximize the effectiveness of the limited data by introducing multiple related forecasting tasks. This method enhances the learning process by enabling the model to learn shared representations across different tasks, although the physical number of data remains unchanged. The TFT component, which is optimized for feature learning, is integrated to further improve the model's performance. Based on a dataset from a large exposition building in Hangzhou, we conducted several forecasting experiments. The results demonstrate that MTLTFT outperforms most baseline methods (such as LSTM, GRU, N-HiTS) in terms of Root Mean Squared Error (RMSE) and Mean Absolute Percentage Error (MAPE), suggesting that MTLTFT is a promising approach for the forecasting of building power consumption and other similar tasks. [ABSTRACT FROM AUTHOR]

Since the beginning of the new century, information technology has advanced by leaps and bounds, and intelligent technology has made breakthroughs, speech recognition, and image recognition. In the development of medium and long-term exhibition brands, intelligence and modernization are taken as one of the development tasks. The visual communication design of brand logo is the graphical post symbol language of brand trademark, which is the silent transmission of brand. As long as you see a certain brand logo, its product characteristics and values can emerge in your mind. It is very easy to identify. Graphics, colors, and fonts are its main visual elements. Exhibition is a very promising industry in the modern business economy, and it is one of the best platforms for enterprises to promote their brands. Paying attention to the brand visual communication design of exhibitions is of great significance and value to enhance the overall impression of enterprises in the minds of consumers. This article explores the value and principles of corporate brand in the exhibition industry. Research shows that corporate brand visual communication design in exhibitions should be based on the brand architecture system, reflect the connotation of brand culture, and highlight brand design innovation. Taking corporate brand visual communication design in the exhibition industry as the research object, to explore its design value, the value of corporate brand visual communication design in commercial exhibitions is very great, and enterprises must attach great importance to commercial exhibitions. From the perspective of visual communication design, it can be parsed into three levels: color, space shaping, and graphic and text conformity. To reconstruct brand design, companies must make layout, innovation, and reconstruction of these three levels and strengthen commercial exhibitions. The impact and appeal of the visual communication design of the Chinese enterprise brand can truly enhance the influence and popularity of the enterprise brand and ultimately promote the sustainable development of the enterprise brand. [ABSTRACT FROM AUTHOR]

The noise corruption problem commonly exists in hyperspectral images (HSIs) and severely affects the accuracy of hyperspectral unmixing algorithms. The noise formulation existing in HSIs is relatively complex and would change in conjunction with different devices and imaging settings. For real applications, applying denoising approaches without accurate close-to-reality noise modeling before unmixing may not improve, but rather degrade the unmixing performance. This study proposes a robust hyperspectral unmixing method with practical learning-based hyperspectral image denoising. We formulated a close-to-reality noise model for hyperspectral data and provide a calibration approach for the noise parameters. On the basis of the calibrated noise model, synthetic data were generated and used for training a KST-based denoising network. The noisy hyperspectral data were firstly denoised by the trained denoising network and were then used to perform the unmixing process. A variety of unmixing algorithms can be integrated into our method to improve the accuracy of unmixing in noisy situations. In the experiments, several widely used unmixing algorithms were employed to verify the effect of the proposed method. The experimental results on both synthetic and real demonstrated that our proposed method can handle HSI data with various gain settings and helps to improve the unmixing performance effectively. [ABSTRACT FROM AUTHOR]

The rapid analysis of thermal stress and deformation plays a pivotal role in the thermal control measures and optimization of the structural design of satellites. For achieving real-time thermal stress and thermal deformation analysis of satellite motherboards, this paper proposes a novel Multi-Task Attention UNet (MTA-UNet) neural network which combines the advantages of both Multi-Task Learning (MTL) and U-Net with an attention mechanism. Furthermore, a physics-informed strategy is used in the training process, where partial differential equations (PDEs) are integrated into the loss functions as residual terms. Finally, an uncertainty-based loss balancing approach is applied to weight different loss functions of multiple training tasks. Experimental results show that the proposed MTA-UNet effectively improves the prediction accuracy of multiple physics tasks compared with Single-Task Learning (STL) models. In addition, the physics-informed method brings less error in the prediction of each task, especially on small data sets. [ABSTRACT FROM AUTHOR]

The commutation failure of high voltage direct current (HVDC) systems could lead to unstable operation of the alternating current/direct current (AC/DC) hybrid power grid. The commutation voltage distortion caused by harmonics is a considerable but unclear factor of commutation failure. According to the control switching process of HVDC systems, the commutation voltage-time area method is employed to analyze and reveal the influence mechanism of harmonic components of commutation voltage on first and subsequent commutation failures. Considering the distortion characteristics of AC voltage, a predictive commutation failure suppression strategy considering multiple harmonics of commutation voltage is proposed. In this strategy, the new extinction angle and the zero-crossing offset angle after voltage distortion are calculated considering the harmonic components so as to obtain the compensation margin of the lag trigger angle by combining the correction margin with the voltage change rate. Moreover, the tuning method of parameters of extinction angle and voltage prediction variables are provided. Finally, a case study based on CIGRE standard HVDC system is performed and analyzed by using power systems computer-aided design (PSCAD) software. Compared with the International Council on Large Electric systems (CIGRE) standard test model and traditional commutation failure prevention (CFPREV) control model, the results verify that the proposed strategy can effectively reduce the risk of first and subsequent commutation failures and improve the sensitivity of CFPREV control. [ABSTRACT FROM AUTHOR]

Novel TiO2 nanoparticles-coated CNTs (TiO2@CNTs) fabricated by the alcohol-thermal method were used as the reinforcement to prepare aluminum matrix composites through high-intensity ultrasonic-assisted casting, followed by heat treatment. The results of optical microscope showed that the optimum heat treatment process was solution treatment (495 °C, 2 h) + aging treatment (180 °C, 12 h). Under this condition, the Al2Cu and Al2CuMg phases were uniformly precipitated in the composites, and most of them were in a discrete state. TEM results revealed that TiO2 nanoparticles dispersed on the surface of CNTs played the role of an interlayer structure between CNTs and matrix, locking the CNTs and improving the CNTs–Al interfacial bonding. The ultimate tensile strength (UTS) and yield strength (YS) of 1.0 wt%TiO2@CNTs/2024 composite after T6 heat treatment reach 324 MPa and 219 MPa, respectively, which exhibited enhanced UTS and YS than the monolithic 2024 alloy. This was attributed to the synergistic strengthening of multi-mechanisms, such as grain refinement strengthening, load transfer strengthening, dislocation strengthening and, especially, Orowan strengthening. [ABSTRACT FROM AUTHOR]

For long-distance and bulk-power delivery of new energy, high-voltage direct current (HVDC) is a more effective way than high-voltage alternative current (HVAC). In view of the current capacity disparity between line commutated converter (LCC) and voltage source converter (VSC), a hybrid hierarchical HVDC topology with parallel operation of 800 kV and 400 kV DC lines is investigated. The optimal current allocation method for hybrid hierarchical HVDC is proposed distinct from the same rated current command configuration method of high-voltage and low-voltage converters in traditional topology. Considering the transmission loss reduction of the HVDC system, a multi-order fitting function of transmission loss including LCC converter stations, VSC converter stations and DC lines is established. To minimize the transmission loss and the voltage deviation of key DC nodes comprehensively, a multi-objective genetic algorithm and maximum satisfaction method are utilized to obtain the optimal allocation value of rated current command for high-voltage and low-voltage converters. Through the optimization model, an improved constant current controller based on the current allocation strategy is designed. The hybrid hierarchical HVDC system model is built in PSCAD software, and simulation results verify the effectiveness of the proposed topology and optimal current allocation strategy. [ABSTRACT FROM AUTHOR]

When wind power is transmitted via high-voltage direct current (HVDC), the problem of high-voltage ride-through (HVRT), caused by direct-current (DC) blocking must be seriously taken into account. All the wind turbines in a wind farm are usually equivalent to a single turbine in the existing research on HVRT, which ignores the generator terminal voltage distribution in a wind farm. In view of the fact that the severity of fault voltage felt by each wind turbine in the field is different, an improved HVRT strategy considering voltage distribution is proposed in this article. First, this article analyzes the mechanism of voltage swell failure caused by DC blocking, and the characteristics of the generator terminal voltage distribution in wind farms. Second, the reactive power characteristic equations of the synchronous condenser and the doubly-fed induction generator (DFIG) are derived. Third, based on the extraction of the key node voltage, this article takes the key node voltage as the compensation target, and put forwards a HVRT strategy combining the synchronous condenser and wind turbine. Finally, the simulation is carried out to demonstrate the effectiveness of the proposed strategy in improving the HVRT capability of all wind turbines. [ABSTRACT FROM AUTHOR]

Luteoloside is a member of the flavonoids family that exhibits several bioactivities including anti-microbial and anti-cancer activities. However, the antiviral activity of luteoloside against enterovirus 71 (EV71) and the potential mechanism(s) responsible for this effect remain unknown. In this study, the antiviral potency of luteoloside against EV71 and its inhibitory effects on 3C protease activity were evaluated. First, we investigated the cytotoxicity of luteoloside against rhabdomyosarcoma (RD) cells, which was the cell line selected for an in vitro infection model. In a subsequent antiviral assay, the cytopathic effect of EV71 was significantly and dose-dependently relieved by the administration of luteoloside (EC50 = 0.43 mM, selection index = 5.3). Using a plaque reduction assay, we administered luteoloside at various time points and found that the compound reduced EV71 viability in RD cells rather than increasing defensive mobilization or viral absorption. Moreover, biochemical studies focused on VP1 (a key structural protein of EV71) mRNA transcript and protein levels also revealed the inhibitory effects of luteoloside on the EV71 viral yield. Finally, we performed inhibition assays using luteoloside to evaluate its effect on recombinant 3C protease activity. Our results demonstrated that luteoloside blocked 3C protease enzymatic activity in a dose-dependent manner (IC50 = 0.36 mM) that was similar to the effect of rutin, which is a well-known C3 protease inhibitor. Collectively, the results from this study indicate that luteoloside can block 3C protease activity and subsequently inhibit EV71 production in vitro. [ABSTRACT FROM AUTHOR]

Abstract: Similar to auxin, hydrogen sulfide (H2S), mainly produced by l-cysteine desulfhydrase (DES; EC 4.4.1.1) in plants, could induce lateral root formation. The objective of this study was to test whether H2S is also involved in auxin-induced lateral root development in tomato (Solanum lycopersicum L.) seedlings. We observed that auxin depletion-induced down-regulation of transcripts of SlDES1, decreased DES activity and endogenous H2S contents, and the inhibition of lateral root formation were rescued by sodium hydrosulfide (NaHS, an H2S donor). However, No additive effects were observed when naphthalene acetic acid (NAA) was co-treated with NaHS (lower than 10 mM) in the induction of lateral root formation. Subsequent work revealed that a treatment with NAA or NaHS could simultaneously induce transcripts of SlDES1, DES activity and endogenous H2S contents, and thereafter the stimulation of lateral root formation. It was further confirmed that H2S or HS−, not the other sulfur-containing components derived from NaHS, was attributed to the stimulative action. The inhibition of lateral root formation and decreased of H2S metabolism caused by an H2S scavenger hypotaurine (HT) were reversed by NaHS, but not NAA. Molecular evidence revealed that both NaHS- or NAA-induced modulation of some cell cycle regulatory genes, including the up-regulation of SlCDKA;1, SlCYCA2;1, together with simultaneous down-regulation of SlKRP2, were differentially reversed by HT pretreatment. To summarize, above results clearly suggested that H2S might, at least partially, act as a downstream component of auxin signaling to trigger lateral root formation. [Copyright &y& Elsevier]

Carbon monoxide (CO) has recently proven to be an important bioactive or signaling molecule in mammalian cells. Its effects are mainly mediated by nitric oxide (NO) and cyclic GMP (cGMP). In Vicia faba leaves, CO production and heme oxygenase (HO) activity, an important CO synthetic enzyme, are first reported to increase in response to ABA treatment, which could result in stomatal closure. Interestingly, ABA-induced stomatal closure in V. faba guard cells is partially blocked when the synthetic CO inhibitor ZnPP, or the CO/NO scavenger Hb is added. Furthermore, we show that, exogenously applied CO donor, hematin, and CO aqueous solution not only result in the enhancement of CO release, but also time-dependently induce stomatal closure, and the latter is mimicked by the application of an NO donor SNP. The above-mentioned stomatal closure effects are differentially reversed by the addition of tungstate, a potent inhibitor of NO synthetic enzyme nitrate reductase (NR), the specific NO scavenger cPTIO, ZnPP, or Hb. During treatment for 4 h, SNP, 0.01 % CO aqueous solution or hematin significantly triggers NO synthesis, whereas cPTIO, or tungstate approximately fully inhibits NO fluorescence. Additionally, application of the GC inhibitor ODQ blocks CO-induced stomatal closure. This inhibition could be reversed when 8-Br-cGMP is added. Thus, the above results suggest that CO produced by HO is involved in ABA-induced stomatal closure, and NO and cGMP may function as downstream intermediates in the CO signaling responsible for stomatal closure. [ABSTRACT FROM AUTHOR]

Melamine sponge (MS) has the characteristics of multilayer network structure, high porosity, adjustable pore structure, and low price, which is considered to be an ideal material for oil leakage treatment. Here, a facile, economical, environmental friendly, and one step reaction was developed to fabricate Ag nanoparticles (NPs) decorated MS composite with tannic acid (TA) as a reducing agent. By reduction reaction, the super-hydrophobic and super-oleophylic surface of the MS–TA–Ag composite was formed, demonstrating a single selectivity for oil and water. Thus, the adsorption capacity of MS–TA–Ag composites for various oils/organic solvents can reach 48~129 times its own weight and and display superior efficiency to separate oil/organic solvent from the water. In addition, the MS–TA–Ag composite has stable super-hydrophobicity and reusability. It is exciting that modified MS exhibits excellent chemical stability properties after a long processing time with strong alkali, strong acids, and salt solutions. The simple strategy provides a method for the preparation of large-scale oil spill cleaning and recovery materials. [ABSTRACT FROM AUTHOR]

Lonicera japonica Thunb, rich in chlorogenic acid (CHA), is used for viral upper respiratory tract infection treatment caused by influenza virus, parainfluenza virus, and respiratory syncytial virus, ect in China. It was reported that CHA reduced serum hepatitis B virus level and death rate of influenza virus-infected mice. However, the underlying mechanisms of CHA against the influenza A virus have not been fully elucidated. Here, the antiviral effects and potential mechanisms of CHA against influenza A virus were investigated. CHA revealed inhibitory against A/PuertoRico/8/1934(H1N1) (EC50 = 44.87 μM), A/Beijing/32/92(H3N2) (EC50 = 62.33 μM), and oseltamivir-resistant strains. Time-course analysis showed CHA inhibited influenza virus during the late stage of infectious cycle. Indirect immunofluorescence assay indicated CHA down-regulated the NP protein expression. The inhibition of neuraminidase activity confirmed CHA blocked release of newly formed virus particles from infected cells. Intravenous injection of 100 mg/kg/d CHA possessed effective antiviral activity in mice, conferring 60% and 50% protection from death against H1N1 and H3N2, reducing virus titres and alleviating inflammation in the lungs effectively. These results demonstrate that CHA acts as a neuraminidase blocker to inhibit influenza A virus both in cellular and animal models. Thus, CHA has potential utility in the treatment of the influenza virus infection. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases, referring to as the progressive loss of structure and function of neurons, constitute one of the major challenges of modern medicine. Traditional Chinese herbs have been used as a major preventive and therapeutic strategy against disease for thousands years. The numerous species of medicinal herbs and Traditional Chinese Medicine (TCM) compound formulas in nervous system disease therapy make it a large chemical resource library for drug discovery. In this work, we collected 7362 kinds of herbs and 58,147 Traditional Chinese medicinal compounds (Tcmcs). The predicted active compounds in herbs have good oral bioavailability and central nervous system (CNS) permeability. The molecular docking and network analysis were employed to analyze the effects of herbs on neurodegenerative diseases. In order to evaluate the predicted efficacy of herbs, automated text mining was utilized to exhaustively search in PubMed by some related keywords. After that, receiver operator characteristic (ROC) curves was used to estimate the accuracy of predictions. Our study suggested that most herbs were distributed in family of Asteraceae, Fabaceae, Lamiaceae and Apocynaceae. The predictive model yielded good sensitivity and specificity with the AUC values above 0.800. At last, 504 kinds of herbs were obtained by using the optimal cutoff values in ROC curves. These 504 herbs would be the most potential herb resources for neurodegenerative diseases treatment. This study would give us an opportunity to use these herbs as a chemical resource library for drug discovery of anti-neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Light intensity and nitrogen concentration of nutrient solution are considered crucial for the contents of vitamin C and nitrate in cultivated leaf vegetables. We here investigated the effects of various combinations of light intensity (60, 140 and 220 μmol m −2 s −1 ) and nitrogen concentration (7, 15 and 23 mmol L −1 ) of the solution on the growth, photosynthetic characteristics, vitamin C and nitrate content of lettuce. Our results demonstrate that the lettuce had the largest dry biomass at the high illumination of 220 μmol m −2 s −1 and low nitrogen of 7 mmol L −1 . The higher light and low nitrogen also contributed to the accumulation of vitamin C and decrease of nitrate in lettuce leaves. The effect of nitrogen supply on chlorophyll concentrations was more efficient under low light than high illumination. Our results reveal that there was an obvious interaction between light intensity and nitrogen available for the photosynthesis, yield and quality of lettuce. This study provides valuable insights into the combinational regulation of light intensity and nitrogen supply for improving growth and nutritional quality of vegetables grown in greenhouse and plant factory. [ABSTRACT FROM AUTHOR]

Abstract: Although carbon monoxide (CO) has always been regarded as a toxic gas, recent reports suggested that it is one of the products of heme oxygenase (HO; EC 1.14.99.3) catalysis in animals, and could confer beneficial cytoprotection against oxidative damage. Here, we investigated the effects of exogenous putative CO donor hematin and CO aqueous solution on rice seed germination under 100mM NaCl salt stress. Both hematin and CO aqueous solution dose-dependently attenuated the inhibition of seed germination and seedling growth caused by salinity. Moreover, 1.0μM hematin and 5% CO-saturated aqueous solution activated amylase activity, thus accelerating the formation of reducing sugar and total soluble sugar. Furthermore, hematin and CO aqueous solution induced catalase (CAT) and superoxide dismutase (SOD) activities, thus resulting in the alleviation of oxidative damage, as indicated by the decrease of thiobarbituric acid reactive substances (TBARS) content. Such above CO-induced effects were also confirmed by using semi-quantitative RT-PCR, including the up-regulation of expression patterns of α-amylase, CAT and Cu/Zn-SOD genes. Also, the similar function of hematin might contribute to endogenous HO-derived CO, since addition of the CO-specific synthetic inhibitor zinc protoporphyrin IX (ZnPPIX) and CO scavenger hemoglobin (Hb) reversed above effects. Meanwhile, further results also proved that treatment with hematin for 36h could result in the potent induction of HO-1 transcript, HO activity and CO content in the germinating seeds. Collectively, these results indicated that CO performed an advantageous effect on attenuation of inhibition of seed germination and seedling growth induced by salt stress, and alleviated oxidative damage via activating anti-oxidant enzymes. [Copyright &y& Elsevier]

Tolerance to acid stress is a crucial property of probiotics against gastric acids. The malolactic enzyme pathway is one of the most important acid resistance systems in lactic acid bacteria. It has been reported that the malolactic enzyme pathway was regulated by the transcriptional regulator, MleR. However, regulatory mechanisms underlying malolactic enzyme pathway to cope with acid stress remain unknown. In this study, the acid tolerance ability of the ΔmleR deletion strain was significantly lower than that of the wild-type strain, and the complementation of the mleR gene into the ΔmleR strain restored the acid tolerance of the ΔmleR strain, indicating that MleR was involved in acid tolerance response of Lacticaseibacillus paracasei L9. Real-time quantitative PCR and transcriptional fusion experiments confirmed MleR-activated transcription of the mleST gene cluster. Furthermore, MleR was confirmed to directly bind to the promoter region of the mleST operon using ChIP assays and EMSAs. The transcription start site G of the mleST operon was located at position -198 relative to the start codon of the mleS gene. The region from -80 to -61 upstream of the transcription start site was determined to be essential for MleR binding. Moreover, L-malic acid acted as an effector for MleR to activate the transcription of the mleST operon in a dose-dependent manner. These results revealed the regulatory mechanism behind MleR-mediated activation of the malolactic enzyme pathway to enhance acid tolerance in Lc. paracasei L9. IMPORTANCE Lacticaseibacillus paracasei is extensively used as probiotics in human health and fermented dairy production. Following consumption, Lc. paracasei is exposed to a variety of physico-chemical stresses, such as low pH in the stomach and bile salts in the intestines. The high acidity of the stomach severely inhibits bacterial metabolism and growth. Therefore, the acid tolerance response is critical for Lc. paracasei to survive. It has been reported that the malolactic enzyme (MLE) pathway plays an important role for LAB to resist acid stress. However, the regulatory mechanism has not yet been investigated. In this study, we determined that the LysR-type regulator MleR positively regulated the MLE pathway to enhance acid tolerance by binding -80 to -61 upstream of the transcription start site of the mleST operon. Further, L-malic acid acts as a co-inducer for MleR transcriptional regulation. Our study provides novel insights into acid tolerance mechanisms in LAB., Competing Interests: The authors declare no conflict of interest.

Purpose: Hypertension prevalence is mounting at a great pace in the People's Republic of China and poses a serious threat to health care systems. Medication nonadherence is one of the key factors in controlling high blood pressure. Our study uses two-arm cluster randomized controlled trial to investigate whether personal consultation by postgraduate pharmacy students and short message services (SMS) is effective in improving medication adherence and blood pressure control. Patients and methods: The trial will involve 384 treated patients in 8 community health care centers (CHCs). The 8 CHCs will be randomly assigned to intervention and control group in a ratio of 1:1. Patients in the intervention group will receive a personal consultation which identifies the barriers to medication adherence and SMS reminders which will be sent at 3-day intervals while patients in the control group will receive standard pharmaceutical care. Personal consultation by pharmacy students will be delivered at months 0 and 3. SMS messages will include educational information about normal blood pressure, complications of hypertension, salt intake, healthy diet, smoking cessation, regular exercise, weight control, antihypertensive medication schedule and treatment. Both groups will be followed for 6 months in order to compare their medication adherence and blood pressure at months 0, 3 and 6. The primary clinical outcome is the change in mean blood pressure and medication adherence measured at baseline, months 3 and 6. Secondary outcome is the proportion of patients reaching controlled blood pressure at months 3 and 6. Discussion: Pharmacy students led consultation will be conducted in the process of physical examination and SMS reminders which is at low cost, may be a feasible way to address the high prevalence of hypertension in the People's Republic of China., Competing Interests: Dr Morisky is the developer/owner of the copyrighted and trademarked protected Morisky Medication Adherence Scale and sells MMAS licenses and consulting services through MMAS Research LLC, 14725 NE 20th St., Bellevue, Washington 98007. Dr Morisky also reports personal fees from MMAS Research LLC, during the conduct of the study; receives personal fees from MMAS Reasearch, LLC, outside the submitted work. The authors report no other conflicts of interest in this work.

Enterovirus 71 (EV71) is a key pathogen of hand, foot and mouth disease (HFMD) in children under 6 years of age. The antiviral potency of antioxidant isochlorogenic acid C (ICAC) extracted from foods was evaluated in cellular and animal models. First, the cytotoxicity of ICAC on Vero cells was investigated. The viral plaques, cytopathic effects and yield induced by EV71 infection were obviously reduced by ICAC, which was consistent with the investigation of VP1 transcripts and protein expression. Moreover, the mortality, weight loss and limb paralysis of mice caused by EV71 challenge were remarkably relieved by ICAC injection, which was achieved through decreases in the viral load and cytokine secretion in the mouse brain. Further biochemical assays showed that ICAC modulated several antioxidant enzymes involved in reduced and oxidized glutathione (GSH and GSSG) homeostasis, including glutathione reductase (GR), glutathione peroxidase (GPX), and glucose-6-phosphate dehydrogenase (G6PD), resulting in restoration of the GSH/GSSG ratio and reactive oxygen species (ROS) level. Finally, the antiviral effects of ICAC were dose-dependently disrupted by BSO, a biosynthesis inhibitor of GSH. This study indicated that ICAC acted as an antioxidant and prevented EV71 infection by modulating the redox homeostasis of glutathione.

Metabolism of molecular hydrogen (H₂) in bacteria and algae has been widely studied, and it has attracted increasing attention in the context of animals and plants. However, the role of endogenous H₂ in lateral root (LR) formation is still unclear. Here, our results showed that H₂-induced lateral root formation is a universal event. Naphthalene-1-acetic acid (NAA; the auxin analog) was able to trigger endogenous H₂ production in tomato seedlings, and a contrasting response was observed in the presence of N -1-naphthyphthalamic acid (NPA), an auxin transport inhibitor. NPA-triggered the inhibition of H₂ production and thereafter lateral root development was rescued by exogenously applied H₂. Detection of endogenous nitric oxide (NO) by the specific probe 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA) and electron paramagnetic resonance (EPR) analyses revealed that the NO level was increased in both NAA- and H₂-treated tomato seedlings. Furthermore, NO production and thereafter LR formation induced by auxin and H₂ were prevented by 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO; a specific scavenger of NO) and the inhibitor of nitrate reductase (NR; an important NO synthetic enzyme). Molecular evidence confirmed that some representative NO-targeted cell cycle regulatory genes were also induced by H₂, but was impaired by the removal of endogenous NO. Genetic evidence suggested that in the presence of H₂, Arabidopsis mutants nia2 (in particular) and nia1 (two nitrate reductases (NR)-defective mutants) exhibited defects in lateral root length. Together, these results demonstrated that auxin-induced H₂ production was associated with lateral root formation, at least partially via a NR-dependent NO synthesis., Competing Interests: The authors declare no conflict of interest.