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Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFβ inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease. Engineered human models of hearts are needed to study pathology and repair. Here, the authors develop a model which replicates the phased remodelling process. The model is then used to study signalling pathway modulators for their therapeutic potential in a mini-repair model. [ABSTRACT FROM AUTHOR]

Glycosphingolipids (GSLs) are essential components of cell membranes, particularly enriched in the nervous system. Altered molecular distributions of GSLs are increasingly associated with human diseases, emphasizing the significance of lipidomic profiling. Traditional GSL analysis methods are hampered by matrix effect from phospholipids and the difficulty in distinguishing structural isomers. Herein, we introduce a highly sensitive workflow that harnesses magnetic TiO2 nanoparticle-based selective enrichment, charge-tagging Paternò–Büchi reaction, and liquid chromatography-tandem mass spectrometry. This approach enables mapping over 300 distinct GSLs in brain tissues by defining sugar types, long chain bases, N-acyl chains, and the locations of desaturation and hydroxylation. Relative quantitation of GSLs across multiple structural levels provides evidence of dysregulated gene and protein expressions of FA2H and CerS2 in human glioma tissue. Based on the structural features of GSLs, our method accurately differentiates human glioma with/without isocitrate dehydrogenase genetic mutation, and normal brain tissue. The molecular profiling of glycosphingolipids (GSLs) is hindered by the coexistence of abundant phospholipids and diverse isomers. The authors introduce a highly sensitive workflow that maps out the structural atlas of neutral GSLs, previously deemed a "dark space" within the lipidome. [ABSTRACT FROM AUTHOR]

Surface cracks are commonly observed in coatings and films. When structures with coatings are subject to stretching, opening mode cracks are likely to form on the surface, which may further lead to other forms of damage, such as interfacial delamination and substrate damage. Possible crack forms include cracks extending towards the interface and channeling across the film. In this paper, a two-dimensional numerical model is proposed to obtain the structural strain energy at arbitrary crack lengths for bilayer structures under uniaxial tension. The energy release rate and structural stress intensity factors can be obtained accordingly, and the effects of geometry and material features on fracture characteristics are investigated, with most crack patterns being confirmed as unstable. The proposed model can also facilitate the analysis of the stress distribution in periodic crack patterns of films. The results from the numerical model are compared with those obtained by the finite element method (FEM), and the accuracy of the theoretical results is demonstrated. [ABSTRACT FROM AUTHOR]

Dramatic alterations in epigenetic landscapes are known to impact genome accessibility and transcription. Extensive evidence demonstrates that senescent cells undergo significant changes in chromatin structure; however, the mechanisms underlying the crosstalk between epigenetic parameters and gene expression profiles have not been fully elucidated. In the present study, we delineate the genome-wide redistribution of accessible chromatin regions that lead to broad transcriptome effects during senescence. We report that distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac-occupied enhancer regions, where they are responsible for elevated flanking senescence-associated secretory phenotype (SASP) expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, moves away from H3K27ac-labled SAAs to allow for prominent chromatin accessibility reconstruction during senescence. The enhanced SAAs signal driven by TEAD4 suppression subsequently induces a robust increase in the expression of adjacent SASP genes and the secretion of downstream factors, which contribute to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry, and further reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulates the overall transcriptional program of SASP genes. [ABSTRACT FROM AUTHOR]

Ultrasonic testing (UT) is increasingly combined with machine learning (ML) techniques for intelligently identifying damage. Extracting significant features from UT data is essential for efficient defect characterization. Moreover, the hidden physics behind ML is unexplained, reducing the generalization capability and versatility of ML methods in UT. In this paper, a generally applicable ML framework based on the model interpretation strategy is proposed to improve the detection accuracy and computational efficiency of UT. Firstly, multi-domain features are extracted from the UT signals with signal processing techniques to construct an initial feature space. Subsequently, a feature selection method based on model interpretable strategy (FS-MIS) is innovatively developed by integrating Shapley additive explanation (SHAP), filter method, embedded method and wrapper method. The most effective ML model and the optimal feature subset with better correlation to the target defects are determined self-adaptively. The proposed framework is validated by identifying and locating side-drilled holes (SDHs) with 0.5λ central distance and different depths. An ultrasonic array probe is adopted to acquire FMC datasets from several aluminum alloy specimens containing two SDHs by experiments. The optimal feature subset selected by FS-MIS is set as the input of the chosen ML model to train and predict the times of arrival (ToAs) of the scattered waves emitted by adjacent SDHs. The experimental results demonstrate that the relative errors of the predicted ToAs are all below 3.67% with an average error of 0.25%, significantly improving the time resolution of UT signals. On this basis, the predicted ToAs are assigned to the corresponding original signals for decoupling overlapped pulse-echoes and reconstructing high-resolution FMC datasets. The imaging resolution is enhanced to 0.5λ by implementing the total focusing method (TFM). The relative errors of hole depths and central distance are no more than 0.51% and 3.57%, respectively. Finally, the superior performance of the proposed FS-MIS is validated by comparing it with initial feature space and conventional dimensionality reduction techniques. [ABSTRACT FROM AUTHOR]

A lipidome comprises thousands of lipid species, many of which are isomers and isobars. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), although widely used for lipidomic profiling, faces challenges in differentiating lipid isomers. Herein, we address this issue by leveraging the orthogonal separation capabilities of hydrophilic interaction liquid chromatography (HILIC) and trapped ion mobility spectrometry (TIMS). We further integrate isomer-resolved MS/MS methods onto HILIC-TIMS, which enable pinpointing double bond locations in phospholipids and sn-positions in phosphatidylcholine. This system profiles phospholipids at multiple structural levels with short analysis time (<10 min per LC run), high sensitivity (nM detection limit), and wide coverage, while data analysis is streamlined using a home-developed software, LipidNovelist. Notably, compared to our previous report, the system doubles the coverage of phospholipids in bovine liver and reveals uncanonical desaturation pathways in RAW 264.7 macrophages. Relative quantitation of the double bond location isomers of phospholipids and the sn-position isomers of phosphatidylcholine enables the phenotyping of human bladder cancer tissue relative to normal control, which would be otherwise indistinguishable by traditional profiling methods. Our research offers a comprehensive solution for lipidomic profiling and highlights the critical role of isomer analysis in studying lipid metabolism in both healthy and diseased states. The existence of large number of isomers poses challenges for lipidomic analysis. The authors integrate hydrophilic interaction liquid chromatography, trapped ion mobility, and isomer-resolved MS/MS into a single system, enabling deep profiling of phospholipidomes at fast speed and wide coverage. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study was aimed to investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) PET/CT for evaluating focal liver lesions (FLLs) with [18F]FDG non-avidity. Methods: From January 2021 to March 2022, this prospective study included 80 FLLs that were not avid on [18F]FDG PET/CT from 37 patients, then underwent [18F]FAPI PET/CT. All patients with FLL(s) with biopsy-proof or follow-up confirmation were categorized into four subgroups (20 hepatocellular carcinomas [HCCs]/5 non-HCC malignancies/4 inflammatory FLLs/8 benign noninflammatory FLLs). The diagnostic value of [18F]FAPI for detecting liver malignancy was determined by visual evaluation. Differences in the maximum standardized uptake value (SUVmax) and lesion-to-background ratio (LBR) obtained from [18F]FAPI PET/CT among the four subgroups were analyzed by semiquantitative analysis. Results: Among the thirty-seven enrolled participants (34 males; median age 57 years, range 48–67 years), on visual evaluation, the sensitivity, specificity, and accuracy of [18F]FAPI PET for detecting liver malignancy in the patient-based analysis were 96.0% (24/25), 58.3% (7/12), and 83.8% (31/37), respectively. On semiquantitative analysis, the SUVmax and LBR of [18F]FAPI PET in liver malignancy (33 HCC lesions; 19 non-HCC malignant lesions) were significantly higher than those in 11 benign noninflammatory FLLs [HCC: SUVmax: 6.4 vs. 4.5, P = 0.017; LBR: 5.1 vs. 1.5, P = 0.003; non-HCC: SUVmax: 5.5 vs. 4.5, P = 0.008; LBR: 4.4 vs. 1.5, P = 0.042]. Notably, there was no significant difference in the SUVmax of [18F]FAPI PET between 33 HCC lesions and 17 inflammatory FLLs (6.4 vs. 8.2, P = 0.37), but the LBR of [18F]FAPI PET in HCC were significantly lower than that in inflammatory FLLs (5.1 vs. 9.1, P = 0.003). Conclusions: [18F]FAPI PET/CT shows high sensitivity in detecting HCC and non-HCC malignancy with [18F]FDG non-avidity. [18F]FAPI might be a promising radiopharmaceutical for the differential diagnosis of benign noninflammatory FLLs and liver malignancy with [18F]FDG non-avidity. [ABSTRACT FROM AUTHOR]

In addition, although no significant difference in sarcomere structure was observed between EPSC-CMs and iPSC-CMs, the EPSC-CM-derived engineered heart tissue (EHT) (Fig. These authors contributed equally: Li Li, Zhongjun Wan Dear Editor, The availability of functional human cardiomyocytes is essential for cardiac disease modeling, drug screening, and cell therapy, whereas donor human cardiomyocytes are incredibly scarce. However, whether EPSCs can efficiently generate other lineages such as cardiomyocytes and how the EPSC-derived cardiomyocytes (EPSC-CMs) function compared with ESC/iPSC-CMs have not been studied yet. [Extracted from the article]

In this study, vanadium dioxide thin films were fabricated on Al2O3 (0001) substrates by sol-gel method and subsequent annealing process. The effects of annealing temperature on the structure, chemical state, surface morphology and electrical properties of the films were systematically studied. The results displayed that with the annealing temperature increasing up to 520 °C, the composition evolution experienced four processes: the reduction of V5+ to V4+ (or V3+), the comproportionation of V5+/V3+ to V4+, the oxidation of V3+ to V4+, and the secondary reduction of V5+ to V3+. Accompanied with the secondary reduction at 520 °C, the disappearance of grain boundaries was observed on the film surface. Furthermore, as the annealing temperature increased from 420 °C to 470 °C and then 520 °C, the prepared films showed good phase transition property with the resistance change up to nearly four orders of magnitude, and the phase transition temperatures were 62.8 °C, 61.8 °C and 61.1 °C respectively, showing a slow downward trend. The results not only revealed the mutual transformation of various vanadium oxides during the annealing treatment, but also supplied some clues for optimizing the parameters for VO2 film preparation with high quality. Highlights: VO2 films were prepared on Al2O3 (0001) by sol-gel method and subsequent annealing process. The composition evolution image with annealing temperature is proposed in terms of XPS results. Accompanied by the secondary reduction process, the grain boundaries disappear synchronously. Both the Tc and the hysteresis width can be reduced by higher annealing temperature. [ABSTRACT FROM AUTHOR]

An unprecedented number of COVID-19 vaccination campaign are under way worldwide. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases. The safety of spike-based adenovirus type-5 vectored COVID-19 vaccine is evaluated, showing it neither affects the survival and function of human cardiac cells and engineered heart tissues nor aggravates heart damage in mice after ischemic injury. [ABSTRACT FROM AUTHOR]

Cardiac excitation-contraction coupling requires dyads, the nanoscopic microdomains formed adjacent to Z-lines by apposition of transverse tubules and junctional sarcoplasmic reticulum. Disruption of dyad architecture and function are common features of diseased cardiomyocytes. However, little is known about the mechanisms that modulate dyad organization during cardiac development, homeostasis, and disease. Here, we use proximity proteomics in intact, living hearts to identify proteins enriched near dyads. Among these proteins is CMYA5, an under-studied striated muscle protein that co-localizes with Z-lines, junctional sarcoplasmic reticulum proteins, and transverse tubules in mature cardiomyocytes. During cardiac development, CMYA5 positioning adjacent to Z-lines precedes junctional sarcoplasmic reticulum positioning or transverse tubule formation. CMYA5 ablation disrupts dyad architecture, dyad positioning at Z-lines, and junctional sarcoplasmic reticulum Ca2+ release, leading to cardiac dysfunction and inability to tolerate pressure overload. These data provide mechanistic insights into cardiomyopathy pathogenesis by demonstrating that CMYA5 anchors junctional sarcoplasmic reticulum to Z-lines, establishes dyad architecture, and regulates dyad Ca2+ release. Heart muscle cells exhibit exquisitely organized subcellular features that enable efficient and coordinated heart muscle contraction, but little is known about how it is achieved. Here the authors show that CMYA5 organizes cardiomyocyte calcium release units and aligns them to sarcomeres, leading to abnormal calcium release, cardiac dysfunction, and inability to tolerate pressure overload, when absent. [ABSTRACT FROM AUTHOR]

Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice. [ABSTRACT FROM AUTHOR]

Hydrogels have been extensively used in many fields. Current synthesis of functional hydrogels requires incorporation of functional molecules either before or during gelation via the pre-organized reactive site along the polymer chains within hydrogels, which is tedious for polymer synthesis and not flexible for different types of hydrogels. Inspired by sandcastle worm, we develop a simple one-step strategy to functionalize wet hydrogels using molecules bearing an adhesive dibutylamine-DOPA-lysine-DOPA tripeptide. This tripeptide can be easily modified with various functional groups to initiate diverse types of polymerizations and provide functional polymers with a terminal adhesive tripeptide. Such functional molecules enable direct modification of wet hydrogels to acquire biological functions such as antimicrobial, cell adhesion and wound repair. The strategy has a tunable functionalization degree and a stable attachment of functional molecules, which provides a tool for direct and convenient modification of wet hydrogels to provide them with diverse functions and applications. Functionalisation of hydrogels can be difficult to achieve and often requires modification of polymers before gelation. Here, the authors report on a sandcastle worm inspired adhesive tripeptide for the post gelation functionalisation of wet hydrogels, demonstrating the addition of different functionality. [ABSTRACT FROM AUTHOR]

Implantation-caused foreign-body response (FBR) is a commonly encountered issue and can result in failure of implants. The high L-serine content in low immunogenic silk sericin, and the high D-serine content as a neurotransmitter together inspire us to prepare poly-DL-serine (PSer) materials in mitigating the FBR. Here we report highly water soluble, biocompatible and easily accessible PSer hydrogels that cause negligible inflammatory response after subcutaneous implantation in mice for 1 week and 2 weeks. No obvious collagen capsulation is found surrounding the PSer hydrogels after 4 weeks, 3 months and 7 months post implantation. Histological analysis on inflammatory cytokines and RNA-seq assay both indicate that PSer hydrogels show low FBR, comparable to the Mock group. The anti-FBR performance of PSer hydrogels at all time points surpass the poly(ethyleneglycol) hydrogels that is widely utilized as bio-inert materials, implying the potent and wide application of PSer materials in implantable biomaterials and biomedical devices. Implantation-caused foreign-body response is a commonly encountered issue and can result in failure of implants. Here, the authors demonstrate that a highly water soluble, biocompatible, and easily accessible poly-DL-serine hydrogel can mitigate foreign-body response. [ABSTRACT FROM AUTHOR]

The loss regularity of nitrogen (N), phosphorus (P), and chemical oxygen demand (CODMn) of runoff under different rainfall intensity and different management practices in Phyllostachys praecox cv. prevernalis forest land was studied. The total nitrogen (TN) and CODMn concentration in runoff were significantly correlated with the rainfall intensity under the three management modes named as control, fertilization, and cover. Moreover, N mainly lost in the form of nitrate (NO3−-N). Generally, the relationship between total and dissolved phosphorus (TP and DP) loss in the three management modes was estimated in following orders: coverage > fertilization > control. The loss of P was mainly in the granular state, and the loss of DP only accounted negligible amount of the TP loss. The loss of CODMn was closely related to the magnitude of rainfall intensity. Results revealed that CODMn concentration in runoff under fertilization and cover management was significantly correlated with the rain fall intensity. [ABSTRACT FROM AUTHOR]

Emergency use authorization of COVID vaccines has brought hope to mitigate pandemic of coronavirus disease 2019 (COVID-19). However, there remains a need for additional effective vaccines to meet the global demand and address the potential new viral variants. mRNA technologies offer an expeditious path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on the spike (S) glycoprotein of SARS-CoV-2. Several mRNA constructs of S-protein, including wild type, a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), as well as others, were tested in animal models for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques, and for efficacy in a Syrian golden hamster model. The selected 2P/GSAS vaccine formulation, designated MRT5500, elicited potent nAbs as measured in neutralization assays in all three preclinical models and more importantly, protected against SARS-CoV-2-induced weight loss and lung pathology in hamsters. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate (NHP), thus alleviating a hypothetical concern of potential vaccine-associated enhanced respiratory diseases known associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for entering clinical development. [ABSTRACT FROM AUTHOR]

Myh7 is a classic biomarker for cardiac remodeling and a potential target to attenuate cardiomyocyte (CM) hypertrophy. This study aimed to identify the dominant function of Myh7 after birth and determine whether its removal would affect CM maturation or contribute to reversal of pathological hypertrophy phenotypes. The CASAAV (CRISPR/Cas9-AAV9-based somatic mutagenesis) technique was used to deplete Myh6 and Myh7, and an AAV dosage of 5 × 109 vg/g was used to generate a mosaic CM depletion model to explore the function of Myh7 in adulthood. CM hypertrophy was induced by transverse aortic constriction (TAC) in Rosa26Cas9-P2A-GFP mice at postnatal day 28 (PND28). Heart function was measured by echocardiography. Isolated CMs and in situ imaging were used to analyze the structure and morphology of CM. We discovered that CASAAV successfully silenced Myh6 and Myh7 in CMs, and early depletion of Myh7 led to mild adulthood lethality. However, the Myh7 PND28-knockout mice had normal heart phenotype and function, with normal cellular size and normal organization of sarcomeres and T-tubules. The TAC mice also received AAV-Myh7-Cre to produce Myh7-knockout CMs, which were also of normal size, and echocardiography demonstrated a reversal of cardiac hypertrophy. In conclusion, Myh7 has a role during the maturation period but rarely functions in adulthood. Thus, the therapeutic time should exceed the period of maturation. These results confirm Myh7 as a potential therapeutic target and indicate that its inhibition could help reverse CM hypertrophy. [ABSTRACT FROM AUTHOR]

Cell adhesion has tremendous impact on the function of culture platforms and implants. Cell-adhesive proteins and peptides have been extensively used for decades to promote cell adhesion, however, their application suffers from their easy enzymatic degradation, difficulty in large-scale preparation and expensiveness. To develop the next-generation cell-adhesive materials, we mimic the cell adhesion functions and mechanisms of RGD and KRSR peptides and design cell-adhesive cationic-hydrophobic amphiphilic β-amino acid polymers that are stable upon proteolysis and easily prepared in large scale at low cost. The optimal polymer strongly promotes cell adhesion, using preosteoblast cell as a model, by following dual mechanisms that are independent of sequence and chirality of the statistic copolymer. Our strategy opens avenues in designing the next-generation cell-adhesive materials and may guide future studies and applications. Cell adhesion peptides like RGD are important to biomedical applications but suffer from proteolysis as well as processing and cost issues. Here, the authors report on the development of cationic-hydrophobic amphiphilic β-amino acid polymers which function as cell adhesion motifs but are resistant to proteolysis. [ABSTRACT FROM AUTHOR]

Due to the traditional grid-connected current control method of single Proportional Integral (PI) and Repetitive Control (RC) strategies, the photovoltaic inverter output current will have a distortion problem, which can not only maintain the stability of the whole photovoltaic system, but also the current quality of the photovoltaic inverter grid-connected system is reduced in the case of high-order LCL photovoltaic inverter control system operation. So, a strategy of PI + repetitive control in two-phase stationary frame is proposed. The introduction of the weighting coefficient m of the PI controller branch can enhance the adjustment ability of the PI link and accelerate the responding speed to meet the dynamic characteristics of the entire operating system, while the other weighting coefficient n on the repetitive controller branch can increase the correction capability and eliminate the steady-state error to meet system steady-state requirements. The scheme not only simplifies the coordinate transformation and decoupling calculation process, but also improves the harmonics suppression ability of the photovoltaic inverter and reduces the total harmonic distortion rate of the grid-connected current. At the same time, with the load operation mode change, the system can also retain better stability and keep a fast dynamic response capability, and the grid current can be able to return to a stable state in one cycle. Finally, the effectiveness of theoretical analysis and the strategy is verified by simulation. [ABSTRACT FROM AUTHOR]

Adsorption capacities of CH4, CO2, CO, N2 and H2 on NaY zeolite were measured at 298 K, 318 K, 338 K and 358 K with pressure ranged from 0 to 10 bar. The order of adsorption capacity was CO2 ≫ CH4 > CO > N2 ≫ H2. The experiment data were fitted by the Langmuir, Toth and Sips equations. The fitting relativity of above models were also compared. Moreover, the isosteric heat of adsorption were calculated by the Clausius–Clapeyron equation, the results showed that the adsorption heat of CO2 is the largest (41.89764 kJ/mol with adsorption loading of 5.8 mmol/g) and that of H2 is the smallest. Finally, the selectivity of binary mixture was predicted according to the IAS theory. [ABSTRACT FROM AUTHOR]

Vigorously developing high-tech industry has been considered to be an effective way to coordinate economic growth with excessive carbon dioxide (CO2) emissions. However, previous studies have not explored the heterogeneous impacts of high-tech industry on CO2 emissions in regions with different levels of high-tech industry development, and not distinguished the direct and indirect impacts. Based on STIRPAT model, this study investigates the impacts of high-tech industry development on CO2 emissions in China between 2005 and 2016. Adopting the K-medians cluster method, effects in regions with high, middle, and low levels of high-tech industry development are considered. Indirect effects of high-tech industry development on CO2 emissions by affecting industry structure upgrades and economic growth are explored. Empirical results illustrate a positive U-shaped nonlinear link between the level of high-tech industry development and CO2 emissions at the national level and regional (high, middle, and low) level. In terms of indirect impacts, high-tech industry development attenuates the reduction of CO2 emissions due to industry structure upgrades, and promotes economic growth to increase CO2 emissions slightly. The indirect impact intensity gradually decreases as the level of high-tech industry development decreases across three regions. Reasonable implications of our findings are proposed. [ABSTRACT FROM AUTHOR]

In this study, an efficient PID control system has been designed for a vacuum pressure swing adsorption (VPSA) process which used silica gel to capture CO2 from dry flue gas. Changes of CO2 composition in feed gas are set as disturbances and vary from 12.0 to 15.0% to make simulation work more closely to reality. Meanwhile, adsorption step time duration was set to change consistently according to the feedback of CO2 purity in product. PID control strategy built in software gPROMS is employed in this paper. The competence of the control system is firstly analyzed by a transient impulse of CO2 content in feed gas (15.0% dropped to 12.0%). Then random pulse is added to test the ability of the control system to reject the unknown disturbances and track the set point. Detailed changes in bed under open and closed-loop are listed and made comparisons. Results demonstrate that the model shows an enhanced performance in the presence of random disturbances under closed-loop control compared with the open-loop operation. And this proves that closed-loop feedback PID control can be used to improve the CO2 capture of VPSA process operations. [ABSTRACT FROM AUTHOR]

A two-bed, six-step vacuum pressure swing adsorption (VPSA) process using LiLSX zeolite for industrial-scale 80% oxygen production with rapid cycling was investigated by numerical simulation and optimization. keeping the structural parameters of the VPSA devices unchanged and ensuring the purity of oxygen never be lower than 80%, the operating variables were optimized to achieve the target of minimum power consumption and maximum yield, which can maximize the devices’ potential performance for various production requirements. In the case of minimum power consumption, after optimization, the minimum power consumption was reduced from 0.313 to 0.289 kWh Nm−3 O2, meanwhile, the productivity fell from 106.42 to 93.75 Nm3 h−1 ton−1. In the maximum productivity case, a high productivity of O2 was achieved (117.87 Nm3 h−1 ton−1) but the power consumption rose to 0.324 kWh Nm−3 O2. A subsequent detailed analysis was carried out to provide insights into these observations and compare the impact of the decision variables on the process performance. [ABSTRACT FROM AUTHOR]

The increasing wall stress as is elicited by arterial hypertension promotes their reorganization in the vessel wall which may lead to arterial stiffening and contractile dysfunction. The nuclear factor of activated T cells 5 (NFAT5) pathway plays a role in regulating growth and differentiation in various cell types. We investigated whether the NFAT5 pathway was involved in the regulation of biomechanical stretch-induced human arterial smooth muscle cell (HUASMC) proliferation, inflammation, and migration. Herein, we showed that stretch promoted the expression of NFAT5 in human arterial smooth muscle cells and regulated through activation of c-Jun N-terminal kinase under these conditions. This may contribute to an improved activity of HUASMCs and thus promote reorganization in vascular remodeling processes such as hypertension-induced arterial stiffening and contractile dysfunction. [ABSTRACT FROM AUTHOR]

Sterigmatocystin (ST) is a common contaminant detected in food and animal feed that has been recognized as a possible human carcinogen. Our previous studies demonstrate that ST causes DNA damage and subsequently triggers cell cycle arrest in G and apoptosis in immortalized human gastric epithelial cells (GES-1). Recently, studies have shown that in certain contexts, cells with DNA damage may escape checkpoint arrest and enter mitosis without repairing the damage. The term for this process is 'checkpoint adaptation,' and it increases the risk of unstable genome propagation, which may contribute to carcinogenesis. Thus, we aimed to investigate whether checkpoint adaptation occurs in GES-1 cells treated with ST and explored the underlying molecular mechanisms that contribute to this phenotype. In this study, we found that ST treatment for 24 h in GES-1 cells led to an initial G arrest; however, a fraction of GES-1 cells became large and rounded, and the number of p-H3-positive cells increased sharply after ST treatment for 48 h. Moreover, collection of the large and rounded cells by mechanical shake-off revealed that the majority of these large cells were found in the mitotic phase of the cell cycle. Importantly, we found that these rounded cells entered mitosis despite damaged DNA and that a small subset of this cell population survived and continued to propagate. These results suggest that ST induces an initial G arrest that is subsequently followed by G phase checkpoint adaptation, which may potentially promote genomic instability and result in tumorigenesis. Furthermore, we showed that activation of Chk1 contributes to the G arrest in GES-1 cells that are treated with ST for 24 h and that prolonged treatment of cells with ST for 48 h led to a decrease in the total protein and phosphorylation levels of Chk1 in mitotic cells, indicating that checkpoint adaptation may be driven by inactivation of Chk1. Knockdown studies confirmed that cells entered mitosis following inactivation of Chk1. Taken together, we show that ST treatment for 24 h activates Chk1 and induces a G arrest in GES-1 cells. However, prolonged ST treatment for 48 h led to Chk1 inactivation in GES-1 cells, which promotes checkpoint adaptation and entry of cells into mitosis despite damaged DNA. Importantly, checkpoint adaptation in GES-1 cells treated with ST may potentially promote genomic instability and drive tumorigenesis. [ABSTRACT FROM AUTHOR]

A labeled green fluorescent polystyrene sulfonate (LNaPSS) has been synthesized using atom transfer radical polymerization of a styrene sulfonate monomer with a fluorescent co-monomer, fluorescein thiocyanate-vinyl aniline. As a result this 100 % sulfonated polymer contains no hydrophobic patches along the chain backbone besides the fluorescent marker itself. The concentration of the fluorescent monomer was kept low to maintain the characteristic properties of the anionic polyelectrolyte, LNaPSS. ATRP conditions facilitated the production of polymers spanning a range of molecular weights from 35,000 to 175,000 in gram-scale batches with polydispersity indices of 1.01-1.24. Molecular weight increased with the monomer to initiator ratio. Gel permeation chromatography results show a unimodal distribution, and the polymer structure was also confirmed by H NMR and FT-IR spectroscopy. Fluorescence spectroscopy confirmed covalent bonding of fluorescein isothiocyanate to the polymer, indicating that the polymer is suitable as a probe in fluorescence microscopy. To demonstrate this ability, the polymer was used to locate structural features in salt crystals formed during drying, as in the evaporation of sea mist. A second application to probe diffusion studies is also demonstrated. [ABSTRACT FROM AUTHOR]

The widespread and improper use of pyrethroid insecticides, such as deltamethrin, has resulted in the evolution of resistance in many mosquito species, including Culex pipiens pallens. With the development of high-throughput sequencing, it is possible to massively screen pyrethroid resistance-associated gene. In this study, we used Illumina-Solexa transcriptome sequencing to identify genes that are expressed differently in deltamethrin-susceptible and -resistant strains of Culex pipiens pallens as a critical knowledge base for further studies. A total of 4,961,197,620 base pairs and 55,124,418 reads were sequenced, mapped to the Culex quinquefasciatus genome and assembled into 17,679 known genes. We recorded 1826 significantly differentially expressed genes (DEGs). Among them, 1078 genes were up-regulated and 748 genes were down-regulated in the deltamethrin-resistant strain compared to -susceptible strain. These DEGs contained cytochrome P450 s, cuticle proteins, UDP-glucuronosyltransferases, lipases, serine proteases, heat shock proteins, esterases and others. Among the 1826 DEGs, we found that the transcriptional levels of CYP6AA9 in the laboratory populations was elevated as the levels of deltamethrin resistance increased. Moreover, the expression levels of the CYP6AA9 were significantly higher in the resistant strains than the susceptible strains in three different field populations. We further confirmed the association between the CYP6AA9 gene and deltamethrin resistance in mosquitoes by RNA interfering (RNAi). Altogether, we explored massive potential pyrethroid resistance-associated genes and demonstrated that CYP6AA9 participated in the pyrethroid resistance in mosquitoes. [ABSTRACT FROM AUTHOR]

Insecticide resistance has been a major public health challenge. It is impendent to study the mechanism on insecticide resistance. In our previous study, 14 differentially accumulated insect cuticle proteins (ICPs) based on insecticide resistance proteomes and transcriptomes were found in the deltamethrin-resistant (DR) and -susceptible (DS) strains of Culex pipiens pallens. To investigate if these ICPs are associated with deltamethrin resistance, different transcriptional levels of the 14 ICPs were detected in the DS and DR strains from laboratory and field populations by using quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of the 14 ICPs were also measured after short-term exposure of the DS strain to deltamethrin. The full-length complementary DNA (cDNA) of CpCPLCG5 gene, which encodes one of the 14 ICPs, was cloned from Cx. pipiens pallens. Homology analysis and phylogenetic analysis were carried out with some other insects. Furthermore, small interfering RNA (siRNA) was used to knockdown the expression level of CpCPLCG5 gene for characterizing its contribution to deltamethrin resistance. The results showed that the expression level of CpCPLCG5 gene was higher in DR strain than in DS strain both in laboratory and field populations while the other 13 ICPs were downregulated. The full-length cDNA of CpCPLCG5 gene was 732 bp, with the ORF of 390 bp and deduced 129 amino acids (GenBank/KF723314,2013). Knockdown of CpCPLCG5 gene increased the susceptibility of the DR strain while the expression level of the other 13 ICPs elevated. Our findings indicate that the cuticle proteins are associated with deltamethrin resistance in Cx. pipiens pallens. [ABSTRACT FROM AUTHOR]

It is reported that CLU rs2279590 polymorphism is significantly associated with Alzheimer's disease (AD) in European ancestry. Recent studies investigated rs2279590 polymorphism in Asian population (Chinese, Japanese and Korean). Four studies showed negative association and two studies showed weak association between rs2279590 and AD. We believe that the weak association or no association may be caused by the relatively small sample size in Asian population. Here, we reinvestigated the association in Asian population. Meanwhile, to investigate the genetic heterogeneity of the rs2279590 polymorphism in Asian and Caucasian populations, we searched the PubMed and AlzGene databases and selected 11 independent studies (6 studies in Asian population and 5 studies in Caucasian population) including 20,655 individuals (8,605 cases and 12,050 controls) for meta-analysis. Our results showed significant association between rs2279590 polymorphism and AD in Asian population with P = 2.00E−04 and P = 2.00E−04 using additive and recessive models, respectively. We observed no significant heterogeneity between Asian and Caucasian populations. We believe that our results may be helpful to understand the mechanisms of CLU in AD pathogenesis and will be useful for future genetic studies in AD. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) regulate gene expression and biological processes including embryonic development, innate immunity, and infection in many species. Emerging evidence indicates that miRNAs are involved in drug resistance. However, little is known about the relationship between the miRNAs and insecticide resistance in mosquitos. Here, we reported that conserved miR-278-3p and its target gene are critical for pyrethroid resistance in Culex pipiens pallens. We found that CYP6AG11 is the target of miR-278-3p, through bioinformatic analysis and experimental verification. The expression level of miR-278-3p was lower, whereas the level of CYP6AG11 was higher in deltamethrin-resistant strain, which were detected using quantitative reverse transcription PCR (qRT-PCR). We also found that CYP6AG11 was regulated by miR-278-3p via a specific target site with the 3′ untranslated region (UTR) by luciferase reporter assay. In addition, overexpression of CYP6AG11 in the mosquito C6/36 cells showed better proliferation than the cells with empty vector when treated by deltamethrin at different concentrations. Moreover, the overexpression of miR-278-3p through microinjection led to a significant reduction in the survival rate, and the level of CYP6AG11 was simultaneously reduced. These results indicated that miR-278-3p could regulate the pyrethroid resistance through CYP6AG11. [ABSTRACT FROM AUTHOR]

(BaCa)(ZrTi)TaO ceramics (BCZTT, 0 ≤ x ≤ 3.0 mol%) were prepared via a conventional solid-state reaction method, and the effect of Ta substitution on the microstructure and electrical properties of the BCZTT ceramics was investigated. A pure perovskite structure was obtained in all of these samples. The microstructure of the BCZT ceramics is strongly affected by Ta doping. Low-concentration Ta addition ( x = 0.1 mol%) promotes the grain growth of the BCZT ceramics. However, high-concentration Ta addition ( x > 0.5 mol%) effectively hinders the grain growth. The dielectric, ferroelectric and piezoelectric properties of the BCZT ceramics are improved by addition of a small amount of Ta. For the ceramics with x = 0.3 mol%, electrical performance reaches optimum: ε = 7,770, T (the temperature of the dielectric maximum) = 101.8 °C, P = 17.9 μC/cm, P = 9.1 μC/cm, E = 0.54 kV/mm and d = 303 pC/N. The T of the BCZTT decreases with the increasing Ta concentration. The relaxor properties of undoped and Ta-doped BCZT ceramics were depicted, and the diffusivity increases with the increasing Ta contents. [ABSTRACT FROM AUTHOR]