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• The VUMAT subroutine for the N-H shear-modified GTN model was written. • Conventional and shear parameters of the N-H shear-modified GTN model were calibrated. • The established FEM results for the failure process and mechanical properties of dieless clinching joints are close to the experiments. • The failure mechanisms and processes of various joints were revealed from micro and macro perspectives. In this work, the failure behavior of dieless clinching joints for AA5052-H32 aluminum alloy under cross tension and tensile shear loading conditions was investigated by experimental and simulation methods. Firstly, The VUMAT subroutine for the N–H shear-modified GTN model (Proposed by Nahshon and Hutchinson, a modified GTN model considering hole shear effects) was written. Subsequently, the conventional and shear parameters calibration was accomplished. A finite element model (FEM) for the failure process of dieless clinching joints based on the N–H shear-modified GTN microscopic damage model, elimination of large deformation mesh distortion and consideration of the material hardening history was established. In addition, the deformation, damage and destruction processes of the joint under two loading conditions were analyzed. And macro/microfracture analysis of the failed joints was performed to further reveal the failure behavior. The results show that the established FEM of the failure process agrees well with the experimental results and failure modes are consistent. The model accuracy in predicting the tensile and shear loads is 91.9% and 92.7%, respectively. This provides a reference for the process design and joint arrangement of the dieless clinching joints in practical applications. [ABSTRACT FROM AUTHOR]

Tumor microenvironment-activated prodrugs have emerged as a promising strategy in precision medicine. However, the endogenous stimuli in the tumor microenvironment are often insufficient and unevenly distributed, impeding efficient and rapid prodrug conversion, necessitating the incorporation of complementary therapeutic strategies to amply treatment effectiveness. This study presents a self-synergistic therapeutic approach that combines hypoxia-activated paclitaxel prodrug (pro-PTX) with near-infrared-II (NIR-II) light-triggered photothermal therapy (PTT) for boosted tumor treatment. Initially, an organic polymer with strong NIR-II light harvesting capability, efficient photo-to-heat conversion, and excellent photostability was meticulously synthesized by introducing electron-withdrawing trifluoromethyl substituent. The high-performance NIR-II photothermal polymer then served as the matrix to encapsulate the hypoxia-responsive pro-PTX prodrug, forming the nanocore, on which the cell membrane derived from natural killer (NK) cells was further cloaked. The biomimetic nanopaltform exhibited a superior affinity towards tumor cells compared to normal cells, owing to the inherent tumor-recognition capability of NK cell membrane proteins. Upon exposure to NIR-II laser, the photothermal agent induced localized hyperthermia, facilitating not only direct tumor eradication but also exacerbating hypoxia within the tumor microenvironment. This, in turn, expedited the release of hypoxia-responsive prodrugs. Consequently, the synergistic effect of NIR-II PTT and chemotherapy efficiently induced cancer cell apoptosis and inhibited tumor growth. The developed nanoplatform, integrating hypoxia-responsive prodrug, high-performance NIR-II PTT agent-mediated complementary phototherapy, and NK cell-inspired active targeting, represents a promising strategy for precise and boosted tumor treatment. [Display omitted] • A nanoplatform integrates hypoxia-responsive prodrug, NIR-II PTT phototherapy, and NK cell-inspired active targeting. • Photothermal tumor ablation disrupted blood flow, creating severe hypoxia and expediting prodrug release. • NIR-II PTT and prodrug combo enhanced cancer cell apoptosis, suppressed tumor growth, and reduced pulmonary metastasis. [ABSTRACT FROM AUTHOR]

Analyzing the impact of urban land expansion efficiency (ULEE) on ecosystem services (ESs) is crucial to constructing high-quality territorial spatial patterns within urban agglomerations (UAs). While numerous studies have investigated the coercion and disturbance of urban sprawl on the ecological environment, research examining the impact of urban sprawl from an efficiency perspective remains relatively rare. In this study, ten UAs of different levels of development in China are selected as the research objects, and prefecture-level cities are used as the primary research units. CO 2 emissions are included as undesired outputs in the measurement and research framework of expansion efficiency to reflect the vision and requirements of emission reduction and carbon neutrality. At the same time, the Spatial Durbin Model (SDM) is used to reveal the impact of ULEE on ESs in years 2005–2021. The main results are as follows: (1) The ULEE within the entire UAs areas exhibited a fluctuating trend across different periods. Efficiency variations were evident among UAs with different development levels. Spatially, the UAs in the central region showed relatively low ULEE, while the northwest and southeast UAs displayed relatively high ULEE. Besides, the expansion efficiency of core cities in each UA exceeded that of surrounding cities. (2) The ecosystem service value (ESV) within the ten UAs demonstrated a consistent downward trend. In terms of the rate of ESV decline among UAs with varying developmental levels, breeding UAs exhibited the most rapid decline, followed by growing UAs, while mature UAs experienced the slowest decline. (3) Over the study period, the ULEE in UA areas positively contributed to enhancing ESs, with varying effects observed across different time frames. Natural factors directly influenced ES changes, thereby affecting both ULEE and Es dynamics. In contrast, changes in social factors indirectly caused changes in ESs. This study underscores the importance of a comprehensive assessment of ULEE and ESs to provide a scientific reference for formulating high-quality social and economic development and territorial spatial planning. [ABSTRACT FROM AUTHOR]

The performance of Fe 3 O 4 /attapulgite (APT) nanoparticles in Pb(II) adsorption from aqueous solutions could be improved by modifying the particles with aminopropyltriethoxysilane (APTS) and then combining with chitosan (CS) into beads. After preparing the APTS-Fe 3 O 4 /APT@CS beads, their surface morphology and crystal phases were analyzed by Fourier-transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. The magnetic properties of APTS-Fe 3 O 4 /APT@CS were studied by a vibrating sample magnetometer, while their heat resistance and stability were characterized by thermal weight analysis. A recycling test and comparison of adsorption capacities were also carried out. The adsorption capacity of Fe 3 O 4 /APT was improved by the modification with APTS and CS. The adsorption process conforms to the pseudo-second-order kinetic and Langmuir adsorption isotherm models. The adsorption of Pb(II) reaches a maximum of 625.34 mg/g, which compares favorably with other reported adsorbents. The results show that APTS-Fe 3 O 4 /APT@CS is a promising hybrid adsorbent for effective removal of Pb(II) from water. [ABSTRACT FROM AUTHOR]

Abstract Particles with a diameter of <2.5 μm (PM 2.5) have serious adverse-effects on human health, which have caused widespread public concern in recent decades. Currently, most of the existing research on PM 2.5 have used linear regression analysis; very few studies on the subject have been conducted using non-linear models. This study adopts a panel threshold model, which is seldom used in environmental studies, to examine the non-linear effects of environmental regulation and economic growth on PM 2.5 in 30 OECD countries, and we also explore the key driving socio-economic factors for PM 2.5 emissions. The results of our analysis show that, along with an increase in environmental policy stringency, PM 2.5 emissions first rise and then show no significant correlations, and thus a reduction in emissions can be expected if current trends continue. As for GDP per capita, significant and negative correlations are found across the three phases divided by the panel threshold model, indicating a promoting effect for PM 2.5 mitigation. In addition, public expenditure on the air sector correlated positively with PM 2.5 concentrations, expanding the share of service economy reward to reduce air pollution, and urban population ratio exhibits an inverted U-shaped pattern. Future studies may shed more light on the regulation-PM 2.5 nexus, and more studies are needed to confirm the existence of bi-directional correlations between economic development and air pollution. Graphical abstract Unlabelled Image Highlights • Environmental regulation show different impacts on PM 2.5 at high-, mid- and low-level phases; • GDP per capita is negatively correlated with PM 2.5 at 1% level; • Expansion of service industry reduces pollution; • An inverted U-shaped relationship exist between urbanization and pollution. [ABSTRACT FROM AUTHOR]

The present work developed a three-equation local thermal non-equilibrium (LTNE) model to model the initial effect on the internal thermal conduction in the solid phase of porous medium. The two energy equations in the original LTNE model were extended with a third equation to govern the dimensionless thermal penetration depth for the internal thermal conduction in the solid phase, I , which can describe the initial effect. The model was validated by comparisons between an analytical solution of the I equation and exact solutions of thermal conduction problems and between the macro-scale and the pore-scale numerical simulations. The comparisons demonstrate that the three-equation LTNE model is more accurate than the two-equation LTNE model with a constant I during the initial period. An important similarity number, η , is obtained for the enhanced geothermal system (EGS) heat extraction problem from the dimensionless three-equation LTNE model, which measures the internal thermal conduction effect in the solid phase of a porous medium. The initial effect in the EGS heat extraction can be neglected for η < 0.5. Criteria for degeneration of the three-equation LTNE model are proposed. [ABSTRACT FROM AUTHOR]

Muscle wasting increases morbidity and mortality and is related to chronic kidney disease (CKD) and dialysis. It is still unclear whether ferroptosis occurs during this progression and whether it is a potential intervention target for the treatment of CKD-related muscle injury. The objective is to identify potential compounds for treating ferroptosis and muscle wasting and explore the potential mechanisms in vivo / in vitro. Initially, we explored whether ferroptosis is present in the skeletal muscle of 5/6 nephrectomized (NPM) mice via RNA-Seq analysis, TUNEL staining, Oil red O staining, MDA/GSH/GSSG level detection and real-time quantitative PCR (qPCR). Subsequently, utilizing our established molecular phenotyping strategy, we screened potential traditional Chinese herb-derived compounds for alleviation of muscle wasting and ferroptosis. HE staining, Oil red O staining, TUNEL staining, immunofluorescence staining, MDA/GSH/GSSG level detection, Fe level detection, western blotting and qPCR were applied to assess the effects of the identified compound on muscle wasting and ferroptosis and explore the potential mechanism. Furthermore, RNA-Seq analysis, ChIP-Seq analysis and further experiments in vitro were performed to determine the role of Hedgehog signaling in the effect of Lobetyolin (LBT) on ferroptosis. In NPM mice, skeletal muscle dysfunction, lipogenesis, reduced GSH/GSSG ratio, decreased GSH content, increased MDA production and and higher levels of ferroptosis markers were observed. LBT treatment (30 mg/kg or 50 mg/kg) significantly alleviates skeletal muscle injury by inhibiting ferroptosis. Additionally, in an in vitro investigation, C2C12 cells exposed to Indolyl sulfate (IS) induced ferroptosis and LBT treatment (20 μM and 50 μM) protected C2C12 from such injury, consistent with the results from the in vivo analysis. Furthermore, it was found LBT increased the levels of protein involving Hedgehog signaling pathway (SMO and GLI1), and rescue analysis revealed that this pathway played a crucial role in the regulation of ferroptosis. Further experiments demonstrated that LBT upregulated a series of suppressors of ferroptosis by activating Gli1 transcription. LBT alleviates CKD-induced muscle injury by inhibiting ferroptosis through activation of the Hedgehog signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases are the major cause of mortality in patients with advanced chronic kidney diseases. The predominant abnormality observed among this population is cardiac dysfunction secondary to myocardial remodelings, such as hypertrophy and fibrosis, emphasizing the need to develop potent therapies that maintain cardiac function in patients with end-stage renal disease.Aims: To identify potential compounds and their targets as treatments for cardiorenal syndrome type 4 (CRS) using molecular phenotyping and in vivo/in vitro experiments.Methods: Gene expression was assessed using bioinformatics and verified in animal experiments using 5/6 nephrectomized mice (NPM). Based on this information, a molecular phenotyping strategy was pursued to screen potential compounds. Picrosirius red staining, wheat germ agglutinin staining, Echocardiography, immunofluorescence staining, and real-time quantitative PCR (qPCR) were utilized to evaluate the effects of compounds on CRS in vivo. Furthermore, qPCR, immunofluorescence staining and flow cytometry were applied to assess the effects of these compounds on macrophages/cardiac fibroblasts/cardiomyocytes. RNA-Seq analysis was performed to locate the targets of the selected compounds. Western blotting was performed to validate the targets and mechanisms. The reversibility of these effects was tested by overexpressing Osteopontin (OPN).Results: OPN expression increased more remarkably in individuals with uremia-induced cardiac dysfunction than in other cardiomyopathies. Lobetyolin (LBT) was identified in the compound screen, and it improved cardiac dysfunction and suppressed remodeling in NPM mice. Additionally, OPN modulated the effect of LBT on cardiac dysfunction in vivo and in vitro. Further experiments revealed that LBT suppressed OPN expression via the phosphorylation of c-Jun N-terminal protein kinase (JNK) signaling pathway.Conclusions: LBT improved CRS by inhibiting OPN expression through the JNK pathway. This study is the first to describe a cardioprotective effect of LBT and provides new insights into CRS drug discovery. [ABSTRACT FROM AUTHOR]