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Building extraction aims to extract building pixels from remote sensing imagery, which plays a significant role in urban planning, dynamic urban monitoring, and many other applications. UNet3+ is widely applied in building extraction from remote sensing images. However, it still faces issues such as low segmentation accuracy, imprecise boundary delineation, and the complexity of network models. Therefore, based on the UNet3+ model, this paper proposes a 3D Joint Attention (3DJA) module that effectively enhances the correlation between local and global features, obtaining more accurate object semantic information and enhancing feature representation. The 3DJA module models semantic interdependence in the vertical and horizontal dimensions to obtain feature map spatial encoding information, as well as in the channel dimensions to increase the correlation between dependent channel graphs. In addition, a bottleneck module is constructed to reduce the number of network parameters and improve model training efficiency. Many experiments are conducted on publicly accessible WHU,INRIA and Massachusetts building dataset, and the benchmarks, BOMSC-Net, CVNet, SCA-Net, SPCL-Net, ACMFNet, MFCF-Net models are selected for comparison with the 3DJA-UNet3+ model proposed in this paper. The experimental results show that 3DJA-UNet3+ achieves competitive results in three evaluation indicators: overall accuracy, mean intersection over union, and F1-score. The code will be available at https://github.com/EnjiLi/3DJA-UNet3Plus. [ABSTRACT FROM AUTHOR]

Dielectric microspheres naturally possess unique optical properties by which the light's focus and confinement can be manipulated on a microscale. Combining microspheres and optical or Raman microscopy, super‐resolution imaging beyond the diffraction limit and enhancement of Raman signals are demonstrated to provide abundant spectroscopic information on materials. However, microsphere‐aided super‐resolution scanning photocurrent imaging remains challenging to date. Here, based on the photonic nanojet mechanism, a super‐resolution photocurrent and spectral microscopy equipped with a scanning tip with silica dielectric microspheres are presented. With such microsphere‐aided microscopy, order of magnitude enhancements for single‐point Raman and photoluminescence signals can be achieved, and the spatial resolutions for photocurrent and spectral mapping surpass the best resolution of the original confocal system restricted by the diffraction limit. This versatile system enables correlative super‐resolution spectral and photocurrent imaging, serving as a reliable tool for comprehensively understanding and uncovering the optoelectronic properties of materials. [ABSTRACT FROM AUTHOR]

The informativeness and discriminativeness of features collaboratively ensure high-accuracy Facial Expression Recognition (FER) in the wild. Most of existing methods use the single-path deep convolutional neural network with softmax loss for basic FER, while they cannot deal with the challenging situations of the compound FER in the wild, because they fail to learn informative and discriminative features in a targeted manner. To this end, we present an Informative and Discriminative Feature Learning (IDFL) framework that consists of two key components: the Multi-Path Attention Convolutional Neural Network (MPACNN) and Balanced Separate loss (BS loss), for both basic and compound high-accuracy FER in the wild. Specifically, MPACNN leverages different paths to learn diverse features. These features are then adaptively fused into informative ones via an attention module, such that the model can adequately capture detailed information for both basic and compound FER. The BS loss maximizes the inter-class distance of features and minimizes the intra-class one. In this way, the features are discriminative enough for high-accuracy FER in the wild. Particularly, the BS loss is invoked as the objective function of MPACNN, so the model can learn informative and discriminative features at the same time, yielding better performance. Seven databases are utilized to evaluate the proposed method, and the results demonstrate that our method achieves state-of-the-art performance on both basic and compound expressions with good generalization ability. Moreover, our model contains fewer parameters and can be trained faster than other related models. [ABSTRACT FROM AUTHOR]

Facial Expression Recognition (FER) is a long-standing but challenging research problem in computer vision. Existing approaches mainly focus on single-label emotional prediction, which cannot handle the complex multi-label FER task because of the coupling behavior of multiple emotions on a single facial image. To this end, in this paper, we propose a novel Self-supervised Exclusive-Inclusive Interactive Learning (SEIIL) method to facilitate discriminative multi-label FER in the wild, which can effectively handle the coupled multiple sentiments with limited unconstrained training data. Specifically, we construct an emotion disentangling module to capture the inclusive and exclusive characteristics of facial expressions, which can decouple the compound numerous emotions on an image. Moreover, an adaptively-weighted ensemble technique is conceived to aggregate category-level latent exclusive embeddings, and then a conditional adversarial interactive learning module is designed to fully leverage the complementary between the inclusive and formulated latent representations. Furthermore, to tackle the insufficient data for training, we introduce a self-supervised learning strategy to augment the amount and diversity of facial images, which can endow the model with advanced generalization ability. Under this strategy, the proposed two modules can be concurrently utilized in our SEIIL to jointly handle the coupled emotions and alleviate the overfitting problem. Extensive experimental results on six databases illustrate the superb performance of our method against state-of-the-art baselines. [ABSTRACT FROM AUTHOR]

It is essential to guarantee product quality by detecting defects in industrial printed labels. Defect detection based on reference comparison is a common method to achieve this task. However, this method yields poor performance under large deformations of printed labels, due to the lack of accurate registration ability between testing images and reference images. Therefore, it is an urgent task to achieve accurate image registration for printed label defect detection. In this paper, a coarse-to-fine end-to-end registration network, named APPR-Net, is proposed to deal with the large deformation. First, we adopt a strategy of image patch splitting and stitching to improve the scalability of image resolution. Second, we design a four-stream affine transformation module followed by a multi-scale pyramid registration network, where a coarse registration is obtained by the former module and then gradually refined by the later network in a coarse-to-fine manner. Third, we introduce a distortion loss function to constrain the text distortion of the warped image after image registration. Finally, to simulate printed labels with defects and large deformation, we build a synthetic database based on real-world industrial printed labels for performance comparison. The results demonstrate that the proposed APPR-Net significantly outperforms other compared methods. • Propose a coarse-to-fine registration network to deal with large deformation. • Take advantages of image patch splitting and stitching strategy. • Design a four-stream affine transformation module followed by a pyramid network. • Introduce a distortion loss function to constrain text distortions. • Build a synthetic database based on real-world printed labels. [ABSTRACT FROM AUTHOR]

Currently, the planting of 'Qi-Nan' is continuously increasing, yet a substantial amount of 'Qi-Nan' leaves have not been properly exploited. To improve the 'Qi-Nan' tree 's utilization value, 'Qi-Nan' leaves were used as a raw material. An ultrasound-assisted method was performed to obtain the flavonoids from the 'Qi-Nan' leaves, followed by optimization of the extraction factors using a one-way and response surface methodology to enhance the extraction of flavonoids. Subsequently, the composition of the flavonoids, as well as their bioactive abilities, were analyzed by ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS) and in vitro activity testing methods. The findings demonstrated that a 1:50 material-to-liquid ratio, 60% ethanol concentration, and ultrasound-assisted extraction time of 30 min were the ideal procedures for extracting flavonoids (flavonoid content: 6.68%). Meanwhile, the 'Qi-Nan' leaves possessed the antioxidant and medicinal potential to prevent diabetes and Alzheimer 's disease, as evidenced by the semi-inhibitory concentrations (IC50 values) of flavonoid extracts for scavenging DPPH• free radicals, scavenging ABTS•+ free radicals, inhibiting acetylcholinesterase, and inhibiting α-glucosidase, which were 12.64 μg/mL, 66.58 μg/mL, 102.31 μg/mL, and 38.76 μg/mL, respectively, which indicated that the 'Qi-Nan' leaves possessed the properties of antioxidant and medicinal potential for the prevention of Alzheimer 's disease and diabetes. [ABSTRACT FROM AUTHOR]

β-Catenin is a unique intracellular protein functioning as an integral component of the cell-cell adherens complex and a principal signaling protein mediating canonical Wnt signaling. Little is known about its function in adult kidneys in the normal physiologic state or after acute kidney injury (AKI). To study this, we generated conditional knockout mice in which the β-catenin gene was specifically disrupted in renal tubules (Ksp-β-cat−/−). These mice were phenotypically normal with no appreciable defects in kidney morphology and function. In the absence of β-catenin, γ-catenin functionally substituted for it in E-cadherin binding, thereby sustaining the integrity of epithelial adherens junctions in the kidneys. In AKI induced by ischemia reperfusion or folic acid, the loss of tubular β-catenin substantially aggravated renal lesions. Compared with controls, Ksp-β-cat−/− mice displayed higher mortality, elevated serum creatinine, and more severe morphologic injury. Consistently, apoptosis was more prevalent in kidneys of the knockout mice, which was accompanied by increased expression of p53 and Bax, and decreased phosphorylated Akt and survivin. In vitro activation of β-catenin by Wnt1 or stabilization of β-catenin protected tubular epithelial cells from apoptosis, activated Akt, induced survivin, and repressed p53 and Bax expression. Hence, endogenous β-catenin is pivotal for renal tubular protection after AKI by promoting cell survival through multiple mechanisms. [ABSTRACT FROM AUTHOR]

During renal fibrogenesis, tubular epithelial-mesenchymal transition is closely associated with peritubular inflammation; however, it is not clear whether these two processes are connected. We previously identified the inhibitor of differentiation-1 (Id1), a dominant negative antagonist of basic helix-loop-helix transcription factors, as a major trigger of tubular cell dedifferentiation after injury. Id1 was induced selectively in degenerated proximal tubule and collecting duct epithelia after injury and was present in both the cytoplasm and nucleus, suggesting shuttling between these two compartments. Interestingly, the upregulation of Id1 was associated with peritubular inflammation in mouse and human nephropathies. In vitro, Id1 potentiated NF-κB signaling and augmented RANTES expression in kidney epithelial cells, which led to an enhanced recruitment of inflammatory cells. Id1 also induced Snail1 expression and triggered tubular epithelial dedifferentiation. In vivo, genetic ablation of Id1 in mice reduced peritubular inflammation and decreased tubular expression of RANTES following ureteral obstruction. Mice lacking Id1 were also protected against myofibroblast activation and matrix expression, leading to a reduced total collagen deposition in obstructive nephropathy. Thus, these results indicate that Id1 shuttles between nucleus and cytoplasm, and promotes peritubular inflammation and tubular epithelial dedifferentiation, suggesting that these two events are intrinsically coupled during renal fibrogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Based on heat and mass transport mechanism of film type cooling, which was combined with an on-site test on counter flow film type cooling tower, a mathematical model on the evaporation and cooling efficiency and effectiveness has been developed. Under typical climatic conditions, air conditioning load and the operating condition, the mass and heat balances have been calculated for the air and the cooling water including the volume of evaporative cooling water. Changing rule has been measured and calculated between coefficient of performance (COP) and chiller load. The influences of air and cooling water parameters on the evaporative cooling efficiency were analyzed in cooling tower restrained by latent heat evaporative cooling, and detailed derivation and computation revealed that both the evaporative cooling efficiency and effectiveness of cooling tower are the same characteristics parameters of the thermal performance of a cooling tower under identical assumptions. [ABSTRACT FROM AUTHOR]

Abstract: A state-owned glass production enterprise introduces the strategic investor to carry on the assets reorganization, including the purchase of two float glass production lines with subsequent technology transformations and the construction of a new float glass production line with domestic leading technology. The fuel consumption structure has changed from coal-burning to natural gas or fuel oil. The following auditing procedures were followed according to Chinese national standards. These procedures include constituting an ordinance on energy management, strengthening the energy measurement and data statistical system, and improving production lines as well as energy-saving measures. Production scale expanded approximately twice during the period of audit. Comprehensive energy consumption was 2.58ton coal equivalent (tce) at aqual in heat value (AHV refers to energy consumed to generate each kWh of electric power, each m3 of oxygen, nitrogen, hydrogen, or each kg of steam. The term of AHV provides a unification measurement criterion for fossil fuels consumed before the energy transformation.) account per 10,000 Yuan output value, and 2.17tce at heat value equivalent (HVE) account. Comprehensive energy consumption per unit of product was 15.35kg coal equivalent (kce) per weight box. The percentage of energy cost among total cost reduced from 51.19% in 2007 to 46.48% in 2008. Consequently, the comprehensive energy conversion level holds a leading position among peers in China. [Copyright &y& Elsevier]

Abstract: Vitamin D, especially its most active metabolite 1,25-dihydroxyvitamin D3 or calcitriol, is essential in regulating a wide variety of biologic processes, such as calcium homeostasis, immune modulation, cell proliferation and differentiation. Clinical studies show that the circulating level of calcitriol is substantially reduced in patients with chronic renal insufficiency. Administration of active Vitamin D results in significant amelioration of renal dysfunction and fibrotic lesions in various experimental models of chronic kidney diseases. Active Vitamin D elicits its renal protective activity through multiple mechanisms, such as inhibiting renal inflammation, regulating renin–angiotensin system and blocking mesangial cell activation. Recent studies indicate that calcitriol induces anti-fibrotic hepatocyte growth factor expression, which in turn blocks the myofibroblastic activation and matrix production in interstitial fibroblasts. Furthermore, in vivo and in vitro studies demonstrate that active Vitamin D effectively blocks tubular epithelial to mesenchymal transition (EMT), a phenotypic conversion process that plays a central role in the evolution of renal interstitial fibrosis. Together, it is becoming increasingly clear that a high level of active Vitamin D may be obligatory in the maintenance of normal kidney structure and function. Thus, supplementation of active Vitamin D could be a rational strategy for the therapeutics of chronic kidney diseases. [Copyright &y& Elsevier]

Under pathologic conditions, renal tubular epithelial cells can undergo epithelial to mesenchymal transition (EMT), a phenotypic conversion that is believed to play a critical role in renal interstitial fibrogenesis. However, the underlying mechanism that governs this process remains largely unknown. Here we demonstrate that integrin-linked kinase (ILK) plays an important role in mediating tubular EMT induced by TGF-beta1. TGF-beta1 induced ILK expression in renal tubular epithelial cells in a time- and dose-dependent manner, which was dependent on intracellular Smad signaling. Forced expression of ILK in human kidney proximal tubular epithelial cells suppressed E-cadherin expression and induced fibronectin expression and its extracellular assembly. ILK also induced MMP-2 expression and promoted cell migration and invasion in Matrigel. Conversely, ectopic expression of a dominant-negative, kinase-dead form of ILK largely abrogated TGF-beta1-initiated tubular cell phenotypic conversion. In vivo, ILK was markedly induced in renal tubular epithelia in mouse models of chronic renal diseases, and such induction was spatially and temporally correlated with tubular EMT. Moreover, inhibition of ILK expression by HGF was associated with blockade of tubular EMT and attenuation of renal fibrosis. These findings suggest that ILK is a critical mediator for tubular EMT and likely plays a crucial role in the pathogenesis of chronic renal fibrosis. [ABSTRACT FROM AUTHOR]

MAE100P polymer particles in aqueous media may have a core–shell structure with a hydrophilic shell and a hydrophobic core. The MAE100P films prepared from aqueous dispersions had greater tensile strengths compared to the films cast from organic solutions. The crosslinking of ionic aggregates or the hydrogen-bonding at the particles' interface may be the primarily mechanism of film formation and likely dominate the physicochemical properties of films. The ionization of surface carboxylic-acid groups alters film properties by changing the amount of ionic aggregates and thereby changing film characteristics. [Display omitted] Generally, an organic-solvent-based film is denser and tougher than a corresponding aqueous-dispersion-based film. However, Kollicoat® MAE100P films prepared from aqueous dispersions had greater tensile strengths compared to the films cast from organic solutions. It was proposed that MAE100P polymer particles in aqueous media had a core–shell structure with a hydrophilic shell and a hydrophobic core. The hydrophilic shell was rich in ionized methacrylic acid (MAA) groups and the hydrophobic core primarily contained unionized MAA and ethyl acrylate (EA). As a result, ionized MAA formed a continuous phase which worked as a rigid frame and greatly improved the mechanical properties of aqueous-dispersion-based films. In order to prove this theory and investigate the effect of ionization level on this polymer system, the properties of pH, turbidity, zeta potential, and particle size of MAE100P dispersions were measured as a function of ionization level. The tensile strengths and thermal and mechanical properties of MAE100P films prepared from organic solution or aqueous dispersions of different ionization levels were investigated as well. FTIR was used to characterize the polymer films. Drug release in 0.1 N HCl from coated pellets was studied using the basket method. The experimental results showed that the original MAE100P polymer particles (if not specified, the ionization level is 6%) had a highly-charged surface. The properties of polymer aqueous dispersions were significantly changed by the ionization levels. Aqueous-dispersion-based MAE100P films or coats were stronger and comparable to or somewhat more effective in inhibiting drug diffusion than were organic-solvent-based coats. The tensile strength initially increased and then decreased with an increase of ionization level, while the water-uptake rate by the films continuously increased. Two endothermic peaks were observed in the DSC thermograms for cured MAE100P films. The high-T g endothermic peak increased with an increase in ionization level, while the low-T g peak didn't exhibit significant change except for the 18% ionization film. In the dynamic mechanical analysis, two relaxations in the storage modulus were observed in the aqueous-dispersion-based films. These data may suggest a two-phase structure in the form of a core–shell structure. The tensile-strength ratio for aqueous-dispersion–based films over organic-solvent-based films for MAE100P was close to that reported for films formed from polymer substances/particles with core–shell structures. In summary, the core–shell structure might result in a two-phase structure in the bulk MAE100P film prepared from aqueous dispersion. This special structure led to significantly-improved mechanical properties for aqueous-dispersion-based MAE100 films. The ionization levels had complicated effects on the polymer system by increasing the amount of ionic aggregates while also solubilizing the polymer and changing the mechanism of film formation. [ABSTRACT FROM AUTHOR]

Multi-modal emotion recognition in conversation is challenging because of the difficulty to jointly leverage the information from heterogeneous text, acoustic, and visual modalities. Recent context-aware methods usually design a graph structure to model dependencies of utterances and speakers, or integrate Multi-modal information. However, they typically lack a sufficient extraction of unimodal context, and rarely explore the emotion consensus prototypes among different samples with the same label. For solving these problems, in this paper, we propose a Graph Context extraction and Consensus-aware Learning (GCCL) framework to excavate context-sensitive fusion features and simulate the emotion evocation process during the emotion consensus learning. Specifically, GCCL contains a well-designed graph-based module to capture speaker, temporal and modality dependencies and integrate information from different modalities. Then, we design an emotion consensus learning unit to mine the most typical feature of each category in each modality. A speaker-guided contrastive learning loss is further proposed to guarantee the diversity between different individuals and the semantic consistency between distinct modalities. Moreover, we construct a consensus-aware unit with an attention-based memory mechanism to preserve semantic correlations among different samples on the category-level. Extensive experimental results on two conversational datasets demonstrate that the proposed GCCL outperforms the state-of-art methods. Code is available at https://github.com/gityider/GCCL. [ABSTRACT FROM AUTHOR]

Automated multi-label chest X-ray (CXR) image classification has recently made significant progress in clinical diagnosis based on the advanced deep learning techniques. However, most existing methods mainly focus on analyzing locality visual cues from a single image but fail to leverage the underlying explicit correlations among different images for precise disease diagnosis. By contrast, an experienced radiologist expertizes in transferring knowledge from previous tasks to diagnose the present radiograph. To enable the machine like a radiologist, this paper proposes a novel Semantic Similarity Graph Embedding (SSGE) framework, which explicitly explores the semantic similarities among images to optimize the visual feature embedding for improving the performance of multi-label CXR images classification. Specifically, the proposed SSGE framework contains three main components: the image feature embedding (IFE) module, similarity graph construction (SGC) module, and semantic similarity learning (SSL) module. To realize interactive teaching and learning between visual and semantic information, the proposed SSGE framework is built on the “Teacher-Student” (semantic-visual) learning mechanism. With the guidance and supervision of the cross-image similarity graph generated by the SGC module, the SSL module leverages Graph Convolutional Network (GCN) to adaptively recalibrate the multi-image feature representations extracted from the IFE module, which guarantees their semantic consistency. Furthermore, we propose a novel re-weighting strategy to learn a more optimal semantic-similarity graph for the information propagation of the GCN layers. Extensive experiments on two benchmark datasets demonstrate the effectiveness of the proposed method in comparison with some state-of-the-art baselines. [ABSTRACT FROM AUTHOR]

Stone matrix asphalt and asphalt concrete mixture with 13.2 mm nominal maximum aggregate size (named SMA13 and AC13, respectively) are widely used in the surface course of asphalt pavement in China. Generally, the pavement performance of SMA13 is superior to that of AC13, while the cost of the former is significantly higher than that of the latter. The objective of this paper was to develop a new hot mix asphalt (named SMAC13) whose performance and cost are between SMA13 and AC13. A boundary sieve size (BSS) of 2.36 mm was selected between fine and coarse aggregates. Based on the union set of aggregate gradation ranges of SMA13 and AC13, the family of gradation curves in the forms of S shapes were designed in terms of the BSS passing rate. According to the evaluation of the skeleton interlock of coarse aggregate of the gradation curve family, the aggregate gradation range of SMAC13 was determined. Also, the performance of three kinds of asphalt mixtures were compared through laboratory tests. The results indicated that SMA13 shows the best rutting resistance, followed by SMAC13 then AC13, while in terms of low-temperature performance in resistance to cracking, the sequence is SMAC13, AC13, and SMA13. The sequence of water stability is AC13, SMAC13, and SMA13. Furthermore, the cost of SMAC13 is 25% less than that of SMA13. Therefore, SMAC13 can be used as an alternative for the surface course of asphalt pavement in terms of performance and cost. [ABSTRACT FROM AUTHOR]

This paper focuses on the input-to-state stability for a general class of stochastic multi-group models with multi-dispersal. By incorporating graph theory with Lyapunov method as well as stochastic analysis techniques, novel sufficient criteria are derived, which are in the form of Lyapunov-type theorem and coefficient-type criterion, respectively. Moreover, to show the applicability of our findings, we employ coefficient-type criterion to analyze the input-to-state stability for stochastic coupled oscillators. Finally, a numerical example and its simulations are offered to demonstrate the validity and feasibility of the theoretic results. [ABSTRACT FROM PUBLISHER]

Continuous innovation in artificially-induced agarwood technology is increasing the amount of agarwood and substantially alleviating shortages. Agarwood is widely utilized in perfumes and fragrances; however, it is unclear whether the overall pharmacological activity of induced agarwood can replace wild agarwood for medicinal use. In this study, the volatile components, total chromone content, and the differences in the overall activities of wild agarwood and induced agarwood, including the antioxidant, anti-acetylcholinesterase, and anti-glucosidase activity were all determined. The results indicated that both induced and wild agarwood's chemical makeup contains sesquiterpenes and 2-(2-phenylethyl)chromones. The total chromone content in generated agarwood can reach 82.96% of that in wild agarwood. Induced agarwood scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals and inhibited acetylcholinesterase activity and α-glucosidase activity with IC50 values of 0.1873 mg/mL, 0.0602 mg/mL, 0.0493 mg/mL, and 0.2119 mg/mL, respectively, reaching 80.89%, 93.52%, 93.52%, and 69.47% of that of wild agarwood, respectively. Accordingly, the results distinguished that induced agarwood has the potential to replace wild agarwood in future for use in medicine because it has a similar chemical makeup to wild agarwood and has comparable antioxidant, anti-acetylcholinesterase, and anti-glucosidase capabilities. [ABSTRACT FROM AUTHOR]

The impairment in endothelial progenitor cell (EPC) functions results in dysregulation of vascular homeostasis and dysfunction of the endothelium under diabetic conditions. Improving EPC function has been considered as a promising strategy for ameliorating diabetic vascular complications. Liraglutide has been widely used as a therapeutic agent for diabetes. However, the effects and mechanisms of liraglutide on EPC dysfunction remain unclear. The capability of liraglutide in promoting blood perfusion and angiogenesis under diabetic conditions was evaluated in the hind limb ischemia model of diabetic mice. The effect of liraglutide on the angiogenic function of EPC was evaluated by cell scratch recovery assay, tube formation assay, and nitric oxide production. RNA sequencing was performed to assess the underlying mechanisms. Liraglutide enhanced blood perfusion and angiogenesis in the ischemic hindlimb of db/db mice and streptozotocin-induced type 1 diabetic mice. Additionally, liraglutide improved tube formation, cell migration, and nitric oxide production of high glucose (HG)-treated EPC. Assessment of liraglutide target pathways revealed a network of genes involved in antioxidant activity. Further mechanism study showed that liraglutide decreased the production of reactive oxygen species and increased the activity of nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 deficiency attenuated the beneficial effects of liraglutide on improving EPC function and promoting ischemic angiogenesis under diabetic conditions. Moreover, liraglutide activates Nrf2 through an AKT/GSK3β/Fyn pathway, and inhibiting this pathway abolished liraglutide-induced Nrf2 activation and EPC function improvement. Overall, these results suggest that Liraglutide represents therapeutic potential in promoting EPC function and ameliorating ischemic angiogenesis under diabetic conditions, and these beneficial effects relied on Nrf2 activation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Corrosion-resistant, easy-to-clean and reusable stainless steel microfluidic chip was successfully applied to prepare nanocrystals. • The mixing performance of three microfluidic chips was simulated by computational fluid dynamics (CFD) software. • Two different sizes of nanocrystals were prepared by the stainless steel chip, and their oral bioavailability was compared. Microfluidic technology has not been extensively utilized in nanocrystals manufacture, although it has been used in the production of liposomes and LNPs. This is mainly due to concerns including blockage of narrow pipes and corrosion of organic solvents on chips. In this study, a detachable stainless steel microfluidic chip with split-and-recombine (SAR) structure was engraved and used to prepare curcumin nanocrystal suspensions by a microfluidic-antisolvent precipitation method. A simulation study of the mixing activities of three chip structures was conducted by COMSOL Multiphysics software. Then the curcumin nanocrystals preparation was optimized by Box-Behnken design to screen different stabilizers and solvents. Two curcumin nanocrystals formulations with an average particle size of 59.29 nm and 168.40 nm were obtained with PDIs of 0.131 and 0.058, respectively. Compared to curcumin powder, the formulation showed an increase in dissolution rate in 0.1 M HCL while pharmacokinetic study indicated that C max was increased by 4.47 and 3.14 times and AUC 0-∞ were 4.26 and 3.14 times greater. No clogging or deformation of the chip was observed after long usage. The results demonstrate that the stainless steel microfluidic chips with SAR structure have excellent robustness and controllability. It has the potential to be applied in GMP manufacturing of nanocrystals. [ABSTRACT FROM AUTHOR]

Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction. Reperfusion itself paradoxically leads to further cardiomyocyte death and systolic dysfunction. Ischemia/reperfusion (I/R) injury can eliminate the benefits of reperfusion therapy in patients and causes secondary myocardial injury. Mitochondrial dysfunction and structural disorder are the basic driving force of I/R injury. We summarized the basic relationship and potential mechanisms of mitochondrial injury in the development of I/R injury. Subsequently, this review summarized the natural products (NPs) that have been proven to targeting mitochondrial therapeutic effects during I/R injury in recent years and related cellular signal transduction pathways. We found that these NPs mainly protected the structural integrity of mitochondria and improve dysfunction, such as reducing mitochondrial division and fusion abnormalities, improving mitochondrial Ca2+ overload and inhibiting reactive oxygen species overproduction, thereby playing a role in protecting cardiomyocytes during I/R injury. This data would deepen the understanding of I/R-induced mitochondrial pathological process and suggested that NPs are expected to be transformed into potential therapies targeting mitochondria. [Display omitted] • Mitochondrial reactive oxygen species have emerged as an important mechanism of myocardial ischemia/reperfusion injury. • In ischemia/reperfusion-induced cardiac injury, natural products can target mitochondria to exert cardioprotection. • Natural products are potential therapies to protect mitochondria against ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Background In most patients, acute kidney injury (AKI) represents the combined effects of ischemic, toxic and inflammatory insults. No effective pharmacologic interventions have been developed to prevent AKI or to improve outcomes to date. Cyclosporine A (CsA) is a calcineurin inhibitor that mediates T-cell receptor signaling, suppresses inflammatory cytokine expression and inhibits leukocyte migration. It is also a potent inhibitor of mitochondrial permeability, protecting cells from death. These properties make it a potentially valuable drug to prevent or treat AKI. It does, however, carry a significant risk of nephrotoxicity, especially with chronic use. By contrast, a single dose of CsA may be protective while limiting the risk of nephrotoxicity. Methods We conducted a controlled animal experiment in male CD-1 mice. Specifically, mice were subjected to folic acid (FA)-induced AKI and then randomly assigned to sham operation or one of three dosage of CsA treatment groups. Results Intraperitoneal injection of FA consistently induced AKI. Serum interleukin (IL)-6 and urinary neutrophil gelatinase-associated lipocalin (NGAL) rose 1 day after FA injection. Compared to sham treatment, one dose (1 and 5 mg/kg body weight) of CsA significantly reduced kidney tubular cell apoptosis, serum creatinine, blood urea, serum IL-6 and urinary NGAL 2 days after FA injection. It was also shown to block the inflammatory mediator tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) expression, nuclear factor kappa-B (NFκB) activation, inflammatory cell infiltration and interstitial fibrosis 14 days after treatment in a dose-dependent fashion. By contrast, a dose of 10 mg/kg body weight CsA resulted in nephrotoxicity in the setting of FA-induced AKI. Conclusions A single dose of CsA, currently used for organ transplant, significantly protects mice from FA-induced AKI, presumably through inhibition of cell death, inflammatory reaction, interstitial cell infiltration and fibrosis. The protective effects have the potential to open a completely new line of investigation in the prevention and treatment of AKI. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β1 (TGF-β1) upregulation occurs in virtually all chronic kidney diseases and is associated with podocyte injury and proteinuria; however, the mechanisms contributing to this in vivo are ambiguous. In vitro, incubation of podocytes with TGF-β1 induced Wnt1 expression, β-catenin activation, and stimulated the expression of Wnt/β-catenin downstream target genes. Ectopic expression of Wnt1 or β-catenin mimicked TGF-β1, induced Snail1, and suppressed nephrin expression. The Wnt antagonist, Dickkopf-1, blocked TGF-β1-induced β-catenin activation, Snail1 induction, and nephrin suppression. In vivo, ectopic expression of TGF-β1 induced Wnt1 expression, activated β-catenin, and upregulated Wnt target genes such as Snail1, MMP-7, MMP-9, desmin, Fsp1, and PAI-1 in mouse glomeruli, leading to podocyte injury and albuminuria. Consistently, concomitant expression of Dickkopf-1 gene abolished β-catenin activation, inhibited TGF-β1-triggered Wnt target gene expression, and mitigated albuminuria. Thus, canonical Wnt/β-catenin signaling mediates TGF-β1-driven podocyte injury and proteinuria. These studies suggest that Wnt/β-catenin signaling may be exploited as a therapeutic target for the treatment of proteinuric kidney diseases. [ABSTRACT FROM AUTHOR]

• Fungi extracted from wild agarwood can improve the yield and quality of agarwood. • Four fungi are the species found novel as inoculant for agarwood formation. • The best time to harvest agarwood when the trees inoculated with fungi for one year. • A. sinensis is more suitable for the fungal inducer than A. crassna. Agarwood has high economic value and wide uses, however, the amount of wild agarwood is scarce. Wild agarwood with high oil content may contain strains associated with agarwood production. To improve the formation of agarwood, we produced fungal inducers from a high-oil wild agarwood block containing enrichment fungi. We investigated the composition of strains and inoculated the fungal inducers into Aquilaria trees. We analyzed the content of alcohol-soluble extract, essential oil, agarotetraol, 2-(2-phenylethyl)chromone, 6,7-dimethoxy-2-(2-phenylethyl)chromone and total chromone, and the chemical components of alcohol-soluble extract. We aimed to assess agarwood quality through these evaluations. The results demonstrated that fungi extracted from wild agarwood with high oil content can effectively improve the yield and quality of agarwood, and Gongronella butleri , Saitozyma podzolica , Cladorrhinum bulbillosum , Humicola grisea and Tetracladium marchalianum were the species found novel as inoculant for agarwood formation. After 12 months of inoculation, agarwood produced using A. sinensis had higher quality, the contents of alcohol-soluble extract, essential oil, total chromones, and the total relative contents of sesquiterpenes and chromones were 21.73 % ±2.97 %, 6.07 % ±0.47 %, 12.30 % ±2.21 %, and 97.59 %, respectively. Over 6–18 months of inoculation, agarotetrol content decreased, and 2-(2-phenylethyl) chromone and 6,7-dimethoxy-2-(2-phenylethyl)chromone content first increased and then decreased. [ABSTRACT FROM AUTHOR]

The main stem oil constituents include elemicin (39.9%), methyl eugenol (14.3%), benzaldehyde (12.0%), cinnamaldehyde, and ( I E i )-(8.9%) and ( I Z i )-methyl isoeugenol (6.1%), see Table 1. The main components are elemicin and methyl eugenol [[4]]. [Extracted from the article]

The object of this study is the wood of Phoebe bournei (Hemsl.) Yang. Firstly, the macroscopic and microscopic structural characteristics of P. bournei wood were studied, and then the wood was compared with other species of the same genus. Through GC-MS technology, the volatile substance composition of P. bournei wood was studied, and the common volatile substance compositions were analyzed by using correlation analysis, principal component analysis (PCA), and orthogonal partial least square discriminant model analysis (OPLS-DA) models. The purpose of this study was to determine the significantly different components of P. bournei wood in comparison to three similar species in the same genus and explore whether these can be used as a chemical pattern recognition method for this wood. The results showed that 11 common components were found in all the P. bournei wood samples. Through the correlation analysis between the samples of P. bournei from different sources, they had a strong interrelation and high correlation coefficient. P. bournei wood could be initially distinguished from the wood of the other three similar species of the same genus by PCA. Through OPLS-DA modeling and calculation the classification effect of the model was more obvious. The variable information used to analyze the experimental model was more complete, and the model had a strong prediction ability. With the combination of the load diagram (S-plot) and variable contribution index (VIP), variable components were preliminarily screened, and then inter-group t-test and variable content analysis were conducted for the samples. The results show that the OPLS-DA model analysis of valerianol and agarspirol has obvious differences, which can be used to distinguish wood of P. bournei from three other tree species of the same genus. [ABSTRACT FROM AUTHOR]

Agarwood is a dark resinous wood, of high quality and in a short period, can be formed after inoculation with the efficient fungus in Aquilaria sinensis. However, the action site and mechanism of the fungus inducing the agarwood formation remain unclear. In this work, the efficient fungal infection was used to induce agarwood formation on A. sinensis , and samples were collected according to inoculation time. Subsequently, the xylem structure, histochemistry, defense enzyme activities, and the accumulation and in-situ distribution of chemical composition were investigated. The transition layer (TL) was the critical layer for the continuous accumulation of agarwood, and began to appear in the injection of fungal inducers for 15 days (15D). The parenchyma cells of the xylem rays and interxylary phloem were the main action site of fungus in the formation and accumulation of agarwood. The sesquiterpenes and 2-(2-phenylethyl) chromones (PECs) were mainly accumulated in the agarwood layer (AL) and decay layer (DL), while their relative contents were highest in the injection of fungal inducers for 30 days and 180 days (30D and 180D), respectively. Among them, PECs appeared earlier than sesquiterpenes, and both were flindersia-type PECs. They were mainly concentrated in the cell corners and intercellular layer of the cell wall. In addition, Redundancy analysis (RDA) and Mantel test revealed that the different layer percentage (DLP), phenylalanine ammonia lyase (PAL), and starch grains (SG) were the drivers of PECs, and catalase (CAT) was the driver of sesquiterpenes. Therefore, this study will provide a theoretical foundation for revealing the mechanism of fungus-induced agarwood formation and inducing high-quality and high-yielding agarwood in the future. • The transition layer (TL) was the critical layer for the continuous accumulation of agarwood, and began to appear in 15D. • The parenchyma cells of the xylem rays and interxylary phloem were the action site of fungus in the agarwood formation. • The 2-(2-phenylethyl) chromones (PECs) and sesquiterpenes mainly concentrated in the cell corners and intercellular layer. • The different layer percentage, PAL and starch grains were the drivers of PECs, and CAT was the driver of sesquiterpenes. [ABSTRACT FROM AUTHOR]

β-Catenin is a unique intracellular protein functioning as an integral component of the cell-cell adherens complex and a principal signaling protein mediating canonical Wnt signaling. Little is known about its function in adult kidneys in the normal physiologic state or after acute kidney injury (AKI). To study this, we generated conditional knockout mice in which the β-catenin gene was specifically disrupted in renal tubules (Ksp-β-cat-/-). These mice were phenotypically normal with no appreciable defects in kidney morphology and function. In the absence of β-catenin, γ-catenin functionally substituted for it in E-cadherin binding, thereby sustaining the integrity of epithelial adherens junctions in the kidneys. In AKI induced by ischemia reperfusion or folic acid, the loss of tubular β-catenin substantially aggravated renal lesions. Compared with controls, Ksp-β-cat-/- mice displayed higher mortality, elevated serum creatinine, and more severe morphologic injury. Consistently, apoptosis was more prevalent in kidneys of the knockout mice, which was accompanied by increased expression of p53 and Bax, and decreased phosphorylated Akt and survivin. In vitro activation of β-catenin by Wnt1 or stabilization of β-catenin protected tubular epithelial cells from apoptosis, activated Akt, induced survivin, and repressed p53 and Bax expression. Hence, endogenous β-catenin is pivotal for renal tubular protection after AKI by promoting cell survival through multiple mechanisms. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β1 (TGF-β1) upregulation occurs in virtually all chronic kidney diseases and is associated with podocyte injury and proteinuria; however, the mechanisms contributing to this in vivo are ambiguous. In vitro, incubation of podocytes with TGF-β1 induced Wnt1 expression, β-catenin activation, and stimulated the expression of Wnt/β-catenin downstream target genes. Ectopic expression of Wnt1 or β-catenin mimicked TGF-β1, induced Snail1, and suppressed nephrin expression. The Wnt antagonist, Dickkopf-1, blocked TGF-β1-induced β-catenin activation, Snail1 induction, and nephrin suppression. In vivo, ectopic expression of TGF-β1 induced Wnt1 expression, activated β-catenin, and upregulated Wnt target genes such as Snail1, MMP-7, MMP-9, desmin, Fsp1, and PAI-1 in mouse glomeruli, leading to podocyte injury and albuminuria. Consistently, concomitant expression of Dickkopf-1 gene abolished β-catenin activation, inhibited TGF-β1-triggered Wnt target gene expression, and mitigated albuminuria. Thus, canonical Wnt/β-catenin signaling mediates TGF-β1-driven podocyte injury and proteinuria. These studies suggest that Wnt/β-catenin signaling may be exploited as a therapeutic target for the treatment of proteinuric kidney diseases. [ABSTRACT FROM AUTHOR]

Proteinuria is a primary clinical symptom of a large number of glomerular diseases that progress to end-stage renal failure. Podocyte dysfunctions play a fundamental role in defective glomerular filtration in many common forms of proteinuric kidney disorders. Since binding of these cells to the basement membrane is mediated by integrins, we determined the role of integrin-linked kinase (ILK) in podocyte dysfunction and proteinuria. ILK expression was induced in mouse podocytes by various injurious stimuli known to cause proteinuria including TGF-beta1, adriamycin, puromycin, and high ambient glucose. Podocyte ILK was also found to be upregulated in human proteinuric glomerular diseases. Ectopic expression of ILK in podocytes decreased levels of the epithelial markers nephrin and ZO-1, induced mesenchymal markers such as desmin, fibronectin, matrix metalloproteinase-9 (MMP-9), and alpha-smooth muscle actin (alpha-SMA), promoted cell migration, and increased the paracellular albumin flux across podocyte monolayers. ILK also induced Snail, a key transcription factor mediating epithelial-mesenchymal transition (EMT). Blockade of ILK activity with a highly selective small molecule inhibitor reduced Snail induction and preserved podocyte phenotypes following TGF-beta1 or adriamycin stimulation. In vivo, this ILK inhibitor ameliorated albuminuria, repressed glomerular induction of MMP-9 and alpha-SMA, and preserved nephrin expression in murine adriamycin nephropathy. Our results show that upregulation of ILK is a convergent pathway leading to podocyte EMT, migration, and dysfunction. ILK may be an attractive target for therapeutic intervention of proteinuric kidney diseases. [ABSTRACT FROM AUTHOR]

Tissue-type plasminogen activator (tPA) is one of the major components in the matrix proteolytic network whose role in the pathogenesis of renal interstitial fibrosis remains largely unknown. Here, we demonstrate that ablation of tPA attenuated renal interstitial fibrotic lesions in obstructive nephropathy. Mice lacking tPA developed less morphological injury and displayed a reduced deposition of interstitial collagen III and fibronectin as well as total tissue collagen in the kidneys after sustained ureteral obstruction, when compared with their wild-type counterparts. Deficiency of tPA selectively blocked tubular epithelial-to-myofibroblast transition (EMT), but did not affect myofibroblastic activation from interstitial fibroblasts. A marked decrease in matrix metalloproteinase-9 (MMP-9) induction was found in the obstructed kidneys of tPA(-/-) mice, which led to a dramatic preservation of the structural and functional integrity of tubular basement membrane (TBM). In vitro, tPA induced MMP-9 gene expression and protein secretion in renal interstitial fibroblasts. Thus, increased tPA is detrimental in renal interstitial fibrogenesis through a cascade of events that lead to MMP-9 induction, TBM destruction, and promotion of EMT. Our findings establish a crucial and definite importance of EMT in the pathogenesis of renal interstitial fibrosis at the whole-animal level. [ABSTRACT FROM AUTHOR]

Transcription of SARS-CoV-2 mRNA requires sequential reactions facilitated by the replication and transcription complex (RTC). Here, we present a structural snapshot of SARS-CoV-2 RTC as it transitions toward cap structure synthesis. We determine the atomic cryo-EM structure of an extended RTC assembled by nsp7-nsp8 2 -nsp12-nsp13 2 -RNA and a single RNA-binding protein, nsp9. Nsp9 binds tightly to nsp12 (RdRp) NiRAN, allowing nsp9 N terminus inserting into the catalytic center of nsp12 NiRAN, which then inhibits activity. We also show that nsp12 NiRAN possesses guanylyltransferase activity, catalyzing the formation of cap core structure (GpppA). The orientation of nsp13 that anchors the 5′ extension of template RNA shows a remarkable conformational shift, resulting in zinc finger 3 of its ZBD inserting into a minor groove of paired template-primer RNA. These results reason an intermediate state of RTC toward mRNA synthesis, pave a way to understand the RTC architecture, and provide a target for antiviral development. • Structure of SARS-CoV-2 elongation complex with nsp9 has been determined • Nsp9 binds to the catalytic center of the nsp12 (RdRp) NiRAN domain • The nsp12 NiRAN domain catalyzes the formation of the cap core structure (GpppA) • The structure reveals an intermediate state for RTC in cap synthesis Yan et al. present a cryo-EM structure of the SARS-CoV-2 replication and transcription complex that includes the single RNA-binding protein nsp9. The structural snapshot provides insight into how the viral machinery catalyzes a crucial step in viral mRNA cap synthesis, which is important for virus survival. [ABSTRACT FROM AUTHOR]