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ObjectiveCopy number changes at Chromosomal 16p13.11 have been implicated in a variety of human diseases including congenital cardiac abnormalities. The clinical correlation of copy number variants (CNVs) in this region with developmental abnormalities remains controversial as most of the patients inherit the duplication from an unaffected parent.MethodsWe performed CNV analysis on 164 patients with defective left-right (LR) patterning based on whole genome-exome sequencing (WG-ES) followed by multiplex ligation-dependent probe amplification (MLPA) validation. Most cases were accompanied with complex congenital heart disease (CHD).ResultsCNVs at 16p13.11 were identified in a total of 21 cases, accounting for 12.80% (21/164) evaluated cases. We observed a marked overrepresentation of chromosome 16p13.11 duplications in cases when compared with healthy controls according to literature reports (15/164, 9.14% versus 0.09% in controls). Notably, in two independent family trios, de novo 16p13.11 micro-duplications were identified in two patients with laterality defects and CHD. Moreover, 16p13.11 micro-duplication was segregated with the disease in a family trio containing 2 affected individuals. Notably, five coding genes, NOMO1, PKD1P3, NPIPA1, PDXDC1, and NTAN1, were potentially affected by micro-CNV at 16p13.11 in these patients.ConclusionOur study provides new family-trio based evidences to support 16p13.11 micro-duplications predispose individuals to defective cardiac left-right patterning and laterality disorder.

Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though the precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors in the chronic social defeat stress (CSDS) model of depression. This study investigated whether the spleen contributes to the antidepressant-like effects of arketamine in the CSDS model. We found that splenectomy significantly inhibited arketamine's antidepressant-like effects in CSDS-susceptible mice. RNA-sequencing analysis identified the oxidative phosphorylation (OXPHOS) pathway in the prefrontal cortex (PFC) as a key mediator of splenectomy's impact on arketamine's effects. Furthermore, oligomycin A, an inhibitor of the OXPHOS pathway, reversed the suppressive effects of splenectomy on arketamine's antidepressant-like effects. Specific genes within the OXPHOS pathways, such as COX11, UQCR11 and ATP5e, may contribute to these inhibitory effects. Notably, transforming growth factor (TGF)-β1, along with COX11, appears to modulate the suppressive effects of splenectomy and contribute to arketamine's antidepressant-like effects. Additionally, SRI-01138, an agonist of the TGF-β1 receptor, alleviated the inhibitory effects of splenectomy on arketamine's antidepressant-like effects. Subdiaphragmatic vagotomy also counteracted the inhibitory effects of splenectomy on arketamine's antidepressant-like effects in CSDS-susceptible mice. These findings suggest that the OXPHOS pathway and TGF-β1 in the PFC play significant roles in the antidepressant-like effects of arketamine, mediated through the spleen-brain axis via the vagus nerve.

Abstract To assess the ameliorative effect of ursodeoxycholic acid (UDCA) on hydrogen peroxide (H2O2)-induced hepatocyte injury. In our in vivo experiments, we modelled hyperlipidemia in ApoE−/− mice subjected to a 3-month high-fat diet and found that HE staining of the liver showed severe liver injury and excessive H2O2 was detected in the serum. We modelled oxidative stress injury in L02 cells by H2O2 in vitro and analyzed the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and related genes. UDCA significantly improved the level of oxidative stress in H2O2-injured L02 cells (P

Thyroid-stimulating hormone (TSH) is a pituitary hormone that stimulates the thyroid gland to produce and release thyroid hormones, primarily thyroxine and triiodothyronine. These hormones are key players in body–brain communication, influencing various physiological processes, including the regulation of metabolism (both peripheral and central effects), feedback mechanisms, and lipid metabolism. Recently, the increasing incidence of abnormal lipid metabolism has highlighted the link between thyroid function and lipid metabolism. Evidence suggests that TSH can affect all bodily systems through body–brain communication, playing a crucial role in growth, development, and the regulation of various physiological systems. Lipids serve dual purposes: they are involved in energy storage and metabolism, and they act as vital signaling molecules in numerous cellular activities, maintaining overall human health or contributing to various diseases. This article reviews the role of TSH in regulating lipid metabolism via body–brain crosstalk, focusing on its implications for common lipid metabolism disorders such as obesity, atherosclerosis, nonalcoholic fatty liver disease, neuropsychiatric disorders (including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and depression), and cerebrovascular disorders such as stroke.

With the development and advancements of modern industry, the application of enhanced tubes is becoming more and more extensive in various engineering domains and technological applications. When water is used as the working fluid for thermal energy utilization, there is a large chance of accumulating a large amount of fouling on the surface of the enhanced tubes. This paper establishes a mathematical model of the local fouling deposition of calcium carbonate in enhanced tubes. The model is used to simulate and compare the local fouling characteristics of CaCO3 in different tubes. In addition, a study is conducted on the effects of different inlet flow rates, water temperature, and calcium carbonate concentrations on the local fouling resistance of bellows tubes. The results showed that the local fouling resistance (average) and local fouling resistance of enhanced tubes is smaller than that of circular tubes. Additionally, the bellows tubes yielded the best scale inhibition effect. The obtained local fouling resistance is also found to change periodically along the length of the tube. The local fouling resistance decrease with an increase in the inlet flow rate and wall temperature, and increases with an increase in the calcium carbonate solution concentration.

Abstract The development of atherosclerosis (AS) is closely linked to changes in the plaque microenvironment, which consists primarily of the cells that form plaque and the associated factors they secrete. The onset of inflammation, lipid deposition, and various pathological changes in cellular metabolism that accompany the plaque microenvironment will promote the development of AS. Numerous studies have shown that oxidative stress is an important condition that promotes AS. The accumulation of reactive oxygen species (ROS) is oxidative stress’s most important pathological change. In turn, the effects of ROS on the plaque microenvironment are complex and varied, and these effects are ultimately reflected in the promotion or inhibition of AS. This article reviews the effects of ROS on the microenvironment of atherosclerotic plaques and their impact on disease progression over the past five years and focuses on the progress of treatment strategies based on scavenging ROS of nanoparticles for AS. Finally, we also discuss the prospects and challenges of AS treatment.

Background: Environmental concerns about petroleum-based plastic packaging materials and the growing demand for food have inspired researchers and the food industry to develop food packaging with better food preservation and biodegradability. Nanocomposites consisting of nanofillers, and synthetic/biopolymers can be applied to improve the physiochemical and antimicrobial properties and sustainability of food packaging. Scope and approach: This review summarized the recent advances in nanofiller and their applications in improved food packaging systems (e.g., nanoclay, carbon nanotubes), active food packaging (e.g., silver nanoparticles (Ag NPs), zinc oxide nanoparticles (ZnO NPs)), intelligent food packaging, and degradable packaging (e.g., titanium dioxide nanoparticles (e.g., TiO2 NPs)). Additionally, the migration processes and related assessment methods for nanofillers were considered, as well as the use of nanofillers to reduce migration. The potential cytotoxicity and ecotoxicity of nanofillers were also reviewed. Key findings: The incorporation of nanofillers may increase Young’s modulus (YM) while decreasing the elongation at break (EAB) (y = −1.55x + 1.38, R2 = 0.128, r = −0.358, p = 0.018) and decreasing the water vapor (WVP) and oxygen permeability (OP) (y = 0.30x − 0.57, R2 = 0.039, r = 0.197, p = 0.065). Meanwhile, the addition of metal-based NPs could also extend the shelf-life of food products by lowering lipid oxidation by an average of approx. 350.74% and weight loss by approx. 28.39% during the longest storage period, and significantly increasing antibacterial efficacy against S. aureus compared to the neat polymer films (p = 0.034). Moreover, the migration process of nanofillers may be negligible but still requires further research. Additionally, the ecotoxicity of nanofillers is unclear, as the final distribution of nanocomposites in the environment is unknown. Conclusions: Nanotechnology helps to overcome the challenges associated with traditional packaging materials. Strong regulatory frameworks and safety standards are needed to ensure the appropriate use of nanocomposites. There is also a need to explore how to realize the economic and technical requirements for large-scale implementation of nanocomposite technologies.

The utilization of bismuth as a sensing material for the detection of heavy metal ions has gained significant attention due to its exceptional interfacial activity and selective absorption properties. However, it also poses challenges in terms of agglomeration and its inferior electrical conductivity during the synthesis process. This paper employed a facile in situ synthesis and electrodeposition approach to uniformly grow a bismuth film on a conductive carbon cloth, designated as Bi/Ag@CC. The Bi/Ag@CC electrode material exhibited benign electrochemical properties, enabling its application for detecting Pb2+ in tap water and lake water samples. Furthermore, this work investigated the impact of electrochemical parameters, including electrolyte pH, deposition potential and pre-enrichment time, on the detection performance. The results demonstrated the sensor’s wide linear range (from 20 to 400 ppb) and detection limits (0.15 ppb) for heavy metal ion detection, along with excellent anti-interference capabilities and satisfactory repeatability, with an RSD of less than 2.31% (n = 6). This paper offers a novel strategy for positioning the bismuth-based composite as a promising candidate for practical electrochemical sensing applications.

The integration of advanced sensor technologies has significantly propelled the dynamic development of robotics, thus inaugurating a new era in automation and artificial intelligence. Given the rapid advancements in robotics technology, its core area—robot control technology—has attracted increasing attention. Notably, sensors and sensor fusion technologies, which are considered essential for enhancing robot control technologies, have been widely and successfully applied in the field of robotics. Therefore, the integration of sensors and sensor fusion techniques with robot control technologies, which enables adaptation to various tasks in new situations, is emerging as a promising approach. This review seeks to delineate how sensors and sensor fusion technologies are combined with robot control technologies. It presents nine types of sensors used in robot control, discusses representative control methods, and summarizes their applications across various domains. Finally, this survey discusses existing challenges and potential future directions.

Nucleoporins (NUPs) constitute integral nuclear pore protein (NPC) elements. Although traditional NUP functions have been extensively researched, evidence of additional vital non-NPC roles, referred to herein as non-classical NUP functions, is also emerging. Several NUPs localise at the ciliary base. Indeed, Nup188, Nup93 or Nup205 knockdown results in cilia loss, impacting cardiac left–right patterning in models and cell lines. Genetic variants of Nup205 and Nup188 have been identified in patients with congenital heart disease and situs inversus totalis or heterotaxy, a prevalent human ciliopathy. These findings link non-classical NUP functions to human diseases. This mini-review summarises pivotal NUP interactions with NIMA-related kinases or nephronophthisis proteins that regulate ciliary function and explores other NUPs potentially implicated in cilia-related disorders. Overall, elucidating the non-classical roles of NUPs will enhance comprehension of ciliopathy aetiology.

Abstract In this study, we identified that a conserved circular RNA (circRNA) DICAR, which was downregulated in diabetic mouse hearts. DICAR had an inhibitory effect on diabetic cardiomyopathy (DCM), as the spontaneous cardiac dysfunction, cardiac cell hypertrophy, and cardiac fibrosis occurred in DICAR deficiency (DICAR +/− ) mice, whereas the DCM was alleviated in DICAR-overexpressed DICAR Tg mice. At the cellular level, we found that overexpression of DICAR inhibited, but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis. At the molecular level, we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects. The synthesized DICAR junction part (DICAR-JP) exhibited a similar effect to the entire DICAR. In addition, the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls, which was consistent with the decreased DICAR expression in diabetic hearts. DICAR and the synthesized DICAR-JP may be drug candidates for DCM.

Hepatic fibrosis is an important pathological manifestation of chronic schistosome infection. Patients with advanced schistosomiasis show varying degrees of abnormalities in liver fibrosis indicators and bilirubin metabolism. However, the relationship between hepatic fibrosis in schistosomiasis and dysregulated bilirubin metabolism remains unclear. In this study, we observed a positive correlation between total bilirubin levels and the levels of ALT, AST, LN, and CIV in patients with advanced schistosomiasis. Additionally, we established mouse models at different time points following S. japonicum infection. As the infection time increased, liver fibrosis escalated, while liver UGT1A1 consistently exhibited a low expression, indicating impaired glucuronidation of bilirubin metabolism in mice. In vitro experiments suggested that SEA may be a key inhibitor of hepatic UGT1A1 expression after schistosome infection. Furthermore, a high concentration of bilirubin activated the NF-κB signaling pathway in L-O2 cells in vitro. These findings suggested that the dysregulated glucuronidation of bilirubin caused by S. japonicum infection may play a significant role in schistosomiasis liver fibrosis through the NF-κB signaling pathway.

Outer membrane vesicles (OMVs) are spherical, nano-sized particles of bilayer lipid structure secreted by Gram-negative bacteria. They contain a series of cargos from bacteria and are important messengers for communication between bacteria and their environment. OMVs play multiple roles in bacterial survival and adaptation and can affect host physiological functions and disease development by acting on host cell membranes and altering host cell signaling pathways. This paper summarizes the mechanisms of OMV genesis and the multiple roles of OMVs in the tumor microenvironment. Also, this paper discusses the prospects of OMVs for a wide range of applications in drug delivery, tumor diagnosis, and therapy.

Myeloid RNA regulator of Bim-induced death (Morrbid) is a newly identified leukocyte-specific long noncoding RNA (lncRNA). However, the expression and biological functions of Morrbid in cardiomyocytes and heart disease are currently unclear. This study was meant to determine the role of cardiac Morrbid in acute myocardial infarction (AMI) and to identify the potential cellular and molecular mechanisms involved. We found that both human and mouse cardiomyocytes could express a significant amount of Morrbid and that its expression was increased in cardiomyocytes with hypoxia or oxidative stress as well as in mouse hearts with AMI. Overexpression of Morrbid reduced the myocardial infarct size and cardiac dysfunction, whereas the infarct size and cardiac dysfunction deteriorated in cardiomyocyte-specific Morrbid-KO (Morrbidfl/fl/Myh6-Cre) mice. We identified that Morrbid had a protective effect against hypoxia- or H2O2-induced apoptosis; this was also confirmed in vivo in mouse hearts after AMI. We further discovered that serpine1 was a direct target gene of Morrbid that was involved in the Morrbid-mediated protective effect on cardiomyocytes. In summary, we have found, for the first time to our knowledge, that the cardiac Morrbid is a stress-enhanced lncRNA that protects hearts from AMI via antiapoptosis through its target gene serpine1. Morrbid may be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Abstract Background Abnormalities in cilia ultrastructure and function lead to a range of human phenotypes termed ciliopathies. Many tetratricopeptide repeat domain (TTC) family members have been reported to play critical roles in cilium organization and function. Results Here, we describe five unrelated family trios with multisystem ciliopathy syndromes, including situs abnormality, complex congenital heart disease, nephronophthisis or neonatal cholestasis. Through whole-exome sequencing and Sanger sequencing confirmation, we identified compound heterozygous mutations of TTC12 and TTC21B in six affected individuals of Chinese origin. These nonsynonymous mutations affected highly conserved residues and were consistently predicted to be pathogenic. Furthermore, ex vivo cDNA amplification demonstrated that homozygous c.1464 + 2 T > C of TTC12 would cause a whole exon 16 skipping. Both mRNA and protein levels of TTC12 were significantly downregulated in the cells derived from the patient carrying TTC12 mutation c.1464 + 2 T > C by real-time qPCR and immunofluorescence assays when compared with two healthy controls. Transmission electron microscopy analysis further identified ultrastructural defects of the inner dynein arms in this patient. Finally, the effect of TTC12 deficiency on cardiac LR patterning was recapitulated by employing a morpholino-mediated knockdown of ttc12 in zebrafish. Conclusions To the best of our knowledge, this is the first study reporting the association between TTC12 variants and ciliopathies in a Chinese population. In addition to nephronophthisis and laterality defects, our findings demonstrated that TTC21B should also be considered a candidate gene for biliary ciliopathy, such as TTC26, which further expands the phenotypic spectrum of TTC21B deficiency in humans.

Abstract As an important component of the immunosuppressive tumor microenvironment (TME), it has been established that mesenchymal stem cells (MSCs) promote the progression of tumor cells. MSCs can directly promote the proliferation, migration, and invasion of tumor cells via cytokines and chemokines, as well as promote tumor progression by regulating the functions of anti-tumor immune and immunosuppressive cells. MSCs-derived extracellular vesicles (MSCs-EVs) contain part of the plasma membrane and signaling factors from MSCs; therefore, they display similar effects on tumors in the immunosuppressive TME. The tumor-promoting role of macrophage migration inhibitory factor (MIF) in the immunosuppressive TME has also been revealed. Interestingly, MIF exerts similar effects to those of MSCs in the immunosuppressive TME. In this review, we summarized the main effects and related mechanisms of tumor-associated MSCs (TA-MSCs), TA-MSCs-EVs, and MIF on tumors, and described their relationships. On this basis, we hypothesized that TA-MSCs-EVs, the MIF axis, and TA-MSCs form a positive feedback loop with tumor cells, influencing the occurrence and development of tumors. The functions of these three factors in the TME may undergo dynamic changes with tumor growth and continuously affect tumor development. This provides a new idea for the targeted treatment of tumors with EVs carrying MIF inhibitors.

The autonomous shipping industry is increasingly focusing on enhancing the safety and reliability of software-based systems. Conducting a risk assessment is a requirement for demonstrating the safety equivalence of autonomous ships based on such systems to conventional vessels. Traditional risk assessment models, however, primarily focus on hardware failures, often overlooking potential software-related failures and functional inadequacies. This study proposes a framework integrating Software Failure Mode and Effects Analysis (FMEA), System–Theoretic Process Analysis (STPA), and Bayesian Network (BN) for risk identification of autonomous ship software systems. The results of a case study reveal that the framework sufficiently addresses the multifaceted nature of risks related to software in autonomous ships. Based on the findings of this study, we suggest the need for standardization of software architecture development in the autonomous ship industry and highlight the necessity for an enhanced understanding of AI-specific risks and the development of tailored risk assessment methodologies.

In view of the time-consuming and laborious manual picking and sorting of strawberries, the direct impact of image recognition accuracy on automatic picking and the rapid development of deep learning(DL), a Faster Regions with Convolutional Neural Network features (R-CNN) strawberry recognition method that combines Mixup data augmentation, a ResNet(Residual Network)50 backbone feature extraction network and a Soft-NMS (Non-Maximum Suppression) algorithm, named the MRS Faster R-CNN, is proposed. In this paper, the transfer learning backbone feature extraction network VGG (Visual Geometry Group) 16 and ResNet50 are compared, and the superior ResNet50 is selected as the backbone network of MRS Faster R-CNN. The data augmentation method of Mixup image fusion is used to improve the learning and generalization ability of the model. The redundant bboxes (bounding boxes) are removed through Soft-NMS to obtain the best region proposal. The freezing phase is added to the training process, effectively reducing the occupation of video memory and shortening the training time. After experimental verification, the optimized model improved the AP (Average Precision) values of mature and immature strawberries by 0.26% and 5.34%, respectively, and the P(Precision) values by 0.81% and 6.34%, respectively, compared to the original model (R Faster R-CNN). Therefore, the MRS Faster R-CNN model proposed in this paper has great potential in the field of strawberry recognition and maturity classification and improves the recognition rate of small fruit and overlapping occluded fruit, thus providing an excellent solution for mechanized picking and sorting.

Abstract Background Bio-entity Coreference Resolution (CR) is a vital task in biomedical text mining. An important issue in CR is the differential representation of identical mentions as their similar representations may make the coreference more puzzling. However, when extracting features, existing neural network-based models may bring additional noise to the distinction of identical mentions since they tend to get similar or even identical feature representations. Methods We propose a context-aware feature attention model to distinguish similar or identical text units effectively for better resolving coreference. The new model can represent the identical mentions based on different contexts by adaptively exploiting features, which enables the model reduce the text noise and capture the semantic information effectively. Results The experimental results show that the proposed model brings significant improvements on most of the baseline for coreference resolution and mention detection on the BioNLP dataset and CRAFT-CR dataset. The empirical studies further demonstrate its superior performance on the differential representation and coreferential link of identical mentions. Conclusions Identical mentions impose difficulties on the current methods of Bio-entity coreference resolution. Thus, we propose the context-aware feature attention model to better distinguish identical mentions and achieve superior performance on both coreference resolution and mention detection, which will further improve the performance of the downstream tasks.

In the inflammatory microenvironment, there are numerous exosomes secreted by immune cells (Macrophages, neutrophils, dendritic cells), mesenchymal stem cells (MSCs) and platelets as intercellular communicators, which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors. Due to their good biocompatibility, accurate targeting, low toxicity and immunogenicity, these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors. Therefore, the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention. Here we review current knowledge and techniques for exosome identification, isolation, modification and drug loading. More importantly, we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis (RA), osteoarthritis (OA), atherosclerosis (AS), and inflammatory bowel disease (IBD). Finally, we also discuss their potential and challenges as anti-inflammatory drug carriers.

Aiming at the problem that the back module of the existing nursing bed chair is difficult to realize the mutual change between the postures of the nursing bed and wheelchair，a new type of back plate mechanism is proposed. A serial backplane spatial combination mechanism is formed by connecting multiple mechanisms with single function，and its spatial freedom is analyzed to meet the motion demand. The target size is parameterized，and the optimal position of the support connecting rod，backplane and support frame hinge is obtained using the minimum inclusive area method. According to the geometric relationship and statics analysis result of the backplane mechanism，the JC35D electric push rod with rated stroke and working stroke of 175 mm and 230 mm and self-locking force of 1 000 N is used as the driving mechanism. The backplane mechanism of the nursing bed chair is designed according to the optimized parameters and the drive device type，and the overall virtual prototype is assembled by SolidWorks. The simulation finite element analysis plug-in is used to analyze the stress of the backplane under the posture of the nursing bed chair，and the safety and reliability of the structural strength are verified. Under the posture of nursing bed，Adams View software is used to carry out the static rollover simulation test of the mechanism，and the stability requirement of the backplane under the rollover test load is verified.

Abstract Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation. Acox2 knockout (−/−) mice spontaneously developed liver cancer with marked lymphocytic infiltrate. Tandem-affinity purification coupled with mass spectrometry analysis revealed that Acox2 interacted with methylcrotonoyl-CoA carboxylase followed by co-immunoprecipitation confirmation. Here we reported that non-histone lysine crotonylation (Kcr) levels were downregulated in Acox2 −/− mice livers. Interestingly, Kcr signals were concentrated in the nucleus of tumor cells but mostly located in the cytoplasm of adjacent normal liver cells of Acox2 −/− mice. Quantitative analysis of the global crotonylome further revealed that 54% (27/50) of downregulated non-histone Kcr sites were located in mitochondrial (11/50) and peroxisomal (17/50) enzymes including Ehhadh, Scp2, Hsd17b4, Crot, Etfa, Cpt1a, Eci1/2, Hadha, Etfdh, and Idh2. Subsequent site-directed mutagenesis and transcriptome analysis revealed that Ehhadh K572cr might have site-specific regulatory roles by downregulating TOP3B expression that lead to increased DNA damage in vitro. Our findings suggested Acox2 is a regulator of Kcr that might play critical role on hepatic metabolic homeostasis.

Although the deep learning method has achieved some results in the challenging task of repairing the missing areas of images over the years, there is no report on the images disturbed by the laser entering the field of view. We propose a restoration model that can restore the laser interference image, the corresponding countermeasure network deep learning model and a new model training method, and no additional manual marking work is required in the data training set. After a large number of experiments, the loss function can rapidly converge under this method, accurately give the reasonable reconstruction results of the image disturbed by laser, and significantly improve the scores of many common image quality evaluation methods: high-quality repair results are obtained on the laser interference composite dataset of face (CelebA), Stanford automobile, aircraft, buildings (Facade) and satellite images. The model used in paper has the characteristics of fast training speed, strong robustness, modular model design and wide application.

Due to the complexity and uncertainty of decision-making, probabilistic linguistic term sets (PLTSs) are currently important tools for qualitative evaluation of decision-makers. The asymmetry of evaluation information can easily lead to the loss of subjective preference information for decision-makers, and the existing operation of decision-maker evaluation information fusion operators is difficult to solve this problem. To solve such problems, this paper proposes some new operational methods for PLTSs based on Dombi T-conorm and T-norm. Considering the interrelationships between the input independent variables of PLTSs, the probabilistic linguistic weighted Dombi Bonferroni mean Power average (PLWDBMPA) operators are extended and the properties of these aggregation operators are proposed. Secondly, the PLWDBMPA operator is used to fuse the evaluation information of decision-makers, avoiding the loss of decision information as much as possible. This paper uses social media platforms and web crawler technology to obtain online comments from users on decision-making to obtain the public’s attitude towards decision events. TF-IDF and Word2Vec are used to calculate the weight of alternatives on each attribute. Under traditional group decision-making methods and integrating the wisdom of the public, a novel multi-attribute group decision-making method based on TODIM method is proposed. Finally, the case study of Turkey earthquake shelter selection proves this method is scientific and effective. Meanwhile, the superiority of this method was further verified through comparisons with the PL-TOPSIS, PLWA, SPOTIS and PROMETHEE method.

Magnesium alloys, being the lightest structural metals, have garnered significant attention in various fields. The characterization of inelastic behavior has been extensively investigated by researchers due to its impact on structural component performance. However, the occurrence of twinning in the absence of any applied driving force during unloading has lacked reasonable explanations. Moreover, the influence of deformation mechanisms other than twinning on inelastic behavior remains unclear. In this study, uniaxial tension and compression tests were conducted on hot-rolled magnesium alloy plates, and neutron diffraction experiments were employed to characterize the evolution of macroscopic mechanical response and microscopic mechanisms. Additionally, a twinning and detwinning (TDT) model based on the elastic visco-plastic self-consistent (EVPSC) model has been proposed, incorporating back stress to describe the deformation behavior during stress relaxation. This approach provides a comprehensive understanding of the inelastic behavior of magnesium alloys from multiple perspectives and captures the influence of microscale mechanisms. A thorough understanding of the inelastic behavior of magnesium alloys and a reasonable explanation for the occurrence of twinning under zero-stress conditions offer valuable insights for the precise design of magnesium alloy structures.

The hyperbolic problem has a unique entropy solution, which maintains the entropy inequality. As such, people hope that the numerical results should maintain the discrete entropy inequalities accordingly. In view of this, people tend to construct entropy stable (ES) schemes. However, traditional numerical schemes cannot directly maintain discrete entropy inequalities. To address this, we here construct an ES finite difference scheme for the nonlinear hyperbolic systems of conservation laws. The proposed scheme can not only maintain the discrete entropy inequality, but also enjoy high-order accuracy. Firstly, we construct the second-order accurate semi-discrete entropy conservative (EC) schemes and ensure that the schemes meet the entropy identity when an entropy pair is given. Then, the second-order EC schemes are used as a building block to achieve the high-order accurate semi-discrete EC schemes. Thirdly, we add a dissipation term to the above schemes to obtain the high-order ES schemes. The term is based on the Weighted Essentially Non-Oscillatory (WENO) reconstruction. Finally, we integrate the scheme using the third-order Runge–Kutta (RK) approach in time. In the end, plentiful one- and two-dimensional examples are implemented to validate the capability of the scheme. In summary, the current scheme has sharp discontinuity transitions and keeps the genuine high-order accuracy for smooth solutions. Compared to the standard WENO schemes, the current scheme can achieve higher resolution.

In this study, the flavor compounds of Camellia seed oils obtained by four processes were characterized by headspace solid phase microextraction/gas chromatography/mass spectrometry (HS-SPME/GC/MS). A variety of about 76 volatile flavor compounds were identified from all the oil samples. Of the four processing processes, the pressing process can retain a lot of volatile components. Among these, compounds nonanal and 2-undecenal were predominantly in the majority of the samples. Meanwhile, other compounds such as octyl ester formic acid, octanal and 2-nonenal (E), 3-acetyldihydro 2(3H)-furanone, (E)-2-decenal, dihydro-5-penty 2(3H)-furanone, nonanoic acid, and dodecane were also among the most consistently found compounds among the oil samples analyzed. The principal component analysis carried out to categorize the data produced seven clusters of the total oil samples based on the number of flavor compounds obtained in each sample. This categorization would lead to understanding the components which highly contributed to the characteristic volatile flavor and build up the flavor profile of Camellia seed oil.

Micro-credit for poverty alleviation is an important financial measure of targeted poverty reduction and rural revitalization in China. This paper employs the OLS model and Logit model to empirically test the effect of micro-credit for poverty alleviation on the income level and stability of income growth of farmers based on the field survey data of 458 registered poverty-stricken farmer households in Fuping County and Quyang County of Hebei Province. The results suggest that micro-credit for poverty alleviation can increase farmers’ income, stabilize the growth of their income, and exert significant short-term and long-term effects on income growth and poverty alleviation. The specialized farmer cooperatives, the scale of production and operation, the proportion of family labor force, and the education level of the head of the farmer’s household exert a significantly positive effect on the farmers’ income and the stable growth of their income. There is a significant interaction between micro-credit for poverty alleviation and specialized farmer cooperatives. The physical conditions of family members exert a negative effect on the stable growth of their income, and other financing channels have no significant effect.

Abstract Site-directed mutagenesis for large plasmids is a difficult task that cannot easily be solved by the conventional methods used in many laboratories. In this study, we developed an effective method for Site-directed Mutagenesis for Large Plasmids (SMLP) based on a PCR technique. The SMLP method combines several effective approaches, including a high-efficiency DNA polymerase for the large DNA amplification, two independent PCR reactions and a fast recombinational ligation. Using this method, we have achieved a variety of mutants for the filamin A gene (7.9 kb) cloned in the pcDNA (5.4 kb) or the pLV-U6-CMV-EGFP (9.4 kb) plasmids, indicating that this method can be applied to site-directed mutagenesis for the plasmids up to 17.3 kb. We show that the SMLP method has a greater advantage than the conventional methods tested in this study, and this method can be applied to substitution, deletion, and insertion mutations for both large and small plasmids as well as the assembly of three fragments from PCR reactions. Altogether, the SMLP method is simple, effective, and beneficial to the laboratories that require completing the mutagenesis of large plasmids.

Grape cracking is a common phenomenon that can reach more than 50% in some varieties and can cause enormous economic losses. “Li Xiu” grapes in different developmental stages were treated with calcium chloride (5 g/L), and the cracking rate and related biochemical and genetic indices were measured in the fruit ripening stage. The results showed that calcium treatment during the flowering period could significantly reduce grape cracking. Based on the experimental results, there are several reasons as follows: first, calcium spraying during the flowering period was more favorable to calcium absorption in grapes, and the increased calcium content in the peels helped to improve the mechanical properties of the peels, thus increasing crack resistance; second, calcium treatment reduced the expression levels of genes related to glucose metabolism, which in turn reduced PG and cellulase activities, delaying the degradation of pectin and cellulose and resulting in more structural integrity of the peels; third, calcium treatment increased fruit hardness and reduced fruit ventral pressure by decreasing the expression levels of ABA-related genes and synthesis of endogenous abscisic acid (ABA), soluble sugars (SSs), and total soluble solids (TSSs).

Cells experience various osmotic perturbation, but cellular osmosensing mechanisms remain obscure. Here, the authors report that cells recognize osmotic stress from the inside through macromolecular crowding-driven and poly(ADP-ribose)-conditioned liquid–liquid phase separation.

The isolation of proanthocyanidins from raspberries and their antioxidant activity remains an ongoing challenge. Optimization of ultrasound-assisted extraction method of raspberry proanthocyanidins by response surface analysis. Assessment of the effect of AB-8 macroporous adsorption on obtaining proanthocyanidin monomers of different composition and evaluation of their antioxidant activity. Determination of protective effects of proanthocyanidins by cell proliferation assay. Under the optimized extraction conditions of 60% ethanol, material-to-liquid ratio of 1:30, ultrasonic extraction temperature of 44°C, time of 2 h, and power of 450 watts (W), the yield of proanthocyanidins was 0.914%. The four separated proanthocyanidins, D1, D2, D3, D4, showed dose-dependent antioxidant activities, with D2 having the best antioxidant effect. 100 μg/ml of D2 could scavenge above 90% free radicals and achieve above 85% of human cell survival rate. The identified extraction conditions and antioxidant activities may drive the development of potential health-promoting ingredients.

Multi-attribute group decision making is widely used in the real world, and many scholars have done a lot of research on it. The public’s focus on emergencies can provide an important reference for emergency handling decision making in the social media big data environment. Due to the complexity of emergency handling decision making, the asymmetry of user evaluation information is easy to cause the loss of important information. It is very important to mine valuable information for decision making through online reviews. Then, a generalized extended hybrid distance measure method between the probabilistic linguistic term sets is proposed. Based on this, an extended GDMD-PROMETHEE large-scale multi-attribute group decision-making method is proposed as well, which can be used to decision making under symmetric information and asymmetric information. Firstly, web crawler technology is used to explore the topics of public concern of emergency handling on social media platforms, and use k-means cluster analysis to classify the crawling variables, then the attributes and subjective weights of emergency handling plans are obtained by TF-IDF and Word2vec technology. Secondly, in order to better retain the linguistic evaluation information from decision-makers, a new generalized probabilistic hybrid distance measure method based on Hamming distance is proposed. Considering the difference of decision makers’ evaluation, the objective weight of decision makers is calculated by combining the maximum deviation method with the new extended hybrid Euclidean distance. On this basis, the comprehensive weights of the attributes are calculated by combining subjective and objective factors. Meanwhile, this paper realizes the distance measures and information fusion of probabilistic linguistic term sets under cumulative prospect theory, and the ranking results of the emergency handling plans based on the extended GDMD-PROMETHEE algorithm are given. Finally, the feasibility and effectiveness of the extended GDMD-PROMETHEE algorithm are verified by the case study of the explosion accident handling decision making of Shanghai “6.18” Petrochemical, and the comparative analyses between the several traditional algorithms demonstrate the extended GDMD-PROMETHEE algorithm is more scientific and superior in this paper.

It is difficult to collect training samples for all types of synthetic aperture radar (SAR) targets. A realistic problem comes when unseen categories exist that are not included in training and benchmark data at the time of recognition, which is defined as open set recognition (OSR). Without the aid of side-information, generalized OSR methods used on ordinary optical images are usually not suitable for SAR images. In addition, OSR methods that require a large number of samples to participate in training are also not suitable for SAR images with the realistic situation of collection difficulty. In this regard, a task-oriented OSR method for SAR is proposed by distribution construction and relation measures to recognize targets of seen and unseen categories with limited training samples, and without any other simulation information. The method can judge category similarity to explain the unseen category. Distribution construction is realized by the graph convolutional network. The experimental results on the MSTAR dataset show that this method has a good recognition effect for the targets of both seen and unseen categories and excellent interpretation ability for unseen targets. Specifically, while recognition accuracy for seen targets remains above 95%, the recognition accuracy for unseen targets reaches 67% for the three-type classification problem, and 53% for the five-type classification problem.

This paper investigated the effects of different particle sizes and addition levels of purple sweet potato flour (PSPF) on the rheological properties and moisture states of wheat dough. There was deterioration in the pasting and mixing properties of the dough, due to the addition of PSPF (0~20% substitution), which was reduced by decreasing the particle size of the PSPF (260~59 μm). Dynamic rheology results showed that PSPF enhanced the elasticity of the dough, providing it solid-like processability. PSPF promoted the binding of gluten proteins and starch in the dough, resulting in a denser microstructure. Differential scanning calorimetry and low-field nuclear magnetic resonance showed that PSPF converted immobilized water and freezable water to bound water and non-freezable water in the dough, making the dough more stable, and that the reduction in PSPF particle size facilitated these processes. Our results provide evidence for the great application potential of purple sweet potatoes for use in flour-based products.

Abstract Defective left–right (LR) organization involving abnormalities in cilia ultrastructure causes laterality disorders including situs inversus (SI) and heterotaxy (Htx) with the prevalence approximately 1/10,000 births. In this study, we describe two unrelated family trios with abnormal cardiac LR patterning. Through whole-exome sequencing (WES), we identified compound heterozygous mutations (c.805-1G >C; p. Ile269GlnfsTer8/c.1117dupA; p.Thr373AsnfsTer19) (c.29T>C; p.Ile10Thr/c.356A>G; p.His119Arg) of NEK3, encoding a NIMA (never in mitosis A)-related kinase, in two affected individuals, respectively. Protein levels of NEK3 were abrogated in Patient-1 with biallelic loss-of function (LoF) NEK3 mutations that causes premature stop codon. Subsequence transcriptome analysis revealed that NNMT (nicotinamide N-methyltransferase) and SIRT2 (sirtuin2) was upregulated by NEK3 knockdown in human retinal pigment epithelial (RPE) cells in vitro, which associates α-tubulin deacetylation by western blot and immunofluorescence. Transmission electron microscopy (TEM) analysis further identified defective ciliary ultrastructure in Patient-1. Furthermore, inner ring components of nuclear pore complex (NPC) including nucleoporin (NUP)205, NUP188, and NUP155 were significantly downregulated in NEK3-silenced cells. In conclusion, we identified biallelic mutations of NEK3 predispose individual to abnormal cardiac left–right patterning via SIRT2-mediated α-tubulin deacetylation and downregulation of inner ring nucleoporins. Our study suggested that NEK3 could be a candidate gene for human ciliopathies.

Background. MicroRNA-576-5p (miR-576-5p) plays an important role in different human cancers. However, the biological function of miR-576-5p in papillary thyroid carcinoma (PTC) is still unclear. In this study, we explored the function and specific role of miR-576-5p in PTC. Methods. Expression levels of miR-576-5p in PTC patient tissues and cell lines were determined by reverse transcription-quantitative polymerase chain reaction (qRT‒PCR). Cell counting using cell counting kit-8 (CCK-8), wound healing, and Transwell assays were performed to evaluate the effect of miR-576-5p on the proliferation, migration, and invasion of TPC-1 cells. Expression levels of mitogen-activated protein kinase 4 (MAPK4) and phosphorylation levels of protein kinase B (AKT), extracellular regulated protein kinase (ERK), and P38 mitogen-activated protein kinase (P38) were detected by western blotting or immunohistochemistry (IHC). Results. The expression level of miR-576-5p in PTC tissues and TPC-1 cells was significantly increased. In vitro, overexpression of miR-576-5p promoted the proliferation, migration, and invasion of TPC-1 cells. In addition, MAPK4 was highly expressed in PTC tissues, and miR-576-5p could upregulate the expression of MAPK4. Interestingly, MAPK4 knockdown reversed cell proliferation but not migration and invasion in TPC-1 cells after miR-576-5p was overexpressed. Moreover, overexpression of miR-576-5p induced activation of the AKT pathway in TPC-1 cells, and MAPK4 gene knockout reversed this AKT pathway activation. Conclusion. In this study, we found that miR-576-5p was significantly overexpressed in PTC tissues and TPC-1 cells. In addition, miR-576-5p promoted the proliferation of TPC-1 cells by enhancing expression of MAPK4 and activating the AKT pathway.

Abstract Background Seed dormancy is a prevailing condition in which seeds are unable to germinate, even under favorable environmental conditions. Harvested Brassica oleracea (Chinese cabbage) seeds are dormant and normally germinate (poorly) at 21 °C. This study investigated the connections between ethylene, nitric oxide (NO), and karrikin 1 (KAR1) in the dormancy release of secondary dormant Brassica oleracea seeds. Results NO and KAR1 were found to induce seed germination, and stimulated the production of ethylene and 1-aminocyclopropane-1-carboxylic acid (ACC), and both ethylene biosynthesis enzyme ACC oxidase (ACO) [1] and ACC synthase (ACS) [2]. In the presence of NO and KAR1, ACS and ACO activity reached maximum levels after 36 and 48 h, respectively. The inhibitor of ethylene 2,5-norbornadiene (NBD) had an adverse effect on Brassica oleracea seed germination (inhibiting nearly 50% of germination) in the presence of NO and KAR1. The benefits from NO and KAR1 in the germination of secondary dormant Brassica oleracea seeds were also associated with a marked increase in reactive oxygen species (ROS) (H2O2 and O2˙ˉ) and antioxidant enzyme activity at early germination stages. Catalase (CAT) and glutathione reductase (GR) activity increased 2 d and 4 d, respectively, after treatment, while no significant changes were observed in superoxide dismutase (SOD) activity under NO and KAR1 applications. An increase in H2O2 and O2˙ˉ levels were observed during the entire incubation period, which increasing ethylene production in the presence of NO and KAR1. Abscisic acid (ABA) contents decreased and glutathione reductase (GA) contents increased in the presence of NO and KAR1. Gene expression studies were carried out with seven ethylene biosynthesis ACC synthases (ACS) genes, two ethylene receptors (ETR) genes and one ACO gene. Our results provide more evidence for the involvement of ethylene in inducing seed germination in the presence of NO and KAR1. Three out of seven ethylene biosynthesis genes (BOACS7, BOACS9 and BOACS11), two ethylene receptors (BOETR1 and BOETR2) and one ACO gene (BOACO1) were up-regulated in the presence of NO and KAR1. Conclusion Consequently, ACS activity, ACO activity and the expression of different ethylene related genes increased, modified the ROS level, antioxidant enzyme activity, and ethylene biosynthesis pathway and successfully removed (nearly 98%) of the seed dormancy of secondary dormant Brassica olereace seeds after 7 days of NO and KAR1 application.

Having nursery rapeseed (Brassica napus L.) seedlings at a high density in a tray is an indispensable step to realizing mechanized transplanting for rapeseed. The reduction in seedling quality caused by high sowing density is one of the key factors affecting transplanting quality and yield. Uniconazole has been considered as a potential plant growth regulator to improve plant growth under diverse unfavorable circumstances. In two sowing densities (400 and 800 seeds per tray), an experiment was carried out between 2021 and 2022 to investigate the effects of uniconazole seed-coating treatments on pre-transplant and post-transplant seedling characteristics. The results demonstrate that uniconazole treatment can effectively reduce the high-density-induced reduction in seedling dry matter and leaf area, stem thinness, and stem and petiole overgrowth. Further evidence that uniconazole can improve seedling quality, enhance yield, and lessen yield loss due to high-density sowing was provided by yield at maturity. However, because of the uncontrolled growth during the late stage in the tray, the relative growth rate of seedlings after transplant in the transplant shock stage revealed that lower doses of uniconazole treatment have a negative effect on the seedling recovery. The results of principal coordinate analysis and partial correlation analysis proved that the yield and net assimilation rate were related to the improvement of seedling high-density tolerance by uniconazole treatment. Consequently, 500–750 mg L−1 uniconazole coating per 100 g of seeds in 5 mL is recommended by this study, considering the potential risk of seedling emergence and growth caused by an overdose of uniconazole treatment.

High land use efficiency is the key to improving total factor productivity, and also an important force behind achieving sustained economic growth. Existing studies have mainly focused on the land use efficiency of the industry sector. Yet, the issue of land use efficiency of the service sector (SLUE) has been largely overlooked. This study examines regional differences and efficiency decomposition by using a slack based model (SBM) of undesirable output, and the Malmquist productivity index (MPI) under a data envelopment analysis framework. The results reveal that: (1) In China, the land use efficiency of the service sector is unbalanced, showing an inverted growth law of “low in developed areas and high in backward areas”. (2) The land use efficiency of the service sector can be decomposed into technical progress, pure technical efficiency, and scale efficiency. From the decomposition results, the growth rate of pure technical efficiency presents a trend of “low in the east and high in the west”; the scale efficiency also falls into the situation of weak group growth. Technological progress has maintained steady improvement. (3) The coordinated improvement of land use efficiency of the service sector needs to focus on resolving the “beggar-thy-neighbor” issue caused by existing large regional differences. In this article, the puzzle of land use efficiency differences in the service industry is well solved, and thus provides valuable enlightenment for the benign growth of service industries in countries and regions around the world.

Traditional deep learning methods such as convolutional neural networks (CNN) have a high requirement for the number of labeled samples. In some cases, the cost of obtaining labeled samples is too high to obtain enough samples. To solve this problem, few-shot learning (FSL) is used. Currently, typical FSL methods work well on coarse-grained image data, but not as well on fine-grained image classification work, as they cannot properly assess the in-class similarity and inter-class difference of fine-grained images. In this work, an FSL framework based on graph neural network (GNN) is proposed for fine-grained image classification. Particularly, we use the information transmission of GNN to represent subtle differences between different images. Moreover, feature extraction is optimized by the method of meta-learning to improve the classification. The experiments on three datasets (CIFAR-100, CUB, and DOGS) have shown that the proposed method yields better performances. This indicates that the proposed method is a feasible solution for fine-grained image classification with FSL.

Preeclampsia: when cells aren’t invasive enough Cancer-associated proteins play a role in preeclampsia, a potentially life-threatening disorder of pregnancy marked by high blood pressure and protein in the urine. The causes of preeclampsia are poorly understood, but the tissue that nourishes the fetus, the placenta, is known to be involved. Knowing that for healthy placenta formation, cells called trophoblasts must show cancer cell-like behavior and invade the developing tissue, Li-Ping Jin and Kai Wang at Tongji University School of Medicine in Shanghai, China, and co-workers investigated the role of cancer-associated LOX proteins, previously linked to cell invasiveness. Preeclamptic placentas showed low LOX levels, poor trophoblast invasion, and excessive formation of collagen, an important connective tissue. Further analysis showed that this excessive collagen is broken down, becoming the diagnostic urinary protein. These results illuminate potential markers for early diagnosis and treatment of preeclampsia.

Prostate cancer-associated transcript 1 (PCAT-1) is a newly identified long non-coding RNA comprising two exons, located in the Chr8q24 gene desert approximately 725 kb upstream of the MYC oncogene. PCAT-1 is dysregulated and acts as an oncogene in different types of cancers and has been implicated in several processes correlated with carcinogenesis, such as cell proliferation, invasion, metastasis, apoptosis, cell cycle, chemoresistance, and homologous recombination. The mechanisms underlying the effects of PCAT-1 are complex and involve multiple factors and signaling pathways. In this paper, we systematically review the multiple pathological functions of PCAT-1 in diverse malignancies to elucidate its potential molecular mechanisms and to provide new directions for future research.

The traditional intelligent diagnosis methods of rotating machinery generally require feature extraction of the raw signals in advance. However, it is a very time-consuming and laborious process for extracting the sensitive feature information to improve classification performance. Deep learning method, as a novel machine learning approach, can simultaneously achieve feature extraction and pattern classification. With the characteristics of Deep Belief Network (DBN) and one-dimensional Convolutional Neural Network (1D-CNN) (e.g. learning complex nonlinear, sparse connection and weight sharing), a precise diagnosis method based on the combination of DBN and 1D-CNN is proposed. Firstly, the DBN composed of three pre-trained restricted Boltzmann machines (RBMs) is constructed to achieve feature extraction and dimensionality reduction of the high-dimensional raw data. Secondly, the low-dimensional features extracted by DBN are fed into 1D-CNN for further extracting the abstract features. Finally, Soft-max classifier is employed to identify different operating conditions of rotating machinery. The superiority of the proposed method is validated by comparison with several state-of-the art fault diagnosis methods on two experimental cases. Meanwhile, the proposed method is tested in different background noises and on the imbalanced datasets. The results show that it has higher efficiency and accuracy than the state-of-the art fault diagnosis methods.

Different settlements and instabilities of unsaturated subgrade subjected to wetting have been paid increasing attention in the southeast coastal areas of China. However, the treatments are costly when they are used in engineering. In addition, the long-term performances of the treatments are unclear. Based on seepage theory for unsaturated soils, a novel subgrade using a capillary barrier was proposed in this study to reduce the different settlements and stabilities. Compared with previous studies, a capillary barrier was merely applied in the landfill. The long-term performance and feasibility of a capillary barrier applied in a tilted subgrade slope is worthy of study, particularly in humid climates. Using Geo-Studio, the feasibility was verified by comparing a conventional subgrade with a subgrade using a capillary barrier in southeast coastal areas in terms of pore-water pressure, water content, settlement, and the safety factor. The numerical results showed that the subgrade using a capillary barrier could provide significant improvements in the performance of reducing the impact of pore-water pressure distribution it suffered from, so as to lead to smaller different settlements. The vertical settlement of the pavement using a capillary barrier over a 1 year period was 1 cm. Compared with a conventional subgrade, the settlement fell by 94%, and the safely factor increased by 15% for the subgrade using the capillary barrier.

Background: Our previous study revealed aberrant miR-4463 expression in the vascular tissues of patients with arteriosclerosis obliterans of the lower extremities (ASO), but the role of miR-4463 was largely ambiguous. In the current study, we aimed to explore the function of miR-4463 in hypoxia-induced endothelial cells and determine its molecular mechanisms. Methods: CCK-8 assay and flow cytometry were performed to evaluate cell viability and apoptosis. Adenovirus carrying mRFP-GFP-LC3 was employed to monitor cellular autophagy, and mitochondrial membrane potential was determined by JC-1 staining. Moreover, dual-luciferase reporter gene assay, qPCR, western blot and siRNA analysis were carried out to explore the potential molecular mechanisms. Results: Hypoxia significantly elevated the miR-4463 expression in primary human umbilical vein endothelial cells (HUVEC). Overexpression of miR-4463 inhibited hypoxia-induced autophagy by suppressing the formation of autophagosomes and autolysosomes, resulting in reduced cell viability and increased apoptosis, and these effects were reversed by miR-4463 inhibitor. Furthermore, activation of autophagy induced by miR-4463 inhibitor attenuated HUVECs apoptosis in hypoxic conditions. Mechanically, the results of the dual-luciferase reporter gene assay discovered that miR-4463 directly targeted Unc-51 like kinase 1 (ULK1). The silence of ULK1 blocked miR-4463 inhibitor-activated autophagy and further facilitated apoptosis under hypoxic conditions. Conclusions: Our findings indicate that miR-4463 is an essential regulator of hypoxia-induced autophagy and apoptosis in endothelial cells via directly targeting ULK1. Inhibition of miR-4463 might be a potential strategy to protect endothelial cells and maintain vascular function in patients with lower limb ischemia and its complications.

In recent years, Internet of things (IoT) devices are playing an important role in business, education, medical as well as in other fields. Devices connected to the Internet is much more than the number of world population. However, it may face all kinds of attacks from the Internet easily for its accessibility. As we all know, most attacks against IoT devices are based on Web applications. So protecting the security of Web services can effectively improve the situation of IoT ecosystem. Conventional Web attack detection methods highly rely on samples, and artificial intelligence detection results are uninterpretable. Hence, this article introduced a supervised detection algorithm based on benign samples. Seq2Seq algorithm is been chosen and applied to detect malicious web requests. Meanwhile, the attention mechanism is introduced to label the attack payload and highlight labeling abnormal characters. The results of experiments show that on the premise of training a benign sample, the precision of proposed model is 97.02%, and the recall is 97.60%. It explains that the model can detect Web attack requests effectively. Simultaneously, the model can label attack payload visually and make the model “interpretable.”

Background/Aims: Vascular complications are the main reasons for disability and mortality associated with type 2 diabetes mellitus (T2DM) and numerous microRNAs (miRNAs) are involved in this process. Our previous study demonstrated that miR-4463 was increased in the plasma of T2DM patients combined with arteriosclerosis of low extremity artery (ASO). However, the role of miR-4463 remains unclear. Methods: miR-4463 expression in the vascular tissues of patients with ASO and T2DM and in human umbilical vein endothelial cells (HUVECs) was detected by qPCR. Cell survival and apoptosis was analyzed via Cell Counting Kit-8 and flow cytometry assays, respectively. Protein expression was determined by Western blot and protein subcellular localization was detected with immunofluorescence. A dual-luciferase assay was used to elucidate the target gene of miR-4463. Results: miR-4463 was elevated in the vascular tissues of patients with T2DM and ASO. In HUVECs, both 25 mmol/L glucose (high glucose, HG) and hypoxia induced miR-4463 expression. Downregulation of miR-4463 promoted HUVEC survival and reduced cell apoptosis under HG and/or hypoxic conditions by facilitating the expression of protein phosphatase-1 nuclear targeting subunit (PNUTS), X-linked inhibitor of apoptosis protein (XIAP), p-AKT, p-Bad, increased the Bcl-2/Bax ratio, as well as downregulated cleaved caspase 3 expression. Mechanistically, we identified PNUTS as a direct target gene of miR-4463. Both the inhibition of AKT phosphorylation and silencing of PNUTS diminished the effect of miR-4463 on HUVEC apoptosis. Moreover, downregulation of miR-4463 enhanced PNUTS to enable PTEN nuclear localization, which resulted in AKT phosphorylation. Conclusion: Our results suggest that downregulation of miR-4463 attenuates cell apoptosis by directly enhancing PNUTS expression to promote PTEN nuclear localization, subsequently activating AKT signaling pathway in HUVECs under HG and/ or hypoxic conditions.

Background/Aims: Inflammatory response is a determinant in the pathological progression of acute pancreatitis (AP). Previous studies have shown that the activation of hedgehog (Hh) signaling is a remarkable change in caerulein-induced AP. However, the relationship between Hh signaling and inflammation is largely ambiguous. Methods: The AP mouse model was induced by injection of cerulein, and histological staining and serum enzymology assays were used to evaluate the establishment of AP. Western blot assay was used to determine the protein levels, cleavage of apoptotic proteins, and activation of the NF-κB signaling pathway. Cytokine array was used to screen inflammatory cytokines, and target cytokines’ transcriptional expression and serum levels were examined by real-time PCR and enzyme-linked immunosorbent assay, respectively. Results: The key transcriptional factor in Hh signaling, Gli2, was upregulated in the pancreas and other tissues during the process of AP, and it seems to be a characteristic feature of local inflammation in pancreatic tissue and systemic inflammatory response in multiple organs. The inflammatory NF-κB pathway is required for the activation of Hh signaling, as blockade of the NF-κB pathway by pyrrolidine dithiocarbamate impaired the Gli2 upregulation. Manipulation of Gli2 expression altered the activation of the NF-κB pathway correspondingly, as well as the cell apoptosis in cerulein-induced AP. Moreover, Gli2 upregulation changed the cytokine expression profile in mouse pancreatic acinar cells, mainly decreasing the pro-inflammatory cytokines interleukin (IL)-6, interferon-γ, and FasL. The anti-inflammatory cytokine IL-10 was upregulated by Gli2 overexpression. Interdiction of Gli2 by the Gli-specific inhibitor GANT61 exacerbated AP in mice and altered the balance of inflammatory cytokines. Conclusions: This study indicates that Hh activation during AP development is a negative feedback of the inflammatory response, restricting inflammatory injury to the pancreas and other tissues. Thus, manipulation of Hh signaling should shed light on limiting inflammation and alleviating AP damage.

Context: Astaxanthin (ASX), a xanthophyll carotenoid derived from microalgae Haematococcus pluvialis, mitigating skin photoaging and age-related skin diseases by its antioxidant and anti-inflammatory effects in animal studies. Objective: The aim was to systematically evaluate if ASX applications have anti-ageing effects in humans. Methods: A comprehensive search of PubMed, Scopus and Web of Science found a total of eleven studies. Nine randomised, controlled human studies assessed oral ASX effects and two open-label, prospective studies evaluated topical, oral-topical ASX effects on skin ageing. GetData Graph Digitizer was used to extract mean values and standard deviations of baseline and endpoint, and Cochrane Collaboration’s tool assessed RoB for all included studies. Review Manager 5.4 was used to conduct meta-analysis of RCTs; the results were reported as effect size ± 95% confidence interval. Results: Oral ASX supplementation significantly restored moisture content (SMD = 0.53; 95% CI = 0.05, 1.01; I2 = 52%; p = 0.03) and improved elasticity (SMD = 0.77; 95% CI = 0.19, 1.35; I2 = 75%; p = 0.009) but did not significantly decrease wrinkle depth (SMD = −0.26; 95% CI = −0.58, 0.06; I2 = 0%; p = 0.11) compared to placebo. Open-label, prospective studies suggested slightly protective effects of topical and oral-topical ASX applications on skin ageing. Conclusions: Ingestion and/or topical usages of ASX may be effective in reducing skin ageing and have promising cosmetical potential, as it improves moisture content and elasticity and reduces wrinkles.