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The anisotropic hole transport along [0001] and [11 2 ¯ 0] in the p-doped (10 1 ¯ 0) GaN layer was compared for layers grown on bulk (10 1 ¯ 0) GaN substrates and on (10 1 ¯ 0) sapphire. The sheet resistance along [0001] was 1.1 times larger on GaN substrates and even 1.2 times larger on sapphire than that along [11 2 ¯ 0]. The anisotropic hole transport on bulk GaN substrates is due to the anisotropy of the hole's effective mass and the different contribution of carriers in different bands, whereas the larger anisotropy for GaN on sapphire is also due to additional scattering at stacking faults. The annealing process of metal Mg applied to the m-plane p-type GaN successfully results in a robust p-type ohmic contact, functioning as a p + + layer. [ABSTRACT FROM AUTHOR]

Herein, we designed alkylated lysine-dendron oxytocin amphiphiles (ALOAs) 1G-OTK and 2G-OTK, which were self-assembled into spherical nanoparticles and nanostrips, respectively, and showed superior stability compared to native oxytocin. We found similar trends in the functional activity of ALOAs and native OT for human oxytocin receptor. This work may inspire the development of peptide drugs for clinical applications. [ABSTRACT FROM AUTHOR]

Abstract Milk contains bioactive compounds that have multiple essential benefits. Milk-derived small extracellular vesicles (M-sEVs) have emerged as novel bioactive milk components with various beneficial biological functions and broad applications. The M-sEVs from different mammalian sources have similar composition and bioactive functions. The digestive stability and biocompatibility of the M-sEVs provide a good foundation for their physiological functions. Evidence suggests that M-sEVs promote intestinal, immune, bone, neural, liver, and heart health and show therapeutic effects against cancer, indicating their potential for use in functional foods. In addition, M-sEVs can be developed as natural delivery carriers owing to their superior structural characteristics. Further studies are needed to elucidate the relationship between the specific components and functions of M-sEVs, standardize their extraction processes, and refine relevant clinical trials to advance the future applications of M-sEVs. This review summarizes the structure and composition of M-sEVs isolated from different milk sources and discusses several common extraction methods. Since the introduction of M-sEVs for digestion and absorption, studies have been conducted on their biological functions. Furthermore, we outline the theoretical industrial production route, potential application scenarios of M-sEVs, and the future perspectives of M-sEV research. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a chronically progressive fibrotic pulmonary disease characterized by an uncertain etiology, a poor prognosis, and a paucity of efficacious treatment options. Dexmedetomidine (Dex), an anesthetic-sparing alpha-2 adrenoceptor (α2AR) agonist, plays a crucial role in organ injury and fibrosis. However, the underlying mechanisms of IPF remain unknown. Methods: In our study, the role of Dex in murine pulmonary fibrosis models was determined by Dex injection intraperitoneally in vivo. Fibroblast activation and myofibroblast differentiation were assessed after Dex treatment in vitro. The activation of MAPK pathway and the expression of Adenosine A2B receptor (ADORA2B) were examined in lung myofibroblasts. Moreover, the role of ADORA2B in Dex suppressing myofibroblast differentiation and pulmonary fibrosis was determined using the ADORA2B agonist BAY60-6583. Results: The results revealed that Dex could inhibit Bleo-induced pulmonary fibrosis in mice. In vitro studies revealed that Dex suppressed TGF-β-mediated MAPK pathway activation and myofibroblast differentiation. Furthermore, Dex inhibits myofibroblast differentiation and pulmonary fibrosis via downregulating ADORA2B expression. Conclusions: Our findings suggest Dex as a potential therapeutic agent for pulmonary fibrosis. Dex may alleviate lung fibrosis and myofibroblast differentiation through the ADORA2B-mediated MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

MRI is the primary imaging approach for diagnosing prostate cancer. Prostate Imaging Reporting and Data System (PI-RADS) on multiparametric MRI (mpMRI) provides fundamental MRI interpretation guidelines but suffers from inter-reader variability. Deep learning networks show great promise in automatic lesion segmentation and classification, which help to ease the burden on radiologists and reduce inter-reader variability. In this study, we proposed a novel multi-branch network, MiniSegCaps, for prostate cancer segmentation and PI-RADS classification on mpMRI. MiniSeg branch outputted the segmentation in conjunction with PI-RADS prediction, guided by the attention map from the CapsuleNet. CapsuleNet branch exploited the relative spatial information of prostate cancer to anatomical structures, such as the zonal location of the lesion, which also reduced the sample size requirement in training due to its equivariance properties. In addition, a gated recurrent unit (GRU) is adopted to exploit spatial knowledge across slices, improving through-plane consistency. Based on the clinical reports, we established a prostate mpMRI database from 462 patients paired with radiologically estimated annotations. MiniSegCaps was trained and evaluated with fivefold cross-validation. On 93 testing cases, our model achieved a 0.712 dice coefficient on lesion segmentation, 89.18% accuracy, and 92.52% sensitivity on PI-RADS classification (PI-RADS ≥ 4) in patient-level evaluation, significantly outperforming existing methods. In addition, a graphical user interface (GUI) integrated into the clinical workflow can automatically produce diagnosis reports based on the results from MiniSegCaps. [ABSTRACT FROM AUTHOR]

TGFBR2, a key regulator of the TGFβ signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin β5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFβ signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFβ signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies. • Knocking down ITGB5 inhibits TGFβ/Smad-mediated epithelial-mesenchymal transition activity and GC metastasis. • ITGB5 governs the endosomal recycling of TGFBR2 to the cell surface via SNX17-mediated vesicular trafficking, thereby augmenting the activity of the TGFβ-Smad2/3 pathway. • TGFβ induces the upregulation of ITGB5 expression through the phosphorylated Smad2/3 complex binding to the ITGB5 promoter region, establishing a positive feedback loop. [ABSTRACT FROM AUTHOR]

Intermittent bus lanes (IBLs) can improve road capacity by allowing other regular vehicles to drive in the idle space of a dedicated bus lane. However, excessive vehicles in the IBL will cause additional bus delays. To avoid such problems, this study proposes a method to determine the capability of IBL permitted for regular vehicles first, and then use it as the total amount restriction of lane-borrowing vehicles to implement a bus lane control strategy that will improve road capacity and avoid additional bus delays. A model for calculating the capability of IBL is also provided. Vehicles between two buses are designated as potentially lane-borrowing vehicles that could follow the buses to leave the road section. The evolution process of these vehicles in the unit is analyzed using kinematic wave theory to obtain the formed traffic queue length. Using the rear bus trajectory to set the length limit on the traffic queue, the estimated total amount of lane-borrowing vehicles is corrected to establish the final capability of the IBL. The applicability of the method was evaluated from three perspectives: bus departure interval, road traffic saturation, and near-side bus stop. The simulation results showed that the proposed method can guarantee no additional bus delay compared to the situation of a dedicated bus lane. It can also improve road capacity more than traditional IBL under any degree of saturation and bus departure interval. Compared with traditional IBL, the average travel time of regular vehicles is shorter, except when the degree of saturation is high and the bus departure interval is large. [ABSTRACT FROM AUTHOR]

[Display omitted] • Rapid co-deposition of dopamine and APTS was used to construct superhydrophilic membranes. • Superhydrophilic membrane had an effective oil repellency with underwater oil contact angle of ∼163.5°. • Superhydrophilic membrane has a fast gravity-driven filtration for oil-in-water emulsions with a separation efficiency of >99.9 % • Incorporation of Cu NPs and polydopamine enables the membranes with complete antibacterial activity. Substantial discharge of industrial oily wastewater calls for an efficient and sustainable treatment for resource recovery. Superwetting membranes offer a feasible approach to fractionate oil species and water from oily wastewater for addressing this technical challenge. In this study, we proposed a useful strategy for constructing a superhydrophilic membrane with superior antibacterial properties through rapid co-deposition of dopamine and 3-aminopropyltriethoxysilane (APTS) initiated by ammonium persulfate on the Cu nanoparticles-loaded porous PVDF substrate. The resultant superhydrophilic membrane yielded an underwater oil contact angle of 163.5°, enabling a fast and robust gravity-driven filtration for various oil-in-water emulsions with a separation efficiency of >99.9 %. Additionally, incorporating of Cu nanoparticles and polydopamine endowed the superhydrophilic membrane with superior antibacterial activity (100 % inhibition efficiency against Escherichia coli), and thereby remarkably enhancing the anti-biofouling performance. This study provides a viable approach to design high-performance membranes for separation of oil-in-water emulsions, with promising applications in the industrial and environmental sectors. [ABSTRACT FROM AUTHOR]

Purpose: Hydronephrosis is the dilation of the pelvicalyceal system due to the urine flow obstruction in one or both kidneys. Conventionally, renal pelvis anterior–posterior diameter (APD) was used for quantifying hydronephrosis in medical images (e.g., ultrasound, CT, and functional MRI). Our study aimed to automatically detect and quantify the fluid and kidney areas on ultrasonography, using a deep learning approach. Methods: An attention-Unet was used to segment the kidney and the dilated pelvicalyceal system with fluid. The gold standard for diagnosing hydronephrosis was the APD > 1.0 cm. For semi-quantification, we proposed a fluid-to-kidney-area ratio measurement, i.e., renal pelvicalyceal area with fluid kidney area , as a deep learning-derived biomarker. Dice coefficient, confusion matrix, ROC curve, and Z-test were used to evaluate the model performance. Linear regression was applied to obtain the fluid-to-kidney-area ratio cutoff for detecting hydronephrosis. Results: For regional kidney segmentation, the Dice coefficients were 0.92 and 0.83 for the kidney and dilated pelvicalyceal system, respectively. The sensitivity and specificity of detecting dilated pelvicalyceal system were 0.99 and 0.83, respectively. The linear equation was fluid-to-kidney-area ratio = (0.213 ± 0.004) × APD (in cm) for 95% confidence interval on the slope with R2 = 0.87. The fluid-to-kidney-area ratio cutoff for detecting hydronephrosis was 0.213. The sensitivity and specificity for detecting hydronephrosis were 0.90 and 0.80, respectively. Conclusion: Our study confirmed the feasibility of deep learning characterization of the kidney and fluid, showing an automatic pediatric hydronephrosis detection. [ABSTRACT FROM AUTHOR]

A magnetic double-crosslinked nanocomposite hydrogel beads that can be used for water treatment were prepared through the construction of ionic bonds and borate bonds, using sodium alginate, poly(vinyl alcohol) and graphene oxide/ferroferric oxide nanocomposites (GO/Fe3O4) as raw materials. The characterization studies of the prepared hydrogel beads were performed by XRD, FTIR, XPS, SEM, and TGA. The adsorption process was investigated by varying the dye, GO/Fe3O4 contents, pH, adsorbent dosage and initial dye concentration. The highest removal efficiency of cationic dye methylene blue by the prepared hydrogel beads could reach 95.2%. The adsorption kinetics experimental results confirmed that the adsorption of methylene blue on the prepared hydrogel beads was mainly chemisorption, and the intraparticle diffusion was the only rate-controlling. After five cycles of use, the prepared hydrogel beads could still remove >94% of methylene blue in solution. The mechanism analysis based on FTIR and XPS measurements illustrated that the excellent removal efficiency of the hydrogel beads was mainly due to the hydrogen bonding and electrostatic attraction between hydrogel beads and methylene blue molecules. This investigation revealed that a low-cost, high-efficiency, magnetically separable adsorption material has been successfully prepared, which has potential application value for the removal of cationic compounds in wastewater. [ABSTRACT FROM AUTHOR]

Background: Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC).Methods: We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results: No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively.Conclusions: BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis. [ABSTRACT FROM AUTHOR]

An eight weeks feeding trial was conducted to investigate the effects of dietary lipid levels on growth performance, lipid metabolism and immune response of Japanese seabass (Lateolabrax japonicus). Five diets were formulated with gradient dietary lipid levels (79.6, 104.4, 129.1, 154.9 and 178.6 g kg−1). Results revealed that growth and feed utilization of fish were significantly lower in group L178.6 than other groups (p < 0.05). Lipid accumulation in whole body, muscle and intraperitoneal were increased with increasing dietary lipid levels. The mRNA levels of adipose triglyceride lipase, carnitine palmitoyl transferase 1, acetyl CoA carboxylase, cholesterol 7 alpha‐hydroxylase and retinoid X receptor in liver were also increased with increasing dietary lipid levels (p < 0.05). The mRNA levels of apolipoprotein A1 and peroxisome proliferator activating receptor α were higher in fish fed L178.6 than those fed other diets. Oxidative stress in plasma and liver were induced when dietary lipid exceed 154.9 g kg−1. L154.9 and L178.6 significantly increased the inflammatory related gene expression of fish. These results suggested that high‐fat diet impaired the growth performance and induced lipid accumulation, inflammation and apoptosis of Japanese seabass. The suitable dietary lipid level of Japanese seabass may not exceed 129.1 g kg−1. [ABSTRACT FROM AUTHOR]

Human milk is universally regarded as the gold standard to fulfill nutrition needs of infants. Lactoferrin (LF) is a major multiple bioactive glycoprotein in human milk but little is presented in infant formula. LF can resist digestion in the infant gastrointestinal tract and is absorbed into the bloodstream in an intact form to perform physiological functions. Evidence suggest that LF prevents pathogen infection, promotes immune system development, intestinal development, brain development and bone health, as well as ameliorates iron deficiency anemia. However, more clinical studies of LF need to be further elucidated to determine an appropriate dosage for application in infant formula. LF is sensitive to denaturation induced by processing of infant formula such as heat treatments and spay drying. Thus, further studies should be focus on maximizing the retention of LF activity in the infant formula process. This review summarizes the structural features of LF. Then the digestion, absorption and metabolism of LF in infants are discussed, followed by the function of LF for infants. Further, we summarize LF in infant formula and effects of processing of infant formula on bioactivities of LF, as well as future perspectives of LF research. [ABSTRACT FROM AUTHOR]

Seed dispersal is a key component of the interactions between plants and animals. There is little research on the effects of lizard seed dispersal, which is more common on islands than elsewhere. In this study, the effects of the passage of Capparis spinosa seeds through Teratoscincus roborowskii lizard digestive tracts on the seed coats, water uptake rates and germination rates were investigated. In addition, the spatial patterns of fecal deposition by lizards in various microhabitats were assessed. Our results showed that the mean retention time (MRT) of mealworms was significantly longer than that of C. spinosa seeds in both adult and juvenile lizards. The defecation rate of C. spinosa tended to be lower than that of mealworms, which might be beneficial for seed dispersal. It was determined that the longer MRT of C. spinosa seeds enhanced the permeability of the seed coats, which promoted fast water uptake, broke seed dormancy and increased the seed germination rate. Furthermore, the seeds that passed through the digestive tracts of lizards were deposited in favorable germination microhabitats. By enhancing seed germination and depositing intact and viable seeds in safe potential recruitment sites, the lizard T. roborowskii acts, at least qualitatively, as an effective disperser of C. spinosa. [ABSTRACT FROM AUTHOR]

Objective: To develop a deep neural network for the detection of inflammatory spine in short tau inversion recovery (STIR) sequence of magnetic resonance imaging (MRI) on patients with axial spondyloarthritis (axSpA).A total 330 patients with axSpA were recruited. STIR MRI of the whole spine and clinical data were obtained. Regions of interests (ROIs) were drawn outlining the active inflammatory lesion consisting of bone marrow edema (BME). Spinal inflammation was defined by the presence of an active inflammatory lesion on the STIR sequence. The 'fake-color' images were constructed. Images from 270 and 60 patients were randomly separated into the training/validation and testing sets, respectively. Deep neural network was developed using attention UNet. The neural network performance was compared to the image interpretation by a radiologist blinded to the ground truth.Active inflammatory lesions were identified in 2891 MR images and were absent in 14,590 MR images. The sensitivity and specificity of the derived deep neural network were 0.80 ± 0.03 and 0.88 ± 0.02, respectively. The Dice coefficient of the true positive lesions was 0.55 ± 0.02. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the deep neural network was 0.87 ± 0.02. The performance of the developed deep neural network was comparable to the interpretation of a radiologist with similar sensitivity and specificity.The developed deep neural network showed similar sensitivity and specificity to a radiologist with four years of experience. The results indicated that the network can provide a reliable and straightforward way of interpreting spinal MRI. The use of this deep neural network has the potential to expand the use of spinal MRI in managing axSpA.Methods: To develop a deep neural network for the detection of inflammatory spine in short tau inversion recovery (STIR) sequence of magnetic resonance imaging (MRI) on patients with axial spondyloarthritis (axSpA).A total 330 patients with axSpA were recruited. STIR MRI of the whole spine and clinical data were obtained. Regions of interests (ROIs) were drawn outlining the active inflammatory lesion consisting of bone marrow edema (BME). Spinal inflammation was defined by the presence of an active inflammatory lesion on the STIR sequence. The 'fake-color' images were constructed. Images from 270 and 60 patients were randomly separated into the training/validation and testing sets, respectively. Deep neural network was developed using attention UNet. The neural network performance was compared to the image interpretation by a radiologist blinded to the ground truth.Active inflammatory lesions were identified in 2891 MR images and were absent in 14,590 MR images. The sensitivity and specificity of the derived deep neural network were 0.80 ± 0.03 and 0.88 ± 0.02, respectively. The Dice coefficient of the true positive lesions was 0.55 ± 0.02. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the deep neural network was 0.87 ± 0.02. The performance of the developed deep neural network was comparable to the interpretation of a radiologist with similar sensitivity and specificity.The developed deep neural network showed similar sensitivity and specificity to a radiologist with four years of experience. The results indicated that the network can provide a reliable and straightforward way of interpreting spinal MRI. The use of this deep neural network has the potential to expand the use of spinal MRI in managing axSpA.Results: To develop a deep neural network for the detection of inflammatory spine in short tau inversion recovery (STIR) sequence of magnetic resonance imaging (MRI) on patients with axial spondyloarthritis (axSpA).A total 330 patients with axSpA were recruited. STIR MRI of the whole spine and clinical data were obtained. Regions of interests (ROIs) were drawn outlining the active inflammatory lesion consisting of bone marrow edema (BME). Spinal inflammation was defined by the presence of an active inflammatory lesion on the STIR sequence. The 'fake-color' images were constructed. Images from 270 and 60 patients were randomly separated into the training/validation and testing sets, respectively. Deep neural network was developed using attention UNet. The neural network performance was compared to the image interpretation by a radiologist blinded to the ground truth.Active inflammatory lesions were identified in 2891 MR images and were absent in 14,590 MR images. The sensitivity and specificity of the derived deep neural network were 0.80 ± 0.03 and 0.88 ± 0.02, respectively. The Dice coefficient of the true positive lesions was 0.55 ± 0.02. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the deep neural network was 0.87 ± 0.02. The performance of the developed deep neural network was comparable to the interpretation of a radiologist with similar sensitivity and specificity.The developed deep neural network showed similar sensitivity and specificity to a radiologist with four years of experience. The results indicated that the network can provide a reliable and straightforward way of interpreting spinal MRI. The use of this deep neural network has the potential to expand the use of spinal MRI in managing axSpA.Conclusion: To develop a deep neural network for the detection of inflammatory spine in short tau inversion recovery (STIR) sequence of magnetic resonance imaging (MRI) on patients with axial spondyloarthritis (axSpA).A total 330 patients with axSpA were recruited. STIR MRI of the whole spine and clinical data were obtained. Regions of interests (ROIs) were drawn outlining the active inflammatory lesion consisting of bone marrow edema (BME). Spinal inflammation was defined by the presence of an active inflammatory lesion on the STIR sequence. The 'fake-color' images were constructed. Images from 270 and 60 patients were randomly separated into the training/validation and testing sets, respectively. Deep neural network was developed using attention UNet. The neural network performance was compared to the image interpretation by a radiologist blinded to the ground truth.Active inflammatory lesions were identified in 2891 MR images and were absent in 14,590 MR images. The sensitivity and specificity of the derived deep neural network were 0.80 ± 0.03 and 0.88 ± 0.02, respectively. The Dice coefficient of the true positive lesions was 0.55 ± 0.02. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the deep neural network was 0.87 ± 0.02. The performance of the developed deep neural network was comparable to the interpretation of a radiologist with similar sensitivity and specificity.The developed deep neural network showed similar sensitivity and specificity to a radiologist with four years of experience. The results indicated that the network can provide a reliable and straightforward way of interpreting spinal MRI. The use of this deep neural network has the potential to expand the use of spinal MRI in managing axSpA. [ABSTRACT FROM AUTHOR]

Microbial source tracking (MST) technology represents an innovative approach employed to trace fecal contamination in environmental water systems. The performance of primers may be affected by amplification techniques, target primer categories, and regional differences. To investigate the influence of these factors on primer recognition performance, a meta-analysis was conducted on the application of MST in water environments using three databases: Web of Science, Scopus, and PubMed (n = 2291). After data screening, 46 studies were included in the final analysis. The investigation encompassed Polymerase Chain Reaction (PCR)/quantitative PCR (qPCR) methodologies, dye-based (SYBR)/probe-based (TaqMan) techniques, and geographical differences of a human host-specific (HF183) primer and other 21 additional primers. The results indicated that the primers analyzed were capable of differentiating host specificity to a certain degree. Nonetheless, by comparing sensitivity and specificity outcomes, it was observed that virus-based primers exhibited superior specificity and recognition capacity, as well as a stronger correlation with human pathogenicity in water environments compared to bacteria-based primers. This finding highlights an important direction for future advancements. Moreover, within the same category, qPCR did not demonstrate significant benefits over conventional PCR amplification methods. In comparing dye-based and probe-based techniques, it was revealed that the probe-based method's advantage lay primarily in specificity, which may be associated with the increased propensity of dye-based methods to produce false positives. Furthermore, the heterogeneity of the HF183 primer was not detected in China, Canada, and Singapore respectively, indicating a low likelihood of regional differences. The variation among the 21 other primers may be attributable to regional differences, sample sources, detection techniques, or alternative factors. Finally, we identified that economic factors, climatic conditions, and geographical distribution significantly influence primer performance. [Display omitted] • Meta-analysis for primers and impact factors to their recognition performance. • Viruses-based primers showed a better specificity and recognition ability. • Regional differences of HF183 was not observed in China, Canada, and Singapore. • The influence factors from sample to environment of 21 primers had been listed. • Meta-analysis of economy, climate, and geographic zone on the primers. [ABSTRACT FROM AUTHOR]

Microglia activation contributes to Alzheimer's disease (AD) etiology, and microglia migration is a fundamental function during microglia activation. The repressor element-1 silencing transcription factor (REST), a powerful transcriptional factor, was found to play a neuroprotective role in AD. Despite its possible role in disease progression, little is known about whether REST participates in microglia migration. In this study, we aimed to explore the function of REST and its molecular basis during microglia migration under Aβ1-42-treated pathological conditions. When treated by Aβ1-42 REST was upregulated through JAK2/STAT3 signal pathway in BV2 cells. And transwell coculture system was used to evaluate cell migration function of microglia-like BV2. Small interfering RNA (siRNA) targeting progranulin (PGRN) were delivered into BV2 cells, and results showed that PGRN functions to promote BV2 migration. REST expression was inhibited by sh-RNA, which induced BV2 cell migration obviously. On the contrary, REST was overexpressed by REST recombinant plasmid transfection, which repressed BV2 cell migration, indicating that REST may act as a repressor of cell migration. To more comprehensively examine the molecular basis, we analyzed the promoter sequence of PGRN and found that it has the potential binding site of REST. Moreover, knocking-down of REST can increase the expression of PGRN, which confirms the inhibiting effect of REST on PGRN expression. Further detection of double luciferase reporter gene also confirmed the inhibition of REST on the activity of PGRN promoter, indicating that REST may be an inhibitory transcription factor of PGRN which governs microglia-like BV2 cell migration. In conclusion, the present study demonstrates that transcription factor REST may act as a repressor of microglia migration through PGRN. [ABSTRACT FROM AUTHOR]

Background: Isocitrate dehydrogenase wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, yet only 27% of isocitrate dehydrogenase WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood.Methods: We investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients' specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6-8 per group). The statistical significance between groups was determined using two-tailed Student t tests.Results: We demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knock down or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; hazard ratio = 3.94, 95% confidence interval = 1.87 to 8.28; P < .001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, P = .03), which decreased dramatically after surgery.Conclusions: Our results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM. [ABSTRACT FROM AUTHOR]

Bacillus cereus is a common foodborne pathogen in dairy environment, which is hard to remove for its strong biofilm forming ability. In our study, Clean-in-place (CIP) regime and benzalkonium bromide (BK) were used in combination to enhance biofilm removal effectiveness. The CIP regime (1.5% NaOH at 65 °C for 10 min-water rinse-1% HNO 3 at 65 °C for 10 min-water rinse) often used in dairy industry only achieved a 4.69 log reduction/cm2. A step of 5000 μg/mL BK following this CIP regime could effectively remove the biofilm cells on stainless steel, and biofilm cells were removed to below detection limit. The efficacy of BK in inhibiting Bacillus cereus was investigated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of BK against Bacillus cereus were 6.25 μg/mL and 25 μg/mL. The antimicrobial activity of BK took effect by inducing intracellular proteins and electrolytes leakage. Moreover, the microstructure of extracellular matrix was broken under confocal microscopy (CLSM) and the amounts of proteins, polysaccharides and DNA in extracellular matrix reduced by 44.8%, 69.2% and 60.9% respectively after treatment of 5000 μg/mL BK. By detecting the zeta potential of biofilm extracellular matrix and contact angle assay, we found BK could bind to extracellular matrix with electrostatic interaction and increasing the hydrophilicity of biofilm, making biofilm removal easier. So, BK combined with CIP regime could be used as an effective strategy to remove Bacillus cereus biofilm. • CIP regimes which combined with BK removed Bacillus cereus biofilm efficiently. • BK could damage Bacillus cereus membrane, making cellular contents leakage. • BK could increase the hydrophilicity of biofilm. making biofilm removal easier. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is prevalent in southern China. EBV DNA is the most useful biomarker in NPC. However, the value of EBV DNA in posttreatment NPC patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. Methods: Sixty-four eligible NPC patients were enrolled between December 2022 and February 2023. Patients who met the following criteria were included: had non-metastatic NPC, completed radical treatment, were first firstly infected with SARS-CoV-2 and their EBV DNA changed from undetectable to detectable. Results: At the end of follow-up, 81.25% (52/64) of patients were confirmed not to relapse with undetectable EBV DNA (no-relapse). In addition, 18.75% (12/64) of patients experienced relapse with consistent detection of EBV DNA (yes-relapse). For all 64 patients, the average time from diagnosis of coronavirus disease 2019 (COVID-19) to detection of detectable EBV DNA was 35.41 days (2 to 139 days). For 52 no-relapse patients, the average time from EBV DNA changing from detectable to undetectable was 63.12 days (6 to 147 days). The levels of EBV DNA were greater in yes-relapse patients than that in no-relapse patients, and the average of EBV DNA levels were 1216 copies/ml and 53.18 copies/ml, respectively. Using 62.3 copies/mL as the threshold, the area under the curve for EBV DNA was 0.88 for distinguishing yes-relapse patients from no-relapse patients. The sensitivity and specificity were 81.97% (95% CI 0.71–0.95) and 86.67% (95% CI 0.70–0.95), respectively. Conclusion: For NPC patients infected with SARS-CoV-2, EBV DNA alone is insufficient for monitoring relapse after radical therapy. Long-term follow-up and underlying mechanistic investigations of EBV DNA changes are urgently needed. [ABSTRACT FROM AUTHOR]

Glutamate and γ‑aminobutyric acid (GABA) transporters serve central roles in normal neuronal activity and are associated with numerous pathological brain conditions, including ischemia and epilepsy. However, the interplay between these transporters in ischemia remains unclear. In the present study, the expression levels of the excitatory amino acid carrier 1 (EAAC1) and GABA transporter 1 (GAT1) were analyzed in vivo and in vitro within ischemic models by immunofluorescence, western blot and RT‑qPCR. Cell survival rates were analyzed following altered expression of these transporters within neuronal cells by flow cytometry. Expression levels of EAAC1 were reduced within the cerebrum of focal cerebral ischemic middle cerebral artery occlusion rat models as well as in primary neurons cultured under hypoxia. However, GAT1 expression levels were slightly elevated under ischemic conditions. The altered expression levels of EAAC1 and GAT1 were combined within neuron cells and the effects were investigated. Apoptotic analysis revealed that EAAC1 suppression and overexpression of GAT1 increased neuronal cell apoptosis under hypoxic conditions; however, EAAC1 overexpression combined with GAT1 knockdown reduced neuronal cell apoptosis under hypoxic conditions. The present study detected the expression levels of the glutamate and GABA transporters under hypoxia, in association with ischemia. The results indicated that, increased expression of EAAC1 combined with GAT1 suppression may provide protective effects in the treatment of epilepsy and ischemia. [ABSTRACT FROM AUTHOR]

Objective Autophagy plays a prominent role in the pathogenesis of plaques formation and progression of atherosclerosis (AS). The cysteine protease legumain is known to participate in atherogenesis, but its function and underlying mechanism in AS macrophages remain unclear. Methods The expressions of legumain in plaques isolated from AS patients and in macrophages stimulated with oxLDL were examined. Moreover, we effectively altered legumain expression in macrophages to characterize the effect of legumain on oxLDL-induced macrophage apoptosis. The expression of apoptotic and autophagic factors was analysed. Results Legumain was present in plaques, and its expression was upregulated in macrophages treated with oxLDL. Suppressing legumain significantly increased oxLDL-induced macrophage apoptosis and the expression of caspase 3, caspase 9 and Bax. However, legumain overexpression decreased macrophage apoptosis upon oxLDL exposure and the levels of caspase 3, caspase 9 and Bax. In addition, recombinant legumain protein suppressed macrophage apoptosis. Biochemical experiments revealed that legumain deficiency decreased the levels of Beclin1 and LC3, whereas increased legumain expression increased the levels of Beclin1 and LC3 significantly. Conclusion Legumain regulates oxLDL-induced macrophage apoptosis by enhancing the autophagy pathway, which may also influence the vulnerability of atherosclerotic plaques. [ABSTRACT FROM AUTHOR]

Abstract: Bacillus cereus is an important foodborne pathogen that can cause emesis and diarrhea. The aim of this study was to find the phenotypic properties of Bacillus cereus enabling its persistence in dairy plants, and identify the corresponding genotypic features. The toxin gene profile, multilocus sequence typing (MLST), biofilm-forming capability and the alkali and acid tolerance of the biofilms of the strains were analyzed. All strains were positive for one or more toxin genes tested, except for A20. The three main toxin genes were nheABC (74.07%), bceT (73.37%), and ces (48.15%), followed by entFM (40.74%) and cytK (33.33%), but no strain harbored hblABD . A total of 17 ST-types were generated among 27 isolates by MLST, and clustered into four groups. Although no significant difference was found in the tolerance of biofilm to acid and alkali among four MLST groups, the strains of MLST groupⅠhad stronger biofilm formation capability. The biofilm was formed on stainless steel coupons, of which the OD values of A1, B16 and B18 were more than 1.0, and close to each other in the phylogenetic tree. Persistence survival strategies analysis showed that strains can be divided into three groups: 15 strains without persistence strategies; two strains were capable of forming biofilm may be effectively inactivated by hot-acid or hot-alkali; ten isolates were capable of forming biofilm and possessing the tolerance of biofilm to acid and alkali, which should be under strict supervision and control in the future. [ABSTRACT FROM AUTHOR]

In present study, a micro membrane-less photoelectrochemical cell (μML-PEC) is developed for simultaneous hydrogen and electricity productions in the presence of methanol, in which the photoanode of a TiO 2 film is consisted of a compact layer at the bottom and a porous layer on the top. The experimental results indicate the PEC miniaturization, and the membrane elimination, and the addition of a compact layer can enhance the mass, electron and photon transfer, which eventually boosts the performance. The performance of the developed μML-PEC is also evaluated under various operating conditions, including the light intensity, methanol and electrolyte concentrations and flow rate. It is shown that the maximum power density increases and the fill factor (FF) and solar-to-hydrogen conversion efficiency (STH) decrease with increasing the light intensity. For the electrolyte concentration, the maximum power density and STH and FF all increases with increasing the electrolyte concentration. Once the electrolyte is high enough, its effect become insignificant. Besides, the increase of the methanol concentration and the decrease of the flow rate are beneficial for the improvement in the performance. The obtained results reveal that the μML-PEC developed in this work shows the promising potential for simultaneously producing electricity and hydrogen in the presence of methanol. [ABSTRACT FROM AUTHOR]

Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis. According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups. We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1. Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases. Screening a library of compounds identifies several inhibitors of TNF-induced necroptosis, including Ibrutinib as an inhibitor of RIPK3 and Quizartinib as an indirect RIPK1 kinase activity inhibitor. [ABSTRACT FROM AUTHOR]

Partially dephosphorylated bovine beta-casein has great potential to become a novel infant formula base in the future. At present, there are few studies on the self-association properties of partially dephosphorylated bovine beta-casein, which are very essential and important for its processing and application. This study investigated the self-association properties and physical stability of partially dephosphorylated bovine beta-casein. Partially dephosphorylated bovine beta-casein was prepared using phosphatase and the dephosphorylated isoforms were precisely identified through UPLC-ESI-MS. Afterwards, the self-association properties of partially dephosphorylated bovine beta-casein at different protein concentrations, temperatures, CaCl 2 concentrations and pH were studied. Partially dephosphorylated bovine beta-casein was more sensitive to increases in protein concentration (0.03%–0.25%), temperature (4–54 °C), CaCl 2 concentration (0–9 mM) and pH (4–8) and prone to form large protein aggregates compared with native beta-casein (>1 μm vs < 100 nm). However, the protein aggregation results at pH 4 were exceptional, with partially dephosphorylated beta-casein forming smaller aggregates than native beta-casein (<30 nm vs > 300 nm). The physical stability of native and partially dephosphorylated beta-casein solutions was also determined and the results were in agreement with above-mentioned results of protein aggregation. The decrease in negative charge caused by the loss of phosphate groups seemed to be responsible for the difference in self-association properties between native and partially dephosphorylated beta-casein. These findings will provide effective guidance for infant formula manufacturers. [Display omitted] • Dephosphorylated β-CN was more sensitive to temperature, CaCl 2 concentration and pH. • Dephosphorylated β-CN underwent flocculation and formed larger aggregates. • Self-association property of dephosphorylated β-CN was related to negative charge decrease. [ABSTRACT FROM AUTHOR]

Tubeimoside-1 (TBMS1) exerts its anticancer effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of its anti-tumor effects has not been fully elucidated, especially the signaling pathways involved in the early stage of TBMS1 stimulation. In this study, we employed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics approach and identified 439 proteins that exhibit significant differential expressions in NCI-H460 lung cancer cells upon exposure to TBMS1. Gene ontology and network analysis using DAVID and STRING on-line tools revealed that several nucleolar stress (ribosomal biogenesis) response proteins were differentially regulated by TBMS1. Functional validation demonstrated that TBMS1-induced NCI-H460 cell cytotoxicity involved nucleolar stress-induced p53/murine double minute clone 2 (MDM2), mTOR, and NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

Objective Multiple mechanisms participated in the cell death after fluid percussion traumatic brain injury (TBI). In the present study, we evaluated the effect on cell death in the injured cortex after fluid percussion TBI and investigated a possible role of autophagy. Methods TBI model was induced by a fluid percussion TBI device. Moderate hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 hours. All rats were killed at 6 or 24 hours after TBI. Results Cleaved caspase 3 evaluated with Western blotting and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling-positive cells in injured cortex were significantly increased 6 hours after fluid percussion TBI and were further up-regulated 24 hours after TBI, dramatic up-regulation of Beclin-1 and protein light chain-3 expression levels was also observed. Further up-regulation of biomarkers of autophagy, attenuation of caspase 3 up-regulation and reduction of cell death was observed after 4 hours of hypothermia. Immunofluorescence analysis for cell localization demonstrated that protein light chain-3- and Beclin-1-positive cells included neurons and glial cells in the injured cortex after TBI and hypothermic treatment. By ultrastructural observation, autolysosomes in injured cortex were significantly increased at 6 and 24 hours after TBI and were further up-regulated after TBI hypothermic treatment. Conclusions These data suggest that hypothermic treatment could attenuate TBI-induced cell death in this fluid percussion TBI model, possibly through activation of autophagy pathway. [ABSTRACT FROM AUTHOR]

Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI) followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were randomly divided into four groups: sham injury with normothermia group (37°C); sham injury with hypothermia group (32°C); TBI with normothermia group (TNG; 37°C); and TBI with hypothermia group (THG; 32°C). Injury was induced by a fluid percussion TBI device. Moderate hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 h. All rats were killed at 24 h after fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; terminal deoxynucleoitidyl transferase-mediated nick end labeling staining was used to determine cell death in ipsilateral hippocampus. Immunohistochemistry and western blotting of microtubule-associated protein light chain 3 (LC3), Beclin-1, as well as transmission electron microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell death index was 27.90±2.36% in TNG and 14.90±1.52% in THG. Expression level of LC3 and Beclin-1 were significantly increased after TBI and were further up-regulated after post-TBI hypothermia. Further, ultrastructural observations showed that there was a marked increase of autophagosomes and autolysosomes in ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that moderate hypothermia significantly attenuated cell death and increased autophagy in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy pathway may participate in the neuroprotective effect of post-TBI hypothermia. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) have the tolerogenic potential to regulate adaptive immunity and induce allografts acceptance. Here we investigated whether blockade of the CD40 pathway could enhance the immune tolerance induced by DC2.4 cells modified to express Jagged-1 (JAG1-DC) in heart transplantation. Results showed that JAG1-DC treatment combined with anti-CD40L monoclonal antibody (mAb) administration significantly prolonged cardiac allograft survival in mice, with long-term survival (>110 days) of 50% of the allografts in the recipients. The therapy specifically inhibited the immune response, induced alloantigen-specific T-cell hyporesponsiveness, upregulated transforming growth factor-β synthesis and increased the population of regulatory T cells (Tregs) driven by Jagged-1-Notch activation. These results highlight the potential application of gene therapy to induce alloantigen-specific Tregs effectively by providing the Jagged-1 stimulation. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease with poor prognosis and few treatment options. Dapper homolog 2 (DACT2), a member of the DACT gene family, plays crucial roles in tissue development and injury. However, its functions and molecular mechanisms in IPF remain largely unknown. We aimed to investigate the role of DACT2 in the development of pulmonary fibrosis and the therapeutic potential of targeting DACT2 related signaling pathways. In our study, adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression was assessed in several mice models of experimental pulmonary fibrosis in vivo. The role of DACT2 in lung myofibroblast differentiation was determined by DACT2 overexpression in vitro. The glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level and lactate levels of myofibroblasts were detected after DACT2 overexpression. The LDHA degradation rate and colocalization with lysosomes were monitored as well. Intratracheal administration of AAV6-mediated DACT2 overexpression apparently attenuated pulmonary fibrosis in experimental pulmonary fibrosis models. In vitro experiments revealed that DACT2 inhibited TGF-β-induced myofibroblast differentiation by promoting lysosome-mediated LDHA degradation and thus suppressing glycolysis in myofibroblasts. In conclusion, our findings support for DACT2 as a novel pharmacological target for pulmonary fibrosis treatments. [ABSTRACT FROM AUTHOR]

• Self-doped TiO 2 nanotube array photoanode is developed for μVPFB. • Visible-light response of TiO 2 is enabled by self-doping. • Nanotube array structure enhances separation of electron-hole pairs. • The developed photoanode shows enhanced solar energy storage performance. In this work, a self-doped TiO 2 nanotube array (SD-TNA) photoanode was developed through a facile method for a microfluidic all-vanadium photoelectrochemical flow battery (μVPFB) to achieve better solar energy storage performance. The TEM, XPS and XRD results confirmed successful self-doping, for which the light absorption range of the developed photoanode was extended to visible light. Meanwhile, one-dimensional nanotube structure promoted electron transport to enhance the separation of electrons and holes. The miniaturization of the flow battery reduced mass transfer resistance. Because of these merits, the μVPFB with the SD-TNA photoanode yielded a relatively stable photocurrent density as high as 0.10 mA cm−2, which was much better than the conventional TNA photoanode, presenting about 100% improvement. The improvements in the photocurrent density and vanadium ion conversion rate could be achieved by upgrading both the intensity of light and concentration of vanadium ion. [ABSTRACT FROM AUTHOR]

The Ti60 titanium alloy, as one of high-temperature titanium alloys, has good creep resistance against high temperature, excellent thermostability at the servicing temperature of 600°C. The microstructure and the phases are investigated through Optical microscopy (OM), Scanning electron microscopy (SEM) and X-ray diffraction analysis (XRD) after thermohydrogenation treatment of the Ti60 titanium alloy. The grains have been refined significantly through the thermohydrogenation treatment, and the occurrence and disappearance of the hydride phase is a main mechanism of grain refinement in the thermohydrogenation treatment of Ti60 titanium alloy. [Copyright &y& Elsevier]

Asparagine endopeptidase (AEP), also called legumain, is currently the only known cysteine protease that specifically cleaves peptide bonds in asparaginyl residue in the mammalian genome. Since 2003, AEP has been reported to be widely expressed in a variety of carcinomas and is considered a potential therapeutic target. In the following years, researchers intensively investigated the substrates of AEP and the mechanism of AEP in partial tumors. With the identification of substrate proteins such as P53, integrin αvβ3, MMP-2, and MMP-9, the biochemical mechanism of AEP in carcinomas is also more precise. This review will clarify the probable mechanisms of AEP in the progression of breast carcinoma, glioblastoma, gastric carcinoma, and epithelial ovarian carcinoma. This review will also discuss the feasibility of targeted therapy with AEP inhibitor (AEPI) in these carcinomas. [ABSTRACT FROM AUTHOR]

AbstractDuring the application of Whey proteins (WPs), they often have complex interactions with saccharides (Ss), another important biopolymer in food substrate. The texture and sensory qualities of foods containing WPs and Ss are largely influenced by the interactions of WPs-Ss. Moreover, the combination of WPs and Ss is possible to produce many excellent functional properties including emulsifying properties and thermal stability. However, the interactions between WPs-Ss are complex and susceptible to some processing conditions. In addition, with different interaction ways, they can be applied in different fields. Therefore, the non-covalent interaction mechanisms between WPs-Ss are firstly summarized in detail, including electrostatic interaction, hydrogen bond, hydrophobic interaction, van der Waals force. Furthermore, the existence modes of WPs-Ss are introduced, including complex coacervates, soluble complexes, segregation, and co-solubility. The covalent interactions of WPs-Ss in food applications are often formed by Maillard reaction (dry or wet heat reaction) and occasionally through enzyme induction. Then, two common influencing factors, pH and temperature, on non-covalent/covalent bonds are introduced. Finally, the applications of WPs-Ss complexes and conjugations in improving WP stability, delivery system, and emulsification are described. This review can improve our understanding of the interactions between WPs-Ss and further promote their wider application. [ABSTRACT FROM AUTHOR]

Sepsis is a life‐threatening organ dysfunction that endangers patient lives and is caused by an imbalance in the host defense against infection. Sepsis continues to be a significant cause of morbidity and mortality in critically sick patients. Oxymatrine (OMT), a quinolizidine alkaloid derived from the traditional Chinese herb Sophora flavescens Aiton, has been shown to have anti‐inflammatory effects on a number of inflammatory illnesses according to research. In this study, we aimed to evaluate the therapeutic effects of OMT on sepsis and explore the underlying mechanisms. We differentiated THP‐1 cells into THP‐1 macrophages and studied the anti‐inflammatory mechanism of OMT in a lipopolysaccharide (LPS)‐induced THP‐1 macrophage sepsis model. Activation of the receptor for advanced glycation end products (RAGE), as well as NF‐κB, was assessed by Western blot analysis and immunofluorescence staining. ELISA was used to measure the levels of inflammatory factors. We found that OMT significantly inhibited HMGB1‐mediated RAGE/NF‐κB activation and downstream inflammatory cytokine production in response to LPS stimulation. Finally, an in vivo experiment was performed on septic mice to further study the effect of OMT on injured organs. The animal experiments showed that OMT significantly inhibited HMGB1‐mediated RAGE/NF‐κB activation, protected against the inflammatory response and organ injury induced by CLP, and prolonged the survival rate of septic mice. Herein, we provide evidence that OMT exerts a significant therapeutic effect on sepsis by inhibiting the HMGB1/RAGE/NF‐κB signaling pathway. [ABSTRACT FROM AUTHOR]

eIF3, a multi-subunit complex with numerous functions in canonical translation initiation, is known to interact with 40S and 60S ribosomal proteins and translation elongation factors, but a direct involvement in translation elongation has never been demonstrated. We found that eIF3 deficiency reduced early ribosomal elongation speed between codons 25 and 75 on a set of ∼2,700 mRNAs encoding proteins associated with mitochondrial and membrane functions, resulting in defective synthesis of their encoded proteins. To promote elongation, eIF3 interacts with 80S ribosomes translating the first ∼60 codons and serves to recruit protein quality-control factors, functions required for normal mitochondrial physiology. Accordingly, eIF3e+/− mice accumulate defective mitochondria in skeletal muscle and show a progressive decline in muscle strength. Hence, eIF3 interacts with 80S ribosomes to enhance, at the level of early elongation, the synthesis of proteins with membrane-associated functions, an activity that is critical for mitochondrial physiology and muscle health. • eIF3—via eIF3e—promotes mRNA selective early translation elongation • eIF3e-dependent mRNAs encode membrane, secretory, and organelle targeted proteins • eIF3 travels with 80S ribosomes until nascent chains emerge for subcellular targeting • In vivo , eIF3e promotes mitochondrial function and skeletal muscle health Lin et al. discovered that, in addition to its function in canonical translation initiation, multi-subunit eIF3 migrates with post-initiation 80S ribosomes to promote early translation elongation of mRNAs encoding organellar, secretory, and membrane-targeted proteins. Loss of eIF3's elongation and subcellular targeting activity leads to mitochondrial and skeletal muscle dysfunction. [ABSTRACT FROM AUTHOR]

Background: Myeloid cell leukaemia 1 (MCL1) is a pro-survival Bcl-2 family protein that plays important roles in cell survival, proliferation, differentiation and tumourigenesis. MCL1 is a fast-turnover protein that is degraded via an ubiquitination/proteasome-dependent mechanism. Although several E3 ligases have been discovered to promote the ubiquitination of MCL1, the deubiquitinating enzyme (DUB) that regulates its stability requires further investigation. Methods: The immunoprecipitation was used to determine the interaction between OTUD1 and MCL1. The ubiquitination assays was performed to determine the regulation of MCL1 by OTUD1. The cell viability was used to determine the regulation of BH3-mimetic inhibitor induced cell death by OTUD1. The survival analysis was used to determine the relationship between OTUD1 expression levels and the survival rate of cancer patients. Results: By screening a DUB expression library, we determined that the deubiquitinating enzyme OTUD1 regulates MCL1 protein stability in an enzymatic-activity dependent manner. OTUD1 interacts with MCL1 and promotes its deubiquitination. Knockdown of OTUD1 increases the sensitivity of tumour cells to the BH3-mimetic inhibitor ABT-263, while overexpression of OTUD1 increases tumour cell tolerance of ABT-263. Furthermore, bioinformatics analysis data reveal that OTUD1 is a negative prognostic factor for liver cancer, ovarian cancer and specific subtypes of breast and cervical cancer. Conclusions: The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein. Thus, OTUD1 could be considered as a therapeutic target for curing these cancers. [ABSTRACT FROM AUTHOR]

Withania somnifera (L.) Dunal, known as Ashwagandha, has long been used in traditional medicine in Ayurveda, India, a representative adaptogen. The main active constituents of W. somnifera are withanolides, and the root is often used as a medicine with a wide range of pharmacological activities, which can be used to treat insomnia, neurasthenia, diabetes mellitus and skin cancer. Whole-component qualitative and quantitative analyses were performed on W. somnifera. We explored the ameliorative effect of the adaptogen representative plant W. somnifera on the senescence events of MGO-injured fibroblasts and its action mechanism and verified the hypotheses that WS can inhibit the accumulation of AGEs and regulate the dynamic balance among the components of the ECM by modulating the expression of integrin β1 receptor; as a result, WS maintains cellular behavioural and biological functions in a normal range and retards the aging of skin from the cellular level. In this study, the components of WS were first qualitatively and quantitatively analysed by HPLC fingerprinting and LC-MS detection. Second, a model of MGO-induced injury of CML-overexpressing fibroblasts was established. ELISA was used to detect CML expression and the synthesis of key extracellular matrix ECM protein components COL1, FN1, LM5 and TNC synthesis; CCK-8 was used to detect cell viability; EDU was used to detect cell proliferation capacity; fluorescence was used to detect cell adhesion capacity; and migration assay were used to detect cell migration capacity; qRT-PCR was used to detect the regulatory pathway TGF-β1 and MMP-2, MMP-9 in ECMs; immunofluorescence was used to detect the expression of ITGB1; and WB was used to detect the expression of COL1, FN1, LM5, Tnc, TGF-β1, MMP-2, MMP-9 and ITGB1. In total, 27 active ingredients were analysed from WS, which mainly consisted of withanolide components, such as withaferin A and withanolide A. Based on the model of MGO-induced fibroblast senescence injury, WS significantly inhibited CML synthesis. By up-regulating the expression of integrin β1, it upregulated the expression of the TGF-β1 gene, which is closely related to the generation of ECMs, downregulated the expression of the MMP-2 and MMP-9 genes, which are closely related to the degradation of ECMs, maintained the dynamic balance of the four types of ECMs, and improved cell viability as well as proliferation, migration and adhesion abilities. WS can prevent cellular behavioural dysfunction and delay skin ageing by reducing the accumulation of CML, upregulating the expression of the ITGB1 receptor, maintaining the normal function of ECM-integrin receptor interaction and preventing an imbalance between the production and degradation of protein components of ECMs. The findings reported in this study suggest that WS as a CML inhibitor can modulate ECM-integrin homeostasis and has great potential in the field of aging retardation. [Display omitted] • Taking a representative adaptogen plant, the Withania somnifera (L.) Dunal, as an example, we studied the mechanism by which it exerts the efficacy of slowing down the aging damage of the extracellular matrix in the dermal layer of the skin. • Verify that MGO induces a series of changes in skin aging damage by inducing an increase in CML expression levels. WS (the root extracts of W. somnifera (L.) Dunal) ameliorates this adverse process. • Validation MGO induces disruption of ECMs (COL1, FN1, LM5, Tnc)-integrin β1 homeostasis by inducing an increase in the expression level of TGF-β1 and a decrease in the expression level of MMP-2, MMP-9, which ultimately leads to impaired cell behavioral functions (migration, adhesion, proliferation ability). WS was able to restore ECMs-integrin homeostasis and alleviate the impaired cell behavioral functions caused by MGO. [ABSTRACT FROM AUTHOR]

Background and Objective. White matter lesions (WMLs) are imaging changes characterized by hyperintensities on T2-weighted or FLAIR images, which are closely related to the decline of cognitive function. However, the etiology and pathogenesis of WMLs remain undetermined. The aim of this study was to analyze the relationship between adiponectin levels and cognitive decline in persons with or without white matter lesions. Method. In the present study, 126 patients, 90 cases in the WML group and 36 cases in the control group, were analyzed to explore the relationship between adiponectin and WMLs. All patients underwent an MRI scan to assess whether white matter lesions happened. And the serum levels of adiponectin were detected by ELISA. Results. In this study, according to Fazekas criteria, WMLs were divided into different severity groups. With the increase of WML score, the level of adiponectin decreased, and linear correlation analysis shows that adiponectin is negatively correlated with the severity of white matter lesions (p < 0.001). And adiponectin level was significantly positively correlated with MoCA score (p < 0.05). Moreover, adiponectin in the WMLs combined with the cognitive impairment group was significantly reduced (p < 0.01). Conclusion. The level of adiponectin is independently associated with WMLs and cognitive function, which suggests that adiponectin may be a protective factor for WMLs and cognitive function. [ABSTRACT FROM AUTHOR]

Human milk is the gold standard for the nutrition of infants. Human milk oligosaccharides (HMOs) are structurally diverse sugars highly abundant in human milk but not present in infant formula. The interest in HMOs has gradually increased in recent years due to their beneficial functions on infants. Here we summarize the structures and composition of HMOs, and compare the differences of oligosaccharides in human and other mammals. The absorption and metabolism of HMOs are discussed. Then we discuss existing studies on the functional biology of HMOs. Additionally, the structure-function relationships of HMOs are presented. Finally, this review summarizes the oligosaccharides in recent infant formula as well as limitations and future perspectives of HMOs research. The structures and composition of HMOs are affected by many factors. Large amounts of HMOs are metabolized by gut microbiota, and few are absorbed into circulation to perform physiological functions. Evidences from in vitro and in vivo studies, as well as clinical trials suggest that HMOs modulate gut microbiota, reduce pathogen adhesion, modulate epithelial cell and immune responses, reduce the risk of necrotizing enterocolitis and promote brain development and cognition. The specific structure determines different functions. Currently two HMOs, 2′-fucosyllactose and Lacto- N -Neotetraose, have been demonstrated safe and well-tolerated to be added into infant formula. However, the application in HMOs has been limited due to their insufficient availability. Thus, basic and clinical studies of HMOs need to be further elucidated. • The structures and composition of human milk oligosaccharides are summarized. • The absorption and metabolism of human milk oligosaccharides are discussed. • The biological functions of human milk oligosaccharides are reviewed. • The structure-function relationships of human milk oligosaccharides are presented. • The limitations and future perspectives of HMOs research are outlined. [ABSTRACT FROM AUTHOR]

In this study, an atmospheric‐pressure nanosecond impulse discharge initiated above the pyrrole microemulsion surface is applied to polymerize pyrrole and obtain a polypyrrole film. The films obtained under different number of plasma discharge times and duration of argon gas input time are investigated using a field emission scanning electron microscope. Results show that the roughness and thickness of the polypyrrole film can be tuned by controlling discharge times and the gas feed time. Four‐point sheet resistance measurements of the films reflect that those with a smoother and more complete surface have better electrical conductivity. The films are identified as polypyrrole by Fourier‐transform infrared spectroscopy, X‐ray diffraction, and X‐ray photoelectron spectrometry. Also, N2 is a critical factor in polymerizing polypyrrole and the gas–liquid plasma polymerization mechanism, which has three steps, is discussed. [ABSTRACT FROM AUTHOR]

In vitro diagnosis (IVD) is pivotal in modern medicine, enabling early disease detection and treatment optimization. Omics technologies, particularly proteomics and metabolomics, offer profound insights into IVD. Despite its significance, omics analyses for IVD face challenges, including low analyte concentrations and the complexity of biological environments. In addition, the direct omics analysis by mass spectrometry (MS) is often hampered by issues like large sample volume requirements and poor ionization efficiency. Through manipulating their size, surface charge, and functionalization, as well as the nanoparticle‐fluid incubation conditions, nanomaterials have emerged as a promising solution to extract biomolecules and enhance the desorption/ionization efficiency in MS detection. This review delves into the last five years of nanomaterial applications in omics, focusing on their role in the enrichment, separation, and ionization analysis of proteins and metabolites for IVD. It aims to provide a comprehensive update on nanomaterial design and application in omics, highlighting their potential to revolutionize IVD. [ABSTRACT FROM AUTHOR]

Probabilistic forecasts of wind power generation play a significant role in operation management and decision-making for wind power producers and power system operators. This study introduces a novel joint quantile model based on the use of Mercer's kernels in the vector-valued RKHSs (Reproducing Kernel Hilbert Spaces) for the nonparametric probabilistic forecasts of wind power. The proposed approach takes the autocorrelation of the (nonlinearly) transformed input and output into consideration and improves the model flexibility by constructing composite kernels. Besides, the model is optimized by a new meta-heuristics algorithm named Multi-Objective Salp Swarm Optimization Algorithm (MSSA), which mathematically models and mimics the behavior of salp swarms for solving multiple objective optimization problems. Under this model framework, several conditional quantiles of wind power can be estimated and predicted at the same time. Moreover, due to the joint estimation process, the problem of quantile curve crossing can be effectively weakened during the process of model training. The qualitative and quantitative performances of the proposed method are tested and verified on a set of real case studies. The results show that the proposed algorithm provides superior outputs compared to the well-known and recent algorithms in the literature. • The proposed model can provide multiple quantile predictions simultaneously. • It is the first time to construct composite kernels for the joint quantile model. • This paper considers the autocorrelation of the transformed input and output. • This study uses a new meta-heuristics algorithm to optimize the proposed model. [ABSTRACT FROM AUTHOR]

• Residential energy consumption has become the second-largest energy sector after the industrial sector. • The impact of urbanization on residential energy consumption is heterogeneous across income stages. • The impact of urbanization on residential energy consumption is heterogeneous across urbanization stages. • Urbanization has a positive effect on residential electricity consumption and shows heterogeneity across regions. • Urbanization contributes more to increase of rural residential electricity consumption than that of urban's. Against the background of the continuous development of urbanization, the urbanization process can lead to substantial changes in residential energy consumption and structures. Residential energy consumption has become the second-largest energy sector after the industrial sector. The paper studies the impact of urbanization on residential energy consumption using annual Chinese provincial data from 1996 to 2014. The results show the following. First, the impact of urbanization on residential energy consumption is heterogeneous across different per-capital income stages and urbanization stages. Second, urbanization has a positive effect on residential electricity consumption with a coefficient of 1.1 and shows heterogeneity across regions. Third, a higher urbanization rate leads to an increase in both urban and rural residential electricity consumption, with a more substantial impact on the latter. As a result, the increase in the urbanization rate contributes to shrinking the gap between urban and rural residential electricity consumption. Finally, based on the conclusions set forth above, policy implications for sustainable urbanization development under the energy constraints are given. [ABSTRACT FROM AUTHOR]

Milk-derived small extracellular vesicles (M-sEVs), a critical bioactive component in breast milk, are believed to have an essential role in health, especially in infant development. In early life, bifidobacteria are a dominant genera in the gastrointestinal tract, which can be regulated by specific compounds such as human milk oligosaccharides. However, little is known about the effects of M-sEVs on bifidobacteria. Here, a novel method to generate high-yield M-sEVs was developed and then representative bifidobacteria species were exposed to those M-sEVs. We found that M-sEVs stimulated the growth of bifidobacteria and were absorbed by the bifidobacteria. Different bifidobacteria species responded variously to the M-sEVs. Next, we demonstrated that M-sEVs altered the mRNA profile of B. longum subsp. infantis , and regulated some genes related to carbohydrate metabolism of B. longum subsp. infantis and other bifidobacteria species to accelerate bifidobacteria growth. Overall, the study revealed the supportive effects of M-sEVs on bifidobacteria, and the mechanisms involved. • M-sEVs promote the growth rate of bifidobacteria and increase bacteria numbers of bifidobacteria. • Different bifidobacteria species respond to the M-sEVs variously. • M-sEVs can be uptake by bifidobacteria and regulate genes expression of bifidobacteria. • M-sEVs promote B. longum subsp. infantis growth by accelerating glucose metabolism. [ABSTRACT FROM AUTHOR]

Background: Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecologic malignancies and has a poor prognosis due to metastasis. Drugs targeting the angiogenesis pathway significantly improve patient outcome. However, the key factors linking angiogenesis and metastasis have not been elucidated. In this study, we found Tie2 expressing monocytes (CD14+Tie2+, TEMs) as key contributors to angiogenesis and metastasis of EOC.Methods: Tissue slides were evaluated by immunofluorescence for the presence of total tissue macrophages and TEMs. The correlation between microvascular density (MVD) values and the TEMs number or ratio was calculated in both ovarian cancer tissues and peritoneum. The rate of TEMs in monocytes was evaluated in the peripheral blood of female healthy donors, benign cysts patients, and EOC patients using flow cytometry. The TEMs rate in ascites from EOC patients was also evaluated by flow cytometry. The concentration of Ang2, as the ligand of Tie2, was examined by ELISA in serum samples of EOC patients, benign cysts patients, and ascites samples of EOC patients. The effects of Ang2 on the migration and the cytokine expression of TEMs were further examined. The pro- angiogenesis activity of TEMs via IGF1 was performed in both in vivo and in vitro. And the IGF1 blocking test was performed using neutralising antibody.Results: TEMs were significantly higher in tumour foci, peripheral blood and ascites in EOC patients. The proportion of TEMs among total tissue macrophages was positively correlated with tumour MVD. In vivo animal results showed that TEMs promoted EOC angiogenesis and metastasis. Further functional and mechanisms studies revealed that concentration of angiopoietin 2 (Ang2), a ligand of Tie2, was elevated in EOC ascites which further recruit TEMs in a dose-dependent manner as a powerful chemokine to TEMs. Recruited TEMs promoted endothelial cell function through IGF1-activated downstream signalling. Blocking secreted IGF1 using inhibiting antibody reduced TEMs mediated angiogenesis and metastasis.Conclusions: TEMs significantly increased in EOC patients and were recruited to tumour loci by the increased Ang2. The increased TEMs have diagnostic value in ovarian cancer and were positively correlated with the MVD in ovarian cancer tissue. Furthermore, TEMs promote angiogenesis via IGF1 in both in vivo and in vitro experimental systems after stimulation by Ang2. Altogether, this study paves the way to develop novel therapy targets as the axis of Ang2-TEMs-IGF1 in EOC. [ABSTRACT FROM AUTHOR]

Background: Asparaginyl endopeptidase (AEP) has been implicated in human cancer development. However, the molecular mechanisms underlying AEP regulation, including the role of pro-AEP activation, remain elusive.Methods: We investigated the regulation of AEP by TRAF6 and its effects on tumor progression and metastasis in cancer cell lines, murine models, and specimens from patients using biochemical analyses, confocal microscopy, immunoelectron microscopy, and migration-invasion assays. The sera of healthy donors and breast cancer patients were examined by enzyme-linked immunosorbent assay, and a tissue array of 314 breast cancer specimens was assessed for AEP and TRAF6 by immunohistochemistry. Furthermore, the effects of AEP inhibitors or monoclonal antibodies on pulmonary metastasis were evaluated in murine models. The statistical significance between groups was determined using two-tailed Student t tests.Results: We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. Disrupting the interaction between pro-AEP and TRAF6 or inhibiting HSP90α reduced pro-AEP secretion and consequently reduced tumor metastasis. Higher circulating AEP levels were detected in the sera of breast cancer patients, and AEP inhibitors or neutralizing antibodies remarkably decreased tumor metastasis in murine models. Notably, TRAF6 and AEP were overexpressed in human breast neoplasms and correlated with poor prognosis. Patients with low AEP/TRAF6 expression survived for a mean of 111 months (95% confidence interval [CI] = 108 to 115 months), whereas those with high AEP/TRAF6 expression survived for a mean of only 61 months (95% CI = 42 to 79 months; P < .001).Conclusions: Our study elucidates a novel mechanism of AEP regulation and an alternative oncogenic pathway for TRAF6 in breast cancer, which suggests that AEP and TRAF6 protein levels may have prognostic implications in breast cancer patients. Thus, AEP may serve as a biomarker as well as new therapeutic target. [ABSTRACT FROM AUTHOR]

Background Asparaginyl endopeptidase (AEP) has been implicated in human cancer development. However, the molecular mechanisms underlying AEP regulation, including the role of pro-AEP activation, remain elusive. Methods We investigated the regulation of AEP by TRAF6 and its effects on tumor progression and metastasis in cancer cell lines, murine models, and specimens from patients using biochemical analyses, confocal microscopy, immunoelectron microscopy, and migration-invasion assays. The sera of healthy donors and breast cancer patients were examined by enzyme-linked immunosorbent assay, and a tissue array of 314 breast cancer specimens was assessed for AEP and TRAF6 by immunohistochemistry. Furthermore, the effects of AEP inhibitors or monoclonal antibodies on pulmonary metastasis were evaluated in murine models. The statistical significance between groups was determined using two-tailed Student t tests. Results We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. Disrupting the interaction between pro-AEP and TRAF6 or inhibiting HSP90α reduced pro-AEP secretion and consequently reduced tumor metastasis. Higher circulating AEP levels were detected in the sera of breast cancer patients, and AEP inhibitors or neutralizing antibodies remarkably decreased tumor metastasis in murine models. Notably, TRAF6 and AEP were overexpressed in human breast neoplasms and correlated with poor prognosis. Patients with low AEP/TRAF6 expression survived for a mean of 111 months (95% confidence interval [CI] = 108 to 115 months), whereas those with high AEP/TRAF6 expression survived for a mean of only 61 months (95% CI = 42 to 79 months; P < .001). Conclusions Our study elucidates a novel mechanism of AEP regulation and an alternative oncogenic pathway for TRAF6 in breast cancer, which suggests that AEP and TRAF6 protein levels may have prognostic implications in breast cancer patients. Thus, AEP may serve as a biomarker as well as new therapeutic target. [ABSTRACT FROM AUTHOR]