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Abstract As one of the most common malignancies, colorectal cancer (CRC) usually starts with a benign lesion and accumulates DNA damage as it progresses to full-fledged cancer. Glycyrrhizin (GL) has been found to alleviate tumor growth and inflammation, while the role of GL influences DNA damage response (DDR) in colorectal cancer remains unclear. GL exposure significantly reduced cell colony formation and viability with a concomitant increase in DNA fragmentation in CRC, meanwhile GL induced apoptosis by activating caspase-3. Moreover, GL induced cell cycle arrest in CRC cells at S phase, which was associated with decreased cyclin D1 in vitro. GL treatment significantly ameliorated tumor growth and promoted DDR in vivo. Mechanism analysis revealed that GL significantly downregulated the NHEJ pathway via inhibiting HMGB1. Finally, the expression of HMGB1 was abnormal regulated in CRC tissue than in adjacent normal tissues and associated with TNM stage and overall survival. Our findings indicate that HMGB1 may be a novel therapeutic target in CRC, a result that GL may serve as a promising drug for CRC treatment.

In the paper, metabolomics techniques based on UHPLC-QE-MS were used to study raw black beans, steaming black beans, and their in vitro digestion products. The results show that the three groups of raw black beans, atmospheric pressure-steamed black beans, and their in vitro digests comprised 922, 945, and 878 characteristic metabolites, respectively, dominated by amino acids, organic acids, polyphenols, and sugars. After screening the differential metabolites, content comparison, the content of amino acids, sugars, and phenolics in black beans was found to be increased after atmospheric steaming. During in vitro digestion, the amino acid content increased and the phenolic content decreased, with amino acid synthesis, phenolic degradation, and conversion predominating. This study provides data to support the changes in black beans metabolites during atmospheric steam processing and in vitro digestion.

Pupil tracking technology is a tracking and detection method that uses eye image information to extract real-time position information of the pupil. Detecting the pilot’s eye movement patterns and characteristics through pupil movement signals is an important part of monitoring the pilot’s physiological characteristics. The current pupil tracking algorithm is prone to problems such as insufficient tracking accuracy and discontinuous pupil signals when faced with problems such as pupil occlusion caused by frequent blinking and loss of pupil information in dark light environments that occur during flight training for pilot students. To increase the tracking accuracy of pilots’ pupils, this paper designs an integrated neural network-based pupil tracking technology for wearable gaze tracking devices in flight training. To solve the above problems, this paper builds a pupil positioning model based on the hybrid neural network by combining the feature pyramid and ViT network. On this basis, we built a hybrid neural network pupil tracking model for occluded pupil images based on the pilot eye data characteristics collected during flight training and designed a new loss function suitable for pupil detection. After verification, the pupil tracking algorithm we proposed has significantly improved the visual tracking accuracy with an error range of less than 5 pixels compared with existing methods, and the tracking accuracy can reach up to 85%. In pilot flight training, this algorithm has better pupil tracking stability, can effectively reduce pupil signal interference caused by pupil occlusion, and can achieve more accurate real-time tracking of pupils.

This study aims to capture subtle changes in the pupil, identify relatively weak inter-class changes, extract more abstract and discriminative pupil features, and study a pupil refinement recognition method based on attention mechanisms. Based on the deep learning framework and the ResNet101 deep residual network as the backbone network, a pupil refinement recognition model is established. Among them, the image preprocessing module is used to preprocess the pupil images captured by infrared spectroscopy, removing internal noise from the pupil images. By using the ResNet101 backbone network, subtle changes in the pupil are captured, weak inter-class changes are identified, and different features of the pupil image are extracted. The channel attention module is used to screen pupil features and obtain key pupil features. External attention modules are used to enhance the expression of key pupil feature information and extract more abstract and discriminative pupil features. The Softmax classifier is used to process the pupil features captured by infrared spectra and output refined pupil recognition results. Experimental results show that this method can effectively preprocess pupil images captured by infrared spectroscopy and extract pupil features. This method can effectively achieve fine pupil recognition, and the fine recognition effect is relatively good.

With the rapid development of wearable biosensor technology, the combination of head-mounted displays and augmented reality (AR) technology has shown great potential for health monitoring and biomedical diagnosis applications. However, further optimizing its performance and improving data interaction accuracy remain crucial issues that must be addressed. In this study, we develop smart glasses based on augmented reality and eye tracking technology. Through real-time information interaction with the server, the smart glasses realize accurate scene perception and analysis of the user’s intention and combine with mixed-reality display technology to provide dynamic and real-time intelligent interaction services. A multi-level hardware architecture and optimized data processing process are adopted during the research process to enhance the system’s real-time accuracy. Meanwhile, combining the deep learning method with the geometric model significantly improves the system’s ability to perceive user behavior and environmental information in complex environments. The experimental results show that when the distance between the subject and the display is 1 m, the eye tracking accuracy of the smart glasses can reach 1.0° with an error of no more than ±0.1°. This study demonstrates that the effective integration of AR and eye tracking technology dramatically improves the functional performance of smart glasses in multiple scenarios. Future research will further optimize smart glasses’ algorithms and hardware performance, enhance their application potential in daily health monitoring and medical diagnosis, and provide more possibilities for the innovative development of wearable devices in medical and health management.

Abstract Background The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation on the basis of preclinical trial reports. Methods Publicly available databases (PubMed, Embase, Medline, Web of Science and Cochrane Library.) and register (Clinicaltrials.gov) were searched to collect treatment outcomes of oncolytic virotherapies (including herpes simplex virus type 1 (HSV), coxsackievirus A21 (CVA21), adenovirus, poxvirus and reovirus) for advanced/unresectable melanoma. Comparisons of treatment response, adverse events (AEs) and survival analyses for different virotherapies were performed by R software based on the extracted data from eligible studies. Results Finally, thirty-four eligible studies were analysed and HSV virotherapy had the highest average complete response (CR, 24.8%) and HSV had a slightly higher average overall response rate (ORR) than CVA21 (43.8% vs 42.6%). In the pooled results of comparing talimogene laherparepve (T-VEC) with or without GM-CSF/ICIs (immune checkpoint inhibitors) to GM-CSF/ICIs monotherapy suggested virotherapy was more efficient in subgroups CR (RR = 1.80, 95% CI [1.30; 2.51], P

The aim of this study was to investigate the potential of adding soya bean dregs insoluble dietary fibre (IDF) modified by jet cavitation combined with cellulase to yoghurt to improve its functional properties (Yoghurt was prepared by adding 10 μL of yoghurt fermenter to 100 mL of milk, fermented to pH 4.5 in a constant temperature incubator at 42 °C, and then stored in a refrigerator at 4 °C after adding IDF separately). The results showed that the modified IDF had a rough structure with high water-holding capacity and sodium cholate adsorption capacity. The addition of modified IDF improved the pH, hardness, and elasticity of the yoghurt. During the entire storage period, the titratable acidity and whey precipitation rate of the modified IDF yoghurt gradually increased, and antioxidant activity gradually decreased, and its titratable acidity, whey precipitation rate, and antioxidant activity had a significant advantage compared with those of the blank group yoghurt. In conclusion, the modified soya bean dregs IDF-added yoghurt prepared by jet cavitation combined with the cellulase method has the potential for sodium cholate adsorption capacity and antioxidant activity, which can confer unique functional properties and improve the pH, texture, and reduce whey precipitation of yoghurt. This study provides a scientific basis for the application of soya bean dregs IDF as a fibre fortifier in yoghurt production and suggests innovative ideas for the design of functional dairy products.

Improving the efficiency of human-computer interaction is one of the critical goals of intelligent aircraft cockpit research. The gaze interaction control method can vastly reduce the manual operation of operators and improve the intellectual level of human-computer interaction. Eye-tracking is the basis of sight interaction, so the performance of eye-tracking will directly affect the outcome of gaze interaction. This paper presents an eye-tracking method suitable for human-computer interaction in an aircraft cockpit, which can now estimate the gaze position of operators on multiple screens based on face images. We use a multi-camera system to capture facial images, so that operators are not limited by the angle of head rotation. To improve the accuracy of gaze estimation, we have constructed a hybrid network. One branch uses the transformer framework to extract the global features of the face images; the other branch uses a convolutional neural network structure to extract the local features of the face images. Finally, the extracted features of the two branches are fused for eye-tracking. The experimental results show that the proposed method not only solves the problem of limited head movement for operators but also improves the accuracy of gaze estimation. In addition, our method has a capture rate of more than 80% for targets of different sizes, which is better than the other compared models.

Many food proteins can be assembled into nanofibrils under pH conditions far from the isoelectric point and with a low ionic strength by heating them for a long period. These food protein nanofibrils (FPN) have outstanding functional and biological properties and are considered sustainable biomaterials in many fields. In this study, we review the recent developments in FPN gels and introduce the key factors in promoting food protein self-assembly in order to create functional gels. The major variables discussed are the morphology of nanofibrils, protein concentration, heating time, and the type and concentration of salts. We also highlight current advances in the formation and properties of different types of FPN gels. In addition, the various applications of FPN gels in bioactive and nutrient delivery, adsorbents for CO2 and toxic pollutants, cell scaffolding biomaterials, biosensors, and others are introduced and discussed.

Abstract Background Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are of potential magnetic resonance imaging (MRI) contrast agents for tumor diagnosis. However, ultrasmall particle size or negative surface charge lead to relative short half-life which limit the utilization of USPIO for in vivo MRI contrast agents. Methods Superparamagnetic Fe3O4 nanoparticles coated with polyacrylic acid (PAA)were synthetized, and modified by 3-amino propanol and 3-diethyl amino propyl amine. The characteristics of superparamagnetic Fe3O4 nanoparticles were investigated through transmission electron microscopy, X-ray diffraction analysis, Zata potential analysis, thermogravimetric analysis, and relaxation properties analysis. Magnetic resonance imaging animal experiment was performed. Results The synthetized nanoparticles were irregular spherical, with small particle size, few agglomeration, and good dispersion in water. After modification, the potential fluctuation of nanoparticles was small, and the isoelectric point of nanoparticles changed to high pH. After 3-amino propanol modification, the weight loss of the curve from 820 to 940 °C was attributed to the decomposition of 3-amino propanol molecules on the surface. The T1 relaxation rate of nanoparticles changed little before and after modification, which proved that the modification didn’t change the relaxation time. Brighter vascular images were observed after 3-amino propanol modification through measurement of magnetic resonance tumor imaging. Conclusion These data indicated the Fe3O4 nanoparticles modified by 3-amino propanol should be a better contrast agent in the field of magnetic resonance tumor imaging.

In complex environments of wireless communication, to improve the communication anti-interference performance, quasi-synchronous frequency-hopping (FH) communication system requires low-hit-zone (LHZ) FH sequence sets with optimal Hamming correlation (HC) properties and flexible parameters. In this paper, based upon cyclotomy theory, two classes of LHZ FH sequence sets with flexible parameters not included in the literatures are designed, and the periodic HC properties of which are analyzed. It turns out that the designed LHZ FH sequence sets are optimal on the maximum periodic HC. And thus the new constructions can be used to provide optimal FH sequence sets for quasi-synchronous FH communication system.

Inferring gaze targeting or gaze following is an effective approach for comprehending human behavior and intentions. This paper employs a non-intrusive appearance-based tracking technique, utilizing a binocular stereo vision camera to capture the face image and head pose to address errors caused by problems such as the disappearance of the eye image and head deflection occlusion in image capture. Each gaze direction is determined based on a single image frame. To improve the classification and detection of the gaze target region by effectively handling head motion and view direction, this paper proposes a hybrid structure for the Swin Transformer gaze target region classification method. The facial image features are extracted using both the ResNet50 model and the Swin Transformer model, followed by fusing head pose features to categorise the gaze target area. The study also compares the classification effects of various structural models. The analysis of the results demonstrates that the hybrid Swin Transformer model outperforms in classifying and detecting the gaze target region, achieving an accuracy rate of 90%. Finally, the research examines the gaze of flight trainees during flight missions by using a heatmap, which lays the groundwork for future analyses of pilot attention and operational intentions during flights.

To thoroughly understand the profile of phenolic phytochemicals in kidney bean seeds cultivated in a cold region, the extractions, contents, antioxidant activities, compositions of free and bound phenols in the seed coat and cotyledon, and also relevant color attributes, were investigated. The results indicated that ultrasound-assisted extraction was an efficient method for free phenols. The bound phenols in seed coat and cotyledon were released more efficiently by alkali-acid and acid-alkali sequential hydrolysis, respectively. Under the optimized extractions, total phenols (TPC), flavonoids (TFC), and anthocyanins (TAC) ranged in 7.81–32.89 mg GAE/g dw, 3.23–15.65 mg RE/g dw, and 0–0.21 mg CE/g dw in the whole seeds of the five common kidney beans. There was a big difference in phenolic distribution between red and white seeds. From whole seed, the phenols in the four red cultivars mainly existed in free state (78.84%) and seed coat (71.56%), while the phenols in the white ‘Sark’ divided equally between free (51.18%) and bound (48.82%) states and consisted chiefly in cotyledon (81.58%). The correlation analyses showed that the antioxidant activities were significantly and positively correlated with TPC and TFC. The phenolic attributes were closely associated with the color of the seed coat. Red seeds had higher total contents of phenols than white seeds. TAC had a positively significant correlation with redness. Brightness and yellowness showed a negatively significant correlation with TPC, TFC, and antioxidant capacities, which were necessarily linked with redness degree and spot in red seeds. The spotted red ‘Yikeshu’ with the most outstanding performance on phenolic attributes was selected to analyze phenolic compounds with UHPLC-QE-MS. Among the 85 identified phenolics, 2 phenolic acids and 10 flavonoids were dominant. The characteristic phenolics in free and bound states were screened in both seed coat and cotyledon, respectively. The available information on the phenolic profile may expand the utilization of kidney beans as a nutritional ingredient in the food industry.

Breast cancer deaths are primarily caused by metastasis. There are several treatment options that can be used to treat breast cancer. There are, however, a limited number of treatments that can either prevent or inhibit the spread of breast tumor metastases. Thus, novel therapeutic strategies are needed. Studies have increasingly focused on the importance of the tumor microenvironment (TME) in metastasis of breast cancer. As the most abundant cells in the TME, cancer-associated fibroblasts (CAFs) play important roles in cancer pathogenesis. They can remodel the structure of the extracellular matrix (ECM) and engage in crosstalk with cancer cells or other stroma cells by secreting growth factors, cytokines, and chemokines, as well as components of the ECM, which assist the tumor cells to invade through the TME and cause distant metastasis. Clinically, CAFs not only foster the initiation, growth, angiogenesis, invasion, and metastasis of breast cancer but also serve as biomarkers for diagnosis, therapy, and prediction of prognosis. In this review, we summarize the biological characteristics and subtypes of CAFs and their functions in breast cancer metastasis, focusing on their important roles in the diagnosis, prognosis, and treatment of breast cancer. Recent studies suggest that CAFs are vital partners of breast cancer cells that assist metastasis and may represent ideal targets for prevention and treatment of breast cancer metastasis.

Soybeans are rich in proteins and phytochemicals such as isoflavones and phenolic compounds. It is an excellent source of peptides with numerous biological functions, including anti-inflammatory, anticancer, and antidiabetic activities. Soy bioactive peptides are small building blocks of proteins that are released after fermentation or gastrointestinal digestion as well as by food processing through enzymatic hydrolysis, often in combination with novel food processing techniques (i.e., microwave, ultrasound, and high-pressure homogenization), which are associated with numerous health benefits. Various studies have reported the potential health benefits of soybean-derived functional peptides, which have made them a great substitute for many chemical-based functional elements in foods and pharmaceutical products for a healthy lifestyle. This review provides unprecedented and up-to-date insights into the role of soybean peptides in various diseases and metabolic disorders, ranging from diabetes and hypertension to neurodegenerative disorders and viral infections with mechanisms were discussed. In addition, we discuss all the known techniques, including conventional and emerging approaches, for the prediction of active soybean peptides. Finally, real-life applications of soybean peptides as functional entities in food and pharmaceutical products are discussed.

Abstract Osteoporosis (OP) is a common bone disease of old age resulting from the imbalance between bone resorption and bone formation. CircRNAs are a class of endogenous non-coding RNAs (ncRNAs) involved in gene regulation and may play important roles in the development of OP. Here, we aimed to discover the OP‑related circRNA–miRNA–mRNA (ceRNA) network and the potential mechanisms. Six microarray datasets were obtained from the GEO database and the OP‑related differentially expressed genes (DEGs), circRNAs (DECs), and miRNAs (DEMs) were screened out from these datasets. Then, combined with the prediction of the relationships between DEGs, DEMs, and DECs, a ceRNA network containing 7 target circRNAs, 5 target miRNAs, and 38 target genes was constructed. Then the RNA-seq verification by using total RNAs isolated from the femurs of normal and ovariectomized Wistar rats indicated that MFAP5, CAMK2A, and RGS4 in the ceRNA network were closely associated with osteoporosis. Function enrichment analysis indicated that the target circRNAs, miRNAs, and genes were involved in the process of MAPK cascade, hormone stimulus, cadherin binding, rRNA methyltransferase, PI3K-Akt signaling pathway, and Vitamin digestion and absorption, etc. Then a circRNA–miRNA–hub gene subnetwork was constructed and the qRT-PCR analysis of human bone tissues from the femoral head was used to confirm that the transcription of hsa_circR_0028877, hsa_circR_0082916, DIRAS2, CAMK2A, and MAPK4 showed a significant correlation with osteogenic genes. Besides, the two axes of hsa_circR_0028877/hsa-miR-1273f/CAMK2A and hsa_circR_0028877/hsa-miR-1273f/DIRAS2 conformed to be closely associated with OP. Additionally, by constructing a drug-target gene network, RKI-1447, FRAX486, Hyaluronic, and Fostamatinib were identified as therapeutic options for OP. Our study revealed the potential links between circRNAs, miRNAs, and mRNAs in OP, suggesting that the ceRNA mechanism might contribute to the occurrence of OP.

Mung bean seeds were treated by a combination of ultrasound and γ-aminobutyric acid (GABA). Effect of these treatments on the free polyphenols content, antioxidant activity, and digestibility of mung bean sprouts was evaluated. Additionally, phenolic compounds were analyzed and identified using a metabolomics approach. The combined ultrasound and GABA treatments significantly enhanced the free polyphenols and flavonoids content (P

Abstract Purpose To investigate the efficacy and safety of pyrotinib in treating patients with human epidermal growth factor receptor type 2 (HER2)‐positive breast cancers with brain metastasis. Patients and Methods This is a multicenter retrospective study, and the HER2‐positive breast cancer patients with brain metastasis were studied. The enrolled patients were given pyrotinib 400 mg orally once per day for 21 days as one cycle, and evaluated every two cycles. All relevant data were detected for final assessments including medical history, clinical examination, histopathology, immunohistochemistry, radiographic imaging, treatment outcome, and adverse events. Results Forty‐two female patients in total were enrolled in this study. The objective response rate (ORR) and disease control rate (DCR) of central nervous system (CNS), were found in 20 of 42 (47.6%) and in 39 of 42 (92.8%), respectively, while for extra‐CNS, the respective ORR and DCR were in 9 of 38 (23.6%) and in 36 of 38 (94.7%), respectively. The compounded ORR and DCR were seen in 17 of 42 (40.4%) and in 39 of 42 (92.8%), respectively. The improvement rate of craniocerebral symptoms after treatment was (19/19) 100% and the median duration was 15 months. The median effective time of brain metastases and other metastases was 43 and 50 days. The median follow‐up time was 22 months (interquartile range, 16.0–24.3 months). The median time for progression in brain metastasis was 16.6 months. The median time to progress for our group patients was 11.1 months. Sixteen patients (36%) with adverse reactions were recorded in the study. Conclusion Pyrotinib combined with chemotherapy/radiotherapy or alone showed significantly greater local control rates and progression free survival (PFS), with manageable toxicity for patients with HER2‐positive breast cancer with brain metastases, and further follow‐up will provide an overall survival (OS) data.

In application, frequency-hopping (FH) communication system often suffers various interferences, such as single frequency narrow-band interference, partial band blocking interference and tracking interference, and so on. For all that, by using optimal Wide-Gap (WG) FH sequences, FH communication system can significantly improve the anti-interference performances. In this paper, the relations between WG FH sequence theoretic bounds published in the journal IEEE Access (Peihua Li et al., 2019) are first made clear, and then five types of generalized methods are presented to design new classes of WG FH sequence sets. It is shown that all designed WG FH sequence sets are optimal according to the bound derived by Peihua Li et al. And by selecting appropriate original sequence sets, many of the optimal WG FH sequence sets can be obtained by our methods. Most importantly, these WG FH sequence sets have new parameters that are not covered in the literature.

IntroductionHeat stress caused by high temperatures has important adverse effects on the safety and health status of humans and animals, and dietary interventions to alleviate heat stress in daily life are highly feasible.MethodsIn this study, the components of mung bean that have heat stress-regulating effects were characterized by in vitro antioxidant indicators and heat stress cell models.ResultsAs a result, 15 target monomeric polyphenol fractions were identified based on untargeted analysis on an ultra performance liquid chromatography coupled with high field quadrupole orbit high resolution mass spectrometry (UHPLC-QE-HF-HRMS) platform and available reports. The results of DPPH and ABTS radical scavenging showed that mung bean polyphenols (crude extract) and 15 monomeric polyphenols had better antioxidant activity, followed by oil and mung bean peptides, while protein and polysaccharides had relatively poor antioxidant activity. Qualitative and quantitative assays for 20 polyphenols (15 polyphenols and 5 isomers) were then established based on platform targets. Vitexin, orientin, and caffeic acid were identified as monomeric polyphenols for heat stress control in mung beans based on their content. Finally, mild (39°C), moderate (41°C), and severe (43°C) heat stress models were successfully constructed based on mouse intestinal epithelial Mode-k cells and human colorectal adenocarcinoma Caco-2 cell lines, all with an optimal heat stress modeling time of 6 h. Screening of mung bean fractions using HSP70 mRNA content, a key indicator of heat stress. As a result, HSP70 mRNA content was significantly up-regulated by different levels of heat stress in both cell models. The addition of mung bean polyphenols (crude extract), vitexin, orientin, and caffeic acid resulted in significant down-regulation of HSP70 mRNA content, and the higher the level of heat stress, the more significant the regulation effect, with orientin having the best effect. Mung bean proteins, peptides, polysaccharides, oils and mung bean soup resulted in increased or no change in HSP70 mRNA levels after most heat stresses.DiscussionThe polyphenols were shown to be the main heat stress regulating components in mung bean. The results of the validation experiments confirm that the above three monomeric polyphenols may be the main heat stress regulating substances in mung bean. The role of polyphenols in the regulation of heat stress is closely linked to their antioxidant properties.

In this work, (1 [Formula: see text])(0.92NaNbO3–0.08BaTiO3)–[Formula: see text]Ca[Formula: see text]La[Formula: see text]TiO3 (NNBT – [Formula: see text]CLT) ceramics were successfully designed and prepared by the solid-state reaction method. Investigations on the structure, dielectric, and energy storage properties were performed. The NNBT – 0.25CLT ceramic with orthorhombic phase at room temperature was found to exhibit extremely small grain size and compacted microstructure. A large [Formula: see text] of 3.1 J/cm3 and a high [Formula: see text] of 91.5% under the electric field of 360 kV/cm were achieved simultaneously in the sample. In addition, the energy storage performance of the sample exhibits thermal stability over the temperature range of 25–140[Formula: see text]C and the frequency range of 5–500 Hz. The charge and discharge tests reveal that the ceramic shows a large current density [Formula: see text] of 965 A/cm2 and power density [Formula: see text] of 154 MW/cm3. This work demonstrates that the NNBT–0.25CLT ceramic is a prospective energy storage material for potential application in the field of pulsed power devices.

There needs to be more information concerning the effect of different milling methods on the physicochemical properties of whole-grain mung bean flour. Therefore, the physicochemical properties of whole grain mung bean flour were analyzed using universal grinders (UGMB), ball mills (BMMB), and vibration mills (VMMB). The results showed that the particle size of the sample after ultrafine grinding treatment was significantly reduced to 21.34 μm (BMMB) and 26.55 μm (VMMB), and the specific surface area was increased. The particle distribution was uniform to a greater extent, and the color was white after treatment. Moreover, the water holding capacity (WHC), oil holding capacity (OHC), and swelling power (SP) increased, and the bulk density and solubility (S) decreased. The Rapid Viscosity Analyzer (RVA) indicated that the final viscosity of the sample after ultrafine grinding was high. Furthermore, rheological tests demonstrated that the consistency coefficient K, shear resistance, and viscosity were decreased. The results of functional experiments showed that the treated samples (BMMB and VMMB) increased their capacity for cation exchange by 0.59 and 8.28%, respectively, bile acid salt adsorption capacity increased from 25.56 to 27.27 mg/g and 26.38 mg/g, and nitrite adsorption capacity increased from 0.58 to 1.17 mg/g and 1.12 mg/g.

Optical coating damage detection is a part of both industrial production and scientific research. Traditional methods require sophisticated expert systems or experienced front-line producers, and the cost of these methods rises dramatically when film types or inspection environments change. In practice, it has been found that customized expert systems imply a significant investment of time and money, and we expect to find a method that can perform this task automatically and quickly, while at the same time the method should be adaptable to the later addition of coating types and the ability to identify damage kinds. In this paper, we propose a deep neural network-based detection tool that splits the task into two parts: damage classification and damage degree regression. Introduces attention mechanisms and Embedding operations to enhance the performance of the model. It was found that the damage type detection accuracy of our model reached 93.65%, and the regression loss was kept within 10% on different data sets. We believe that deep neural networks have great potential to tackle industrial defect detection by significantly reducing the design cost and time of traditional expert systems, while gaining the ability to detect entirely new damage types at a fraction of the cost.

BackgroundPolyphenols play an important role in human nutrition, therefore, how to improve its content with innovative approach is important, and understanding the metabolic pathys is necessary. Mung beans are rich in polyphenols, which made them have physiological functions such as hypoglycemia, antioxidant, and hypotension. However, the content of polyphenols in natural mung bean is relatively low, and it needs to be increased. The methods of increasing polyphenol content in grains and beans by enrichment include physical stress, such as ultrasonic stress, hypoxia stress and ultraviolet radiation, and single exogenous substance stress, such as exogenous amino acids, exogenous sugars. But, the enrichment of polyphenols using exogenous substances in combination with physical stress is less applied. Therefore, this study innovated the use of exogenous γ-aminobutyric acid (GABA) combined with ultrasonic stress to enrich mung bean sprouts polyphenols and enhance their content. The metabolic pathways of the enrichment process were also analyzed to provide a reference for studies related to the enrichment of polyphenols.MethodsMung bean seeds were pretreated with a combination of ultrasound and GABA under different conditions. Single-factor test and response surface methodology were used for optimizing pretreatment conditions of mung bean. Effects of combined pretreatments on the polyphenols content and antioxidant activity of sprouted mung beans were investigated. Additionally, metabolites were identified, and metabolic pathways were analyzed using non-targeted metabolomics techniques.ResultsOptimal conditions of mung bean pretreatment were found to be 370 W for ultrasound power, 40 min for ultrasonication time, 10 mmol/L for GABA concentration, and 8 h for the soaking duration. Under these conditions, the predicted polyphenol content was found to be 4.52 mg GAE/g DW. The pretreatment of mung beans with a combination of ultrasound and exogenous GABA resulted in mung bean sprouts with enhanced polyphenol content and antioxidant activity compared to mung beans germinated without pretreatment. A significant increase in the content of six polyphenols [Genistein, (-)-Epigallocatechin, Epicatechin, Nobiletin, Naringenin, Biochanin A] in the pretreated and germinated mung beans was found, and six metabolic pathways (flavonoid biosynthesis, isoflavones biosynthesis, biosynthesis of phenylpropanoids, anthocyanin biosynthesis, biosynthesis of secondary metabolites, and metabolic pathways) were significantly activated.ConclusionThe obtained results suggest that a combination of ultrasound and exogenous GABA treatment can be used to produce mung bean sprouts with enriched polyphenols content and enhanced antioxidant activity.

Heat stress due to high temperatures can cause heat stroke, pyrexia, heat cramps, heart disease, and respiratory diseases, which seriously affect human health. Vitexin has been shown to alleviate heat stress; however, its mechanism of action remains unclear. Therefore, in this study, we used Caco-2 cells to establish a heat stress model and vitamin C as a positive control to investigate the regulatory effects of vitexin on heat-stress-induced apoptosis and the related mechanisms using Cell Counting Kit-8, flow cytometry, real-time quantitative polymerase chain reaction, and Western blot. The results showed that the mRNA expressions of Hsp27, Hsp70, and Hsp90 induced by heat stress could be effectively inhibited at vitexin concentrations as low as 30 μM. After heat stress prevention and heat stress amelioration in model cells based on this concentration, intracellular reactive oxygen species (ROS) levels and the mRNA level and the protein expression of heat shock proteins (Hsp70 and Hsp90) and apoptotic proteins were reduced. In addition, compared with the heat stress amelioration group, the expression of BCL2 mRNA and its protein (anti-apoptotic protein Bcl-2) increased in the heat stress prevention group, while the expression of BAX, CYCS, CASP3, and PARP1 mRNAs and their proteins (apoptotic proteins Bax, Cytochrome C, cle-Caspase-3, and cle-PARP1) were decreased. In summary, the heat-stress-preventive effect of vitexin was slightly better than its heat-stress-ameliorating effect, and its mechanism may be through the inhibition of intracellular ROS levels and thus the modulation of the expressions of Hsp70 and Hsp90, which in turn protects against heat-stress-induced apoptosis. This study provides a theoretical basis for the prevention and amelioration of heat stress using vitexin.

CYP46A1 is a brain-specific enzyme responsible for cholesterol homeostasis. Inhibition of CYP46A1 activity serves as a therapeutic target for excitatory neurotoxicity. Sesame is a common medicine and food resource; its component lignans possess various pharmacological activities. In this study, the inhibitory effects of sesame lignans on CYP46A1 activity were investigated. Inhibition kinetics analyses revealed that sesamin and sesamolin produce mixed partial competitive inhibition of CYP46A1, while sesamol produces non-competitive inhibition. Notably, molecular simulations revealed that the sesame lignans have excellent orientations within the active cavity of CYP46A1. Importantly, the sesame lignans had high permeability coefficients and low efflux ratios. Furthermore, sesamin significantly reduced the levels of 24S-hydroxycholesterol in rat plasma and brain tissues, and down-regulated the protein expressions of CYP46A1, NMDAR2A, NMDAR2B, and HMGCR. Collectively, sesame lignans exhibit significant inhibitory effects on CYP46A1 activity, highlighting their potential therapeutic role in treating excitatory neurotoxicity.

Buckwheat has beneficial effects on human intestinal health, which is often compounded with wheat to make food. Therefore, the effect of cereals mixture via in vitro fermentation on gut microbes and short-chain fatty acids (SCFAs) were investigated in this study. The mixture of wheat and tartary buckwheat (WT) produced more lactate and acetate, and the mixture of wheat and sweet buckwheat (WE) produced more propionate and butyrate. Compared with wheat (WA), the relative abundance of some beneficial bacteria significantly increased, such as Sutterella in WT and Faecalibacterium in WE. Cereals mixture also affected the expression of functional genes, involved in metabolic pathways and carbohydrate-active enzymes (CAZymes) that modulated SCFAs generation. This study provides new insights into the effects of sweet and tartary buckwheat on intestinal function, which is beneficial to applying both types of buckwheat in practical.

Pilots’ loss of situational awareness is one of the human factors affecting aviation safety. Numerous studies have shown that pilot perception errors are one of the main reasons for a lack of situational awareness without a proper system to detect these errors. The main objective of this study is to examine the changes in pilots’ eye movements during various flight tasks from the perspective of visual awareness. The pilot’s gaze rule scanning strategy is mined through cSPADE, while a hidden semi-Markov model-based model is used to detect the pilot’s visuoperceptual state, linking the correlation between the hidden state and time. The performance of the proposed algorithm is then compared with that of the hidden Markov model (HMM), and the more flexible hidden semi-Markov model (HSMM) is shown to have an accuracy of 93.55%.

Mung bean proteins (MBPs) are highly nutritious food ingredients, but their lack of gluten limits their use in staple foods such as noodles. In this study, MBPs were modified by hydrothermal treatment, and their gel properties and the major structural changes were analyzed at different heating temperatures (25, 65, 75, 85, 95, and 105°C), moisture contents (0, 15, 20, 25, 30, and 35%), and hydrothermal treatment times (0, 15, 30, 45, 60, and 75 min). Thereafter, the modified MBPs (MMBPs) were added to wheat noodles at substitution levels of 3, 6, and 9% to evaluate their effect on the quality of the noodles. The results showed that the hydrothermal treatment significantly improved the gel properties and water absorption capacity of the MBPs and slightly increased their disulfide bond content. When MBPs with a 25% moisture content were heated at 85°C for 60 min, their gel properties notably improved, and their structural changes were maximal. The structural changes revealed that the MBP molecule formed a macromolecular polymer because a significant protein band appeared at about 66.2 kDa. Secondary structure and microstructure analyses revealed that the MBP structure was significantly damaged and that the β-sheet structure increased because of changes in the degree of aggregation between the protein molecules. Compared to the untreated MBPs, the MMBPs significantly improved the cooking quality and texture properties of the noodles, and the addition amount reached more than 6%, whereas that of the untreated MBPs was less than 3%. At this time, the cooking loss and the broken rate of the untreated MBPs group were about 2 times higher than that of the 6% MMBP-treated group. An analysis of changes in the water distribution, rheological properties, and microstructure revealed that intermolecular cross-linking occurred between the MMBPs and wheat dough, which improved the quality of the MMBP-treated noodles. The findings demonstrated that the MMBPs obtained by hydrothermal treatment had a positive effect on the wheat dough properties and noodle quality. These results provide a technical foundation for incorporating novel protein supplements into staple foods.

Cancer patients generally has a high risk of thrombotic diseases. However, anticoagulant therapy always aggravates bleeding risks. Rivaroxaban is one of the most widely used direct oral anticoagulants, which is used as anticoagulant treatment or prophylaxis in clinical practice. The present study aimed to systemically estimate the combination safety of rivaroxaban with tyrosine kinase inhibitors (TKIs) based on human cytochrome P450 (CYPs) and efflux transporters and to explore the drug–drug interaction (DDI) mechanisms in vivo and in vitro. In vivo pharmacokinetic experiments and in vitro enzyme incubation assays and bidirectional transport studies were conducted. Imatinib significantly increased the rivaroxaban Cmax value by 90.43% (p < 0.05) and the area under the curve value by 119.96% (p < 0.01) by inhibiting CYP2J2- and CYP3A4-mediated metabolism and breast cancer resistance protein (BCRP)- and P-glycoprotein (P-gp)-mediated efflux transportation in the absorption phase. In contrast, the combination of sunitinib with rivaroxaban reduced the exposure in vivo by 62.32% (p < 0.05) and the Cmax value by 72.56% (p < 0.05). In addition, gefitinib potently inhibited CYP2J2- and CYP3A4-mediated rivaroxaban metabolism with Ki values of 2.99 μΜ and 4.91 μΜ, respectively; however, it almost did not affect the pharmacokinetics of rivaroxaban in vivo. Taken together, clinically significant DDIs were observed in the combinations of rivaroxaban with imatinib and sunitinib. Imatinib increased the bleeding risks of rivaroxaban, while sunitinib had a risk of reducing therapy efficiency. Therefore, more attention should be paid to aviod harmful DDIs in the combinations of rivaroxaban with TKIs.

Dietary supplementation with mung bean peptides (MBPs) has several health benefits. However, the effect of MBPs on prediabetes and gut microbiota imbalance caused by a high-fat diet (HFD) has not been thoroughly studied. In this study, dietary supplementation with MBPs for 5 weeks significantly reduced HFD-induced body weight gain, hyperglycaemia, hyperlipidaemia, insulin resistance, inflammation, and oxidative stress and alleviated liver and kidney damage in mice. In addition, it significantly reversed the HFD-induced gut microbiota imbalance, increased the gut microbial diversity, and decreased the abundance of Firmicutes and Bacteroidetes in prediabetic mice. Furthermore, we identified Lachnospiraceae_NK4A136 and Lactobacillus as important eubacteria with the potential to alleviate the clinical symptoms of prediabetes. According to PICRUSt2 analysis, the changes in intestinal microflora induced by MBPs diet intervention may be related to the downregulation of expression of genes such as rocR, lysX1, and grdA and regulation of seven pathways, including pyruvate, succinic acid, and butyric acid. Moreover, 17 genera with significantly altered levels in the intestine of HFD-fed mice, including Akkermansia, Roseburia, and Ruminiclostridium, were significantly correlated with 26 important differential metabolites, such as D-glutathione, anti-oleic acid, and cucurbitacin. Overall, these results show that MBPs diet intervention plays a key role in the management of HFD-induced prediabetes.

Imipenem (IMP) possesses a broad spectrum of antibacterial activity; however, nephrotoxicity limits its clinical application in patients with renal insufficiency. In our previous studies, a dipeptide, JBP485, a dipeptide with the chemical structure cyclo-trans-4-L-hydroxyprolyl-L-serine, was found to attenuate drug-induced kidney injury. The current study aimed to explore whether JBP485 could relieve IMP-induced kidney injury and clarify the potential molecular pharmacokinetic mechanism. The effects of JBP485 on IMP nephrotoxicity were evaluated in rabbits and human kidney 2 (HK-2) cells. Drug-drug interactions (DDIs) mediated by organic anion transporters (OATs) and dehydropeptidase-I (DHP-I) were explored through pharmacokinetic studies in rats, metabolism assays in the kidney, and uptake studies in OAT-over-expressing cells. The results revealed that JBP485 significantly ameliorated IMP-induced nephrotoxicity in rabbits. Further, incubation of HK-2 cells with JBP485 or cilastatin markedly improved the cell survival rate, inhibited apoptosis and attenuated mitochondrial damage by improving the stability of IMP and reducing its intracellular accumulation. This suggests that DHP-I and OATs might be involved in the protective effect of JBP485. Furthermore, coadministration with JBP485 significantly increased the IMP’s plasma concentration as well as the area under the plasma concentration-time curve (AUC), while decreasing IMP renal clearance and cumulative urinary excretion. Moreover, JBP485 reduced IMP uptake in kidney slices and OAT1/3-human embryonic kidney 293 (HEK293) cells. At the same time, the metabolism of IMP by DHP-I was inhibited by JBP485 with an IC50 value of 12.15 ± 1.22 μM. Finally, the molecular docking assay revealed a direct interaction between JBP485 and OAT1/3 or DHP-I. In conclusion, JBP485 protected against IMP nephrotoxicity in rabbits and HK-2 cells by improving IMP stability and reducing its intracellular accumulation via simultaneous inhibition of renal OATs and DHP-I. JBP485 is a promising renoprotective agent and could serve as an effective supplement to reduce IMP-induced adverse renal reactions in the clinical setting.

Context The effect of kaempferol, a regulator of oestrogen receptors, on atherosclerosis (AS) and the underlying mechanism is elusive. Objective To explore the effect and mechanism of kaempferol on AS. Methods and materials In vivo, C57BL/6 and apolipoprotein E (APOE)–/– mice were randomly categorized into six groups (C57BL/6: control, ovariectomy (OVX), high-fat diet (HFD); APOE–/–: OVX-HFD, OVX-HFD + kaempferol (50 mg/kg) and OVX-HFD + kaempferol (100 mg/kg) and administered with kaempferol for 16 weeks, intragastrically. Oil-Red and haematoxylin–eosin (HE) staining were employed to examine the effect of kaempferol. In vitro, human aortic endothelial cells (HAECs) were pre-treated with or without kaempferol (5, 10 or 20 μM), followed by administration with kaempferol and oxidized low-density lipoprotein (ox-LDL) (200 μg/mL). The effect of kaempferol was evaluated using flow cytometry, and TdT-mediated dUTP Nick-End Labelling (TUNEL). Results In vivo, kaempferol (50 and 100 mg/kg) normalized the morphology of blood vessels and lipid levels and suppressed inflammation and apoptosis. It also activated the G protein-coupled oestrogen receptor (GPER) and PI3K/AKT/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. In vitro, ox-LDL (200 μg/mL) reduced the cell viability to 50% (IC50). Kaempferol (5, 10 or 20 μM) induced-GPER activation increased cell viability to nearly 10%, 19.8%, 30%, and the decreased cellular reactive oxygen species (ROS) generation (16.7%, 25.6%, 31.1%), respectively, consequently attenuating postmenopausal AS. However, the protective effects of kaempferol were blocked through co-treatment with si-GPER. Conclusions The beneficial effects of kaempferol against postmenopausal AS are associated with the PI3K/AKT/Nrf2 pathways, mediated by the activation of GPER.

This study aimed to clarify that organic anion transporters (OATs) mediate the drug–drug interaction (DDI) between imipenem and cilastatin. After co-administration with imipenem, the plasma concentrations and the plasma concentration-time curve (AUC) of cilastatin were significantly increased, while renal clearance and cumulative urinary excretion of cilastatin were decreased. At the same time, imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1 (hOAT1)-HEK293 and human OAT3 (hOAT3)-HEK293 cells. Probenecid, p-aminohippurate, and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1- and hOAT3-HEK 293 cells, respectively. The uptakes of imipenem and cilastatin in hOAT1- and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells. Moreover, the Km values of cilastatin were increased in the presence of imipenem with unchanged Vmax, indicating that imipenem inhibited the uptake of cilastatin in a competitive manner. When imipenem and cilastatin were co-administered, the level of imipenem was higher compared with imipenem alone both in vivo and in vitro. But, cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1 (DPEP1) was silenced by RNAi technology in hOAT1- and hOAT3-HEK 293 cells. In conclusion, imipenem and cilastatin are the substrates of OAT1 and OAT3. OAT1 and OAT3 mediate the DDI between imipenem and cilastatin. Meanwhile, cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement. Keywords: Imipenem/cilastatin, Renal dipeptidase, Organic anion transporters, Drug–drug interaction

This study aimed to elucidate the potential regulatory mechanism of mung bean peptides (MBPs) on glucolipid metabolism in insulin-resistant mice induced by high-fat diet (HFD) using untargeted serum metabolomics, enzyme linked immunosorbent assay (ELISA), intraperitoneal injection glucose tolerance test (IPGTT), insulin tolerance test (IPITT), and hematoxylin-eosin staining (H&E). The regulatory effect of MBPs for alleviating insulin resistance was studied by measuring body weight, fasting blood glucose (FBG) and serum insulin levels, C-Peptide levels, inflammatory and antioxidant factors, and histopathological observation of C57BL/6 mice. The experimental results showed that dietary intervention with MBPs (245 mg/kg/d) for 5 weeks significantly relieved insulin resistance in HFD mice. The body weight, insulin resistance index, and the levels of FBG, C-Peptide, IL-6, TNF-α, and MDA in the serum of HFD mice significantly decreased (P < 0.05). Conversely, SOD content and pancreatic β cell function index significantly increased (P < 0.05), and the damaged pancreatic tissue was repaired. One biomarker associated with insulin resistance was glycine. In addition, there were four important differential metabolites: pyroglutamate, D-glutamine, aminoadipic acid, and nicotinamide, involved in 12 metabolic pathway changes. It was found that MBPs may regulate amino acid, glycerol phospholipid, fatty acid, alkaloid, and nicotinamide metabolism to regulate the metabolic profile of HFD mice in a beneficial direction.

During the storage and processing of mung beans, proteins and polyphenols are highly susceptible to interactions with each other. Using globulin extracted from mung beans as the raw material, the study combined it with ferulic acid (FA; phenolic acid) and vitexin (flavonoid). Physical and chemical indicators were combined with spectroscopy and kinetic methods, relying on SPSS and peak fit data to statistically analyze the conformational and antioxidant activity changes of mung bean globulin and two polyphenol complexes before and after heat treatment and clarify the differences and the interaction mechanism between globulin and the two polyphenols. The results showed that, with the increase in polyphenol concentration, the antioxidant activity of the two compounds increased significantly. In addition, the antioxidant activity of the mung bean globulin–FA complex was stronger. However, after heat treatment, the antioxidant activity of the two compounds decreased significantly. The interaction mechanism of the mung bean globulin–FA/vitexin complex was static quenching, and heat treatment accelerated the occurrence of the quenching phenomenon. Mung bean globulin and two polyphenols were combined through a hydrophobic interaction. However, after heat treatment, the binding mode with vitexin changed to an electrostatic interaction. The infrared characteristic absorption peaks of the two compounds shifted to different degrees, and new peaks appeared in the areas of 827 cm−1, 1332 cm−1, and 812 cm−1. Following the interaction between mung bean globulin and FA/vitexin, the particle size decreased, the absolute value of zeta potential increased, and the surface hydrophobicity decreased. After heat treatment, the particle size and zeta potential of the two composites decreased significantly, and the surface hydrophobicity and stability increased significantly. The antioxidation and thermal stability of the mung bean globulin–FA were better than those of the mung bean globulin–vitexin complex. This study aimed to provide a theoretical reference for the protein–polyphenol interaction mechanism and a theoretical basis for the research and development of mung bean functional foods.

Host immunogenetic setting is involved in the regulation of human papillomavirus (HPV) infection and development of condyloma acuminatum (CA). We investigated the correlation of two common single nucleotide polymorphisms (SNPs) (−607C/A and −137G/C) of IL-18 with the susceptibility of CA in a large Chinese cohort. Out of 408 CA patients analyzed, 300 had HPV infection transmitted through sexual contact (SC) and 108 through non-sexual contact (NSC). In addition, 360 healthy volunteers were enrolled as controls. SNPs at positions −607C/A and −137G/C in IL-18 promoter were analyzed. Comparing CA patients to healthy controls, no dominant relevance was found between the IL-18 promoter −607 C/A or −137G/C polymorphisms and the CA disease either identified genotypically (p > 0.05) or by allelically (p > 0.05). However, the IL-18 promoter −137G/C polymorphism genotype and allele frequencies in the NSC CA group, but not between in the SC group, were significantly higher than in the controls. There was no dominant relevance between IL-18-607C/A polymorphism genotype and allele frequencies among SC, NSC CA patients, and controls. Our study demonstrates that polymorphism −137G/C in IL-18 promoter is significantly correlated with risk of CA in NSC patients. Keywords: Condyloma acuminatum, Human papillomavirus, Cytokine, Single nucleotide polymorphism, IL-18

To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam, renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats. A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions. Renal slices were taken to examine the uptake of piperacillin and tazobactam. Pharmacokinetic studies of β-lactamase in rats were performed to study the contribution of rOat1/3 to the inhibition of tazobactam on β-lactamase. The AUC (from 2.93 ± 0.58 to 6.52 ± 1.44 mg·min/ml) and the plasma clearance (CLP) (from 2.41 ± 1.20 to 0.961 ± 0.212 ml/min/kg) of tazobactam were both altered after the intravenous coadministration of piperacillin and tazobactam in the bacteremia rats. The renal clearance (CLR) of tazobactam decreased from 1.30 ± 0.50 to 0.361 ± 0.043 ml/min/kg. In summary, there was a beneficial interaction between piperacillin and tazobactam mediated by rOat1 and rOat3. Piperacillin enhances the inhibitory effect of tazobactam on β-lactamase through the inhibition of rOat1 and rOat3 in rats. The contribution rate of rOat1/3 for the synergistic effect was 20% when the two drugs were coadministered. Keywords: Organic anion transporter, Piperacillin, Tazobactam, Drug-drug interaction

Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated in vitro and in rabbits. Our results indicated that imipenem and cilastatin were substrates of hOAT1 and hOAT3. Cilastatin inhibited hOAT1/3-mediated transport of imipenem with IC50 values comparable to the clinical concentration, suggesting the potential to cause a clinical drug–drug interaction (DDI). Moreover, imipenem exhibited hOAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic. KEY WORDS: Imipenem, Cilastatin, Probenecid, OATs, hOAT1, hOAT3, Nephrotoxicity

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans.

Bovine mastitis is an inflammatory condition of the mammary gland often caused by (Staphylococcus aureus) S. aureus infection. The aim of this study was to identify mastitis-related miRNAs and their downstream target genes, and therefore elucidate the regulatory mechanisms involved in disease progression and resistance. Three healthy and three mastitic cows were identified on the basis of the somatic cell count and bacterial culture of their milk, and the histological examination of udder tissues. High-throughput RNA sequencing and bioinformatic analyses revealed that 48 differentially expressed miRNAs (DEMs) in the mastitic udder tissues relative to the healthy tissues. Among 48 DEMs, the expression level of bta-miR-223 was the most up-regulated. Overexpression of the bta-miR-223 in Mac-T cells mitigated the inflammatory pathways induced by S. aureus-derived lipoteichoic acid (LTA). The Cbl proto-oncogene B (CBLB) was identified as the target gene of bta-miR-223, and the direct binding of the miRNA to the CBLB promoter was confirmed by dual luciferase reporter assay using wild-type and mutant 3'-UTR constructs. Furthermore, overexpression of CBLB in the LTA-stimulated Mac-T cells significantly upregulated PI3K, AKT, and phosphorylated NF-κB p65, whereas CBLB knockdown had the opposite effect. Consistent with the in vitro findings, the mammary glands of mice infected with 108CFU/100 μL S. aureus showed high levels of CBLB, PI3K, AKT, and p-NF-κB p65 48 h after infection. Taken together, bta-miR-223 is a predominant miRNA involved in mastitis, and bta-miR-223 likely mitigates the inflammatory progression by targeting CBLB and inhibiting the downstream PI3K/AKT/NF-κB pathway.

Atherosclerosis (AS) is an excessive chronic inflammatory hyperplasia caused by the damage of vascular endothelial cell morphology and function. Changes in mitochondrial internal conformation and increase of reactive oxygen species (ROS) can lead to energy metabolism disorders in mitochondria, which further affects the occurrence of atherosclerosis by impairing vascular endothelial function. Coenzyme Q10 (CoQ10) is one of the components of mitochondrial respiratory chain, which has the functions of electron transfer, reducing oxidative stress damage, improving mitochondrial function and promoting energy metabolism. The main purpose of this study is to investigate the protective effects of CoQ10 against AS by improving mitochondrial energy metabolism. Both in high fat diet (HFD) fed APOE−/− mice and in ox-LDL-treated HAECs, CoQ10 significantly decreased the levels of TG, TC and LDL-C and increased the levels of HDL-C, thus playing a role in regulating lipid homeostasis. Meanwhile, CoQ10 decreased the levels of LDH and MDA and increased the levels of SOD and GSH, thus playing a role in regulating oxidation level. CoQ10 also inhibited the over-release of ROS and increased ATP content to improve mitochondrial function. CoQ10 also decreased the levels of related inflammatory factors (ICAM-1, VCAM-1, IL-6, TNF-α and NLRP3). In order to study the mechanism of the experiment, AMPK and YAP were silenced in vitro. The further study suggested AMPK small interfering RNA (siRNA) and YAP small interfering RNA (siRNA) affected the expression of OPA1, a crucial protein regulating the balance of mitochondrial fusion and division and decreased the therapeutic effects of CoQ10. These results indicated that CoQ10 improved mitochondrial function, inhibited ROS production, promoted energy metabolism and attenuated AS by activating AMPK-YAP-OPA1 pathway. This study provides a possible new mechanism for CoQ10 in the treatment of AS and may bring a new hope for the prevention and treatment of AS in the future.

Background/Aims: The emergence of multidrug resistance (MDR) caused by P-glycoprotein (P-gp) overexpression is a serious obstacle to the treatment of chronic myelocytic leukemia. In recent years, some clinical trials have shown that nelfinavir (NFV), a traditional anti-HIV drug, has anti-cancer effects. Some researchers have also shown NFV might be a potential P-gp inhibitor. This study is aimed at investigating whether nelfinavir can act as an MDR-reversal drug and to clarify its molecular mechanism as well. Methods: K562 and K562/ADR cell lines were applied in the study. Cytotoxicity was detected by CCK-8 reagents. Cell apoptosis was detected by flow cytometry and inverted fluorescence microscopy to detect the binding of apoptotic dyes to cells. Western blot was used to detect the expression of proteins. Drug-protein molecular docking simulation by using Sybyl-x 2.0 software. Results: Non-toxic concentrations of NFV (1.25–5 μM) could reverse Adriamycin (ADR), colchicine, paclitaxel, and imatinib resistance of K562/ADR cells, with reversal indexes of up to 10.8, 7.4, 57, and 9.3, respectively. NFV inhibited P-gp efflux function, as evidenced by the significant increase in the intracellular accumulation of ADR and Rho-123, without affecting P-gp protein and mRNA expression levels. Further ATP content detection and molecular docking simulations showed that NFV could decrease intracellular ATP content and has a high affinity with the active functional regions of P-gp, respectively. When co-administered with ADR, NFV increased intracellular reactive oxygen species as well as blocked the ERK/Akt signaling pathway, leading to cell apoptosis. Conclusion: NFV inhibited P-gp function, decreased intracellular ATP content, and promoted cell apoptosis in K562/ADR cells, thereby reversing MDR. These findings encourage further animal and clinical MDR studies with a combination therapy consisting of NFV and chemotherapeutic drugs.

With the wide application of convolutional neural networks (CNNs), a variety of ship detection methods based on CNNs in synthetic aperture radar (SAR) images were proposed, but there are still two main challenges: (1) Ship detection requires high real-time performance, and a certain detection speed should be ensured while improving accuracy; (2) The diversity of ships in SAR images requires more powerful multi-scale detectors. To address these issues, a SAR ship detector called Duplicate Bilateral YOLO (DB-YOLO) is proposed in this paper, which is composed of a Feature Extraction Network (FEN), Duplicate Bilateral Feature Pyramid Network (DB-FPN) and Detection Network (DN). Firstly, a single-stage network is used to meet the need of real-time detection, and the cross stage partial (CSP) block is used to reduce the redundant parameters. Secondly, DB-FPN is designed to enhance the fusion of semantic and spatial information. In view of the ships in SAR image are mainly distributed with small-scale targets, the distribution of parameters and computation values between FEN and DB-FPN in different feature layers is redistributed to solve the multi-scale detection. Finally, the bounding boxes and confidence scores are given through the detection head of YOLO. In order to evaluate the effectiveness and robustness of DB-YOLO, comparative experiments with the other six state-of-the-art methods (Faster R-CNN, Cascade R-CNN, Libra R-CNN, FCOS, CenterNet and YOLOv5s) on two SAR ship datasets, i.e., SSDD and HRSID, are performed. The experimental results show that the AP50 of DB-YOLO reaches 97.8% on SSDD and 94.4% on HRSID, respectively. DB-YOLO meets the requirement of real-time detection (48.1 FPS) and is superior to other methods in the experiments.

To evaluate the important Vitis amurensis germplasm, the quality characteristics and anthocyanin profiles of the ripe berries of 20 V. amurensis grapes and 11 interspecific hybrids in two consecutive years were analysed. Compared with the V. vinifera grapes, V. amurensis grapes had small berries with low total soluble solids and high titratable acids, and were richer in phenolic compounds except for flanan-3-ols in their skins but had lower phenolic contents in their seeds and showed lower antioxidant activities. An outstanding feature of the V. amurensis grapes was their abundant anthocyanin contents, which was 8.18-fold higher than the three wine grapes of V. vinifera. The anthocyanin composition of V. amurensis was characterized by an extremely high proportion of diglucoside anthocyanins (91.71%) and low acylated anthocyanins (0.04%). Interestingly, a new type of speculated 3,5,7-O-triglucoside anthocyanins was first identified and only detected in V. amurensis grapes and hybrids. Based on the total phenolic and anthocyanin characteristics, V. amurensis grapes were set apart from V. vinifera cultivars and the interspecific hybrids, for the same qualities, fell between them, as assessed by principal component analysis.

miRNA-10a is rhythmically expressed and regulates genes involved in lipid and glucose metabolism. However, the effects of miRNA-10a on obesity and glucose intolerance, as well as on the diurnal pattern of expression of circadian clock genes, remain unknown. We explored the effects of miRNA-10a-5p on insulin resistance and on the diurnal patterns of serum triglycerides and gut microbiota in high-fat diet- (HFD-) fed mice. The results showed that oral administration of miRNA-10a-5p significantly prevented body weight gain and improved glucose tolerance and insulin sensitivity in HFD-fed mice. Administration of miRNA-10a-5p also maintained the diurnal rhythm of Clock, Per2, and Cry1 expression, as well as serum glucose and triglyceride levels. Surprisingly, the diurnal oscillations of three genera of microbes, Oscillospira, Ruminococcus, and Lachnospiraceae, disrupted by HFD feeding, maintained by administration of miRNA-10a-5p. Moreover, a strong positive correlation was found between hepatic Clock expression and relative abundance of Lachnospiraceae, both in control mice (r=0.877) and in mice administered miRNA-10a-5p (r=0.853). Furthermore, we found that along with changes in Lachnospiraceae abundance, butyrate content in the feces maintained a diurnal rhythm after miRNA-10a-5p administration in HFD-fed mice. In conclusion, we suggest that miRNA-10a-5p may improve HFD-induced glucose intolerance and insulin resistance through the modulation of the diurnal rhythm of Lachnospiraceae and its metabolite butyrate. Therefore, miRNA-10a-5p may have preventative properties in subjects with metabolic disorders.

The classification and recognition of radar clutter is helpful to improve the efficiency of radar signal processing and target detection. In order to realize the effective classification of uniform circular array (UCA) radar clutter data, a classification method of ground clutter data based on the chaotic genetic algorithm is proposed. In this paper, the characteristics of UCA radar ground clutter data are studied, and then the statistical characteristic factors of correlation, non-stationery and range-Doppler maps are extracted, which can be used to classify ground clutter data. Based on the clustering analysis, results of characteristic factors of radar clutter data under different wave-controlled modes in multiple scenarios, we can see: in radar clutter clustering of different scenes, the chaotic genetic algorithm can save 34.61% of clustering time and improve the classification accuracy by 42.82% compared with the standard genetic algorithm. In radar clutter clustering of different wave-controlled modes, the timeliness and accuracy of the chaotic genetic algorithm are improved by 42.69% and 20.79%, respectively, compared to standard genetic algorithm clustering. The clustering experiment results show that the chaotic genetic algorithm can effectively classify UCA radar’s ground clutter data.