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Abstract Purpose The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. Methods Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed. Results In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P

Abstract Liver cancer is a common malignant tumor worldwide, traditional Chinese medicine is one of the treatment measures for liver cancer because of its good anti-tumor effects and fewer toxic side effects. Ginsenoside CK (CK) is an active component of ginseng. This study explored the mechanism by which CK induced ferroptosis in liver cancer cells. We found that CK inhibited the proliferation of HepG2 and SK-Hep-1 cells, induced ferroptosis of cells. Ferrostatin-1, an ferroptosis inhibitor, was used to verify the role of CK in inducing ferroptosis of liver cancer cells. Network pharmacological analysis identified the FOXO pathway as a potential mechanism of CK, and western blot showed that CK inhibited p-FOXO1. In cells treated with the FOXO1 inhibitor AS1842856, further verify the involvement of the FOXO pathway in regulating CK-induced ferroptosis in HepG2 and SK-Hep-1 cells. A HepG2 cell–transplanted tumor model was established in nude mice, and CK inhibited the growth of transplanted tumors in nude mice, p-FOXO1 was decreased in tumor tissues, and SLC7A11 and GPX4 expressions were also down-regulated after CK treatment. These findings suggested that CK induces ferroptosis in liver cancer cells by inhibiting FOXO1 phosphorylation and activating the FOXO signaling pathway, thus playing an antitumor role.

Abstract Baculoviruses are insect-infecting pathogens with wide applications as biological pesticides, in vitro protein production vehicles and gene therapy tools. Its cylindrical nucleocapsid, which encapsulates and protects the circular double-stranded viral DNA encoding proteins for viral replication and entry, is formed by the highly conserved major capsid protein VP39. The mechanism for VP39 assembly remains unknown. We use electron cryomicroscopy to determine a 3.2 Å helical reconstruction of an infectious nucleocapsid of Autographa californica multiple nucleopolyhedrovirus, revealing how dimers of VP39 assemble into a 14-stranded helical tube. We show that VP39 comprises a distinct protein fold conserved across baculoviruses, which includes a Zinc finger domain and a stabilizing intra-dimer sling. Analysis of sample polymorphism shows that VP39 assembles in several closely-related helical geometries. This VP39 reconstruction reveals general principles for baculoviral nucleocapsid assembly.

Antioxidant peptides derived from aquatic organisms have attracted tremendous research interest due to their potential applications in human health. Tilapia is one of the most widely farmed aquaculture species globally. The current understanding of tilapia-derived antioxidant peptides is gradually expanding. This review discusses the current knowledge of peptides and protein hydrolysates derived from tilapia muscle, skin, and scales, whose antioxidant capacity has been validated in various cellular and in vivo models. To date, at least 16 peptides and several hydrolysates have been identified from tilapia that protect human and non-human cell models against oxidative injury. Tilapia hydrolysates and peptide mixtures have also shown protective effects in animal models of oxidative stress-associated diseases and exercise-induced oxidative injury and fatigue. The key mechanisms of tilapia hydrolysates and peptide mixtures involve enhancing antioxidant enzyme activities and suppressing radical production. Notably, such hydrolysates also exerted additional in vivo functions, such as anti-inflammatory, anti-diabetic, wound healing, and antiaging properties. Taken together, tilapia-derived antioxidant peptides and hydrolysates represent a valuable source of functional ingredients for applications in functional food, dietary supplements, and therapeutic applications. Continued research into their health benefits is warranted in the future.

Currently, research on the flavor components and their dynamic changes in roasted chicken with a special flavor is rare. In this study, a passion fruit-roasted chicken was prepared, its characteristic flavor components were profiled by flavoromics, and their evolution patterns and precursors were determined. The results showed that the characteristic flavor component with the highest contribution rate was ethyl butyrate (50.44%). In particular, some unique flavor compounds were identified compared with other roasted chicken products available. The main volatile flavor components in all stages of processing were alcohols, esters, and hydrocarbons, 15 to 30 min of roasting is an important stage for establishing the aroma system, and at the end, hydrocarbons were the main volatile compounds. During the 30-day storage period, the characteristic flavor components included ethyl butyrate, ethyl maltol, β-caryophyllene, and guaiacene. In conclusion, passion fruit-roasted chicken contained many characteristic flavor components, which were mainly formed within 15 to 30 min of roasting and were basically stable during the 30-day storage period. In a word, this work prepared a novel roasted chicken and revealed its mechanism of flavor formation at different baking stages and storage periods, which provided references for industrial production.

Abstract Bacillus coagulans have recently revealed its anticancer effects, but few investigations are available on their effects on liver cancer proliferation, and the precise mechanism to mark its impact on apoptosis-related signaling pathways has yet to be elucidated. The aim of this study was to evaluate the anti-proliferative effect of B. coagulans MZY531 and apoptosis induction in the mouse H22 hepatocellular carcinoma cell line. The anti-proliferative activity of B. coagulans MZY531 was evaluated by Cell Counting Kit-8 (CCK-8) assay, and cell apoptosis was revealed with Terminal Deoxynucleotidyl Transferase (TDT)-mediated dUTP Nick-End Labeling (TUNEL) staining and flow cytometric analysis. The expressions of apoptosis-related protein were determined by western blot analysis. The CCK-8 assay revealed that B. coagulans MZY531 inhibited the H22 cells proliferation in a concentration-dependent manner. TUNEL staining revealed an increased apoptosis rate in H22 cells following intervention with B. coagulans MZY531. Furthermore, flow cytometric analysis showed that B. coagulans MZY531 treatment (MOI = 50 and 100) significantly alleviated the H22 cells apoptosis compared with the control group. Western blot analysis found B. coagulans MZY531 significantly decreased level of phospho-PI3K (p-PI3K), phospho-AKT (p-AKT), and phospho-mTOR (p-mTOR) compared with the control group. Furthermore, H22 cells treatment with B. coagulans MZY531 enhanced the expression of caspase-3 and Bax and jeopardized the expression of Bcl-2. Taken together, apoptosis induction and cell proliferation inhibition via PI3K/AKT/mTOR and Bax/Bcl-2/Caspase-3 pathway are promising evidence to support B. coagulans MZY531 as a potential therapeutic agent for cancer.

Abstract Bacillus coagulans has a potential role in improving intestinal injury. However, the specific mechanism is still unclear. In this study, the protective effect of B. coagulans MZY531 on intestinal mucosa injury in cyclophosphamide (CYP)-induced immunosuppressed mice were investigated. The results indicated that the immune organ (thymus and spleen) indices of B. coagulans MZY531 treatment groups were significantly increased compared to the CYP group. B. coagulans MZY531 administration promotes the expression of immune proteins (IgA, IgE, IgG, and IgM). B. coagulans MZY531 could upregulate the ileum levels of IFN-γ, IL-2, IL-4, and IL-10 in immunosuppressed mice. Moreover, B. coagulans MZY531 restores the villus height and crypt depth of the jejunum and alleviates injury of intestinal endothelial cells caused by CYP. Furthermore, the western blotting results showed that B. coagulans MZY531 ameliorated CYP-induced intestinal mucosal injury and inflammatory via up-regulates the ZO-1 pathway and down-regulates the expression of the TLR4/MyD88/NF-κB pathway. After treatment with B. coagulans MZY531, the relative abundance of Firmicutes phylum was dramatically increased, as well as the genera of Prevotella and Bifidobacterium, and reducing harmful bacteria. These findings suggested that B. coagulans MZY531 has a potential immunomodulatory activity on chemotherapy-induced immunosuppression.

This is a paper in the field of ceramics and composites. High-temperature foaming method has been successfully applied to prepare foamed ceramics material by using steel slag and shale slag as the main raw materials. Silicon carbide and borax were used as the foaming agent and fluxing agent, respectively. This paper focused on the influence of steel slag content, SiC addition, borax addition and foaming temperature on the pore structure and properties of foamed ceramics. The experimental results showed that when the steel slag content is 20%, the shale slag is 80%, SiC of 0.5% and borax of 4% are additionally added, the foaming temperature is 1090 ℃ and the holding time is 40 min, the foamed ceramics material has the best properties. Under optimal conditions, the bulk density, compressive strength and thermal conductivity of the foamed ceramics are 0.468 g/cm3, 3.265 MPa and 0.121 W/(m·K), which meets the property requirements of building insulation materials. The main crystal phases are augite phase, quartz phase and diopside phase．

Background: Pregnancy complications of antiphospholipid syndrome (APS) are up to 20–30%. It is of great value to identify well-recognized predictors of adverse pregnancy outcomes (APOs) in APS. This study aims to explore the risk factors for APOs in patients with obstetric APS. Methods: This study included 142 women with APS delivered at Peking University People’s Hospital from February 2014 to August 2022. APOs included fetal death, neonatal death due to complications related to prematurity, preterm delivery

Cagβ is an ATPase in the H. pylori CagType4 secretion system essential for delivering the CagA effector to host cells. Here, authors present crystal structures of hexameric apo-Cagβ and Cagβ trapped in the monomeric state by its regulator CagZ, uncovering the regulatory mechanisms of Cagβ.

Compound K (CK) is the metabolite and final active ingredient of diol-type ginsenosides. In this study, we investigated the effect of CK on mitochondrial apoptosis in SMMC-7721 and BEL-7404 cells and the regulatory mechanism through in vitro and in vivo experiments. The results demonstrated that CK inhibited Hepatocellular carcinoma (HCC) cells proliferation and arrested the cells in G0/G1 phase. CK induces mitochondrial apoptosis in HCC cells and inhibited p-ERK expression. Bcl-2 associated transcription factor 1 (Bclaf1) was distributed in the nucleus and cytoplasm, and CK inhibited its expression. Treatment of a nude mouse xenograft model bearing SMMC-7721 cells with CK decreased the expression of Bclaf1, p-ERK, and Bcl-2 but increased that of Bax. In summary, ginsenoside CK downregulated Bclaf1 expression, inhibited the activation of the ERK pathway, and triggered mitochondrial apoptosis in HCC. These findings uncovered a potential therapeutic strategy leveraging the anti-tumor effects of CK against HCC.

Curcumin, a kind of natural compound extracted from the rhizome of Zingiberaceae such as turmeric, has many pharmacological effects such as anti-cancer effects. This study investigated the effect of curcumin on the invasion and metastasis of hepatocellular carcinoma (HCC) cell lines HepG2 and SK-Hep-1 through the Wnt/β-catenin signalling pathway and the regulatory mechanism of Bcl-2-associated transcription factor 1 (Bclaf1). Curcumin significantly inhibited the migration and invasion of HepG2 and SK-Hep-1 cells and inhibited the Wnt/β-catenin signalling pathway and reduced Bclaf1 expression in human hepatoma cells. In nude mice, intraperitoneal injection of curcumin significantly inhibited the growth of subcutaneously transplanted tumours and reduced lung metastasis of the tumour cells, downregulated the expression of Bclaf1, and inhibited the Wnt/β-catenin pathway. This study suggests that curcumin is a novel candidate drug to prevent cancer metastasis and that Bclaf1 is a new gene target related to the proliferation, invasion, and metastasis of hepatocellular carcinoma.

The experiment was conducted for developing a sugar-free, low-fat and low-calorie angel cake with no-eggy flavour and palatability, so as to broaden the application of mulberry and satisfy the public's demand for novel baked foods. Using single-factors and response surface experiments for optimization of the processing technology, the experiment focused on the effect of main ingredients on the sensory quality and hardness of angel cake, i.e. the amount of mulberry juice, xylitol, egg white and low gluten flour, as well as the baking temperature and time. The texture properties of mulberry sugar-free angel cake and ordinary angel cake were measured under the same storage conditions. The results showed that the optimal processing parameters were: Low gluten flour 45 g, mulberry juice 33 g, xylitol 45 g, egg white 135 g, cream of tarta 3 g, lemon juice 2 g and milk 30 g. The best baking conditions was that the surface fire was 165 ℃ and the primer fire was 150 ℃ with 35 min. Under these conditions, the sensory score of mulberry angel cake was 91.8. The experiments of the texture characteristics of the cakes showed that the addition of mulberry juice could reduce the hardness and chewiness of the cakes with better water holding capacity and softer texture, simultaneously, it could improve the cohesiveness and adhesion, so that the cakes had concentrated stoma and compact structure.

Abstract Primary liver cancer (PLC) is the second leading cause of cancer mortality worldwide, and its morbidity unceasingly increases these years. Hepatitis B virus (HBV) infection accounted for approximately 50% of hepatocellular carcinoma (HCC) cases globally in 2015. Due to the lack of an effective model to study HBV-associated liver carcinogenesis, research has made slow progress. Organoid, an in vitro 3D model which maintains self-organization, has recently emerged as a powerful tool to investigate human diseases. In this review, we first summarize the categories and development of liver organoids. Then, we mainly focus on the functions of culture medium components and applications of organoids for HBV infection and HBV-associated liver cancer studies. Finally, we provide insights into a potential patient-derived organoid model from those infected with HBV based on our study, as well as the limitations and future applications of organoids in liver cancer research.

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.

Objective Infection is a major cause of death in patients with SLE. This study aimed to explore the infection rate in patients with SLE receiving a low dose of intravenous cyclophosphamide (IV-CYC).Methods Clinical parameters of 1022 patients with SLE from 24 hospitals in China were collected. Patients were divided into the short-interval and lower-dose (SILD, 400 mg every 2 weeks) IV-CYC group and the high-dose (HD, 500 mg/m2 of body surface area every month) IV-CYC group. The clinical data and infection rate between the two groups were compared.Results Compared with HD IV-CYC, the infection rate of the SILD IV-CYC group was significantly lower (13.04% vs 22.27%, p=0.001). Respiratory tract infection (10.28% vs 15.23%, p=0.046) and skin/soft tissue infection (1.78% vs 4.3%, p=0.040) were significantly decreased in the SILD IV-CYC group. Moreover, infections occurred most likely in patients with SLE with leucopenia (OR 2.266, 95% CI 1.322 to 3.887, p=0.003), pulmonary arterial hypertension (OR 2.756, 95% CI 1.249 to 6.080, p=0.012) and >15 mg/day of glucocorticoid (OR 2.220, 95% CI 1.097 to 4.489, p=0.027).Conclusions SILD IV-CYC showed a lower frequency of infection events than high-dose IV-CYC in patients with SLE.

BackgroundHome blood pressure telemonitoring (HBPT) is witnessing rapid diffusion worldwide. Contemporary studies documented mainly short-term (6-12 months) effects of HBPT, and there are limited data about its uptake. ObjectiveThe aim of this study was to explore the 3-year use and determinants of HBPT, and the interactions with systolic and diastolic blood pressure (SBP/DBP) and overall blood pressure (BP) control rate. MethodsHBPT records were obtained from a 3-year cohort of 5658 patients with hypertension in Jieshou, Anhui, China, and data from a structured household survey of a random sample (n=3005) of the cohort. The data analysis comprised (1) timeline trajectories of the rates of monthly active HBPT and mean SBP/DBP for overall and subgroups of patients with varied start-month SBP/DBP; and (2) multivariable linear, logistic, and percentile regression analyses using SBP/DBP, BP control rate, and yearly times of HBPT as the dependent variable, respectively. ResultsHBPT was followed by mixed changes in mean monthly SBP/DBP for varied patient groups. The magnitude of changes ranged from –43 to +39 mmHg for SBP and from –27 to +15 mmHg for DBP. The monthly rates of active HBPT all exhibited a rapid and then gradually slower decline. When controlled for commonly reported confounders, times of HBPT in the last year were found to have decreasing correlation coefficients for SBP/DBP (from 0.16 to –0.35 and from 0.11 to –0.35, respectively) and for BP control rate (from 0.53 to –0.62). ConclusionsHBPT had major and “target-converging” effects on SBP/DBP. The magnitude of changes was much greater than commonly reported. BP, variation in BP, and time were the most important determinants of HBPT uptake. Age, education, duration of hypertension, family history, and diagnosis of hypertension complications were also linked to the uptake but at weaker strength. There is a clear need for differentiated thinking over the application and assessment of HBPT, and for identifying and correcting/leveraging potential outdated/new opportunities or beliefs.

Activation of c-MET receptor tyrosine kinase involves hepatocyte growth factor (HGF) and glycosaminoglycans, but the molecular mechanism is still under debate. Here, the authors present cryoEM structures of c-MET bound to two HGF splice variants and heparin, revealing the structural basis for c-MET activation.

Secreted class 3 semaphorins (Sema3s) form tripartite complexes with a plexin receptor and neuropilin co-receptor to transduce signals for neuronal axon guidance and other processes. Here, the authors present the cryo-EM structure of the extracellular Sema3A/PlexinA4/Neuropilin1 complex that provides further insights into the interactions among semaphorin, plexin and neuropilin and reveals long flexible linkers in semaphorin and neuropilin that are important for complex formation.

Sacha inchi meal (SIM) is the residue from the processing of the oil crop sacha inchi. In the present study, biological enzymolysis was performed on SIM protein to obtain hydrolysates, and then the antioxidant and hypoglycemic activities were evaluated. The results showed that the scavenging rates of alkaline protease hydrolysate (SAl) and protamex hydrolysate (SPr) to ABTS free radicals were close to that of vitamin C at 5 mg/mL, amounting to 99.83 ± 0.33% and 100.00 ± 0.09%, respectively. The dipeptidyl peptidase (DPP-IV) inhibitory activities of SPr and SAl were also the highest, at the concentration of 2.5 mg/mL, their inhibition rates were 74.15 ± 0.68% and 56.38 ± 1.51%, respectively, with the IC50 values of 1.007 mg/mL and 2.130 mg/mL, respectively. Moreover, compared with the model group, all the hydrolysates increased the glucose consumption by 187.01–348.79% (at 800 μg/mL) in insulin-resistant HepG2 cells, which were better than positive drug Metformin. In conclusion, SIM protein hydrolysates have significant antioxidant and hypoglycemic activity in vitro; therefore, the hydrolysates could be used as for functional food and pharmaceutical development.

In this study, experimental tests, together with computer analyses, were carried out to identify the essential nutritional markers that can offer protein supplementation-based nutrition support for hypertension. In particular, 16 marine shellfish proteins were firstly screened for in silico hydrolysis by gastrointestinal enzymes and then the binding abilities of the obtained oligopeptides to angiotensin-converting enzyme (ACE) were examined. In addition, the ACE inhibition activities of selected oligopeptides were assayed in vitro. It was discovered that mussel-derived NADH dehydrogenase and AMP-activated protein kinase and razor-clam-derived cytochrome b, NADH dehydrogenase, and ATP synthase were excellent sources of protein that are able to release a high amount of ACE-binding peptides. Meanwhile, four oligopeptides (SCCGY, SSGAW, PICQF, and IQPEW) were detected as strong ACE binders, with IC50 values of 0.09, 0.25, 0.41, and 0.60 mM, respectively. Therefore, our findings demonstrate that shellfish proteins can serve as nutritional support for hypertension when patients are supplemented with these markers. In particular, oligopeptides are identified as the most promising compounds.

Abstract Background Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined. Methods Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1. Results Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC. Conclusions CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.

Abstract Background Aberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure. Methods Quantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay. Results In this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC. Conclusion SNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.

An overhead contact system (OCS) is key to providing power to high-speed railways. OCS detection is an important measure to ensure the safe operation of a high-speed railway. At present, OCS anomaly detection mainly relies on the manual analysis of the images regularly collected by the 4C system, which is very inefficient and can easily miss anomalies. Although some classification and object detection methods based on deep learning can be used for OCS anomaly detection, the effective training of deep networks can be difficult to support due to the small number of anomaly OCS image samples. Considering that most OCS faults are abnormal fasteners, we propose an abnormal detection method based on normal images, called the nested residual encoder-decoder network (NRE-Net). This network consists of two nested encoder-decoder networks, where the encoder is the shared part, and a residual structure is added to the encoding and decoding branches to enhance the feature expression ability. The experimental results show that the method can greatly improve the accuracy of anomaly detection for the CIFAR-10 dataset and OCS fastener dataset. Compared with the previous state-of-the-art approaches, the $F_{1}$ score of the proposed method for the two classes fastener in the OCS fastener dataset has increased by 10.8% and 11.9%, respectively.

Abstract IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-allele CEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML.

Plexins are the receptors for the guidance molecules semaphorins and regulate immunity and the development of the nervous and cardiovascular systems. Here authors present a structure of full-length human PlexinC1 in complex with its ligand A39R, which reveals how inter-domain interactions couple extracellular ligand binding to receptor activation and signaling.

Non-alcoholic steatohepatitis is a potentially progressive hepatic disorder that can lead to end-stage liver disease and hepatocellular carcinoma. The inhibitory effects of proteins and hydrolysates from the liver of newborn piglets on hepatic steatosis in oleic acid-induced hepatocellular carcinoma (HepG2) cells were investigated in vitro. The extracted proteins from the liver of newborn piglets were hydrolysed with papain, pepsin, trypsin and Alcalase. Based on the comparison of different enzyme digestion conditions, a protein hydrolysis protocol was established to obtain hydrolysates with lipid-lowering effect. Trypsin-digested liver protein hydrolysate from newborn piglets exhibited strong antioxidant activity and good inhibitory effects against lipogenesis and cholesterol accumulation in HepG2 cells at the concentration of 150 μg/mL, with a triglyceride decrease of (43±3) % and cholesterol decrease of (31±5) %, compared with model group induced with 0.75 mM oleic acid. The addition of trypsin-digested liver protein hydrolysate from newborn piglets (300 μg/mL) decreased alanine aminotransferase and aspartate aminotransferase activities and increased superoxide dismutase activity. This study demonstrated that the trypsin-digested liver protein hydrolysate from newborn piglets has a potential preventive effect against non-alcoholic fatty liver disease in its early stage, and a potential use as the modulator of lipid overaccumulation in form of food supplements.

Overhead contact systems (OCSs) are the power supply facility of high-speed trains and plays a vital role in the operation of high-speed trains. The dropper is an important guarantee for the suspension system of the OCS. Faults of the dropper, such as slack and breakage, can cause a certain threat to the power supply system. How to use artificial intelligence technologies to detect faults is an urgent technical problem to be solved. Because droppers are very small in whole images, a feasible solution to the problem is to identify and locate the droppers first, then segment them, and then identify the fault type of the segmented droppers. This paper proposes an improved Faster R-CNN algorithm that can accurately identify and locate droppers. The innovations of the method consist of two parts. First, a balanced attention feature pyramid network (BA-FPN) is used to predict the detection anchor. Based on the attention mechanism, BA-FPN performs feature fusion on feature maps of different levels of the feature pyramid network to balance the original features of each layer. After that, a center-point rectangle loss (CR Loss) is designed as the bounding box regression loss function of Faster R-CNN. Through a center-point rectangle penalty term, the anchor box quickly moves closer to the ground-truth box during the training process. We validate the improved Faster R-CNN through extensive experiments on the VOC 2012 and MSCOCO 2014 datasets. Experimental results prove the effectiveness of the proposed network combined with attention feature fusion and center-point rectangle loss. On the OCS dataset, the accuracy using the combination of the improved Faster R-CNN and ResNet-101 reached 86.8% mAP@0.5 and 83.9% mAP@0.7, which was the best performance among all results.

In this study, ultrasound coupled with subcritical water (USW) technology was employed to extract S. platensis protein, and its inhibitory effect on three enzymes (α-amylase, α-glucosidase and dipeptidyl peptidase-4 (DPP-IV)) was evaluated. Subsequently, using insulin resistant-HepG2 cell model, the data presented that the USW-extracted protein significantly (p

Recently, with the growing number of ontologies defined in different languages, to bridge the semantic gaps between them, it is necessary to identify the correspondences between their heterogeneous entities, so-called cross-lingual ontology matching. Due to the complexity and the intricacy of the cross-lingual ontology matching, it is essential to get an expert involved in the matching process to guarantee the alignment's quality. In this paper, we propose an interactive cross-lingual ontology matching technique that makes the user and automatic matcher work together to create high-quality alignments in a reasonable amount of time. In particular, we present a cross-lingual similarity metric to calculate the similarity value of two cross-lingual entities, construct an optimal model for the cross-lingual ontology matching problem, and propose an interactive compact differential evolution (ICDE) algorithm to effectively match the cross-lingual ontologies. The experiment exploits the ontology alignment evaluation initiative (OAEI) multifarm track to test our proposal's performance. The experimental results show that the ICDE significantly outperforms other EA-based matchers and OAEI's participants, and the interacting mechanism can significantly improve the alignment's quality.

Besides the pilot symbols, the received data signals also contain some extra channel state information (CSI), which can be exploited to further improve the channel estimation accuracy. Considering a multi-cell multi-user massive multiple input multiple output (MIMO) with Ricean fading, the spectral efficiency for joint processing of the pilot and data strategy is investigated. Through the mutual information analysis of the multi-cell multi-user massive MIMO system, the intractable expression for the ergodic spectral efficiency is lower bounded and decomposed into three terms, where the explicit physical meanings of them are discussed in detail. Facilitated by the decomposing operation, an asymptotic closed-form expression of the spectral efficiency is obtained, and it is proven to be accurate. Comparing with separate processing, numerical results show that the joint processing outperforms the separate processing in spectral efficiency since the additional CSI is captured. The performance advantage for joint processing over separate processing becomes obvious as the coherence block duration of channels (T) increases. For a long enough T, joint processing eventually approaches the case with perfect CSI in terms of spectral efficiency. In addition, the inter-cell interference heavily reduces the system performance of joint processing when T is relatively small.

Abstract Background Heme oxygenase 1 (HO-1) has been reported to be very important in the pathogenesis or progression of multiple types of cancer. Identification of novel hmox1 binding proteins may reveal undefined oncogenes, tumor suppressors, signaling pathways, and possible treatment targets. Methods Immunoprecipitation and mass spectrometry analyses were used to identify novel regulators of HO-1. The association of the 14–3-3ζ protein with HO-1 and modulation of the stability of HO-1 were investigated by co-immunoprecipitation, immunofluorescence, western blotting, and quantitative RT-PCR. Degradation and in vivo ubiquitination assays were utilized to examine whether 14–3-3ζ stabilizes the HO-1 protein by inhibiting its ubiquitination. The effect of 14–3-3ζ on proliferation was investigated by function assays conducted in vitro using the CCK-8 and colony formation assays and in vivo in a xenograft mouse model. The biological functions of the 14–3-3ζ/HO-1 axis were demonstrated by western blotting and rescue experiments. Using gain-of-function and loss-of-function strategies, we further clarified the impact of 14–3-3ζ/HO-1 complex on the signal transducers and activators of transcription 3 (STAT3) signaling pathway in cancer cells. Results We identified 14–3-3ζ as a novel HO-1 binding protein. The binding inhibited the ubiquitination and proteasome-mediated degradation of HO-1, thus facilitating its stabilization. Enforced expression of 14–3-3ζ significantly promoted cell proliferation in vitro, as well as tumorigenesis in vivo, while 14–3-3ζ knockdown had opposite effects. The data indicated that 14–3-3ζ can stabilize HO-1 expression and thus influence cancer cell proliferation. We further demonstrated the involvement of the STAT3 pathway in 14–3-3ζ/HO-1 regulation of hepatocellular carcinoma cell proliferation. Conclusions Collectively, these data show that 14–3-3ζ regulates the stability of HO-1 to promote cancer cell proliferation and STAT3 signaling activation. The data establish the 14–3-3ζ-HO-1-STAT3 axis as an important regulatory mechanism of cancer cell growth and implicate HO-1 and 14–3-3ζ as potential therapeutic targets in hepatocellular carcinoma.

Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations, we showed that RND1 reinforces the plexin dimerization interface, whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase-binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface.

Localization is recognized among the topmost vital features in numerous wireless sensor network (WSN) applications. This paper puts forward energy-efficient clustering and localization centered on genetic algorithm (ECGAL), in which the residual energy, distance estimation, and coverage connection are developed to form the fitness function. This function is certainly fast to run. The proposed ECGAL exhausts a lesser amount of energy and extends wireless network existence. Finally, the simulations are carried out to assess the performance of the proposed algorithm. Experimental results show that the proposed algorithm approximates the unknown node location and provides minimum localization error.

The inner-surface damage of water conveyance tunnels is the main hidden danger that threatens their safety and leads to serious accidents. The method based on the principle of acoustic reflection is the main means of inspecting damage to water-conveyance tunnels. However, affected by the tunnel environment and equipment noise, the obtained acoustic point cloud model inevitably suffers from noise, which can produce erroneous results. Therefore, we proposed a novel filtering method, called unsharp-mask-guided filtering for 3D point cloud, to reduce the impact of noise on the acoustic point cloud model of water-conveyance tunnels. The proposed method fuses the ideas of guided filtering and the unsharp masking technique and extends them to the 3D point cloud model by considering the position of the point. In addition, edge-aware weighting mean is also used to retain the edge features of the point cloud model while smoothing the noise points. The experimental results show that our method can obtain impressive results and a better performance in both the acoustic point cloud model of the tunnel and the simulated point cloud model than many state-of-the-art methods.

This study aimed to demonstrate that ginsenoside compound K (20 (S)-ginsenoside CK; CK) downregulates Bcl-2-associated transcription factor 1 (Bclaf1), which inhibits the hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis pathway to inhibit the proliferation of liver cancer cells. Treatment of hepatoma cells (Bel-7404 and Huh7) under hypoxic conditions with different concentrations of CK showed that CK inhibited the proliferation of hepatoma cells in a time- and concentration-dependent manner; furthermore, the ability of the cells to form colonies was reduced, and cell growth was blocked in the G0/G1 phase. CK promoted the degradation of HIF-1α ubiquitination in liver cancer cells by regulating the expression of HIF-1α and related ubiquitination proteins; moreover, it reduced the activity of key enzymes involved in glycolysis, the pressure of cellular glycolysis, and the rate of real-time ATP production, thereby inhibiting the glycolysis pathway. It also decreased the expression of Bclaf1 in hypoxic liver cancer cells and thus reduced the ability of Bclaf1 to bind to HIF-1α. CK treatment of Bel-7404 and Huh7 cells with CRISPR/Cas9-engineered knock out of Bclaf1 gene under hypoxic conditions further suppressed the expression of HIF-1α, promoted HIF-1α ubiquitination, and inhibited the glycolysis pathway. In a rat model of primary liver cancer induced by diethylnitrosamine, positron emission tomography and computed tomography scans showed that after CK administration, tumor tissue volumes were reduced and glucose uptake capacity decreased. Increased Bclaf1 and HIF-1α expression promoted the ubiquitination of HIF-1α and inhibited the glycolysis pathway, thereby inhibiting the proliferation of liver cancer cells. In summary, this study confirmed by in vitro and in vivo experiments that in hypoxic liver cancer cells CK downregulates the expression of Bclaf1, inhibits the HIF-1α-mediated glycolysis pathway, and inhibits cell proliferation, suggesting that the CK-mediated effects on Bclaf1 may represent a novel therapeutic approach for the treatment of liver cancer patients.

The Warburg effect (aerobic glycolysis) is a hallmark of cancer and is becoming a promising target for diagnosis and therapy. Phosphoglycerate kinase 1 (PGK1) is the first adenosine triphosphate (ATP)-generating glycolytic enzyme in the aerobic glycolysis pathway and plays an important role in cancer development and progression. However, how microRNAs (miRNAs) regulate PGK1-mediated aerobic glycolysis remains unknown. Here, we show that miR-16-1-3p inhibits PGK1 expression by directly targeting its 3′-untranslated region. Through inhibition of PGK1, miR-16-1-3p suppressed aerobic glycolysis by decreasing glucose uptake, lactate and ATP production, and extracellular acidification rate, and increasing oxygen consumption rate in breast cancer cells. Aerobic glycolysis regulated by the miR-16-1-3p/PGK1 axis is critical for modulating breast cancer cell proliferation, migration, invasion and metastasis in vitro and in vivo. In breast cancer patients, miR-16-1-3p expression is negatively correlated with PGK1 expression and breast cancer lung metastasis. Our findings provide clues regarding the role of miR-16-1-3p as a tumor suppressor in breast cancer through PGK1 suppression. Targeting PGK1 through miR-16-1-3p could be a promising strategy for breast cancer therapy.

Gut microbiota has been implicated in the pathogenesis of many autoimmune diseases. This is still an area of active research given that the role of gut microbiota on the primary immune thrombocytopenia (ITP) remains unclear. In this study, fecal samples of 30 untreated adult primary ITP patients and 29 healthy controls (HCs) were used to investigate the gut microbial community and metabolite profiles. Our results show that fecal bacteria such as Blautia, Streptococcus, and Lactobacillus are enriched, whereas bacteria such as Bacteroides are depleted in ITP patients. Notably, fecal metabolites such as fatty acyls and glycerophospholipids are enriched and strongly correlate with discrepant gut microbiota. Furthermore, combinations of Weissella and Streptococcus anginosus, or Cer (t18:0/16:0), Cer (d18:1/17:0), and 13-hydroxyoctadecanoic acid could provide good diagnostic markers for ITP. Moreover, a strong negative correlation was found between platelet count and altered gut microbiota such as S. anginosus and gut metabolites such as Cer (t18:0/16:0) in ITP. In conclusion, dysbiosis of both gut microbiota and metabolome develops in ITP patients compared to HCs. Several ITP-altered gut bacteria and metabolites can be diagnostic biomarkers for ITP, and are highly correlated with platelet count, suggesting that they may also play a role in ITP pathogenesis.

Objective: This study was conducted to identify the characteristics and prognosis of rapidly progressive interstitial lung disease (RP-ILD) in idiopathic inflammatory myopathy (IIM) and to assess the predictors for poor survival of RP-ILD in IIM.Methods: A total of 474 patients with IIM were enrolled retrospectively according to medical records from Peking University People's Hospital. Clinical and laboratory characteristics recorded at the diagnosis of patients with RP-ILD and chronic ILD (C-ILD) were compared. The Kaplan–Meier estimator and univariate and multivariate analyses were used for data analysis.Results: ILD was identified in 65% (308/474) of patients with IIM. Patients with ILD were classified into two groups based on lung features: RP-ILD (38%, 117/308) and C-ILD (62%, 191/308). RP-ILD resulted in significantly higher mortality in IIM compared with C-ILD (27.4 vs. 7.9%, P < 0.05). In this study, by comparing IIM patients with and without RP-ILD, a list of initial predictors for RP-ILD development were identified, which included older age at onset, decreased peripheral lymphocytes, skin involvement (periungual erythema, skin ulceration, and subcutaneous/mediastinal emphysema), presence of anti-MDA5 antibody, serum tumor markers, etc. Further multivariate Cox proportional hazards model analysis identified that anti-MDA5 positivity was an independent risk factor for mortality due to RP-ILD (P < 0.05), and lymphocytes

Objective: The study aims to investigate the effects of miR-221-3p in bone marrow mesenchymal stem cell (BMMSC)-derived microvesicles (MVs) on cell cycle, proliferation and invasion of acute myelocytic leukemia (AML).Methods: Bioinformatics was used to predict differentially expressed miRNAs (DEmiRNAs) in AML. The morphology of BMMSC-derived MVs was observed under an electron microscope, and the positional relation of MVs and OCI-AML2 cells was observed by a fluorescence microscope. MTT, Transwell, and flow cytometry assays were used to analyze the effects of MVs on OCI-AML2 cells. The targeted relationship between miR-221-3p and CDKN1C was detected by dual luciferase assay.Results: It was verified that miR-221-3p promoted the proliferation, invasion and migration of OCI-AML2 cells, and induced the cell cycle arrest in G1/S phase as well as inhibited cell apoptosis. Further studies showed that MVs promoted the proliferation, migration and invasion of AML, and induced the cell cycle arrest in G1/S phase through miR-221-3p. It was confirmed that miR-221-3p can directly target CDKN1C to regulate cell cycle, proliferation and invasion of AML.Conclusion: miR-221-3p in BMMSC-derived MVs regulated AML cell cycle, cell proliferation and invasion through targeting CDKN1C. miR-221-3p and CDKN1C were considered to be potential targets and biomarkers for the treatment of AML in clinic.

Objective. Antimelanoma differentiation-associated protein 5 (anti-MDA5) autoantibody has been reported in dermatomyositis (DM) to be associated with rapidly progressive interstitial lung disease (RP-ILD). Our study is aimed at determining the clinical characteristics and prognostic factors underpinning anti-MDA5-associated RP-ILD. Methods. Patients with anti-MDA5-associated DM (aMDA5-DM) were identified at the Peking University People’s Hospital. The presence of anti-MDA5 antibody was determined by immunoblotting. Kaplan-Meier, chi-square test, univariate, and multivariate data analyses were used. Results. Out of 213 patients with DM and clinically amyopathic dermatomyositis (CADM), 20.7% (44/213) of patients were identified as aMDA5-DM. Amongst the aMDA5-DM patients, 63.6% (28/44) were identified as having anti-MDA5-associated RP-ILD. During the follow-up, 32.1% (9/28) of patients with anti-MDA5-associated RP-ILD died of respiratory failure. We identified older age and periungual erythema as two independent risk factors for RP-ILD mortality. Age≥57 years at disease onset was significantly associated with poor survival (P=0.02) in patients with anti-MDA5-associated RP-ILD, while patients with periungual erythema had a better survival rate than those without periungual erythema (P

The aim of this study was to isolate and purify anti-obesity peptides from Spirulina platensis protein. Five enzymes (trypsin, alcalase, pepsin, papain and protamex) were used for hydrolysis of the extracted protein. Subsequently, ultrafiltration and gel column chromatography were employed for further purification. The inhibitory effect on pancreatic lipase and 3T3-L1 preadipocytes were evaluated. The results showed that the 3–5 kDa fraction from pepsin digest exhibited good inhibition on lipase (72%), and its chromatographed fractions displayed strong inhibition on 3T3-L1 preadipocytes (72.7–88.1%) but low inhibitory or stimulatory activities on normal liver cells L-O2 (−26.02 to 12.16%). By mass spectrometry, four novel peptides NALKCCHSCPA, LNNPSVCDCDCMMKAAR, NPVWKRK and CANPHELPNK were identified, which exhibited inhibitory effects on 3T3-L1 preadipocytes proliferation (32.29–60.08%). Moreover, NPVWKRK and CANPHELPNK also significantly decreased the accumulation of triglyceride at 600 μg/mL (p

Cognitive radio (CR) provides a radio-access method for unlicensed/secondary users to share the spectrum of licensed/primary users. To improve the energy efficiency of CR networks, we propose an energy-harvesting-aided spectrum sensing and data transmission scheme in this paper. In the proposed scheme, the individual sensing and the cooperative sensing of multi-users are combined corresponding to the strong and weak signal of primary users. Meanwhile, the transmission signal of local decisions in the cooperative sensing and the strong signal of primary users are harvested as RF energy by secondary users. In order to improve the performance of spectrum sensing and energy harvesting, we formulate a multi-objective optimization problem that jointly maximizes the detection probability of the presence of primary user and minimizes the false alarm probability while limiting the least harvested energy and the interference from secondary users on the primary receiver. The multi-objective optimization problem is solved by transferring it into a single objective problem. The single objective problem on the parameters without certain range is transferred into the problem on the parameters with certain range to obtain the final solution. Numerical results prove the effectiveness of our proposed scheme, that is, the interference from primary users on secondary users can improve the global detection probability and the harvested energy at secondary users.

Speech recognition accuracy is severely reduced by the variability caused by stress. Considering the fact that speech under stress is caused by the physiological changes of the vocal folds in the physiological system whose vibration behavior is reflected by glottal flow, this paper presents a method of study on speech under stress based on a physical speech production model and characteristics of glottal flow. The physical model is used to model glottal aerodynamics in the vocal system to represent speech production. The relationship between physical parameters and glottal flow parameters is explored based on the physical model, and the glottal source and physical model are linked. Through studying on the glottal and physical parameters for the neutral and for the speech under stress, features for speech under stress characterizing the vocal folds, vortex-flow interaction, and shape of glottal flow are compared with those of neutral speech. The relations between the proposed parameters and stress-speech production mechanism are discussed. Experiments show that physical parameters representing the stiffness and viscosity of vocal folds, subglottal pressure, and laryngeal ventricle strongly influence the glottal flow. The relations for physical parameters, glottal parameters, and stress production are revealed, and theoretical and experimental bases are provided for stress detection and classification in speech recognition system.

In this study, a magnetic solid-phase extraction (MSPE) method coupled with High-Performance Liquid Chromatography Mass Spectrometry (HPLC–MS/MS) for the determination of illegal basic dyes in food samples was developed and validated. This method was based on Magnetic sulfonated reduced graphene oxide (M-S-RGO), which was sensitive and selective to analytes with structure of multiaromatic rings and negatively charged ions. Several factors affecting MSPE efficiency such as pH and adsorption time were optimized. Under the optimum conditions, the calibration curves exhibited good linearity, ranging from 5 to 60 µg/g with correlation coefficients >0.9950. The limits of detection of 16 basic dyes were in the range of 0.01–0.2 µg/L. The recoveries ranged from 70% to 110% with RSD% < 10%. The results indicate that M-S-RGO is an efficient and selective adsorbent for the extraction and cleanup of basic dyes. Due to the MSPE procedures, matrix effect and interference were eliminated in the analysis of HPLC–MS/MS without the matrix-matched standards. Thus, validation data showed that the proposed MSPE–HPLC–MS/MS method was rapid, efficient, selective, and sensitive for the determination of illegal basic dyes in foods.

MAVS is an essential component of the pathogen-sensing machinery, and functions by forming prion-like filaments. Here the authors show that alternatively translated forms of truncated endogenous MAVS can prevent spontaneous aggregation and degradation in cells to sustain MAVS-mediated immune signalling.