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Abstract Intratumoral heterogeneity poses a significant challenge to the diagnosis and treatment of recurrent glioblastoma. This study addresses the need for non-invasive approaches to map heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient. We developed BioNet, a biologically-informed neural network, to predict regional distributions of two primary tissue-specific gene modules: proliferating tumor (Pro) and reactive/inflammatory cells (Inf). BioNet significantly outperforms existing methods (p

Studying the effect of periodic airflow temperature on the heat dissipation of surrounding rock is the basis for revealing the causes of seasonal mine heat damage. In this work, a heat transfer mathematical model of roadway surrounding rock under periodic airflow temperature was established. By variable separation method, the model was divided into two parts: annual average component and periodic fluctuation component. Then we discretized the model and designed a solution program independently. Finally, a similar heat transfer experiment platform for roadway surrounding rock was set up and the simulation results were verified. The results show that: (i) The maximum error between the model and the experimental data is less than 3.2 %, which verifies the heat transfer model. (ii) As ventilation time increases, the radius of the cooling ring inside the surrounding rock increases in a negative exponential function trend. The annual average unstable heat transfer coefficient falls quickly, and the decrease speed slows down gradually. (iii) With the increase of depth, the amplitude of temperature fluctuation in surrounding rock decreases rapidly in a negative exponential function trend, and the delay phase increases linearly. (iv) The formula of dimensionless wall heat flux wave of surrounding rock was obtained by fitting.

ABSTRACT: The effects of dietary Bacillus subtilis (BS) on the meat quality of broilers were evaluated, with an emphasis on the regulation of muscle fiber types and antioxidant capabilities. One hundred and forty-four Arbor Acres male broilers were divided into 3 treatment groups (0, 300 mg/kg and 500 mg/kg dietary BS) and raised for 35 d. The results suggested that BS improved meat quality by improving the muscular pH, meat color, water holding capacity and shear force. Immunofluorescence staining revealed a positive impact of BS on the muscle fiber transformation in thigh muscles, and the gene/protein expression data from specific muscle fiber types confirmed this finding. BS activated AMP-activated protein kinase (AMPK), silent information regulator 1 and peroxisome proliferator-activated receptor gamma coactivator 1alpha. The postmortem analysis revealed that BS increased the activity of glutathione peroxidase and total antioxidant capacity while decreasing the malondialdehyde content. Additionally, BS increased the gene and protein expression of nuclear factor-like 2 (Nrf2) and activated the Nrf2 signaling pathway, including its downstream factors, such as heme oxygenase-1, catalase, superoxide dismutase and glutathione peroxidase. In conclusion, dietary BS improved meat quality by modifying muscle fiber types and enhancing the antioxidant capacity in broilers.

Abstract The overactivated immune cells in the infectious lesion may lead to irreversible organ damages under severe infections. However, clinically used immunosuppressive anti‐inflammatory drugs will usually disturb immune homeostasis and conversely increase the risk of infections. Regulating the balance between anti‐inflammation and anti‐infection is thus critical in treating certain infectious diseases. Herein, considering that hydrogen peroxide (H2O2), myeloperoxidase (MPO), and neutrophils are upregulated in the inflammatory microenvironment and closely related to the severity of appendectomy patients, an inflammatory‐microenvironment‐responsive nanomedicine is designed by using poly(lactic‐co‐glycolic) acid (PLGA) nanoparticles to load chlorine E6 (Ce6), a photosensitizer, and luminal (Lum), a chemiluminescent agent. The obtained Lum/Ce6@PLGA nanoparticles, being non‐toxic within normal physiological environment, can generate cytotoxic single oxygen via bioluminescence resonance energy transfer (BRET) in the inflammatory microenvironment with upregulated H2O2 and MPO, simultaneously killing pathogens and excessive inflammatory immune cells in the lesion, without disturbing immune homeostasis. As evidenced in various clinically relevant bacterial infection models and virus‐induced pneumonia, Lum/Ce6@PLGA nanoparticles appeared to be rather effective in controlling both infection and inflammation, resulting in significantly improved animal survival. Therefore, the BRET‐based nanoparticles by simultaneously controlling infections and inflammation may be promising nano‐therapeutics for treatment of severe infectious diseases.

Objectives: Clostridium perfringens (C. perfringens) is a significant opportunistic pathogen. This study aims to examine the occurrence of C. perfringens in patients with diarrhoea and food poisoning and compare the genetic similarities with strains found in poultry retail markets and poultry farms in the same city (Tai'an, China). Methods: Clostridium perfringens was isolated from 30 human faecal samples and genotyped using multiplex PCR. The antimicrobial susceptibility test was conducted using the Kirby-Bauer disk diffusion method. Genetic relationships were analysed through Multi-locus sequence typing (MLST) and Phylogenetic analysis. Results: The positive rate of C. perfringens was found to be 96.67%. Among the positive samples, 91.67% of the faecal samples from patients with food poisoning contained type F strains of C. perfringens, while only 16.67% of the samples from diarrhoea cases contained type F. The drug susceptibility test revealed that the majority of isolates displayed broad-spectrum antimicrobial resistance. Out of the 57 isolates tested for drug susceptibility, 89.47% demonstrated resistance to at least three antibiotics. The MLST results indicated that strains originating from the same host and environment tended to be more closely related. However, certain strains associated with food poisoning and diarrhoea in patients shared the same ST and CC as some strains found in the retail market. These strains were also found to be phylogenetically similar to some retail market strains, suggesting potential risks to human health. Conclusions: Therefore, it is crucial to enhance the management of poultry retail markets in order to mitigate these associated risks.

As a VOC, ethanol can be found in human exhaled breath, and its concentration can be used as a biomarker of human liver disease. To detect trace-level concentrations of ethanol, an ultrasensitive ethanol sensor was developed based on a dual-nanoparticle In2O3/SnO2 composite that was prepared by hydrothermal synthesis, and its suspension was dipped on a flat electrode to form a gas sensor. The nanocomposite was characterized by an SEM (scanning electron microscope), XRD (X-ray diffraction), and a TEM (transmission electron microscope), and the nanoparticle structure was observed. The experimental results showed that gas sensors based on the In2O3/SnO2 nanocomposite had higher responses compared to sensors based on pure In2O3. Among the nanocomposites, the one with a In2O3-to-SnO2 mol ratio of 1:8 was used in the sensor with the highest response of 1.41 to 100 ppb ethanol at 150 °C, which also exhibited good repeatability. The ultrasensitive response to ethanol can be attributed to the faster electron migration rate and the increase in oxygen-absorbing sites caused by the n-n heterojunction in the nanocomposite. Due to its low detection limit, good repeatability, and relatively high responses in high humidity, this sensor has a potential application in exhaled breath detection.

Abstract Background Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. Methods The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. Results In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. Conclusion In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

Cellulose nanocrystals (CNCs) with a high content of polar groups were prepared via the oxidation process by controlling the amount of mixed acid, incorporating additional additive of citric acid and vitamin C as active agents, and applying ultrasonic crosslinking. Subsequently, cellulose nanocrystal–silver (CNC–Ag) nanohybrid materials were synthesized via an oxidation hydrolysis reaction, which displayed good dispersibility and high interaction, leading to the hydrogen bonding between polar groups (-OH and -COOH) on the surface of CAC–Ag nanohybrids. The positive effects of hydrogen bonding on the surface of CAC–Ag nanohybrids were confirmed by the high carboxyl group content (2.69 mmol/g) and low contact angle (53.7°) tested. In addition, CAC–Ag nanohybrids showed significant antibacterial activity against both Gram-negative E. coli and Gram-positive S. aureus. These results showed that the high-performance CNC–Ag nanohybrids prepared in this study may be highly suitable as nano-fillers for polyester materials used in antibacterial food packaging.

BackgroundIncreased maternal cortisol secretion has been observed during pregnancy and labor. However, due to the limitations in diagnostic methods, the dynamic change of cortisol during the short period between threatened labor and labor is unknown. In this study, we aim to evaluate the changes in serum cortisol during late pregnancy and full-term labor initiation, verifying if cortisol could serve as a biomarker for the diagnosis of labor initiation from threatened labor.MethodsThis cross-sectional onsite study involved 564 participants of 6 different gestational stages (C: Control; T1: Trimester 1; T3: Trimester 3; E: expectant; TL: threatened labor; L: labor), all patients in the E, TL, and L groups were at full term. The serum cortisol concentration was quantified with a point-of-care test (POCT), and the gestation, age, parity, and BMI of participants were documented. Morning serum cortisol was collected between 8:00 and 10:00 a.m., except for the TL and L group women who were tested upon arrival or during latent labor. With cortisol levels or all five variables, L was distinguished from TL using machine learning algorithms.ResultsSignificant elevation of cortisol concentration was observed between T1 and T3, or TL and L group (P< 0.001). Women belonging to the E and TL group showed similar gestation week and cortisol levels. Diagnosis of labor initiation using cortisol levels (cutoff = 21.46 μg/dL) yielded sensitivity, specificity, and AUC of 86.50%, 88.60%, and 0.934. With additional variables, a higher specificity (89.29%) was achieved. The diagnostic accuracy of all methods ranged from 85.93% to 87.90%.ConclusionSerum cortisol could serve as a potential biomarker for diagnosis of L form TL. The rapid onsite detection of serum cortisol with POCT could facilitate medical decision-making for admission and special treatments, either as an additional parameter or when other technical platforms are not available.

The composition of particulate matter (PM) in poultry farms differs significantly from that of atmospheric PM as there is a higher concentration of microbes on farms. To assess the health effects of PM from poultry farms on pregnant animals, we collected PM from duck houses using a particulate sampler, processed it via centrifugation and vacuum concentration, and subsequently exposed the mice to airborne PM at 0.48 mg/m3 (i.e., low concentration group) and 1.92 mg/m3 (i.e., high concentration group) on the fifth day of pregnancy. After exposure until the twentieth day of pregnancy or spontaneous delivery, mice were euthanized for sampling. The effects of PM from duck houses on the pregnancy toxicity of mice were analyzed using histopathological analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction (qPCR). The results showed that exposure to PM had adverse effects on pregnant mice that reduced their feed intake in both groups. Microscopic lesions were observed in the lungs and placentas of pregnant mice, and the lesions worsened with increased PM concentrations, as shown by alveolar wall thickening, the infiltration of inflammatory cells in pulmonary interstitium, congestion, edema, and cellular degeneration of placenta. In pregnant mice in the high concentration group, exposure to PM significantly increased the expression of inflammatory cytokines in the lungs and placentas, caused oxidative stress, and decreased estrogen level in the blood. Exposure to PM also resulted in the reduced litter sizes of pregnant mice and shorter body and tail lengths in the fetuses delivered. Beyond that, exposure to PM significantly downregulated the levels of antioxidant factor superoxide dismutase and neurotrophic factor Ngf in the brains of fetuses. Collectively, exposure to a high concentration of PM by inhalation among pregnant mice caused significant pregnancy toxicity that led to abnormal fetal development due to inflammatory damage and oxidative stress. These findings established a foundation for future studies on the underlying mechanisms of pregnancy toxicity induced by exposure to PM.

Abstract. Background:. Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. Methods:. A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. Results:. The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. Conclusions:. Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

Abstract Background Biomarker of insulin resistance, namely triglyceride-glucose index, is potentially useful in identifying critically ill patients at high risk of hospital death. However, the TyG index might have variations over time during ICU stay. Hence, the purpose of the current research was to verify the associations between the dynamic change of the TyG index during the hospital stay and all-cause mortality. Methods The present retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV) critical care dataset, which included data from 8835 patients with 13,674 TyG measurements. The primary endpoint was 1-year all-cause mortality. Secondary outcomes included in-hospital all-cause mortality, the need for mechanical ventilation during hospitalization, length of stay in the hospital. Cumulative curves were calculated using the Kaplan–Meier method. Propensity score matching was performed to reduce any potential baseline bias. Restricted cubic spline analysis was also employed to assess any potential non-linear associations. Cox proportional hazards analyses were performed to examine the association between the dynamic change of TyG index and mortality. Results The follow-up period identified a total of 3010 all-cause deaths (35.87%), of which 2477 (29.52%) occurred within the first year. The cumulative incidence of all-cause death increased with a higher quartile of the TyGVR, while there were no differences in the TyG index. Restricted cubic spline analysis revealed a nearly linear association between TyGVR and the risk of in-hospital all-cause mortality (P for non-linear = 0.449, P for overall = 0.004) as well as 1-year all-cause mortality (P for non-linear = 0.909, P for overall = 0.019). The area under the curve of all-cause mortality by various conventional severity of illness scores significantly improved with the addition of the TyG index and TyGVR. The results were basically consistent in subgroup analysis. Conclusions Dynamic change of TyG during hospital stay is associated with in-hospital and 1-year all-cause mortality, and may be superior to the effect of baseline TyG index.

Appropriate soluble carbohydrate (SCHO)-to-NDF ratios in the diet are essential for rumen health. The effects of different SCHO-to-NDF ratios (1.0, 1.5, and 2.0) on rumen barrier function and inflammation in Dumont lambs (n = 18, 6 replicates per treatment) was investigated. The SCHO:NDF ratio was altered by replacing the forage (Leynus chinensis) with corn grain. With an increase in the proportion of SCHO, the final body weight (FBW), average daily gain (ADG), soluble carbohydrate intake (SCHOI), and LPS level increased; and the neutral detergent fiber intake (NDFI), ruminal papillae height, papillae area, and pH decreased (p < 0.05, plin < 0.05). The medium CHO:NDF group had increased claudin-1 mRNA (p < 0.05, plin = 0.005, pquad = 0.003) and protein (p < 0.05, pquad < 0.001) levels; the high CHO:NDF group had increased occludin mRNA and protein (p < 0.05, plin = 0.001) levels. The level of the anti-inflammatory cytokine IL-10 was significantly greater in the medium CHO:NDF group than in the high CHO:NDF group (p < 0.05, pquad < 0.001). With an increase in the ratio of SCHO, the mRNA level and concentration of the proinflammatory cytokines IL-1β, IL-6, and TNF-α linearly increased (p < 0.05, plin < 0.05), and those in the high CHO:NDF group were significantly greater than those in the low CHO:NDF group. The levels of phosphorylated p65 (plin = 0.003), IκB-α (plin < 0.001), and JNK (plin = 0.001) increased linearly, and those in the high CHO:NDF group were significantly greater than those in the other two groups (p < 0.05). Therefore, when the SCHO-to-NDF ratio was increased to 1.5, the rumen epithelium was not affected, but when the ratio was increased to 2.0, NF-κB and MAPK were activated in the rumen epithelium, leading to impaired barrier function and inflammation. The suitable NFC:NDF ratio for the short-term fattening of Dumont lambs was found to be 1.50.

The two-spotted spider mite (Tetranychus urticae) is a constant threat to greenhouse strawberry production. The application of synthetic acaricides is the main method of controlling T. urticae. However, resistance development to traditional acaricides reduces their efficacy and eventually leads to control failure. It is important for strawberry growers to look for new acaricides and application technologies that can limit the harmfulness of T. urticae in environmentally friendly ways. In the current study, laboratory toxicity tests and field trials were performed to screen high-efficiency acaricides, and then application technologies were improved to enhance the management of T. urticae. In the laboratory toxicity tests, the results showed that the LC50 (median lethal concentration) value of cyetpyrafen, cyenopyrafen, cyflumetofen, bifenazate, abamectin, azocyclotin, pyridaben, spirodiclofen, and etoxazole against adult T. urticae was 0.226, 0.240, 0.415, 3.583, 5.531, 25.58, 39.69, 140.3, and 267.7 mg/L, respectively. In addition, the LC50 value of the nine acaricides against eggs of T. urticae was 0.082, 0.097, 0.931, 18.56, 25.52, 45.61, 36.32, 1.954, and 0.040 mg/L, respectively. The field trial results showed that the best control effect was obtained in cyetpyrafen at 300 mL/ha treatment. Cyetpyrafen was chosen for further application technology tests. In the spray volume tests, the results showed that increasing the spray volume from 900 to 1050 L/ha significantly improved the control of T. urticae. In addition, the results from the spray instrument tests demonstrated that the control effects on T. urticae in the ozone spray treatments were significantly higher than those of the conventional and electrostatic sprays 1 and 3 days after treatment (DAT). Therefore, this study suggested that cyetpyrafen effectively controlled T. urticae both in the laboratory tests and in the field trials. Increasing the spray volume and application of ozone spray significantly improved T. urticae management.

Objectives: CHARGE syndrome is a congenital hereditary condition involving multiple systems. Patients are easily misdiagnosed with idiopathic hypogonadotropic hypogonadism (IHH) due to the overlap of clinical manifestations. An accurate clinical diagnosis remains challenging when the predominant clinical manifestation resembles hypogonadotropic hypogonadism. Methods: This original research is conducted based on the genetic finding and analysis of clinical cases. Whole-exome sequencing (WES) and in-silico analyse were performed on two sisters to investigate the pathogenesis in this family. Homology modelling was conducted to evaluate structural changes in the variants. Results: WES and Sanger sequencing revealed two siblings carrying a nonsense mutation (NM_017780.4: c.115C > T) in exon 2 of CHD7 inherited from a mildly affected mother and a missense mutation (NM_015295.3: c.2582T > C) in exon 20 of SMCHD1 inherited from an asymptomatic father. The nonsense mutation in CHD7 was predicted to generate nonsense-mediated decay, whereas the missense mutation in SMCHD1 decreased protein stability. Conclusions: We identified digenic CHD7 and SMCHD1 mutations in IHH-associated diseases for the first time and verified the synergistic role of oligogenic inheritance. It was also determined that WES is an effective tool for distinguishing diseases with overlapping features and establishing a molecular diagnosis for cases with digenic or oligogenic hereditary disorders, which is beneficial for timely treatment, and family genetic counseling.

Background and objectiveGlioblastoma (GBM) is one of the most aggressive and lethal human cancers. Intra-tumoral genetic heterogeneity poses a significant challenge for treatment. Biopsy is invasive, which motivates the development of non-invasive, MRI-based machine learning (ML) models to quantify intra-tumoral genetic heterogeneity for each patient. This capability holds great promise for enabling better therapeutic selection to improve patient outcome.MethodsWe proposed a novel Weakly Supervised Ordinal Support Vector Machine (WSO-SVM) to predict regional genetic alteration status within each GBM tumor using MRI. WSO-SVM was applied to a unique dataset of 318 image-localized biopsies with spatially matched multiparametric MRI from 74 GBM patients. The model was trained to predict the regional genetic alteration of three GBM driver genes (EGFR, PDGFRA and PTEN) based on features extracted from the corresponding region of five MRI contrast images. For comparison, a variety of existing ML algorithms were also applied. Classification accuracy of each gene were compared between the different algorithms. The SHapley Additive exPlanations (SHAP) method was further applied to compute contribution scores of different contrast images. Finally, the trained WSO-SVM was used to generate prediction maps within the tumoral area of each patient to help visualize the intra-tumoral genetic heterogeneity.ResultsWSO-SVM achieved 0.80 accuracy, 0.79 sensitivity, and 0.81 specificity for classifying EGFR; 0.71 accuracy, 0.70 sensitivity, and 0.72 specificity for classifying PDGFRA; 0.80 accuracy, 0.78 sensitivity, and 0.83 specificity for classifying PTEN; these results significantly outperformed the existing ML algorithms. Using SHAP, we found that the relative contributions of the five contrast images differ between genes, which are consistent with findings in the literature. The prediction maps revealed extensive intra-tumoral region-to-region heterogeneity within each individual tumor in terms of the alteration status of the three genes.ConclusionsThis study demonstrated the feasibility of using MRI and WSO-SVM to enable non-invasive prediction of intra-tumoral regional genetic alteration for each GBM patient, which can inform future adaptive therapies for individualized oncology.

Abstract Janus nanoparticles have aroused the interest of scholars because of their highly efficient emulsification of spilled oils in wastewater. In this work, interfacially active Janus hollow glass microparticles (J-HGMPs) of asymmetric wettability were designed and synthesized in order to achieve more efficient separation of emulsified oil droplets from oily wastewater. Surface characteristic techniques such as FTIR, SEM, zeta potential and contact angle measurements had been employed to assess the amphiphilic surface properties of J-HGMPs. The oil removal/recovery performance of J-HGMPs in different oil–water systems and their interfacial activities were studied. As a particulate emulsifier, J-HGMPs could remove/recover > 96% oil from oil–water mixed phase. The results showed that J-HGMPs had strong interfacial activities and anchored firmly at oil/water interfaces. This high adsorption energy was also evaluated and verified via the calculation of Gibbs free energy. Overall, this study provided a novel and low-cost oil recovery method via a convenient buoyancy force that could be effectively applied in the treatment of oil spills while achieving the goal of benign and green environmental protection.

Abstract Background Newcastle disease virus (NDV) strain ZM10, a typical enterotropic avirulent vaccine strain, has been widely used in China for chickens against Newcastle disease. To elucidate its enterotropic mechanism and develop recombiant multivalent vaccines based on it, the reverse genetics system for NDV ZM10 is an indispensable platform. Results A full-length cDNA clone of NDV ZM10 and three supporting plasmids were constructed using the ligation-independent cloning method. Recombinant NDV rZM10 was successfully rescued after these plasmids were co-transfected into BHK-21 cells. Besides, the recombinant virus rZM10-RFP encoding the red fluorescent protein was generated by inserting the RFP gene into the full-length clone of NDV between the P and M genes. These rescued viruses were genetically and biologically identical to the parental strain and showed similar growth kinetics. Conclusion The recovery system of NDV ZM10 strain was established, and can be used as a foundation for research on the enterotropic mechanism and development of multivalent vaccines against viral diseases of livestock and poultry.

Abstract Background Human papilloma virus (HPV) DNA test was applied in cervical cancer screening as an effective cancer prevention strategy. The viral load of HPV generated by different assays attracted increasing attention on its potential value in disease diagnosis and progression discovery. Methods In this study, three HPV testing datasets were assessed and compared, including Hybrid Capture 2 (n = 31,954), Aptima HPV E6E7 (n = 3269) and HPV Cobas 4800 (n = 13,342). Logistic regression models for diagnosing early cervical lesions of the three datasets were established and compared. The best variable factor combination (VL + BV) and dataset (HC2) were used for the establishment of six machine learning models. Models were evaluated and compared, and the best-performed model was validated. Results Our results show that viral load value was significantly correlated with cervical lesion stages in all three data sets. Viral Load and Bacterial Vaginosis were the best variable factor combination for logistic regression model establishment, and models based on the HC2 dataset performed best compared with the other two datasets. Machine learning method Xgboost generated the highest AUC value of models, which were 0.915, 0.9529, 0.9557, 0.9614 for diagnosing ASCUS higher, ASC-H higher, LSIL higher, and HSIL higher staged cervical lesions, indicating the acceptable accuracy of the selected diagnostic model. Conclusions Our study demonstrates that HPV viral load and BV status were significantly associated with the early stages of cervical lesions. The best-performed models can serve as a useful tool to help diagnose cervical lesions early.

Abstract The frequent and massive use of pesticides has led to pesticide residues in apricot, threatening food safety and human health. A reliable and simple modified QuEChERS method with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of 11 pesticides in apricot. Method validation indicated that satisfied linearity (R2 ≥ 0.9959), accuracy (recoveries of 72–119%), sensitivity (limits of detection, 0.03–0.30 μg/kg; limits of quantification, 0.13–1.00 μg/kg), and precision (relative standard deviations ≤ 11.9%), and matrix effects were 0.89–1.13. Apricot samples from different ecological regions in China were collected and tested using the proposed methods. Monitoring results were used to assess the dietary intake risk of Chinese populations of different ages and genders. Dietary risk assessment revealed that the risk quotients were 0.003–1.184% for different gender and age groups in China, indicating none unacceptable public health risk for general population. This work was thus significant in developing a simpler, more efficient and economical analysis method and food safety risks of the 11 pesticides on apricot and facilitated the establishment of maximum residue limits.

Abstract Background Brain metastases (BM) from non-small-cell lung cancer (NSCLC) is the most common brain malignancy. Systemic inflammation biomarkers have recently been evaluated as prognosis indicators in several tumors. The combination of these markers has not been evaluated in NSCLC with BM yet. Here, we explored the predictive value of pretreatment inflammatory biomarkers and established a novel, clinically applicable prognostic index for NSCLC patients with BM. Methods A retrospective investigation of 951 NSCLC patients newly diagnosed with BM at Sun Yat-sen University Cancer Center was conducted. We randomly divided patients into a training cohort (n = 674) or validation cohort (n = 277). Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off values of pretreatment systemic inflammatory indexes. The associations between serum biomarkers and overall survival (OS) were analyzed by Kaplan–Meier curves and Cox proportional models. The resulting prediction model has been externally verified through the validation cohort. Results The optimal cut-off value of the neutrophil–lymphocyte ratio (NLR) in predicting OS was 4.71, while the clinical standard of 40 mg/L was chosen as the optimal cut-off value of albumin. Univariate and multivariate analyses revealed that patients receiving local treatment, chemotherapy, a NLR

Abstract Background Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. Results We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. Conclusion INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.

Abstract Background Assessment of health beliefs and risk perception is a critical means to prevent coronary heart disease, but there are few such studies on assessment in the Chinese population. Given the demonstrated value and widespread use of the Attitudes and Beliefs about Cardiovascular Disease Risk Questionnaire (ABCD), this study was designed to translate it into Chinese, and to evaluate its reliability and validity in a Chinese population. Methods The Chinese version of the ABCD was created using the Beaton translation model, which included forward and backward translation. The reliability and construct validity of the Chinese ABCD were examined in a sample of 353 adults who participated in the public welfare projects of the Chinese National Center for Cardiovascular Diseases in Guilin city, Guangxi. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to examine the factor structure of the Chinse ABCD. The internal consistency of the questionnaire was assessed using Cronbach’s α and corrected item-total correlations. Results We deleted item 7 in the knowledge dimension of the Chinese ABCD and added two items about smoking and sleep knowledge, while retaining 25 of the original items, so that it finally included 27 items. The correlations were .20–.90; the correlations between each item and the total score of the ABCD were .34–.86; and the item-level Content Validity Index (I-CVI) was .86–1.00. The results of the EFA showed that all items were close to .40, and the cumulative variance contribution rate was 63.88%. The model fit was acceptable (χ2 = 698.79, df = 243, χ2/df = 2.87, P

Objective: Doxorubicin (DOX) is commonly used for chemotherapy; however, its clinical value is extremely dampened because of the fatal cardiotoxicity. Leucine zipper protein 1 (LUZP1) plays critical roles in cardiovascular development, and this study is designed for determining its function and mechanism in DOX-induced cardiotoxicity. Methods: Cardiac-specific Luzp1 knockout (cKO) and transgenic (cTG) mice received a single or repeated DOX injections to establish acute and chronic cardiotoxicity. Biomarkers of inflammation, oxidative damage and cell apoptosis were evaluated. Transcriptome and co-immunoprecipitation analysis were used to screen the underlying molecular pathways. Meanwhile, primary cardiomyocytes were applied to confirm the beneficial effects of LUZP1 in depth. Results: LUZP1 was upregulated in DOX-injured hearts and cardiomyocytes. Cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated DOX-associated inflammation, oxidative damage, cell apoptosis and acute cardiac injury. Mechanistic studies revealed that LUZP1 ameliorated DOX-induced cardiotoxicity through activating 5′-AMP-activated protein kinase (AMPK) pathway, and AMPK deficiency abolished the cardioprotection of LUZP1. Further findings suggested that LUZP1 interacted with protein phosphatase 1 to activate AMPK pathway. Moreover, we determined that cardiac-specific LUZP1 overexpression could also attenuate DOX-associated chronic cardiac injury in mice. Conclusion: LUZP1 attenuates DOX-induced inflammation, oxidative damage, cell apoptosis and ventricular impairment through regulating AMPK pathway, and gene therapy targeting LUZP1 may provide novel therapeutic approached to treat DOX-induced cardiotoxicity.

ObjectiveThe purpose of this study was to investigate the effects of different doses of Sophora alopecuroides (SA) on the rumen fermentation and microbial diversity of sheep.MethodsA total of 32 healthy Dumont crossbred male lambs weighing 25.73 ± 2.17 kg were randomly assigned to 4 treatment groups with 8 replicates each: a control group (CG) fed a basal diet with a concentrate-to-forage ratio of 7:3 and three experimental groups - the 0.1% group(TG1), 0.3% group (TG2), and 0.5% group (TG3), which were fed the same basal diet but supplemented with increasing doses of SA.Results(1) Increasing the SA dose led to a significant linear increase (p-< 0.05) in acetate, propionate, butyrate, and total volatile fatty acid (TVFA) concentrations in the rumen, as well as a significant quadratic effect (p-< 0.05) on the propionate concentration. In contrast, there was a significant linear decrease (p-< 0.05) in the NH3-N concentration in the rumen. (2) At the level of rumen bacterial phyla, the abundance of Bacteroidetes in the rumen increased, and that of Firmicutes decreased (p = 0.08). At the genus level, the rumen abundances of Ruminococcus and Phocaeicola of sheep in the three experimental groups were significantly higher than in the control group (p-< 0.05), and the abundances of Clostridiales and Candidatus-Hepatincola were significantly increased in the 0.1% and 0.3% groups (p < 0.05). (3) Regarding rumen anaerobic fungi, the differences between the control group and experimental groups at the phylum level and genus level were not significant (p > 0.05), but the relative abundances of Neocallimastigomycota and Piromyces in the 0.1% group were significantly higher than that in the control group.ConclusionSA addition to a high grain diet could increase the VFA concentration and pH in the sheep rumen, reduce the NH3-N concentration in the rumen and improve rumen fermentation function. Although there was no significant change in rumen bacterial or fungal diversity, SA addition increased the rumen abundances of Bacteroidetes, Ruminococcus, Phocaeicola, Clostridiales, Neocallimastigomycota and Piromyces, decreased the rumen abundance of Firmicutes, and had a positive effect on the rumen microbiota to improve sheep health.

Abstract Hydrogen (H2) sensors are of great significance in hydrogen energy development and hydrogen safety monitoring. However, achieving fast and effective detection of low concentrations of hydrogen is a key problem to be solved in hydrogen sensing. In this work, we combined the excellent gas sensing properties of tin(IV) oxide (SnO2) and zinc oxide (ZnO) with the outstanding electrical properties of reduced graphene oxide (rGO) and prepared palladium (Pd)-doped rGO/ZnO-SnO2 nanocomposites by a hydrothermal method. The crystal structure, structural morphology, and elemental composition of the material were characterized by FE-SEM, TEM, XRD, XPS, Raman spectroscopy, and N2 adsorption–desorption. The results showed that the Pd-doped ZnO-SnO2 composites were successfully synthesized and uniformly coated on the surface of the rGO. The hydrogen gas sensing performance of the sensor prepared in this work was investigated, and the results showed that, compared with the pure Pd-doped ZnO-SnO2 sensor, the Pd-doped rGO/ZnO-SnO2 sensor modified with 3 wt% rGO had better hydrogen (H2)-sensing response of 9.4–100 ppm H2 at 380 °C. In addition, this sensor had extremely low time parameters (the response time and recovery time for 100 ppm H2 at 380 °C were 4 s and 8 s, respectively) and an extremely low detection limit (50 ppb). Moreover, the sensor exhibited outstanding repeatability and restoration. According to the analysis of the sensing mechanism of this nanocomposite, the enhanced sensing performance of the Pd-doped rGO/ZnO-SnO2 sensor is mainly due to the heterostructure of rGO, ZnO, and SnO2, the excellent electrical and physical properties of rGO and the synergy between rGO and Pd.

The purpose of this study was to determine the effects of Sophora alopecuroides (SA) on liver function, liver inflammatory factor levels, antioxidant indexes and transcriptome in sheep. Twenty-four 3-month-old healthy Dumont hybrid lambs weighing 25.73 ± 2.17 kg were randomly divided into three groups: C1 (the control group), fed a concentrate-to-forage ratio of 50:50; H2 (the high-concentration group), fed a concentrate-to-forage ratio of 70:30; and S3 (the SA group), fed a concentrate-to-forage ratio of 70:30 + 0.1% SA. The results showed that the rumen pH values of the C1 and S3 groups were significant or significantly higher than that of the H2 group (p < 0.05 or p < 0.01). The serum ALT, AST and LDH activities and the LPS and LBP concentrations in the sheep serum and liver in the H2 group were significantly or extremely significantly higher than those in the C1 and S3 groups (p < 0.01), and the IL-10 content and SOD, GPX-PX and T-AOC activities showed the opposite trend (p < 0.05 or p < 0.01). KEGG enrichment analysis showed that the differentially expressed genes were significantly enriched in the ECM–receptor interaction and focal adhesion pathways, which are closely related to immune and antioxidant functions (p-adjust < 0.1). In summary, SA could improve the immune and antioxidant functions of lamb livers under high-concentrate conditions and regulate the mechanism of damage on sheep livers, which is caused by high-concentrate diets and through the expression of related genes in the ECM/FAs pathway.

Background and Purpose MicroRNA-125b-5p (miR-125b-5p) is downregulated in patients with gestational hypertension signs. However, the role of miR-125b-5p in pregnancy-induced hypertension (PIH) remains unknown. Methods The human placental microvascular endothelial cells (HPMECs) have undergone hypoxia and reoxygenation (H/R) treatment to establish PIH cellular model. Rats were performed with reduced uterine perfusion pressure (RUPP) operation to establish PIH animal model. Results MiR-125b-5p promoted viability while inhibited the apoptosis of H/R-treated HPMECs by downregulating BMF. MiR-125b-5p alleviated hypertensive symptoms and improved pregnancy outcomes in RUPP rats. Conclusion MiR-125b-5p ameliorates H/R-induced HPMEC dysfunction and attenuates RUPP-induced hypertension in pregnant rats by downregulating BMF.

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive progress and memory loss, which eventually develops into dementia. It can cause personality disorders and decreased quality of life of patients. Currently, AD patients account for 60–70% of global dementia patients and the incidence rate of AD is increasing annually. AD not only causes pain to patients but also brings a heavy burden to the entire family. Studies have found that there is a connection between mitochondrial dysfunction and other biochemical changes in AD like classical neuropathological hallmarks (β-amyloid and tau protein), inflammation pathways, oxidative stress, and so on. Evidence shows that early treatment targeted directly to mitochondria could extend the lifespan of model mice and decrease the relevant neuropathological markers. Therefore, research on the mitochondrial dysfunction of AD can be of potential significance for clinical treatment. To date, few bibliometric analysis articles related to mitochondrial dysfunction of AD have been published. Bibliometric analysis refers to quantitatively analyzing certain aspects of articles like publishers, authors, and countries by using statistical and mathematical methods. Combined with statistical software, a large number of papers can be converted to visualization figures and tables, which provide vital information such as keyword hotspots and the names of contributing authors. Through the bibliometric analysis method, our study aimed to provide study trends and keyword hotpots for researchers to conduct further relevant research in this field.MethodsWe used the Web of Science core collection database as a literature retrieval tool to obtain data related to mitochondrial changes in Alzheimer’s disease during the last 20 years. The retrieval type was [TS = (Alzheimer’s disease)] ND [TS = (mitochondrion)], ranging from January 1, 2000 to June 30, 2022. VOSviewer v1.6.18, Arcgis 10.8, and HistCite pro 2.1 were used to conduct data visualization analysis. VOSviewer v1.6.18 made relevant network visualization maps of the cooperative relationship between relevant countries, institutions, and authors (co-authorship), the frequency of different keywords appearing together (co-occurrence), and the frequency of different articles cited together (co-cited). Arcgis 10.8 created the world map of publications distribution in this field and Histcite pro 2.1 was used to count the local citation score (LCS) of references. In addition, Journal Citation Reports were used to consult the latest journal import factor and JCI quartile.ResultsAs of June 30, 2022, from the Web of Science core collection, we selected 2,474 original articles in English, excluding the document types of the news items, meeting abstracts, and some articles that had little relevance to our theme. The United States acted as the leader and enjoyed a high reputation in this field. The University of California System was the institution that made the greatest contribution (3.64% with 90 papers). Most articles were published in the Journal of Alzheimer’s Disease (8.21%, with 203 papers). The most frequently co-cited journal in Q1 was the Journal of Biological Chemistry (8,666 citations, TLS: 1039591). Russel H. Swerdlow (55 publications) was the most productive author and PH Reddy was the most co-cited author with 1,264 citations (TLS: 62971). The hotpots of mitochondrial dysfunction in AD were as follows: “oxidative stress,” “amyloid-beta-protein,” “tau,” “apoptosis,” “inflammation,” “autophagy,” “precursor protein,” “endoplasmic-reticulum,” “dynamics” and “mitochondrial unfolded protein response.”ConclusionThis bibliometric analysis research will help readers rapidly identify current hotpots and milestone studies related to directions of interest in AD research.

IntroductionPotential nutrient losses and mycotoxin accumulation caused by abnormal fermentation during transportation from cropland to dairy farms leads to the diseases incidence and threatens the health of dairy cows, then further causes financial losses. The aim of this study was to investigate the effects of different transportation times on the nutritional composition, mycotoxins, and microbial communities in whole-plant corn silage (WPCS).MethodsThree groups were subjected to different transport times: DY, short (600 min). WPCS were collected from the same field, and nutrient composition and microbial composition before and after transportation were analyzed.Results and discussionOur results showed that the temperature of WPCS was higher in the ZY and CY groups than in the DY group (P < 0.01). There were no significant differences in dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), ether extract (EE) and starch contents after different transportation times (P > 0.05), whereas the starch and water-soluble carbohydrates (WSC) contents in the CY group was significantly decreased after transport (P < 0.05). Similarly, the concentration of vomitoxin in the DY and CY groups declined markedly (P < 0.05) and the zearalenone content in the DY group also significantly decreased after transportation (P < 0.05). Regarding the analysis of microorganisms in WPCS, UniFrac-distance matrices and Shannon indices showed differences in the ZY group (P < 0.05), but fungal diversities were not influenced by the transport time (P > 0.05). In the ZY group, the relative abundance of Lactiplantibacillus decreased significantly after transportation (P > 0.05), but the relative abundances of unidentified_Chloroplast, Pantoea, Gluconobacter, unidentified Acetobacter and Acinetobacter increased markedly (P < 0.05). In addition, the relative abundances of Acetobacter and Gluconobacter in the CY group increased after transport (P < 0.05). Among fungal communities, a total of three, nine, and ten different fungal flora were observed in the DY, ZY, and CY groups, respectively, although no difference was found in fungal diversity. In conclusion, increased temperature, loss of starch, and mycotoxin variation were found with increased transport time. This might be the result of competition between bacteria and fungi, and novel technologies will need to be utilized for further exploration of the mechanism.

BackgroundThe COVID-19 pandemic has caused significant psychological stress among healthcare workers. This study aimed to clarify the factors that influenced health workers’ posttraumatic stress disorder (PTSD) symptoms.MethodA total of 443 healthcare workers from eight Mental Health Centers in Shandong were recruited to attend an online survey. Participants completed self-evaluation measures of exposure to the COVID-19 environment and PTSD symptoms, as well as measures of potential protective factors such as euthymia and perceived social support.ResultsAbout 45.37% of healthcare workers had severe symptoms of PTSD symptoms. Healthcare workers with more serious PTSD symptoms were significantly related to higher exposure to COVID-19 (r = 0.177, p

Accurate prediction of wind speed is critical for realizing optimal operation of a wind farm in real-time. Prediction is challenging due to a high level of uncertainty surrounding wind speed. This article describes use of a novel Extreme Learning Kalman Filter (ELKF) that integrates the sigma-point Kalman filter with the extreme learning machine algorithm to accurately forecast wind speed sequence using an Artificial Neural Network (ANN)-based state-space model. In the proposed ELKF method, ANNs are used to construct the state equation of the state-space model. The sigma-point Kalman filter is used to address the recursive state estimation problem. Experimental data validations have been implemented to compare the proposed ELKF method with autoregressive (AR) neural networks and ANNs for short-term wind speed forecasting, and the results demonstrated better prediction performance with the proposed ELKF method.

ObjectiveThis study aimed to investigate early brain microstructural changes discovered using magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence and cerebral hemodynamic using TCD for cognitive impairment after acute cerebral infarction.MethodsWe enrolled 43 patients with acute cerebral infarction and 21 healthy people in the study, who were subjected to cognitive assessments, the MP2RAGE sequence, and a cerebral hemodynamic examination. A total of 26 brain regions of interest were investigated. Furthermore, we used cerebral hemodynamics to explain brain microstructural changes, which helped us better understand the pathophysiology of cognitive impairment after acute cerebral infarction and guide treatment.ResultsT1 relaxation times in the left frontal lobe, right frontal lobe, right temporal lobe, left precuneus, left thalamus, right hippocampus, right head of caudate nucleus, and splenium of corpus callosum were substantially different across the three groups, which were significantly correlated with neuropsychological test scores. CI group patients had significantly lower cerebral blood flow velocity than those in the N-CI and Normal groups. The receiver operating curve analysis revealed that most T1 relaxation times had high sensitivity and specificity, especially on the right temporal lobe and right frontal lobe. There was a potential correlation between T1 relaxation times and MMSE scores through TCD parameters.ConclusionThe MP2RAGE sequence can detect alterations in whole brain microstructure in patients with cognitive impairment after acute cerebral infarction. Brain microstructural changes could influence cognitive function through cerebral hemodynamics. T1 relaxation times on the right temporal lobe and the right frontal lobe are expected to be a prospective biomarker of cognitive impairment after acute cerebral infarction.

Wavefront distortion caused by atmospheric turbulence can be described as different types of aberrations, such as piston, tilt, defocusing, astigmatism, coma and so on. The operation of dual deformable mirrors can have mutual coupling effects, which affect the correction effect of wavefront distortion. This study combines a fast-steering mirror (FSM) and a deformable mirror (DM) to form a dual-deformable-mirrors wavefront correction system, and proposes a decoupling algorithm that can correct any specified aberration. In this decoupling algorithm, both the FSM and the DM are controlled using the mode method, and the specific corrected aberrations are obtained based on a limited matrix. The compensation ability of the DM is directly characterized by the mode coefficients of the aberrations, which can achieve independent correction of any order of aberrations and effectively reduce the coupling effect of the dual-deformable-mirrors wavefront correction system. An adaptive optical dual-deformable-mirrors wavefront correction system experiment was built to verify the decoupling algorithm. When the DM corrects the 3rd-, 10th-, and 25th-order aberrations, and the FSM only corrects the 1st- and 2nd-order aberrations, the coupling coefficients are approximately 1.17×10−3, 1.814×10−2 and 7.81×10−3, respectively, and their magnitude reaches 10−2 and below 10−2, respectively. The experimental results show that the decoupling algorithm can effectively suppress the coupling effect between the FSM and the DM.

Abstract Background Clostridium perfringens is an important zoonotic microorganism, which can cause diseases in animals and humans under suitable conditions. Contamination of C. perfringens in chicken products has been reported worldwide, but the genetic diversity and relationship of isolates were seldom analyzed. Objectives The current study was undertaken to investigate the prevalence of C. perfringens from retail chicken products and sick chickens with suspected necrotic enteritis (NE) in Tai'an area, China. Methods In total, 295 samples were collected from Tai'an large poultry retail market and veterinary hospital in 2018, then the isolates were tested for toxin genes, drug resistance and multilocus sequence typing (MLST). Results Overall, 138 (46.78%) samples were determined to be positive for C. perfringens, and 99.37% of the isolates were identified as C. perfringens type A, with the remaining isolates being type F; 18.99% of the isolates were positive for cpb2 gene. Antimicrobial susceptibility testing revealed that 52.27% of the isolates from poultry retail market and diseased chickens showed multiple antibiotic resistance. MLST results showed that 50 analyzed isolates can be divided into 39 sequences types (STs), clustered in three clonal complexes (CCs) and 23 singletons. Although most of the isolates belong to type A, considerable genetic diversity can be observed, with the Simpson's diversity index up to 0.9181. MLST results and phylogenetic analysis showed that a portion of the isolates from humans and chickens were assigned to the same clusters in the phylogenetic tree or found to be in the same CCs, indicating the chicken isolates and the human isolates are related in certain stratification. Conclusions This study showed that the contamination rate of C. perfringens in the local retail chicken products was relatively high. Most of the isolates exhibit broad‐spectrum antimicrobial resistance. The high antibiotic resistance of C. perfringens isolates and the relationship between isolates from human and chicken indicated potential public health risks.

Abstract Background Though massively parallel sequencing has been widely applied to noninvasive prenatal screen for common trisomy, the clinical use of massively parallel sequencing to noninvasive prenatal diagnose monogenic disorders is limited. This study was to develop a method for directly determining paternal haplotypes for noninvasive prenatal diagnosis of monogenic disorders without requiring proband’s samples. Methods The study recruited 40 families at high risk for autosomal recessive diseases. The targeted linked-read sequencing was performed on high molecular weight (HMW) DNA of parents using customized probes designed to capture targeted genes and single-nucleotide polymorphisms (SNPs) distributed within 1Mb flanking region of targeted genes. Plasma DNA from pregnant mothers also underwent targeted sequencing using the same probes to determine fetal haplotypes according to parental haplotypes. The results were further confirmed by invasive prenatal diagnosis. Results Seventy-eight parental haplotypes of targeted gene were successfully determined by targeted linked-read sequencing. The predicted fetal inheritance of variant was correctly deduced in 38 families in which the variants had been confirmed by invasive prenatal diagnosis. Two families were determined to be no-call. Conclusions Targeted linked-read sequencing method demonstrated to be an effective means to phase personal haplotype for noninvasive prenatal diagnosis of monogenic disorders.

IntroductionImmune status was evaluated by means of lymphocyte subset counts and immune factors in cancer. This study analyzed the peripheral blood immune index and survival outcomes in intracranial germ cell tumor (iGCT) patients.MethodsPeripheral blood lymphocyte subset counts and levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), and interferon-γ (IFN) from 133 iGCT patients were collected and retrospectively analyzed. Their clinical information was extracted from the hospital database, and prognosis was confirmed by telephone visit. Patients (n=11) underwent prospective review and their samples of peripheral blood lymphocytes were verified.ResultsA total of 113 (84.2%) patients received comprehensive treatments, including 96 standard therapy (combination of full course chemotherapy and radiology with or without surgery) and 17 comprehensive but non-standard therapy (either without full course chemotherapy or with non-standard radiotherapy) and 98 (73.7%) reached complete or partial response. T lymphocytes (CD3+), cytotoxic T cells (CD3+CD8+ or Tc), and B lymphocytes (CD19+) decreased (p=0.047, p=0.004, and p

Abstract Research on direct targets of traditional Chinese medicine (TCM) is the key to study the mechanism and material basis of it, but there is still no effective methods at present. We took Compound Danshen dropping pills (CDDP) as a study case to establish a strategy to identify significant direct targets of TCM. As a result, thirty potential active kinase targets of CDDP were identified. Nine of them had potential dose-dependent effects. In addition, the direct inhibitory effect of CDDP on three kinases, AURKB, MET and PIM1 were observed both on biochemical level and cellular level, which could not only shed light on the mechanisms of action involved in CDDP, but also suggesting the potency of drug repositioning of CDDP. Our results indicated that the research strategy including both in silico models and experimental validation that we built, were relatively efficient and reliable for direct targets identification for TCM prescription, which will help elucidating the mechanisms of TCM and promoting the modernization of TCM.

Abstract Background Highly empiric use of carbapenem in pyogenic liver abscess (PLA) is widespread problem. However, few studies have examined the association between blood culture and carbapenem use in patients with PLA in China. Thus, we conducted this observational study. Methods The data of patients diagnosed with PLA at two comprehensive tertiary care centers from 2014 to 2020 were retrospectively collected. Demographic and clinical data were analyzed, and univariate and multivariate analyses were performed to investigate the association between blood culture and carbapenem use. Subgroup analysis was conducted to explore whether the effect is different in sepsis. Results Blood culture was performed in 110 (46.0%) patients, of whom 44 (40.0%) patients had positive results for bacterial culture. Extended-spectrum beta-lactamase (ESBL)-positive blood culture isolates were detected in 8 (7.3%) patients. The positivity rate of blood culture in sepsis was higher than in non-sepsis (58.1% vs. 32.9%, P = 0.015). Fewer patients who had a blood culture received carbapenem treatment in comparison to patients without blood culture (19.1% vs. 31.8%, P = 0.026). Multivariate analysis showed that blood culture was independently associated with less carbapenem exposure (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.16–0.68, P = 0.003), and this effect remained significant in the sepsis subgroup (adjusted OR = 0.17, 95% CI: 0.05–0.53, P = 0.002). Conclusion Blood culture had a high positivity rate and was associated with less carbapenem use in PLA, especially those who developed sepsis. More attention should be paid to performing early blood culture and less carbapenem use in PLA.

Background The CHA 2 DS 2 -VASc score has been associated with the prognosis of cardiovascular diseases. This study aimed to explore the association between the CHA 2 DS 2 -VASc score and all-cause mortality in coronary care unit (CCU) patients. Methods The study was based on the Medical Information Mart for Intensive Care (MIMIC) III database. CCU patients were divided into two groups according to CHA 2 DS 2 -VASc score: 0-3 (low risk)，4-9 (intermediate and high risk). The primary outcome was 30-day mortality, and the secondary endpoints included in-hospital, 1-year, and 5-year mortality. Propensity score matching (PSM) and sensitivity analyzes for the confounders were also performed. The restricted cubic splines flexibility model was used to demonstrate the relation between red blood cell volume distribution width (RDW), blood urea nitrogen (BUN), platelet, white blood cell (WBC), hemoglobin, phosphorus, glucose, potassium, sodium and 30-day mortality in the 0-3 score versus the 4-9 score groups after PSM. Results Among 4491 eligible patients, 988 patients with low CHA 2 DS 2 -VASc scores and 988 patients with intermediate and high CHA 2 DS 2 -VASc scores had similar propensity scores and were included in the analyzes. In the survival analysis, the patients with intermediate and high CHA 2 DS 2 -VASc scores were associated with higher 30-day mortality [hazard ratio (HR): 1.11; 95% confidence interval (CI), 1.02–1.20, P = .014], 1-year mortality [HR: 1.13; 95%CI, 1.06–1.19, P

Multidrug resistance (MDR) and lack of targeting specificity are the main reasons why traditional drug therapies fail and produce toxic side effects in cancer chemotherapy. In order to increase targeting specificity and maximize therapeutic efficacy, new intelligent drug delivery systems are needed. In this study, we prepared the hyaluronic acid (HA) conjugated dasatinib (DAS) and D-α-tocopherol acid polyethylene glycolsuccinate (TPGS) copolymer nanoparticles (THD-NPs). The water solubility of the hydrophobic drug DAS was improved by chemically linking with HA. HA can bind to the over-expressed CD44 protein of tumor cells to increase targeting specificity, TPGS can inhibit the activity of P-glycoprotein (P-gp), and increase the intracellular accumulation of drugs. The prepared drug-loaded nanoparticle has a particle size of 82.23 ± 1.07 nm with good in vitro stability. Our in vitro studies showed that THD-NPs can be released more rapidly in a weakly acidic environment (pH = 5.5) than in a normal physiological environment (pH = 7.4), which can realize the selective release of nanoparticles in tumor cells. Compared to free drugs, THD-NPs showed more efficient cellular uptake, effectively increased the cytotoxic effect of DAS on nasopharyngeal carcinoma HNE1 cells drug resistance HNE1/DDP cells and increased the accumulation of drugs in HNE1/DDP cells, which may be due to the inhibitory effect of TPGS on the efflux function of P-gp. In vivo experiments showed that THD-NPs can effectively inhibit tumor growth without obvious side effects. In conclusion, the targeted and pH-sensitive nanosystem, we designed has great potential to overcome drug resistance and increase therapeutic effects in cancer treatment.

Context Previous studies indicate that compound Danshen Dripping Pill (CDDP) improves the adaptation to high-altitude exposure. However, its mechanism of action is not clear. Objective To explore the protective effect of CDDP on hypobaric hypoxia (HH) and its possible mechanism. Materials and methods A meta-analysis of 1051 human volunteers was performed to evaluate the effectiveness of CDDP at high altitudes. Male Sprague-Dawley rats were randomized into 5 groups (n = 6): control at normal pressure, model, CDDP-170 mg/kg, CDDP-340 mg/kg and acetazolamide groups. HH was simulated at an altitude of 5500 m for 24 h. Animal blood was collected for arterial blood-gas analysis and cytokines detection and their organs were harvested for pathological examination. Expression levels of AQP1, NF-κB and Nrf2 were determined by immunohistochemical staining. Results The meta-analysis data indicated that the ratio between the combined RR of the total effective rate and the 95% CI was 0.23 (0.06, 0.91), the SMD and 95% CI of SO2 was 0.37 (0.12, 0.62). Pre-treatment of CDDP protected rats from HH-induced pulmonary edoema and heart injury, left-shifted oxygen-dissociation curve and decreased P50 (30.25 ± 3.72 vs. 37.23 ± 4.30). Mechanistically, CDDP alleviated HH-reinforced ROS by improving SOD and GPX1 while inhibiting pro-inflammatory cytokines and NF-κB expression. CDDP also decreased HH-evoked D-dimer, erythrocyte aggregation and blood hemorheology, promoting AQP1 and Nrf2 expression. Discussion and conclusions Pre-treatment with CDDP could prevent HH-induced tissue damage, oxidative stress and inflammatory response. Suppressed NF-κB and up-regulated Nrf2 might play significant roles in the mechanism of CDDP.

Background: Limited research has been conducted on afebrile pyogenic liver abscess (PLA). This poses a challenge in rapid diagnosis and early tailored care to physicians. In his study, we aimed to compare the clinical characteristics of afebrile and febrile patients with PLA. Methods: We retrospectively analyzed the data of patients with PLA who were admitted to the emergency departments of two university hospitals between January 2014 and March 2020. Patients were classified into afebrile and febrile groups by using body temperature higher than 38°C as the reference standard. The demographic, clinical, and laboratory characteristics of both groups were compared. The primary outcome was all-cause in-hospital mortality and length of hospital stay. Multivariate analysis was performed to define factors associated with afebrile PLA. Results: Of the 239 patients included in this study, 51 patients (21.3%) were afebrile and 188 patients (78.7%) were febrile. There were no differences between the abscess characteristics, laboratory manifestations, and disease severity of both groups; however, age and Charlson score differed between the groups (P = 0.009 and P = 0.011). The all-cause in-hospital mortality rate was much higher in the afebrile PLA group than in the febrile PLA group (9.8% vs. 2.1%, P = 0.011). Regarding the length of stay, no significant differences were noted in the febrile PLA group compared with the afebrile PLA group (18.5% vs 17.3%, P = 0.514). In multivariate analyses, only age greater than 65 years was significantly associated with afebrile PLA. Conclusions: Afebrile patients with PLA tend to be older, have higher Charlson scores, and in-hospital mortality rate than those with febrile patients. PLA patients older than 65 years are more likely to present without fever (

Abstract Background With the rapid development of medical treatment, many patients not only consider the survival time, but also care about the quality of life. Changes in physical, psychological and social functions after and during treatment have caused a lot of troubles to patients and their families. Based on the bio-psycho-social medical model theory, mental health plays an important role in treatment. Therefore, it is necessary for medical staff to know the diseases which have high potential to cause psychological trauma and social avoidance (PTSA). Results Firstly, we obtained diseases which can cause PTSA from literatures. Then, we calculated the similarities of related-diseases to build a disease network. The similarities between diseases were based on their known related genes. Then, we obtained these diseases-related proteins from UniProt. These proteins were extracted as the features of diseases. Therefore, in the disease network, each node denotes a disease and contains the information of its related proteins, and the edges of the network are the similarities of diseases. Then, graph convolutional network (GCN) was used to encode the disease network. In this way, each disease’s own feature and its relationship with other diseases were extracted. Finally, Xgboost was used to identify PTSA diseases. Conclusion We developed a novel method ‘GCN-Xgboost’ and compared it with some traditional methods. Using leave-one-out cross-validation, the AUC and AUPR were higher than some existing methods. In addition, case studies have been done to verify our results. We also discussed the trajectory of social avoidance and distress during acute survival of breast cancer patients.

Clostridium perfringens is an important zoonotic microorganism. The present study was undertaken to investigate prevalence, serotype distribution, antibiotic resistance, and genetic diversity of C. perfringens isolates from 4 duck farms in Shandong, China. In total, 424 samples of cloacal swabs and environment were collected from 3 commercial meat-type duck farms in Tai'an, Liaocheng, and Weifang and one breeder duck farm in Liaocheng between December 2018 and June 2019, of which, 207 (48.82%) samples were determined to be positive for C. perfringens; a total of 402 isolates of C. perfringens were recovered, all of which were identified as type A; 30.85% of the isolates were positive for cpb2 gene; and cpe gene was found in 0.5% of the isolates. Antimicrobial susceptibility testing revealed that some of the isolates exhibited high antibiotic resistance, and 39.14% of the isolates were resistant to at least 5 classes of commonly used antibiotics. Multilocus sequence typing analysis showed that 85 representative isolates encompassed 54 different sequences types (STs), clustered in 5 clonal complexes (CCs) and 40 singletons. ST3, the most common ST in 54 STs, constituting 15.29% of all isolates, was also the most prevalent ST of isolates from the Liaocheng breeder duck farm (farm 3). CC1, the most prolific CC, containing 15.29% of the analyzed isolates, was the popular subtype of isolates from Liaocheng meat duck farm (farm 2). Although all the isolates belong to type A, the genetic diversity varied greatly in different regions; the Simpson's Diversity Index of STs for Liaocheng, Tai'an, and Weifang were 0.5941, 0.9198, and 0.9627, respectively. Some of cloacal isolates and environmental isolates were distributed in the same ST or CC, indicating close genetic relationship between cloacal isolates and environmental isolates. A portion of the strains from humans and ducks was found to be phylogenetically close. The close relationship between strains from humans and ducks, the high antibiotic resistance of C. perfringens, and the cpe-positive isolates indicated potential public health risks.

Acute myocardial infarction (AMI) is one of the leading causes of mortality in cardiovascular diseases. The aim of this study was to investigate whether exosomes from Sirtuin 1 (SIRT1)-overexpressing adipose-derived stem cells (ADSCs) had a protective effect on AMI. The expression of C-X-C chemokine receptor type 7 (CXCR7) was significantly downregulated in peripheral blood endothelial progenitor cells (EPCs) from AMI patients (AMI-EPCs) compared with that in healthy donors, which coincided with impaired tube formation. The exosomes from SIRT1 overexpression in ADSCs (ADSCs-SIRT1-Exos) increased the expression of C-X-C motif chemokine 12 (CXCL12) and nuclear factor E2 related factor 2 (Nrf2) in AMI-EPCs, which promoted migration and tube formation of AMI-EPCs, and overexpression of CXCR7 helped AMI-EPCs to restore the function of cell migration and tube formation. Moreover, CXCR7 was downregulated in the myocardium of AMI mice, and knockout of CXCR7 exacerbated AMI-induced impairment of cardiovascular function. Injection of ADSCs-SIRT1-Exos increased the survival and promoted the recovery of myocardial function with reduced infarct size and post-AMI left ventricular remodeling, induced vasculogenesis, and decreased AMI-induced myocardial inflammation. These findings showed that ADSCs-SIRT1-Exos may recruit EPCs to the repair area and that this recruitment may be mediated by Nrf2/CXCL12/CXCR7 signaling.

Abstract Background The role of ultrasonography-guided percutaneous fine-needle aspiration (PNA) for pyogenic liver abscess (PLA) remains without consensus, especially in abscesses 3 to 6 cm in diameter. The objective of this study was to evaluate the comparative effectiveness and safety of PNA combined with antibiotics. Methods This was a retrospective study of patients with PLA that were from 3 to 6 cm in diameter who treated at two medical centers in Shanghai, China, from January 2014 to March 2019. Patients were divided into groups treated by PNA plus antibiotics or antibiotics alone. Patients demographics and clinical data related diagnosis, antibiotic treatment, and patient outcomes were analyzed. Results Out of a total of 94 PLA patients, 42 (44.7%) patients received PNA combined with antibiotics, and 52 (55.3%) received antibiotics alone. There were no complications related to PNA. In the PNA group, 13 (31.7%) patients with negative blood culture and 8 (19.5%) patients without blood culture were microbiologically confirmed via aspiration. The time for temperature normalization (P

In order to overcome uplink pilot contamination，the technical bottleneck of massive MIMO,and different from the existing parallel parameter design strategy for blind pilot decontamination,a hierarchical parameter design method was proposed,which points out that different system parameters have different effects on the exact spectrum separation of the sample covariance matrix of the received signal.In other words,different parameters have different priority.Next,it was found that to achieve spectral separation,the power of the desired signal didn’t have to be higher than the interference,and the difference between the two was more important.Furthermore,in a more practical scenario where the pilot sequence length was less than the number of base station receiving antennas,a numerical algorithm was given for the first time to achieve the above-mentioned exact spectral separation.Since the hierarchical parament design ensures the exact separation of the asymptotic spectrum,the results show that the proposed scheme is more suitable for practical applications than the existing blind pilot decontamination.

Proportional–integral–derivative (PID) control is the most common control technique used in hydraulic servo control systems. However, the nonlinearity and uncertainty of the hydraulic system make it challenging for PID control to achieve high-precision control. This paper proposes a novel control strategy that combines the soft actor-critic (SAC) reinforcement learning algorithm with the PID method to address this issue. The proposed control strategy consists of an upper-level controller based on the SAC algorithm and a lower-level controller based on the PID control method. The upper-level controller continuously tunes the control parameters of the lower-level controller based on the tracking error and system status. The lower-level controller performs real-time control for the hydraulic servo system with a control frequency 10 times higher than the upper controllers. Simulation experiments demonstrate that the proposed SAC-PID control strategy can effectively address disturbances and achieve high precision control for hydraulic servo control systems in uncertain working conditions compared with PID and fuzzy PID control methods. Therefore, the proposed control strategy offers a promising approach to improving the tracking performance of hydraulic servo systems.