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Objective(s): Our previous study has showed that human amniotic mesenchymal stem cells (hAMSCs) transplantation improves neurological recovery after traumatic spinal cord injury (TSCI) in rats. However, less is known about the effects of exosomes derived from hAMSCs for TSCI. Here, we investigated whether hAMSCs-derived exosomes improve neurological recovery in TSCI rats and the underlying mechanisms. Materials and Methods: A rat traumatic spinal cord injury (TSCI) mode was established using a weight drop device. At 2 hr after TSCI, rats were administered either hAMSCs-derived exosomes or phosphate buffered saline via the tail vein. Locomotor recovery was evaluated by an open-field locomotor rating scale and gridwalk task. Spinal cord water content, hematoxylin and eosin (H&E) staining, Evans blue (EB) dye extravasation, immunofluorescence staining, and enzyme-linked immunosorbent were performed to elucidate the underlying mechanism.Results: hAMSCs-derived exosomes significantly reduced the numbers of ED1+ macrophages/microglia and caspase-3+cells and decreased the levels of reactive oxygen species, myeloperoxidase activity and inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and interleukin-1β. In addition, hAMSCs-derived exosomes significantly attenuated spinal cord water content and Evans blue extravasation, and enhanced angiogenesis and axonal regeneration. Finally, hAMSCs-derived exosomes also significantly reduced the lesion volume, inhibited astrogliosis, and improved functional recovery. Conclusion: Taken together, these findings demonstrate that hAMSCs-derived exosomes have favourable effects on rats after acute TSCI, and that they may serve as an alternative cell-free therapeutic approach for treating acute TSCI.

Abstract Acute myeloid leukemia (AML) is a heterogeneous hematological tumor with poor immunotherapy effect. This study was to develop a monocyte/macrophage-related prognostic risk score (MMrisk) and identify new therapeutic biomarkers for AML. We utilized differentially expressed genes (DEGs) in combination with single-cell RNA sequencing to identify monocyte/macrophage-related genes (MMGs). Eight genes were selected for the construction of a MMrisk model using univariate Cox regression analysis and LASSO regression analysis. We then validated the MMrisk on two GEO datasets. Lastly, we investigated the immunologic characteristics and advantages of immunotherapy and potential targeted drugs for MMrisk groups. Our study identified that the MMrisk is composed of eight MMGs, including HOPX, CSTB, MAP3K1, LGALS1, CFD, MXD1, CASP1 and BCL2A1. The low MMrisk group survived longer than high MMrisk group (P

Abstract Background Glioblastoma, the most common primary malignant tumor of the brain, is associated with poor prognosis. Glioblastoma cells exhibit high proliferative and invasive properties, and glioblastoma stem cells (GSCs) have been shown to play a crucial role in the malignant behavior of glioblastoma cells. This study aims to investigate the molecular mechanisms involved in GSCs maintenance and malignant progression. Methods Bioinformatics analysis was performed based on data from public databases to explore the expression profile of Mitotic arrest deficient 2 like 2 (MAD2L2) and its potential function in glioma. The impact of MAD2L2 on glioblastoma cell behaviors was assessed through cell viability assays (CCK8), colony formation assays, 5-Ethynyl-2ʹ-deoxyuridine (EDU) incorporation assays, scratch assays, and transwell migration/invasion assays. The findings from in vitro experiments were further validated in vivo using xenograft tumor model. GSCs were isolated from the U87 and LN229 cell lines through flow cytometry and the stemness characteristics were verified by immunofluorescence staining. The sphere-forming ability of GSCs was examined using the stem cell sphere formation assay. Bioinformatics methods were conducted to identified the potential downstream target genes of MAD2L2, followed by in vitro experimental validation. Furthermore, potential upstream transcription factors that regulate MAD2L2 expression were confirmed through chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. Results The MAD2L2 exhibited high expression in glioblastoma samples and showed significant correlation with patient prognosis. In vitro and in vivo experiments confirmed that silencing of MAD2L2 led to decreased proliferation, invasion, and migration capabilities of glioblastoma cells, while decreasing stemness characteristics of glioblastoma stem cells. Conversely, overexpression of MAD2L2 enhanced these malignant behaviors. Further investigation revealed that MYC proto-oncogene (c-MYC) mediated the functional role of MAD2L2 in glioblastoma, which was further validated through a rescue experiment. Moreover, using dual-luciferase reporter gene assays and ChIP assays determined that the upstream transcription factor E2F-1 regulated the expression of MAD2L2. Conclusion Our study elucidated the role of MAD2L2 in maintaining glioblastoma stemness and promoting malignant behaviors through the regulation of c-MYC, suggesting its potential as a therapeutic target.

The identification research of hydrogenation catalyst information has always been one of the most important businesses in the chemical industry. In order to aid researchers in efficiently screening high-performance catalyst carriers and tackle the pressing challenge at hand, it is imperative to find a solution for the intelligent recognition of hydrogenation catalyst images. To address the issue of low recognition accuracy caused by adhesion and stacking of hydrogenation catalysts, An image recognition algorithm of hydrogenation catalyst based on FPNC Net was proposed in this paper. In the present study, Resnet50 backbone network was used to extract the features, and spatially-separable convolution kernel was used to extract the multi-scale features of catalyst fringe. In addition, to effectively segment the adhesive regions of stripes, FPN (Feature Pyramid Network) is added to the backbone network for deep and shallow feature fusion. Introducing an attention module to adaptively adjust weights can effectively highlight the target features of the catalyst. The experimental results showed that the FPNC Net model achieved an accuracy of 94.2% and an AP value improvement of 19.37% compared to the original CenterNet model. The improved model demonstrates a significant enhancement in detection accuracy, indicating a high capability for detecting hydrogenation catalyst targets.

Growing evidence has increasingly suggested a potential linkage between the oral microbiome and various diseases, including pancreatic ductal adenocarcinoma (PDAC). However, the utilization of gene-level information derived from the oral microbiome for diagnosing PDAC remains unexplored. In this study, we sought to investigate the novel potential of leveraging genomic signatures associated with antibiotic resistance genes (ARGs) within the oral microbiome for the diagnosis of PDAC. By conducting an analysis of oral microbiome samples obtained from PDAC patients, we successfully identified specific ARGs that displayed distinct sequence abundance profiles correlated with the presence of PDAC. In the healthy group, three ARGs were found to be enriched, whereas 21 ARGs were enriched in PDAC patients. Remarkably, these ARGs from oral microbiome exhibited promising diagnostic capabilities for PDAC (AUROC = 0.79), providing a non-invasive and early detection method. Our findings not only provide novel modal data for diagnosing PDAC but also shed light on the intricate interplay between the oral microbiome and PDAC.

Summary: To investigate whole-slide-level prediction in the field of artificial intelligence identification of dMMR/pMMR from hematoxylin and eosin (H&E) in colorectal cancer (CRC), we established a segmentation-based dMMR/pMMR deep learning detector (SPEED). Our model was approximately 1,700 times faster than that of the classification-based model. For the internal validation cohort, our model yielded an overall AUC of 0.989. For the external validation cohort, the model exhibited a high performance, with an AUC of 0.865. The human‒machine strategy further improved the model performance for external validation by an AUC up to 0.988. Our whole-slide-level prediction model provided an approach for dMMR/pMMR detection from H&E whole slide images with excellent predictive performance and less computer processing time in patients with CRC.

Erythroleukemia is a rare form of acute myeloid leukemia (AML). Its molecular pathogenesis remains vague, and this disease has no specific therapeutic treatments. Previously, our group isolated a series of Carbon 21 (C-21) steroidal glycosides with pregnane skeleton from the root of Cynanchum atratum Bunge. Among them, we found that a compound, named BW18, can induce S-phase cell cycle arrest and apoptosis via the mitogen-activated protein kinase (MAPK) pathway in human chronic myeloid leukemia K562 cells. However, its anti-tumor activity against erythroleukemia remains largely unknown. In this study, we aimed to investigate the anti-erythroleukemia activity of BW18 and the underlying molecular mechanisms. Our results demonstrated that BW18 exhibited a good anti-erythroleukemia activity in the human erythroleukemia cell line HEL and an in vivo xenograft mouse model. In addition, BW18 induced cell cycle arrest at the G2/M phase and promoted megakaryocytic and erythroid differentiation in HEL cells. Furthermore, RNA sequencing (RNA-seq) and rescue assay demonstrated that overexpression of platelet-derived growth factor receptor beta (PDGFRB) reversed BW18-induced megakaryocytic differentiation in HEL cells, but not erythroid differentiation. In addition, the network pharmacology analysis, the molecular docking and cellular thermal shift assay (CETSA) revealed that BW18 could inactivate Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, which might mediate BW18-induced erythroid differentiation. Taken together, our findings elucidated a novel role of PDGFRB in regulating erythroleukemia differentiation and highlighted BW18 as an attractive lead compound for erythroleukemia treatment.

Abstract To compare the safety and effectiveness of surgical treatment of jugular paragangliomas (JPs) following the application of our modified surgical techniques. Fifty-six patients with JPs were analyzed for tumor classification, surgical outcomes, and intratumor blood vessels. The gross total resection in C1–2 (100%) was significantly greater than that in C3 and D (66.7%). Good postoperative facial nerve (FN) function (House–Brackmann I–II) was achieved in 89.5% C1–2 cases, which was not significantly different from C3 and D (93.3%) (P = 0.694). Preoperative and postoperative lower cranial nerve (LCN) deficits correlated with the Fisch’s classification of tumors (P

It is essential to assess the cancer risk for patients with chronic obstructive pulmonary disease (COPD). Comparing gene expression data from patients with lung cancer (a total of 506 samples) and those with cancer-adjacent normal lung tissues (a total of 370 samples), we generated a qualitative transcriptional signature consisting of 2046 gene pairs. The signature was verified in an evaluation dataset comprising 18 subjects with severe disease and 52 subjects with moderate disease (Wilcoxon rank-sum test; p = 7.33 × 10−5). Similar results were obtained in other independent datasets. Among the gene pairs in the signature, 326 COPD stage-related gene pairs were identified based on Spearman’s rank correlation tests and those gene pairs comprised 368 unique genes. Of these 368 genes, 16 genes were significantly dysregulated in COPD rat model data compared with control data. Some of these genes (Dhx16, Upf2, Notch3, Sec61a1, Dyrk2, and Hmmr) were altered when the COPD rat model was treated with traditional Chinese medicines (TCM), including Bufei Yishen formula, Bufei Jianpi formula, and Yiqi Zishen formula. Overall, the signature could predict the cancer incidence-risk of COPD and the identified key genes might provide guidance regarding both the treatment of COPD using TCM and the prevention of cancer in patients with COPD. KEY MESSAGESA cancer risk assessment signature was identified in patients with COPD.The signature is insensitive to batch effects and is well verified.COPD key genes identified in this study might play a crucial role in TCM treatment and cancer prevention.

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4–expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac ejection fraction. Furthermore, genetic ablation of Cspg4-expressing cells resulted in excessive vascular permeability, a decline in cardiac function, and increased mortality in the second week after MI. These data reveal an essential role for cardiac pericytes in the control of vascular homeostasis and the fibrotic response after acute ischemic injury, information that will help guide the development of novel strategies to preserve vascular integrity and attenuate pathological cardiac remodeling.

Anthocyanins are a group of natural pigments acting as stress protectants induced by biotic/abiotic stress in plants. Although the metabolic pathway of anthocyanin has been studied in potato, the roles of miRNAs on the metabolic pathway remain unclear. In this study, a purple tetraploid potato of SD92 and its red mutant of SD140 were selected to explore the regulation mechanism of miRNA in anthocyanin biosynthesis. A comparative analysis of small RNAs between SD92 and SD140 revealed that there were 179 differentially expressed miRNAs, including 65 up- and 114 down-regulated miRNAs. Furthermore, 31 differentially expressed miRNAs were predicted to potentially regulate 305 target genes. KEGG pathway enrichment analysis for these target genes showed that plant hormone signal transduction pathway and plant-pathogen interaction pathway were significantly enriched. The correlation analysis of miRNA sequencing data and transcriptome data showed that there were 140 negative regulatory miRNA-mRNA pairs. The miRNAs included miR171 family, miR172 family, miR530b_4 and novel_mir170. The mRNAs encoded transcription factors, hormone response factors and protein kinases. All these results indicated that miRNAs might regulate anthocyanin biosynthesis through transcription factors, hormone response factors and protein kinase.

Abstract Transition metal alloys are essential for magnetic recording, memory, and new materials-by-design applications. Saturation magnetization in these alloys have previously been measured by conventional techniques, for a limited number of samples with discrete compositions, a laborious and time-consuming effort. Here, we propose a method to construct complete saturation magnetization diagrams for Co–Fe–Ni alloys using scanning Hall probe microscopy (SHPM). A composition gradient was created by the diffusion multiple technique, generating a full combinatorial materials library with an identical thermal history. The composition and crystallographic phases of the alloys were identified by integrated energy dispersive X-ray spectroscopy and electron backscatter diffraction. “Pixel-by-pixel” perpendicular components of the magnetic field were converted into maps of saturation magnetization using the inversion matrix technique. The saturation magnetization dependence for the binary alloys was consistent with the Slater-Pauling behavior. By using a significantly denser data point distribution than previously available, the maximum of the Slater-Pauling curve for the Co–Fe alloys was identified at ~ 32 at% of Co. By mapping the entire ternary diagram of Co–Fe–Ni alloys recorded in a single experiment, we have demonstrated that SHPM—in concert with the combinatorial approach—is a powerful high-throughput characterization tool, providing an effective metrology platform to advance the search for new magnetic materials.

The disordered mining of Dabaoshan lead-zinc mineral resources in Shaoguan has brought serious harm to the regional ecological environment. In order to investigate the heavy metal pollution status and microbial characteristics of soil plant system in mining area, The distribution of heavy metals in the soil, the activity of soil microorganisms and the accumulation characteristics of heavy metals in the dominant plant Miscanthus floridulus were studied. The results indicated that metal element contents of Miscanthus floridulus in sequence were: Zn>Pb>Cu> Cd. This study demonstrated that the elemental content of the Miscanthus floridulus plant showed Zn>Pb>Cu>Cd, with Zn being the most significantly correlated with soil elements, followed by Pb. Compared with the control group, the Miscanthus floridulus-soil system possessed obviously different soil microbial features: intensiver in microbial basal respiration strength, and higher microbial eco-physiological parameters Cmic/Corg and qCO2, but lower in soil microbial biomass. The results showed the soil enzymatic activities decreased significantly with increase of contamination of heavy metals, especially dehydrogenase and urease activities. With the increase of the content of heavy metals in the mining area soil, the intensity of soil biochemical action in the mining area (Q1, Q2) soil decreased significantly, and the biochemical action showed a significant negative correlation with the content of heavy metals in the soil. Compared with the non mining area (Q8) soil, the intensity of soil ammonification, nitrification, N fixation and cellulose decomposition decreased by 43.2%~71.1%, 70.1%~92.1%, 58.7%~87.8% and 55.3%~79.8% respectively. The decrease of soil microbial activity weakened the circulation rate and energy flow of C and N nutrients in the soil of the mining area.

In recent years, with increasing passenger travel demand, high-speed railways have developed rapidly. The stop planning and timetabling problems are the core contents of high-speed railway transport planning and have important practical significance for improving efficiency of passenger travel and railway operation Dong et al. (2020). This study proposes a collaborative optimization approach that can be divided into two phases. In the first phase, a mixed-integer nonlinear programming model is constructed to obtain a stop plan by minimizing the total passenger travel time. The constraints of passenger origin-destination (OD) demand, train capacity, and stop frequency are considered in the first phase. In the second phase, the train timetable is optimized after the stop plan is obtained. A multiobjective mixed-integer linear optimization model is formulated by minimizing the total train travel time and the deviation between the expected and actual departure times from the origin station for all trains. Multiple types of trains and more refined headways are considered in the timetabling model. Finally, the approach is applied to China's high-speed railway, and the GUROBI optimizer is used to solve the models in the above two stages. By analyzing the results, the total passenger travel time and train travel time decreased by 2.81% and 3.34% respectively. The proposed method generates a more efficient solution for the railway system.

Abstract The inhibition of voltage-gated sodium (NaV) channels in somatosensory neurons presents a promising novel modality for the treatment of pain. However, the precise contribution of these channels to neuronal excitability, the cellular correlate of pain, is unknown; previous studies using genetic knockout models or pharmacologic block of NaV channels have identified general roles for distinct sodium channel isoforms, but have never quantified their exact contributions to these processes. To address this deficit, we have utilized dynamic clamp electrophysiology to precisely tune in varying levels of NaV1.8 and NaV1.9 currents into induced pluripotent stem cell-derived sensory neurons (iPSC-SNs), allowing us to quantify how graded changes in these currents affect different parameters of neuronal excitability and electrogenesis. We quantify and report direct relationships between NaV1.8 current density and action potential half-width, overshoot, and repetitive firing. We additionally quantify the effect varying NaV1.9 current densities have on neuronal membrane potential and rheobase. Furthermore, we examined the simultaneous interplay between NaV1.8 and NaV1.9 on neuronal excitability. Finally, we show that minor biophysical changes in the gating of NaV1.8 can render human iPSC-SNs hyperexcitable, in a first-of-its-kind investigation of a gain-of-function NaV1.8 mutation in a human neuronal background.

The association between Toxoplasma gondii (T. gondii) infection and malignancy has attracted increased attention in recent years, but little is known of T. gondii infection among women diagnosed with a gynecological tumor (GT) in China. We conducted a case-control study involving 460 women diagnosed with a GT and 460 age-matched healthy controls (HCs) to estimate the infection process of T. gondii and understand the risk factors of T. gondii infection in patients with a GT. Levels of anti-T. gondii IgG and IgM were measured by enzyme-linked immunoassays every 12 months. After a median follow-up time of 4.3 years (range 4 to 5 years), 55/460 (11.96%) patients with a GT and 15/460 (3.26%) HCs were seroprevalence for T. gondii antibodies, respectively (P = 0.001). IgG antibodies against T. gondii were found in 54 GT patients (11.74%) and 15 HCs (3.26%), respectively (P = 0.001). The seroprevalence of T. gondii IgM antibodies was similar in patients with a GT and with HCs (2.83% vs 1.3%, P = 0.105). Multivariate stepwise logistic regression analysis revealed contact with cats (OR, 6.67; 95% CI [2.89–10.75]; P = 0.001), exposure to soil (OR, 2.16; 95% CI [1.14–4.10]; P = 0.019), being a farm-worker (OR, 4.17; 95% CI [1.20–11.49]; P = 0.006) and history of chemotherapy (OR, 3.16; 95% CI [1.56–6.45]; P = 0.001) to be independent risk factors for T. gondii infection. Women with an ovarian cancer or endometrial cancer had higher T. gondii seroprevalence than that of HCs. Moreover, T. gondii infection in patients with a GT mostly acquired within two years of diagnosis, but the infection in healthy controls had no obvious time characteristics. Here, we demonstrated that T. gondii infection is significantly higher in patients with a GT (especially in women with an ovarian tumor) compared to HCs. Thus, infection with this parasite should be avoided in patients with a GT, and the causal relationship between T. gondii and GTs should be studied in detail.

Cardiovascular diseases, especially atherosclerosis and its complications, are a leading cause of death. Inhibition of the noncanonical IκB kinases TANK-binding kinase 1 and IKKε with amlexanox restores insulin sensitivity and glucose homeostasis in diabetic mice and human patients. Here we report that amlexanox improves diet-induced hypertriglyceridemia and hypercholesterolemia in Western diet–fed (WD-fed) Ldlr–/– mice and protects against atherogenesis. Amlexanox ameliorated dyslipidemia, inflammation, and vascular dysfunction through synergistic actions that involve upregulation of bile acid synthesis to increase cholesterol excretion. Transcriptomic profiling demonstrated an elevated expression of key bile acid synthesis genes. Furthermore, we found that amlexanox attenuated monocytosis, eosinophilia, and vascular dysfunction during WD-induced atherosclerosis. These findings demonstrate the potential of amlexanox as a therapy for hypercholesterolemia and atherosclerosis.

Abstract We derive the evolution equations for two-time correlation functions of a generalized non-Markovian open quantum system based on a modified stochastic Schrödinger equation approach. We find that the two-time reduced propagator, an object that used to be characterized by two independent stochastic processes in the Hilbert space of the system, can be simplified and obtained by taking ensemble average over one single noise. This discovery can save the cost of computation, and accelerate the converging process when taking the average over noisy trajectories. As a result, our method can be widely applied to many open quantum models, especially large-scale systems and extend the quantum regression theory to the non-Markovian case. In the short-time simulations, it is observed a significant difference between Markovian and non-Markovian cases, which can be applied to realize the environmental spectrum detection and enhance the measurement sensitivity in varying open quantum systems.

Abstract. Objective:. To compare the efficacy of adductor canal block and femoral nerve block for pain management in patients with anterior cruciate ligament reconstruction. Methods:. A computerized search was performed in the database of PubMed, Embase, Web of Science and Cochrane Library for randomized controlled trials. The outcome measures included visual analog scale, morphine consumption, quadriceps strength, length of hospitalization and postoperative adverse events. The risk of bias of randomized controlled trials was assessed according to the Cochrane Risk of Bias Tool. All quantitative syntheses were completed using STATA version 14. Results:. Seven randomized controlled trials involving a total of 643 patients were included in our meta-analysis. The present meta-analysis indicated that there were no significant differences between the 2 groups in terms of postoperative pain score, opioid consumption, length of hospitalization or adverse effects after anterior cruciate ligament reconstruction. However, adductor canal block showed superior quadriceps strength and range of motion in the early postoperative period. Conclusion:. Adductor canal block shows similar and adequate analgesia compared to the femoral nerve block in anterior cruciate ligament reconstruction and adductor canal block can preserve a higher quadriceps strength and better range of motion.

Abstract The piezoelectric optomechanical devices supply a promising experimental platform to realize the coherent and effective control and measurement of optical circuits working in Terahertz (THz) frequencies via superconducting electron devices typically working in Radio (MHz) frequencies. However, quantum fluctuations are unavoidable when the size of mechanical oscillators enter into the nanoscale. The consequences of the noisy environment are still challenging due to the lack of analytical tools. In this paper, a semi-classical and full-quantum model of piezoelectric optomechanical systems coupled to a noisy bosonic quantum environment are introduced and solved in terms of quantum-state diffusion (QSD) trajectories in the non-Markovian regime. We show that the noisy environment, particularly the central frequency of the environment, can enhance the entanglement generation between optical cavities and LC circuits in some parameter regimes. Moreover, we observe the critical points in the coefficient functions, which can lead the different behaviors in the system. Besides, we also witness the entanglement transfers between macroscopic objects due to the memory effect of the environment. Our work can be applied in the fields of electric/ optical switches, and long-distance distribution in a large-scale quantum network.

Abstract The present study aimed to investigate the efficacy and toxicity of pegylated liposomal doxorubicin (PLD) in preoperative neoadjuvant chemotherapy for patients with breast cancer by comparing with conventional anthracycline. This study is a non-randomized controlled trial. Prospective analysis was conducted after matching as required. A total of 146 patients with confirmed diagnosis of breast cancer by histopathological examinations were enrolled into the observation group and control group in 1:1 ratio. Each of the cases in the observation group was required to correspond to another in the control group according to the requirements including age, molecular subtype, axillary node status, and regimen of the preoperative neoadjuvant chemotherapy. The chemotherapy was based on regimens consisting of anthracyclines, paclitaxel or docetaxel, and/or platinum. PLD was used at least twice in the observation group, with traditional anthracycline as a contrast in the control group. Clinical responses as well as cardiac side effects and other adverse reactions were evaluated by clinical and imaging examinations such as electrocardiogram (ECG) and color Doppler ultrasound during the chemotherapy. Pathologic examinations were performed following the surgeries after preoperative neoadjuvant chemotherapy. All the patients in both groups completed the preoperative neoadjuvant chemotherapy according to their original regimens. The postoperative pathological evaluation revealed a higher pathologic complete response (PCR) rate and significantly more patients of grade V of the Miller-Payne grading system in the observation group as compared to the control group (p = 0.047). In addition, the observation group recorded an evidently lower occurrence of the adverse cardiac events (p = 0.014), ECG changes (p = 0.048), and the relatively severe adverse reactions such as myelosuppression. Compared with conventional anthracycline drugs, PLD has a better pathologic response and safety performance, as well as a similar clinical effectiveness in preoperative neoadjuvant chemotherapy for breast cancer.

Rett syndrome (RTT) is a severe progressive neurodevelopmental disease characterized by psychomotor regression. The FOXG1 gene is one of the pathogenic genes associated with the congenital Rett variant, which is less studied. Only a few Chinese patients with FOXG1 mutation have been reported. In this study, we describe a Chinese female patient with congenital Rett variant who presented with psycho-motor retardation, developmental regression, microcephaly, seizure, stereotypic hand movement and hypotonia. Targeted high-throughput sequencing was conducted, and a heterozygous FOXG1 mutation [NM_005249.4: c.506dupG (P.G169Gfs* 286)] was identified. It was a frameshift mutation resulting in alteration of the reading frames downstream of the mutation.SIMILAR CASES PUBLISHED: 10. CONFLICT OF INTEREST: None.

Abstract As one of the best-studied RNA binding proteins in plant, pentatricopeptide repeats (PPRs) protein are mainly targeted to mitochondria and/or chloroplasts for RNA processing to regulate the biogenesis and function of the organelles, but its molecular mechanism and role in development remain to be further revealed. Here, we identified a mitochondria-localized P-type small PPR protein, MITOCHONDRION-MEDIATED GROWTH DEFECT 1 (MID1) that is crucial for Arabidopsis development. Mutation in MID1 causes retarded embryo development and stunted plant growth with defects in cell expansion and proliferation. Molecular experiments showed that MID1 is required for the splicing of the nad2 intron 1 in mitochondria. Consistently, mid1 plants display significant reduction in the abundance and activity of mitochondrial respiration complex I, accompanied by abnormal mitochondrial morphology and energy metabolism. Furthermore, MID1 is associated with other trans-factors involved in NICOTINAMIDE ADENINE DINUCLEOTIDE HYDROGEN (NADH) DEHYDROGENASE SUBUNIT 2 (nad2) intron 1 splicing, and interacts directly with itself and MITOCHONDRIAL STABILITY FACTOR 1 (MTSF1). This suggests that MID1 most likely functions as a dimer for nad2 intron 1 splicing. Together, we characterized a novel PPR protein MID1 for nad2 intron 1 splicing.

Design concept evaluation is a huge challenge in the R&D stage of new product development. The information in the assessments often depends on the decision-makers' individual preferences. However, sometimes the decision-makers cannot give precise and complete information because it is very difficult for them to be familiar with all the criteria. In this situation, an incomplete information decision-making matrix is established. In this paper, decision-making methods based on incomplete information are compared in the literature review. Incomplete information determination method using trust mechanism is proved as a proper way to solve this problem, and the missing information are computed based on the alternatives However, in design concept evaluation, experts commonly provide their preferences using linguistic words according to the different attributes. Hence, we propose a three-step Multiple Attributes Group Decision-making (MAGDM) method where the missing value are determined by attributes. In step one, a data repairing method is proposed based on trust theory. After that, in step two, a comprehensive weight determination method combining AHP and entropy is proposed to obtain the weight of index attributes. Finally, the Rough-TOPSIS method is applied in the design scheme ranking step. In the case study, the proposed method is implemented in a tourism product design process to show its effectiveness.

BackgroundHematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD.ObjectivesTo assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects.Study designMeta-analysis.Search methodsRandomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger's test, and the trim and fill method were used to assess publication bias.ResultsIn total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9-67.4) and 80.3% (95% CI 69.7-87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6-81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5-81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4-90.2%; skin, 52.5-80.6%; and liver, 41.8-71.8%. In cGVHD, the response rates were gastrointestinal, 30.1-70.4%; skin, 30.1-84.4%; lung, 27.0-83.0%; and mouth 3.5-98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications.ConclusionsOur systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.

The dysregulation of energy homeostasis in obesity involves multihormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine resistance remains largely unexplored. Murine β3-adrenergic receptor expression in adipocytes is orders of magnitude higher compared with that of other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) and protein expression are dramatically downregulated after ligand exposure (homologous desensitization). β3-Adrenergic receptor downregulation also occurs after high-fat diet feeding, concurrent with catecholamine resistance and elevated inflammation. This downregulation is recapitulated in vitro by TNF-α treatment (heterologous desensitization). Both homologous and heterologous desensitization of Adrb3 were triggered by induction of the pseudokinase TRIB1 downstream of the EPAC/RAP2A/PI-PLC pathway. TRIB1 in turn degraded the primary transcriptional activator of Adrb3, CEBPα. EPAC/RAP inhibition enhanced catecholamine-stimulated lipolysis and energy expenditure in obese mice. Moreover, adipose tissue expression of genes in this pathway correlated with body weight extremes in a cohort of genetically diverse mice and with BMI in 2 independent cohorts of humans. These data implicate a signaling axis that may explain reduced hormone-stimulated lipolysis in obesity and resistance to therapeutic interventions with β3-adrenergic receptor agonists.

In order to study the effect of the rainfall infiltration on water migration in compacted loess, a model device was developed for testing water migration in the soil under rainfall conditions. In this study, the volumetric water content and resistivity of soil were introduced into the model test device. This model test device was applied to the study of water migration characteristics in compacted loess under different rainfall conditions. The results show that the resistivity decreases with the increase of the volumetric water content at the same depth of the loess column. In this way, the characteristics of the water migration can also be reflected from the change of the resistivity. There is an intimate relationship between the resistivity and volumetric water content, dry density. The volumetric water content and dry density are normalized by saturation of loess, arriving the equation of saturation against the resistivity. The characteristics of rainfall infiltration in compacted loess show a particular pattern, which demonstrates that, with the increase of dry density of the loess column, the rainfall infiltration line present "Y", "D" and "Λ" shape distribution respectively, under light rain, heavy rain and rainstorm.

Human dermal fibroblasts (HDFs) play important roles in all stages of wound healing. However, in nonhealing wounds, fibroblasts are prone to aging, resulting in insufficient migration, proliferation and secretion functions. Recent studies have suggested that mesenchymal stromal cells (MSCs) are conducive to wound healing and cell growth through paracrine cytokine signaling. In our studies, we found that conditioned medium of MSCs pretreated with IFN-γ and TNF-α (IT MSC-CM) has abundant growth factors associated with wound repair. Our in vitro results showed that the effects of IT MSC-CM on promoting cell migration, proliferation and activation in HDFs were better than those of conditioned medium from mesenchymal stromal cells (MSC-CM). Moreover, we embedded a scaffold material containing IT MSC-CM and reconfirmed that cell migration and activation were superior to that in the presence of MSC-CM in vivo. Generally, PDGF-BB is perceived as a promoter of the migration and proliferation of HDFs. Moreover, a high level of PDGF-BB in IT MSC-CM was detected, according to which we guess that the effect on HDFs may be mediated by the upregulation of PDGF-BB. These studies all showed the potential of IT MSC-CM to promote rapid and effective wound healing.

Abstract. Background:. There have been few reports of mutations in the beta-myosin heavy chain (MYH7) gene in hypertrophic cardiomyopathy (HCM), which is associated with sudden cardiac death caused by HCM. This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM. We also planned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine. Methods:. From January 2006 to June 2017, autopsy cases were collected from the Department of Pathology, the Affiliated Hospital of Qingdao University. The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death (fatal HCM) and 20 cases without cardiomyopathy. Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction. The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites. Homologous comparison among mutant sites was conducted using BLAST online database. Results:. The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case, resulting in the conversion of threonine (Thr) at position 446 to proline (Pro). In another case, the 1402th nucleotide at exon 14 was converted from T to C, resulting in the conversion of phenylalanine (Phe) at position 468 to leucine (Leu). Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species. Conclusions:. Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene. It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations.

Abstract Background To investigate the relationship between cyclin B1 (CCNB1) gene expression and cavernous sinus invasion in pituitary adenomas. Methods Twenty-four pituitary adenoma tissue samples were examined by RT-qPCR and Western blot to assess the mRNA expression levels and protein levels of CCNB1, E-cadherin and N-cadherin. Correlation analyses between the expression levels of E-cadherin, N-cadherin and CCNB1 were performed. After lentivirus-mediated knockdown of CCNB1 in rat pituitary adenoma cell lines (GH3 and GT1-1), cell function changes were studied. The relationship between CCNB1 and epithelial-mesenchymal transition (EMT) was further verified by animal experiments. Results CCNB1 and N-cadherin gene expression were significantly higher in the invasive pituitary adenomas than in the non-invasive pituitary adenomas. Conversely, E-cadherin expression in the invasive pituitary adenomas was significantly lower. CCNB1 gene expression was downregulated in the GH3 and GT1-1 pituitary adenoma cell lines; N-cadherin expression was also decreased, but E-cadherin expression was increased. These results were confirmed in vivo. After downregulation of CCNB1, cell invasion and migration was significantly reduced in Transwell experiments. Conclusion High CCNB1 expression in pituitary adenoma affects cavernous sinus invasion through EMT.

Neurotoxin β-N-methylamino-L-alanine (BMAA) is hypothesized as an important pathogenic factor for neurodegenerative diseases such as amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS-PDC). Comparative study on the accuracy of BMAA analyzed by the regular LC-MS/MS methods is still limited for different biological matrices. In this study, a free-BMAA sample of cyanobacterium and BMAA-containing positive samples of diatom, mussel, scallop, and oyster were extracted with varied extraction ratios (ER) ranging from 1:20 to 1:2000. These extracts were then purified by MCX cartridges. After SPE purification, these different biological samples were analyzed by two common LC-MS/MS analysis methods, a direct analysis without derivatization by a hydrophilic interaction liquid chromatography (HILIC)-MS/MS and pre-column 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization combined with a C18 column. The results suggested that the recoveries of BMAA spiked in the cyanobacterial sample were close to 100% in the total soluble form extracts with the ER of 1:100 (g/mL) and the precipitated bound form extracts with the ER of 1:500. The recommended ER for the precipitated bound form of BMAA in diatoms and the total soluble form of BMAA in mollusks are 1:500 and 1:50, respectively. The quantitative results determined by the AQC derivatization method were lower than those determined by the direct analysis of the HILIC method in diatom and mollusk samples. The results of the HILIC method without the derivatization process were closer to the true value of BMAA in cyanobacteria. This work contributes to the performance of the solid-phase extraction (SPE) purification protocol and the accuracy of BMAA analysis by LC-MS/MS in diverse biological samples.

Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.

BACKGROUND:Postoperative depression is one of the most common mental disorders in patients undergoing cancer surgery and it often delays postoperative recovery. We investigated whether dezocine, an analgesic with inhibitory effect on the serotonin and norepinephrine reuptake, could relieve postoperative depressive symptoms in patients undergoing colorectal cancer surgery. METHODS:This randomized, controlled, single-center, double-blind trial was performed in the Second Affiliated Hospital of the Army Medical University. A total of 120 patients were randomly assigned to receive either sufentanil (1.3 μg/kg) with dezocine (1 mg/kg) (dezocine group; n = 60) or only sufentanil (2.3 μg/kg) (control group; n = 60) for patient-controlled intravenous analgesia after colorectal cancer surgery. The primary outcome was the Beck Depression Inventory score at 2 days after surgery. The secondary outcomes included the Beck Anxiety Inventory, sleep quality, and quality of recovery scores. RESULTS:Compared with those in the control group, patients in the dezocine group had lower depression scores (7.3±3.4 vs. 9.9±3.5, mean difference 2.6, 95% CI: 1.4-3.9; P

China reported a major outbreak of a novel coronavirus, SARS-CoV2, from mid-January till mid-March 2020. We review the epidemic virus growth and decline curves in China using a phenomenological logistic growth model to summarize the outbreak dynamics using three parameters that characterize the epidemic's timing, rate and peak. During the initial phase, the number of virus cases doubled every 2.7 days (range 2.2-4.4 across provinces). The rate of increase in the number of reported cases peaked approximately 10 days after suppression measures were started on 23-25 January 2020. The peak in the number of reported sick cases occurred on average 18 days after the start of suppression measures. From the time of starting measures till the peak, the number of cases increased by a factor 39 in the province Hubei, and by a factor 9.5 for all of China (range: 6.2-20.4 in the other provinces). Complete suppression took up to 2 months (range: 23-57d.), during which period severe restrictions, social distancing measures, testing and isolation of cases were in place. The suppression of the disease in China has been successful, demonstrating that suppression is a viable strategy to contain SARS-CoV2.

The purpose of this research was to investigate the toxicity of zearalenone (ZEN) on the growth performance, genital organs, serum hormones, biomarkers, and histopathological changes of female gilts and to evaluate the efficacy of Bacillus subtilis ZJ-2019-1 in alleviating ZEN toxicosis in gilts. Twenty-four female gilts were randomly allocated to four groups with six replicates per group and one gilt per replicate, fed on four feeds prepared previously, which were basic diet (control group, C group), ZEN diet (Z group), Zlb diet (Zlb group) containing B. subtilis ZJ-2019-1 in liquid form, and Zdb diet (Zdb group) containing B. subtilis ZJ-2019-1 in dehydrated form. The results showed that the vulva size and relative weight of reproductive organs had no significant difference in the control group, Zlb group, and Zdb group, but were significantly lower than in the Z group (p < 0.05); the relative weight of the liver was lower in the C group, Zlb group, and Zbd group than in the Z group (0.05 < p < 0.1). The concentration of serum glutamate dehydrogenase (GLDH) was lower, but follicle-stimulating hormone (FSH) was higher in the Z group, Zlb group, and Zdb group than in the Z group (0.05 < p < 0.1). Additionally, serum luteinizing hormone (LH) concentration had no significant difference in the C group, Zlb group, and Zdb group but was significantly lower than in the Z group (p < 0.05); estradiol (E2) was significantly lower in the Zlb group and Zdb group than that in C group, but significantly higher than that in Z group (p < 0.05); PRL was significantly higher in the Zlb group and Zdb group than in the C group, but was significantly lower than in Z group (p < 0.05). ZEN and its reduced metabolites were measured in biological samples after enzymatic hydrolysis of the conjugated forms. The concentration of serum ZEN and its metabolite, α-zeralenol (α-ZOL), had no significant difference in Zlb, Zdb, and control groups but was significantly lower than in the Z group (p < 0.05); urine ZEN and its metabolites, α-ZOL and β-zeralenol (β-ZOL), had no significant difference in Zlb, Zdb, and control groups but was significantly lower than in the Z group (p < 0.05). Cell damages were observed in the liver, uterus, and ovary of gilts in the Z group and alleviated in Zlb and Zdb groups, but the loss of oocytes was irreversible in the ovary. The ZEN-contaminated diet caused serious changes in female hormones and brought harm to the livers and reproductive organs, but B. subtilis ZJ-2019-1 could naturally remove the ZEN significantly, which ameliorated the reproductive impairment in gilts caused by ZEN. The addition of B. subtilis ZJ-2019-1 to ZEN-contaminated feeds could ameliorate the toxic effects effectively, regardless of liquid or dry culture. Therefore, the B. subtilis ZJ-2019-1 strain has great potential industrial applications.

Abstract A hydrophobic CCS polymer of poly(benzyl methacrylate) (PBzMA) was prepared in toluene by reversible addition-fragmentation chain transfer (RAFT)-mediated dispersion polymerization. The CCS polymer, with poly(benzyl methacrylate) as the arm and crosslinked N, N′-bis(acryloyl)cystamine (BAC) as the core, was confirmed by characterization with gel permeation chromatography (GPC) and nuclear magnetic resonance (NMR) spectroscopy. Three kinds of oils (toluene, anisole and styrene) were chosen to study the emulsification properties of PBzMA CCS polymer. The oils can be emulsified by CCS polymer to form water-in-oil (w/o) emulsions. Moreover, w/o high internal phase emulsions (HIPEs) can be obtained with the increase of toluene and styrene volume fractions from 75% to 80%. Porous polystyrene monolith and microparticles were prepared from the emulsion templates and characterized by the scanning electronic microscopy (SEM). With the internal phase volume fraction increased, open-pore porous monolith was obtained.

Abstract The axis tilt of light beam in optical system would introduce the dispersion of orbital angular momentum (OAM) spectrum. To deal with it, a two-step method is proposed and demonstrated. First, the tilt angle of optical axis is identified with a deduced relation between the tilt angle and the variation of OAM topological charges with different reference axes, which is obtained with the help of a charge coupled device (CCD) camera. In our experiments, the precision of measured tilt angle is about 10−4 rad with topological charges of −3~3. With the measured angle value, the additional phase delay due to axis tilt can be calculated so that the dispersion of OAM spectrum can be corrected with a simple formula while the optical axis is not aligned. The experimental results indicate that the original OAM spectrum has been successfully extracted for not only the pure state but also the superposed OAM states.

Abstract Chloride is reported to play a significant role in corrosion reactions, products and kinetics of ferrous metals. To enhance the understanding of the effects of soil environments, especially the saline soils with high levels of chloride, on the corrosion of ductile iron and carbon steel, a 3-month corrosion test was carried out by exposing ferrous metals to soils of six chloride concentrations. The surface morphology, rust compositions and corrosion kinetics were comprehensively studied by visual observation, scanning electron microscopy (SEM), X-Ray diffraction (XRD), weight loss, pit depth measurement, linear polarization and electrochemical impedance spectroscopy (EIS) measurements. It showed that chloride ions influenced the characteristics and compositions of rust layers by diverting and participating in corrosion reactions. α-FeOOH, γ-FeOOH and iron oxides were major corrosion products, while β-Fe8O8(OH)8Cl1.35 rather than β-FeOOH was formed when high chloride concentrations were provided. Chloride also suppressed the decreasing of corrosion rates, whereas increased the difficulty in the diffusion process by thickening the rust layers and transforming the rust compositions. Carbon steel is more susceptible to chloride attacks than ductile iron. The corrosion kinetics of ductile iron and carbon steel corresponded with the probabilistic and bilinear model respectively.

Abstract Dysregulation of mRNAs and long non-coding RNAs (lncRNAs) is one of the most important features of carcinogenesis and cancer development. However, studies integrating the expression of mRNAs and lncRNAs to predict the survival of head and neck squamous cell carcinoma (HNSC) are still limited, hitherto. In current work, we identified survival related mRNAs and lncRNAs in three datasets (TCGA dataset, E-TABM-302, GSE41613). By random forest, seven gene signatures (six mRNAs and lncRNA) were further selected to develop the risk score model. The risk score was significantly associated with survival in both training and testing datasets (E-TABM-302, GSE41613, and E-MTAB-1324). Furthermore, correlation analyses showed that the risk score is independent from clinicopathological features. According to Cox multivariable hazard model and nomogram, the risk score contributes the most to survival than the other clinical information, including gender, age, histologic grade, and alcohol taking. The Gene Set Enrichment Analysis (GSEA) indicates that the risk score is associated with cancer related pathways. In summary, the lncRNA-mRNA based risk score model we developed successfully predicts the survival of 755 HNSC samples in five datasets and two platforms. It is independent from clinical information and performs better than clinical information for prognosis.

Background and Aims The link between gut microbiota and type 2 diabetes (T2D) has been addressed by numerous studies. Streptococcus thermophilus from fermented milk products, has been used as a probiotic in previous research. However, whether heat-killed S. thermophilus can improve the glycemic parameters of diabetic rats remains unanswered. In this study, we evaluated the effect of heat-killed S. thermophilus on T2D model rats and the potential mechanisms of the effect. Methods Zucker diabetic fatty (ZDF) rats were used to generate a diabetic rat model induced by feeding a high-fat diet. Heat-killed S. thermophilus were orally administered to normal and diabetic rats for 12 weeks. Intestinal microbiota analysis, histology analysis, oral glucose tolerance test and measurement of inflammatory factors were performed. Results We found that heat-killed S. thermophilus treatment reduced fasting blood glucose levels and alleviated glucose intolerance and total cholesterol in diabetic ZDF rats. Additionally, heat-killed S. thermophilus increased the interleukin 10 while reducing the levels of lipopolysaccharide, interleukin 6, and tumor necrosis factor-α in diabetic ZDF rats. The heat-killed S. thermophilus treatment can normalize the structure of the intestinal and colon mucosal layer of diabetic rats. The characteristics of the gut microbiota in heat-killed S. thermophilus-treated and control rats were similar. At the genus level, the abundances of beneficial bacteria, including Ruminococcaceae, Veillonella, Coprococcus, and Bamesiella, were all significantly elevated by heat-killed S. thermophilus treatment in ZDF diabetic rats. Conclusion Our study supports the hypothesis that treatment with heat-killed S. thermophilus could effectively improve glycemic parameters in T2D model rats. In addition, the potential mechanisms underlying the protection maybe include changing the composition of gut microbiota, reinforcing the intestinal epithelial barrier and the immunity of the intestinal mucosa, decreasing the level of inflammation, and then reducing the insulin resistance.

Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging. This limits our understanding of pathogenesis in the congenital disorders of glycosylation (CDG). We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase – STT3A and STT3B – to monitor the presence and glycosylation status of cell surface glycoproteins. We show reduced abundance of two canonical tyrosine receptor kinases – the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) – at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization. Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A. Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences. Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization. These results provide new insight into CDG pathogenesis and highlight how the surface abundance of some glycoproteins can be dually impacted by abnormal glycosylation.

The zero-speed fin stabilizer is used to stabilize the roll motion of the ship at full speed. It has two working modes, that is the lift-based normal anti-rolling mode and the drag-based zero-speed anti-rolling mode. Different force generation mechanisms cause different control methods, especially in the form of control. The zero-speed fin stabilizer works in a sinusoidal fashion in normal mode, the same as the conventional fin stabilizer. However, its control form at zero speed is not particularly clear. This paper aims to investigate the control form of fin stabilizer at zero speed through a composite method of theoretical analysis and experimental research. Based on the established reaction force model, the forces generated on the fin flapped in sinusoidal and trapezoidal forms are compared and analyzed. It is found that the trapezoidal form flapping with a small half-cycle ratio generates larger force than the sinusoidal flapping form when the flapping amplitude is the same. The forced rolling tank tests with the fins flapping in sinusoidal and trapezoidal forms were conducted. The test results are consistent with the theoretical analysis results, and the trapezoidal flapping form with a proper small half-cycle ratio is recommended for fin stabilizers at zero speed. The control strategy of fin stabilizer at zero speed is obtained based on the further analysis of the force characteristics of the trapezoidal flapping form and the limitations of the actual fin stabilizer actuation system. The model and full scale roll reduction tests at zero speed were conducted, achieving more than 70% and 60% of the anti-rolling effect respectively. The test results further verify the effectiveness, applicability and practicability of the obtained control form and strategy for fin stabilizers in at-anchor conditions, and can be a reference for engineering practice and other similar studies.

Reticuloendotheliosis virus (REV) is the most frequent exogenous virus that contaminates attenuated vaccines. Therefore, it is extremely important to select REV-free specific-pathogen-free (SPF) chicken embryos. Generally, REV infection is assessed by detecting REV antibodies in SPF chickens. This present study seeks to evaluate REV infection by replacing serum antibody detection with yolk antibody detection. A cohort of 40 nineteen-week-old SPF chickens were artificially inoculated with REV, with 32 SPF chickens raised in another isolation environment served as a blank control. Eggs and serum from 23-week-old chickens were sampled, and yolks were diluted separately to ratios of 1:150, 1:200, 1:300 and 1:400, which were detected together with serum. We found that the yolk antibody detection findings at a dilution of 1:300 had the highest coincidence rate compared with that based on serum antibody measurements. At a dilution ratio of 1:300 for yolk antibody, 72 chickens were continuously observed for 10 weeks from 25- to 34-weeks-old. Our findings were based on serum antibody or yolk antibody detection, and the evaluation results were completely consistent. Therefore, all serum antibody-positive chickens were yolk antibody-positive, and vice versa. Accordingly, vaccine producers can estimate REV cleanliness in a poultry farm by sampling yolk antibody titers.

A ride control system (RCS) based linear quadratic regulator (LQR) and genetic algorithm (GA) design is presented, to reduce the heave, roll and pitch motion (three degrees of freedom motion (3 DOF motion)) of the wave piercing catamarans (WPC) in beam waves. A detailed 3 DOF ride control model which consists of the coupling and decoupling relationships between longitudinal and transverse motion is proposed for the WPC vessel. And the complex hydrodynamic coefficients and disturbances induced by beam waves are analyzed. Moreover, two stern flaps are designed for the system in the way of alternate flapping. In the controller design, the LQR method based on GA method is adopted to reduce the 3 DOF motion of the ship. Depending on the robust search mechanism and global optimum of GA, weighting parameters can be obtained to calculate the desired gain. Finally, the motion reduction and motion sickness incidence (MSI) results demonstrate the feasibility and effectiveness of the proposed controller, and the comfort of passengers and crews can also be improved.

To improve the overall welfare levels of sows and to reduce stress levels at late 35-day lactation, we selected targeted behavioral indicators that might be associated with stress. Therefore, we monitored and evaluated the adaptive capability of two different breeds of sows to the farrowing environment. In this study, Damin sows (Large White × Min pig sows, n = 20) and Large White sows (n = 20) were farrowed in individual pens. Saliva was collected and tested for cortisol density at -15 min, and then at +15, 30, 60, 90, 120, 180 and 240 min after an adrenocorticotropic hormone (ACTH) stimulation test conducted at 20, 27 and 34 d post-partum. The postures, including ventral and lateral recumbency to other postures, defecating, urinating, sham-chewing and bar-biting behavior, were observed by video from 07:00 to 09:00 and from 13:00 to 15:00 on the 7th day of each week from the 3rd to the 5th week post-parturition. In addition, the concentrations of salivary interleukin (IL)-6, tumor necrosis factor (TNF)-α and secretory immunoglobulin (SIgA) were assayed after the observed behaviors. The results showed no significant difference between Damin sows and Large White sows in terms of behaviors at the 3rd week. Additionally, there were no significant differences between Damin and Large White sows in terms of the behaviors of ventral recumbency and bar-biting with the exception of lateral recumbency to other postures, sham-chewing, defecation and urination in the fifth week. Meanwhlie, there was significant difference between two breeds in term of ventral recumbency at the 4th week. The result of the ACTH test showed a significant difference between the Damin and Large White sows by the 27th and 34th days postpartum (P

This work presents optimal linear quadratic regulator (LQR) based on genetic algorithm (GA) to solve the two degrees of freedom (2 DoF) motion control problem in head seas for wave piercing catamarans (WPC). The proposed LQR based GA control strategy is to select optimal weighting matrices (Q and R). The seakeeping performance of WPC based on proposed algorithm is challenged because of multi-input multi-output (MIMO) system of uncertain coefficient problems. Besides the kinematical constraint problems of WPC, the external conditions must be considered, like the sea disturbance and the actuators (a T-foil and two flaps) control. Moreover, this paper describes the MATLAB and LabVIEW software plats to simulate the reduction effects of WPC. Finally, the real-time (RT) NI CompactRIO embedded controller is selected to test the effectiveness of the actuators based on proposed techniques. In conclusion, simulation and experimental results prove the correctness of the proposed algorithm. The percentage of heave and pitch reductions are more than 18% in different high speeds and bad sea conditions. And the results also verify the feasibility of NI CompactRIO embedded controller.

OBJECTIVE:Pain management is a huge challenge in the treatment of rheumatoid arthritis (RA), and central sensitization is reportedly involved in the development of pain. The current study was undertaken to explore the possible role of N-methyl-D-aspartate receptors (NMDARs) in the spinal mechanism of central sensitization in RA using a collagen-induced arthritis (CIA) model. METHODS:Mechanical hypersensitivity was assessed in C57BL/6 mice, before and after the induction of CIA via administration of chick type II collagen. Analgesic drugs, receptor antagonist, and kinase inhibitor were administrated intrathecally in the spinal cord. Protein expression and phosphorylation changes were detected via immunoblotting. RESULTS:CIA mice developed significant mechanical hypersensitivity, and spinal administration of the NMDAR antagonist D-2-amino-5-phosphonovaleric acid (D-APV) effectively attenuated peripheral pain hypersensitivity. There was specific enhancement of synaptic NR2B-containing NMDAR (NR2BR) expression in the spinal dorsal horns of the mice. Both the increased total protein expression of NR2B subunit and the enhanced total phosphorylation level of NR2B subunit at 1472 tyrosine promoted the synaptic expression of NMDAR in the mice. Intrathecal injection of tramadol suppressed synaptic NMDAR expression mainly by changing the synaptic phosphorylation state of NR2B subunit at Tyr1472. Extracellular signal-regulated protein kinases 2 (ERK2) activity synchronized with the synaptic expression of NR2BR, which was downregulated by the action of tramadol. CONCLUSION:Specific enhancement of NR2BR in the spinal dorsal horn may be vital for central sensitization in the CIA model of RA. The NR2BR/ERK2 pathway may be a promising target for pain management in RA patients.

Fibromyalgia (FM) and obesity are closely related. However, little is known about how obesity contributes to FM. Importantly, adequate evidence has shown that tumor necrosis factor alpha (TNF-α) plays a critical role in obesity. Thus, we hypothesized that obesity-induced TNF-α release may potentiate FM-associated pain. To test this hypothesis, we investigated the role of TNF-α in the development of FM-like pain in a mouse model of acid saline injection-induced FM. Consistent with previous reports, we showed that repeated acid saline injections induced bilateral mechanical hyperalgesia, and this effect lasted for at least 4 days after acid saline injections. This phenomenon was associated with increased levels of TNF-α in plasma, muscles, and spinal cord. Furthermore, we found that 24 weeks of high fat diet treatment significantly potentiated acid saline-induced bilateral mechanical hyperalgesia. High fat diet-treated mice exhibited robustly increased levels of TNF-α in plasma, muscles, and spinal cord after acid saline injections compared with low fat diet-treated mice. Additionally, using immunofluorescence staining, we found that the number of TNF-α positive cells in dorsal root ganglion (DRG) was increased after acid saline injections, and high fat diet treatment further sensitized this increase. Finally, we reported that acid saline-induced FM-like pain behaviors were abolished in TNFRp55-/- mice, confirming the critical role of TNF-α in the development of FM-like pain. Taken together, our results suggested that high fat diet treatment may sensitize acid saline-induced FM-like pain via increasing TNF-α levels in plasma, muscles, and DRG.