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Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high-risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands.The multivariate Cox proportional hazards regression was used to select recurrence-related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT-PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands.In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence-free survival (RFS). Then, the recurrence-related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012-1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231-0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819-7.194; p 0.001) were significantly correlated with RFS in the TCGA-LIHC cohort. Then, the signature was constructed by the three NKG2D ligands. The predictive effectiveness of this signature was also validated in the OEP000321 dataset and Guilin cohort. Further, HCC patients were classified into low-risk and high-risk subgroups by the predictive score. Compared with the low-risk group, the high-risk group had poor RFS in both training and validation cohorts. Importantly, compared with the low-risk patients with the G1-G2 stage, the levels of infiltrated NK-activated cells and NKG2D expression were both lower in the high-risk patients.The signature based on MICA, ULBP3, and ULBP5 could predict HCC recurrence.

PurposeThe purpose of the study is to address the problems of low accuracy and missed detection of occluded pedestrians and small target pedestrians when using the YOLOX general object detection algorithm for pedestrian detection. This study proposes a multi-level fine-grained YOLOX pedestrian detection algorithm.Design/methodology/approachFirst, to address the problem of the original YOLOX algorithm in obtaining a single perceptual field for the feature map before feature fusion, this study improves the PAFPN structure by adding the ResCoT module to increase the diversity of the perceptual field of the feature map and divides the pedestrian multi-scale features into finer granularity. Second, for the CSPLayer of the PAFPN, a weight gain-based normalization-based attention module (NAM) is proposed to make the model pay more attention to the context information when extracting pedestrian features and highlight the salient features of pedestrians. Finally, the authors experimentally determined the optimal values for the confidence loss function.FindingsThe experimental results show that, compared with the original YOLOX algorithm, the AP of the improved algorithm increased by 2.90%, the Recall increased by 3.57%, and F1 increased by 2% on the pedestrian dataset.Research limitations/implicationsThe multi-level fine-grained YOLOX pedestrian detection algorithm can effectively improve the detection of occluded pedestrians and small target pedestrians.Originality/valueThe authors introduce a multi-level fine-grained ResCoT module and a weight gain-based NAM attention module.

Purpose The purpose of this paper is to develop high-performance Au-coated Ag alloy wires (ACAA wires) and demonstrate the effect of Au coating layers on the bonding performance and oxidation resistance for stable and reliable electronic packaging applications. Design/methodology/approach ACAA wire with a diameter of approximately 25 µm and Au layer thickness of approximately 100 nm were prepared by the continuous casting, plating and wire drawing method. The bonding performance of the ACAA wires were studied through bonding on 3,535 chips. The oxidation resistance of ACAA wires and Ag alloy wires (AA wires) were comparatively studied by means of chemical oxidation tests, accelerated life tests and electrochemical tests systematically. Findings ACAA wires could form axi-symmetrical spherical free air balls with controllable diameter of 1.5∼2.5 times of the wire diameter after electric flame-off process. The ball shear strength of ACAA wire was higher than that of AA wires. Most importantly, because of the surface Au coating layer, the oxidation resistance of ACAA wires was much enhanced. Research limitations/implications ACAA wires with different lengths of heat affected zone were not developed in this study, which limited their application with different loop height requirements. Practical implications With higher bonding strength and oxidation resistance, ACAA wires would be a better choice than previous reported AA wire in chip packaging which require high stability and reliability. Originality/value This paper provides a kind of novel ACAA wire, which possess the merits of high bonding strength and reliability, and show great potential in electronic packaging applications.

Hypoxia, that is, an inadequate oxygen supply, is linked to neurodegeneration and patients with cardiovascular disease are prone to Alzheimer's disease (AD). 2-Oxoglutarate and ferrous iron-dependent oxygenases (2OGDD) play a key role in the regulation of oxygen homeostasis by acting as hypoxia sensors. 2OGDD also have roles in collagen biosynthesis, lipid metabolism, nucleic acid repair, and the regulation of transcription and translation. Many biological processes in which the60 human 2OGDD are involved are altered in AD patient brains, raising the question as to whether 2OGDD are involved in the transition from normal aging to AD. Here we give an overview of human 2OGDD and critically discuss their potential roles in AD, highlighting possible relationships with synapse dysfunction/loss. 2OGDD may regulate neuronal/glial differentiation through enzyme activity-dependent mechanisms and modulation of their activity has potential to protect against synapse loss. Work linking 2OGDD and AD is at an early stage, especially from a therapeutic perspective; we suggest integrated pathology and in vitro discovery research to explore their roles in AD is merited. We hope to help enable long-term research on the roles of 2OGDD and, more generally, oxygen/hypoxia in AD. We also suggest shorter term empirically guided clinical studies concerning the exploration of 2OGDD/oxygen modulators to help maintain synaptic viability are of interest for AD treatment.

A visible-light-promoted hydroxylation of quinoxalin-2(1H)-ones using recyclable graphitic carbon nitride (g-C3N4) as a heterogeneous photocatalyst has been developed. This protocol enables the selective synthesis of various hydroxyl-containing quinoxalin-2(1H)-ones in good to excellent yields under an ambient air atmosphere. Importantly, this heterogeneous catalyst can be used at least six times without significant loss of activity.

Background. Although probiotics have been shown to improve constipation-related symptoms, a clear consensus on the use of probiotics as a constipation-relieving agent has not been reached, which is attributed to the limited available evidence and inconsistent protocols used in existing studies. Method. A randomized, double-blind, placebo-controlled clinical trial is designed to study the efficiency and possible mechanism of action of probiotics for chronic constipation, in which 200 eligible volunteers with chronic constipation will be randomly assigned to a probiotic group (oral Lactobacillus plantarum P9 probiotic powder, 100 billion colony-forming units (CFUs)/day) or a placebo group. Volunteers, treatment distributors, data collectors, and data analysts will be blinded. The primary outcome is the weekly mean frequency of complete spontaneous bowel movements (CSBMs), and secondary outcomes include weekly mean frequency of CSBMs ≥3, weekly mean frequency of spontaneous bowel movements (SBMs), weekly mean stool appearance score, weekly mean difficulty of passing stool score, weekly percentage of volunteers who use auxiliary measures to assist with defecation (WPUAMA), quality-of-life (QOL) score, emotional status score, gut microbiome, and faecal metabolome. Each outcome measure will be assessed at the time points of preadministration (day 0), administration (day 14 and/or 28), and postadministration (day 42) to identify inter- and intragroup differences. Adverse events will be recorded to evaluate the safety of L. plantarum P9. Discussion. The protocol will provide methodological guidance for other similar studies, avoiding methodological bias and ultimately facilitating the formulation of consensus on the use of probiotics as a constipation-relieving agent. In addition, the results are more comprehensive than those of existing studies and may objectively and scientifically reflect the effectiveness of L. plantarum P9 on constipation. If the expected study findings are obtained, L. plantarum P9, taken as a probiotic, may become a complementary choice for chronically constipated patients. This trial is registered with Chinese Clinical Trial Registry (ChiCTR) (no. ChiCTR2000038396) registered on November 22, 2020, https://www.chictr.org.cn/showproj.aspx?proj=54024.

In this work, nitrogen and fluorine co-doped porous carbon nanosheets (NFPCNS) were fabricated from pharmaceutical drug residues derived from the fermentation synthesis of lincomycin hydrochloride via high-temperature pyrolysis and subsequent KOH activation without adding any nitrogen and fluorine reagents. The obtained NFPCNS exhibits an optimized integration of three dimensional interconnected nanosheet structure, large specific surface area of 2912 m

Molybdenum disulfide (MoS2) has been deemed as one of the promising noble-metal-free electrocatalysts for hydrogen evolution reaction (HER), but it suffers from the inert basal plane and low electronic conductivity. Regulating the morphology of MoS2 during the synthesis on conductive substrates is a synergistic strategy for enhancing the HER performance. In this work, vertical MoS2 nanosheets were fabricated on carbon cloth using an atmospheric pressure chemical vapor deposition method. The growth process could be effectively tuned through introducing hydrogen gas during vapor deposition process, resulting in nanosheets with increased edge density. The mechanism for edge-enriching through controlling the growth atmosphere is systematically studied. The as-prepared MoS2 exhibits excellent HER activity due to the combination of optimized microstructures and coupling with carbon cloth. Our findings provide new insights to design advanced MoS2-based electrocatalysts for HER.

Exploring the potential lead compounds for Alzheimer’s disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5′ untranslated region (5′UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor–like protein 6–interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5′UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5′UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5′UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5′UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.

Phase-locking between local field potential and spikes has been widely investigated through neurophysiological analysis. Two indices most frequently adopted traditionally include the mean resultant length and p of the Rayleigh test. However, the traditional method is found less reliable for cases with substantial sample sizes or with bimodal distribution. In this article, K we propose an entropy-based method to detect and measure phase-locking. Simulation results prove that the method can be effectively applied to cases with a relatively large sample size and it can effectively detect phase-locking even under bimodal conditions with two peaks of opposite phases. Furthermore, we propose thresholds to help measure the intensity of spike field phase-locking. We also apply the proposed method to our experimental data and find phase locking with two opposite phases, which would be left out in traditional phase-locking analysis.

Periodicity analysis of sequences generated by a deterministic system is a long-standing challenge in both theoretical research and engineering applications. To overcome the inevitable degradation of the logistic map on a finite-precision circuit, its numerical domain is commonly converted from a real number field to a ring or a finite field. This paper studies the period of sequences generated by iterating the logistic map over ring [Formula: see text] from the perspective of its associated functional network, where every number in the ring is considered as a node, and the existing mapping relation between any two nodes is regarded as a directed edge. The complete explicit form of the period of the sequences starting from any initial value is given theoretically and verified experimentally. Moreover, conditions on the control parameter and initial value are derived, ensuring the corresponding sequences to achieve the maximum period over the ring. The results can be used as ground truth for dynamical analysis and cryptographical applications of the logistic map over various domains.

A convenient and practical method for the synthesis of bioactive ester-containing chroman-4-ones through the cascade radical cyclization of 2-(allyloxy)arylaldehydes and oxalates is described. The preliminary studies suggest that an alkoxycarbonyl radical might be involved in the current transformation, which was generated via the decarboxylation of oxalates in the presence of (NH4)2S2O8.

Gastric cancer (GC) is the most common malignant tumor in the digestive system, traditional radiotherapy and chemotherapy are not effective for some patients. The research progress of immunotherapy seems to provide a new way for treatment. However, it is still urgent to predict immunotherapy biomarkers and determine novel therapeutic targets. In this study, the gene expression profiles and clinical data of 407 stomach adenocarcinoma (STAD) patients were downloaded from The Cancer Genome Atlas (TCGA) portal, and the abundance ratio of immune cells in each sample was obtained via the “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT)” algorithm. Five immune cells were obtained as a result of abundance comparison, and 295 immune-related genes were obtained through differential gene analysis. Enrichment, protein interaction, and module analysis were performed on these genes. We identified five immune cells associated with infiltration and 20 hub genes, of which five genes were correlated with overall survival. Finally, we used Real-time PCR (RT-PCR) to detect the expression differences of the five hub genes in 18 pairs of GC and adjacent tissues. This research not only provides cellular and gene targets for immunotherapy of GC but also provides new ideas for researchers to explore immunotherapy for various tumors.

CRISPR/Cas9 genome editing is a latest success in biotechnology that repurposes a natural biological system for a practical tool in genetic engineering. Site-specific DNA double strand breaks (DSB) induced by the CRISPR nuclease Cas9 allows endogenous cellular repair apparatus to generate desired repair products. Residence of Cas9 on cleaved DNA conceals the DNA ends from recognition by response and repair apparatus, delaying DNA damage response (DDR) and repair. Thus, tight-binding and long residence of Cas9 on DNA target are proposed as a new determinant of DSB repair pathway choice and may collaborate with other endogenous pathway choice regulators to control DSB repair. Accordingly, harnessing the binding and resident behavior of Cas9 not only broadens the application of CRISPR/dCas9 platform, which at least in part depends upon the tight binding and long residence of dCas9, but also minimizes the undesired outcomes of CRISPR/Cas9 genome editing.

Aiming at identifying cropland in the Yangtze River Delta, we used unmanned aerial vehicle (UAV) to obtain high spatial and spectral resolution (HSSR) remote sensing images of a small farm in the southern Jiangsu Province. After feature augmentation and compression, we used two 3D-CNN algorithms and the baseline neural network (Baseline-NN) algorithm to classify the UAV-HSSR images. The classification results showed that these three classification methods could achieve the fine scale classification of all elements in the study area, with an overall accuracy of 86.560%, 85.416%, and 94.926%, and Kappa coefficients of 0.846, 0.833, and 0.936, respectively. The findings of this study indicate that hyperspectral UAV images have significant potential in the classification tasks of highly fragmented small farms, although the salt and pepper phenomenon was observed in the results of the three classification methods.

We report a universal phase reconfiguration phenomenon and a doping strategy to enhance the activity of multivalent nickel sulfides in hydrogen evolution. Based on these, a life-time dynamic structure-activity correlation has been established.

Background: The vein of Marshall ethanol infusion (VOM-EI) provides an opportunity to achieve bidirectional conduction block of mitral isthmus. However, this technique may induce traumatic pericarditis. There is a lack of research on which populations are prone to pericarditis after VOM-EI and how to treat it more effectively. Methods: This retrospective study included 77 consecutive patients who voluntarily underwent persistent atrial fibrillation radiofrequency ablation combined with VOM-EI. With the occurrence of postoperative pericarditis as the end point, the characteristics and risk factors of postoperative pericarditis were analyzed. The curative effect was evaluated by the symptom relief rate of pericarditis 48 hours after treatment. Results: 15 had postoperative pericarditis among the 77 patients, accounting for 19.5%. The hospital stay of the patients with pericarditis was longer than that without pericarditis (10.0 vs 8.0 days, P = 0.045). Of the 15 patients with postoperative pericarditis, 8 received colchicine. Among the patients treated with colchicine, the average treatment intensity was 1.04 mg/d, 7 patients were relieved within 48 hours, and the symptomatic remission rate was 87.5%. Among the remaining 7 patients who did not receive colchicine, only 2 patients had symptomatic remission. Compared with the group without colchicine, the duration of symptoms was significantly shorter (27.88 vs 51.93 hours, P = 0.024). In the multivariate logistic regression analysis, colchicine was the only effective method to relieve the 48 hours symptoms of postoperative pericarditis ( OR =17.500, CI 1.223-250.4, P = 0.035). Conclusion: Postoperative pericarditis is one of the complications of VOM-EI, and colchicine may have a good short-term effect on it.

A technical note describing a simple and inexpensive setup to anneal samples and devices at moderate temperatures in vacuum

Bibliometric analysis has not comprehensively summarized studies of acute pancreatitis (AP)-associated intestinal diseases. This work aimed to evaluate cooperative networks of authors, countries, and institutions and explore the field's developing trends and hot topics.Original articles and reviews of AP-associated intestinal diseases were obtained from the Web of Science Core Collection on October 11, 2021. VOSviewer and CiteSpace software were used to perform co-occurrence analyses for authors, countries, and institutions and detect the highest citation burst.A total of 1634 articles on the intestine associated with AP were identified. The United States, the University of Auckland, and Roland Andersson are the most influential country, research institute, and scholar, respectively. The World Journal of Gastroenterology (73 articles) has the highest number of publications, and Gastroenterology was the most co-cited journal. The top 5 key words are "acute pancreatitis," "bacterial translocation," "management," "gut," and "inflammatory bowel disease." We find that several emergent key words like "gut microbiota," "pathway," "gut barrier," "risk," and "oxidative stress" experienced a continuous and rapid development as new research directions.This bibliometric study summarizes current important perspectives and offers comprehensive guidance on the AP-associated intestinal diseases, which may help researchers choose the most appropriate research directions.

Iatrogenic factors play an important role in H. pylori eradication failure, whereas it can be easily missed. Therefore, we aimed to investigate and analyze these related iatrogenic factors of H. pylori eradication failure. A total of 508 patients who experienced H. pylori eradication failure were included in this study conducted from December 2019 to February 2022. All the patients filled out a questionnaire including demographic characteristics, duration of treatment, regimens, dosage, and time intervals in rescue treatment. In the first-line treatment, 89 patients (17.5%, 89/508) used at least one antibiotic with high resistance rate in triple therapy and 57 patients (11.2%, 57/508) used two antibiotics with high resistance rates or other not recommended antibiotics in quadruple therapy. In the rescue therapy, 85 regimens were repeatedly used as salvage regimens in 58 patients (22.6%, 58/257) and 178 regimens containing antibiotics with high resistance rates were repeatedly used in 85 patients (33.1%, 85/257). To decrease the risk of H. pylori eradication failure, iatrogenic factors need to gain more attention. Clinicians should enhance their education and training to standardize the treatment regimens, better manage the H. pylori infection, and improve the eradication rate eventually.