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Abstract Mosaic ceramics are not limited to use solely as building materials, they also possess artistic value. Artists can create images by arranging and combining mosaic ceramics, resulting in a perfect fusion of large-scale public art for external walls and ceramic materials. However, the current approach for artists to create mosaic ceramic exterior wall art images involves manual laying and assembling of individual mosaic ceramics. This manual process suffers from issues such as low efficiency, eye fatigue, selection errors, and the risk of high-altitude operations. These challenges significantly impact the quality and efficiency of creating mosaic ceramic exterior wall art image images. To address these problems, this paper proposes an automatic mosaic ceramic art image stitching method based on subpixel edge fitting positioning and collaborative operation of multiple robotic arms. Additionally, a new U + I type conveying method is designed for efficient and space-saving transportation of mosaic ceramics. Experimental results demonstrate a high success rate of recognition, absorption, and placement of multi-color mosaic ceramics using this method reaching 95.45%, with a positioning error within 0.5 mm. The method can also adapt to varying levels of light intensity or noise interference. This approach effectively enhances the quality and efficiency of creating mosaic ceramic exterior wall art images and promotes the development of mosaic ceramic exterior wall public art creation.

IntroductionThis study, conducted in China prior to RotaTeq’s launch, examined the epidemiological, molecular, and evolutionary features of the G1P[8] genotype RVA in children admitted with diarrhea, to aid in evaluating its efficacy and impact on G1P[8] RVA in China.MethodsData from the Chinese viral diarrhea surveillance network were collected from January 2016 to December 2018. RVA strains identified as the G1P[8] genotype were subjected to whole-genome sequencing. Neutralizing epitope, amino acid selection pressure, and evolution dynamics analyses on VP7 and VP4 were performed using BioEdit v.7.0.9.0 and PyMOL v.2.5.2, four algorithms (MEME, SLAC, FEL, and FUBAR) in the Datamonkey online software, and the MCMC model in BEAST v. 1.10.4, respectively. Phylogenetic and identity features of 11 genes were assessed by DNAStar and MEGA v.7.ResultsResults showed that the detection rate of G1P[8] in China from 2016 to 2018 was generally low with significant seasonality. The whole genome of G1P[8] of four 2016 childhood diarrhea specimens was successfully sequenced. Phylogenetic and neutralizing epitope analysis showed that Rotavin-M1 might have better protection on G1P[8] prevalent in China than Rotarix and RotaTeq. Two conserved N-glycosylation sites on VP7 of Chinese G1P[8] might affect the protective effect of the vaccine. Evolution rate and selection pressure analysis identified the possibility of rapidly evolving and adapting to the new environment introduced by vaccines of G1P[8], whereas positive selection specific to VP4 indicated the potential tendency to select for dominant traits. Identity and phylogeny analysis showed that Chinese G1P[8] from before 2018 was generally stable with possible genetic recombination among local strains.DiscussionThese findings not only are of great significance for predicting the prevalence of G1P [8] in China, but also provide data reference for evaluating rotavirus vaccine efficacy.

This article introduces the concept of load aggregation, which involves a comprehensive analysis of loads to acquire their external characteristics for the purpose of modeling and analyzing power systems. The online identification method is a computer-involved approach for data collection, processing, and system identification, commonly used for adaptive control and prediction. This paper proposes a method for dynamically aggregating large-scale adjustable loads to support high proportions of new energy integration, aiming to study the aggregation characteristics of regional large-scale adjustable loads using online identification techniques and feature extraction methods. The experiment selected 300 central air conditioners as the research subject and analyzed their regulation characteristics, economic efficiency, and comfort. The experimental results show that as the adjustment time of the air conditioner increases from 5 minutes to 35 minutes, the stable adjustment quantity during the adjustment period decreases from 28.46 to 3.57, indicating that air conditioning loads can be controlled over a long period and have better adjustment effects in the short term. Overall, the experimental results of this paper demonstrate that analyzing the aggregation characteristics of regional large-scale adjustable loads using online identification techniques and feature extraction algorithms is effective.

Abstract Background Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in pancreatic and biliary tract cancers. The aim of this study is to characterize the cfDNA fragmentomics in biliopancreatic cancers and develop an accurate method for cancer detection. Methods One hundred forty-seven patients with biliopancreatic cancers and 71 non-cancer volunteers were enrolled, including 55 patients with cholangiocarcinoma, 30 with gallbladder cancer, and 62 with pancreatic cancer. Low-coverage whole-genome sequencing (median coverage: 2.9 ×) was performed on plasma cfDNA. Three cfDNA fragmentomic features, including fragment size, end motif and nucleosome footprint, were subjected to construct a stacked machine learning model for cancer detection. Integration of carbohydrate antigen 19–9 (CA19-9) was explored to improve model performance. Results The stacked model presented robust performance for cancer detection (area under curve (AUC) of 0.978 in the training cohort, and AUC of 0.941 in the validation cohort), and remained consistent even when using extremely low-coverage sequencing depth of 0.5 × (AUC: 0.905). Besides, our method could also help differentiate biliopancreatic cancer subtypes. By integrating the stacked model and CA19-9 to generate the final detection model, a high accuracy in distinguishing biliopancreatic cancers from non-cancer samples with an AUC of 0.995 was achieved. Conclusions Our model demonstrated ultrasensitivity of plasma cfDNA fragementomics in detecting biliopancreatic cancers, fulfilling the unmet accuracy of widely-used serum biomarker CA19-9, and provided an affordable way for accurate noninvasive biliopancreatic cancer screening in clinical practice.

Abstract Background Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods. Methods To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation–qPCR (MeRIP–qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis. Results Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes. Conclusion In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine.

Abstract Nanofluidic membranes offer exceptional promise for osmotic energy conversion, but the challenge of balancing ionic selectivity and permeability persists. Here, we present a bionic nanofluidic system based on two-dimensional (2D) copper tetra-(4-carboxyphenyl) porphyrin framework (Cu-TCPP). The inherent nanoporous structure and horizontal interlayer channels endow the Cu-TCPP membrane with ultrahigh ion permeability and allow for a power density of 16.64 W m−2, surpassing state of-the-art nanochannel membranes. Moreover, leveraging the photo-thermal property of Cu-TCPP, light-controlled ion active transport is realized even under natural sunlight. By combining solar energy with salinity gradient, the driving force for ion transport is reinforced, leading to further improvements in energy conversion performance. Notably, light could even eliminate the need for salinity gradient, achieving a power density of 0.82 W m−2 in a symmetric solution system. Our work introduces a new perspective on developing advanced membranes for solar/ionic energy conversion and extends the concept of salinity energy to a notion of ionic energy.

Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), also known as lysine (K)-specific demethylase 6A (KDM6A), functions as a tumor suppressor gene or oncogene depending on the tumor type and context. However, its tumor-suppressive mechanisms remain largely unknown. Here, we investigated the clinical significance and biological effects of UTX expression in pancreatic ductal adenocarcinoma (PDA) and determined the potential mechanisms of its dysregulation. UTX expression and its association with clinicopathologic characteristics of PDA patients were analyzed using immunohistochemistry. UTX mRNA and protein expression and their regulation in PDA cell lines were measured using quantitative polymerase chain reaction and Western blot analyses. The biological functions of UTX in PDA cell growth, migration, and invasion were determined using gain- and loss-of-function assays with both in vitro and in vivo animal models. UTX expression was reduced in human PDA cell lines and specimens. Low UTX expression was associated with poor differentiation and prognosis in PDA. Forced UTX expression inhibited PDA proliferation, migration, and invasion in vitro and PDA growth and metastasis in vivo, whereas knockdown of UTX expression did the opposite. Mechanistically, UTX expression was trans-activated by GATA6 activation. GATA6-mediated PDA progression could be blocked, at least partially, by silencing UTX expression. In conclusion, loss of GATA6-mediated UTX expression was evident in human PDA and restored UTX expression suppressed PDA growth and metastasis. Thus, UTX is a tumor suppressor in PDA and may serve as a prognostic biomarker and therapeutic target.

Abstract Introduction Pancreaticobiliary reflux (PBR) can induce gallstone formation; however, its pathogenic mechanism remains unclear. In this study, we explored the mechanism of PBR by the non-targeted metabolomic analysis of bile in patients with PBR. Objective The aim of this study was to investigate the pathogenic mechanism in PBR by the non-targeted metabolomic analysis of bile collected during surgery. Methods Sixty patients who underwent gallstone surgery at our center from December 2020 to May 2021 were enrolled in the study. According to the level of bile amylase, 30 patients with increased bile amylase ( > 110 U/L) were classified into the PBR group, and the remaining 30 patients were classified into the control group (≤ 110 U/L). The metabolomic analysis of bile was performed. Results The orthogonal projections to latent structure-discriminant analysis of liquid chromatography mass spectrometry showed significant differences in bile components between the PBR and control groups, and 40 metabolites were screened by variable importance for the projection value (VIP > 1). The levels of phosphatidylcholine (PC) and PC (20:3(8Z,11Z,14Z)/14:0) decreased significantly, whereas the levels of lysoPC (16:1(9z)/0:0), lysoPC (15:0), lysoPC (16:0), palmitic acid, arachidonic acid, leucine, methionine, L-tyrosine, and phenylalanine increased. Conclusions Significant differences in bile metabolites were observed between the PBR and control groups. Changes in amino acids and lipid metabolites may be related to stone formation and mucosal inflammation.

Goal: Deep learning techniques have made significant progress in medical image analysis. However, obtaining ground truth labels for unlabeled medical images is challenging as they often outnumber labeled images. Thus, training a high-performance model with limited labeled data has become a crucial challenge. Methods: This study introduces an underlying knowledge-based semi-supervised framework called UKSSL, consisting of two components: MedCLR extracts feature representations from the unlabeled dataset; UKMLP utilizes the representation and fine-tunes it with the limited labeled dataset to classify the medical images. Results: UKSSL evaluates on the LC25000 and BCCD datasets, using only 50% labeled data. It gets precision, recall, F1-score, and accuracy of 98.9% on LC25000 and 94.3%, 94.5%, 94.3%, and 94.1% on BCCD, respectively. These results outperform other supervised-learning methods using 100% labeled data. Conclusions: The UKSSL can efficiently extract underlying knowledge from the unlabeled dataset and perform better using limited labeled medical images.

Background: Vascular cognitive impairment (VCI) is the second leading cause of dementia. Cognitive impairment is a common consequence of VCI. However, there is no effective treatment for VCI and the underlying mechanism of its pathogenesis remains unclear. This study to investigate whether artesunate (ART) can improve the learning and memory function in rats with VCI by down-regulating he level of autophagy in cerebral cortex neurons. Methods: The models for VCI were the rat bilateral common carotid artery occlusion (BACCO), which were randomized into three groups including the sham operation group (Sham), model + vehicle group (Model) and model + ART group (ART). Then the animal behaviors were recorded, as well as staining the results of cortical neurons. Western blot was performed to determine the protein expressions of LC3BⅡ/Ⅰ, p-AMPK, p-mTOR, and Beclin-1. Results: Behavioral outcomes and the protein expressions in Model group were supposedly affected by the induction of autophagy in cerebral cortex neurons. Compared to the Model group, ART improved memory impairment in VCI rats. And the expression of LC3BⅡ/Ⅰ, p-AMPK/AMPK, Beclin-1 is significant decreased in the ART group, while significant increases of p-mTOR/mTOR were showed. These results suggest that ART improved learning and memory impairment in VCI rats by down-regulating the level of autophagy in cerebral cortex neurons. Conclusion: The results suggest that autophagy occurs in cerebral cortex neurons in rats with VCI. It is speculated that ART can improve learning and memory impairment in VCI rats by down-regulating the level of autophagy in cerebral cortex neurons.

As a crucial component of the oil transportation system, the oil terminal (or oil tank farm) may often pose some serious threats and damage to the ecological environment and production safety for the oil leakage. An effective emergency management strategy is particularly significant, involving the accurate assessment of leakage time, oil migration path, volume distribution, etc. Therefore, the volume of fluid (VOF) and liquid phase leakage model were applied to investigate the migration and distribution characteristic after the accidental hole occurs in the tank wall, and influence factors including height and diameter of the hole were considered in our study. Results show that the lower the leaking hole position is, the faster the horizontal injection rate of the leakage hole, the increase of the accumulation area of the oil on the ground, and the difference in the overall pressure value at the leakage hole is nearly four times. Under different leakage diameters, the oil spill is symmetrical. The larger the leakage diameter, the higher the amount of oil leakage and the initial leakage speed, the maximum speed is 1.5 times the minimum speed, causing harm to safety and environmental pollution. These results can quickly locate the leakage location of the tank and provide valuable references for emergency management of the oil pipeline transportation system.

IntroductionHypothyroidism has been found to be influenced by gut microbiota. However, it remains unclear which a taxon of gut microbiota plays a key role in this function. Identifying the key bacteria affects hypothyroidism and through what mechanism will be helpful for the prevention of hypothyroidism through specific clinical pathways.Materials and methodsIn Study A, 35 families and 130 genera of gut microbiota are used as exposures, with hypothyroidism as the outcome. The causal effect of the gut microbiota on hypothyroidism is estimated through two-sample Mendelian randomization. Combining the results of the two taxonomical levels, key taxa are selected, which in Study B are investigated for their causal association with multiple generally admitted causes of hypothyroidism and their more upstream factors. For validating and revealing the potential mechanism, enrichment analyses of the related genes and interacting transcription factors were performed.ResultsIn Study A, Defluviitaleaceae (OR: 0.043, 95% CI: 0.005–0.363, P = 0.018)/Defluviitaleaceae_UCG_011 (OR: 0.385, 95% CI: 0.172–0.865, P = 0.021) are significantly causally associated with hypothyroidism at both taxonomical levels. In Study B, Defluviitaleaceae family and Defluviitaleaceae_UCG_011 genus show the causal association with decreased thyroiditis (Family: OR: 0.174, 95% CI: 0.046–0.653, P = 0.029; Genus: OR: 0.139, 95% CI: 0.029–0.664, P = 0.043), decreased subacute thyroiditis (Family: OR: 0.028, 95% CI: 0.004–0.213, P = 0.007; Genus: OR: 0.018, 95% CI: 0.002–0.194, P = 0.013), decreased influenza (Family: OR: 0.818, 95% CI: 0.676–0.989, P = 0.038; Genus: OR: 0.792, 95% CI: 0.644–0.974, P = 0.027), and increased anti-influenza H3N2 IgG levels (Family: OR: 1.934, 95% CI: 1.123–3.332, P = 0.017; Genus: OR: 1.675, 95% CI: 0.953–2.943, P = 0.073). The results of the enrichment analysis are consistent with the findings and the suggested possible mechanisms.ConclusionDefluviitaleaceae of the gut microbiota displays the probability of causally inhibiting the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism” and acts as the potential probiotics to prevent influenza, subacute thyroiditis, and hypothyroidism.

Currently, dairy mastitis caused by Staphylococcus xylosus poses a serious challenge for dairy farming. In this study, we explored the role and mechanism of rhein against S. xylosus with the hope of providing new research ideas to solve mastitis in dairy cows and ensure the source safety of dairy products. Through in vitro antimicrobial studies, we found that the minimum inhibitory concentration (MIC) of rhein was 64 μg/mL, and it significantly interfered with the formation of S. xylosus biofilm at sub-MIC. In experiments on mastitis in mice, rhein alleviated inflammation in mammary tissue, reduced the levels of TNF-α and IL-6, and decreased the number of S. xylosus. To explore the anti-S. xylosus mechanism of rhein, we identified the relevant proteins involved in carbon metabolism (Glycolysis/gluconeogenesis, TCA cycle, Fatty acid degradation) through proteomics. Additionally, proteins associated with the respiratory chain, oxidative stress (proteins of antioxidant and DNA repair), and nitrate respiration were also found to be upregulated. Thus, rhein may act as an antibacterial agent by interfering with the respiratory metabolism of S. xylosus and inducing the production of ROS, high levels of which alter the permeability of bacterial cell membranes and cause damage to them. We measured the concentrations of extracellular β-galactosidase and nucleic acids. Additionally, SEM observation of S. xylosus morphology showed elevated membrane permeability and damage to the cell membrane. Finally, RT-PCR experiments showed that mRNAs of key proteins of the TCA cycle (odhA, mqo) and nitrate respiration (nreB, nreC, narG) were significantly up-regulated, consistent with proteomic results. In conclusion, rhein has good anti-S. xylosus effects in vitro and in vivo, by interfering with bacterial energy metabolism, inducing ROS production, and causing cell membrane and DNA damage, which may be one of the important mechanisms of its antimicrobial activity.

Abstract Objective To isolate a prevalent G9P[8] group A rotavirus (RVA) (N4006) in China and investigate its genomic and evolutionary characteristics, with the goal of facilitating the development of a new rotavirus vaccine. Methods The RVA G9P[8] genotype from a diarrhea sample was passaged in MA104 cells. The virus was evaluated by TEM, polyacrylamide gel electrophoresis, and indirect immunofluorescence assay. The complete genome of virus was obtained by RT-PCR and sequencing. The genomic and evolutionary characteristics of the virus were evaluated by nucleic acid sequence analysis with MEGA ver. 5.0.5 and DNASTAR software. The neutralizing epitopes of VP7 and VP4 (VP5* and VP8*) were analyzed using BioEdit ver. 7.0.9.0 and PyMOL ver. 2.5.2. Results The RVA N4006 (G9P[8] genotype) was adapted in MA104 cells with a high titer (105.5 PFU/mL). Whole-genome sequence analysis showed N4006 to be a reassortant rotavirus of Wa-like G9P[8] RVA and the NSP4 gene of DS-1-like G2P[4] RVA, with the genotype constellation G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1 (G9P[8]-E2). Phylogenetic analysis indicated that N4006 had a common ancestor with Japanese G9P[8]-E2 rotavirus. Neutralizing epitope analysis showed that VP7, VP5*, and VP8* of N4006 had low homology with vaccine viruses of the same genotype and marked differences with vaccine viruses of other genotypes. Conclusion The RVA G9P[8] genotype with the G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1 (G9P[8]-E2) constellation predominates in China and may originate from reassortment between Japanese G9P[8] with Japanese DS-1-like G2P[4] rotaviruses. The antigenic variation of N4006 with the vaccine virus necessitates an evaluation of the effect of the rotavirus vaccine on G9P[8]-E2 genotype rotavirus.

Abstract Objective Arytenoid dislocation (AD) after general anesthesia with endotracheal intubation (EI) is an iatrogenic injury that impairs patient function and requires reduction. We aimed to investigate the risk factors of AD following EI. Methods This retrospective case‐control study involved surgical adults who received EI for general anesthesia at a single institution from June 2010 to June 2020. Cases included all the patients who had AD. We used a ratio of 1:5 to identify patients in the propensity‐matched control group. Results Multivariate analysis of 49 cases with AD and 245 controls without AD demonstrated that the use of a nasogastric (NG) tube (odds ratio [OR], 23.9; 95% confidence interval [CI], 6.8–84.1), undergoing abdominal surgery (OR, 3.7; 95% CI, 1.2–11.9), and an operative time longer than 3 h (OR, 5.2; 95% CI, 2.1–12.9) were risk factors for AD. We did not find significant independent associations between AD and 40 years or older age, gender, body mass index, whether a laryngeal mask airway was used, endotracheal tube size, and EI performers' experience. Conclusion The use of an NG tube, abdominal surgery, and longer operative time were risk factors for AD. Among these, the NG tube application showed a strong association with AD. Preventive measures of informing the patients of the increased risk and providing high‐level patient monitoring can reduce the incidence of AD. Level of Evidence III

The combination of nonlinearity and topology has recently attracted significant attention in the field of optical physics. This work considers a photonic Chern insulator in the nonlinear regime and explores the properties of topological bulk solitons holding the stability and robustness, which contributes to the field of nonlinear topological photonics and provides further physical understandings towards other photonic topological insulators with nonlinearity.

Cancer-associated fibroblasts (CAFs) are a predominant and critical component of the tumour microenvironment. Here, the authors integrate and analyse single-cell RNA-seq data of CAFs across 10 common solid cancer types, identifying their plasticity and interactions with other cell types.

ABSTRACT Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered emerging alphacoronavirus. SADS-CoV shares over 90% genome sequence identity with bat alphacoronavirus HKU2. SADS-CoV was associated with severe diarrhea and high mortality rates in piglets. Accurate serological diagnosis of SADS-CoV infection is key in managing the emerging SADS-CoV. However, thus far there have been no effective antibody-based diagnostic tests for diagnose of SADS-CoV exposure. Here, monoclonal antibody (MAb) 6E8 against SADS-CoV N protein accurately recognized SADS-CoV infection. Then, MAb 6E8 was utilized as a blocking antibody to develop blocking ELISA (bELISA). We customized the rN coating antigen with concentration 0.25 μg/mL. According to receiver operator characteristic curve analysis, the cutoff value of the bELISA was determined as 38.19% when the max Youden index was 0.955, and specificity was 100%, and sensitivity was 95.5%. Specificity testing showed that there was no cross-reactivity with other serum positive swine enteric coronaviruses, such as porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), porcine rotavirus (PoRV), and porcine sapelovirus (PSV). In conclusion, we customized a novel and high-quality blocking ELISA for detection of SADS-CoV infection, and the current bELISA will be linked to a clinical and epidemiological assessment of SADS-CoV infection. IMPORTANCE SADS-CoV was reported to be of high potential for dissemination among various of host species. Accurate serological diagnosis of SADS-CoV infection is key in managing the emerging SADS-CoV. However, thus far there have been no effective antibody-based diagnostic tests for diagnose of SADS-CoV exposure. We customed a novel and high-quality bELISA assay for detection of SADS-CoV N protein antibodies, and the current bELISA will be linked to a clinical and epidemiological assessment of SADS-CoV infection.

Platinum-based drugs are widely used in chemotherapy for various types of cancer and are considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention and have been extensively researched among these drugs. Traditionally, Pt(IV) compounds are reduced to divalent platinum (Pt(II)) after entering cells, causing DNA lesions and exhibiting their anti-tumor effect. However, the available evidence indicates that some Pt(IV) derivatives may differ from the traditional mechanism and exert their anti-tumor effect through their overall structure. This review primarily focuses on the existing literature regarding targeted Pt(II) and Pt(IV) compounds, with a specific emphasis on their in vivo mode of action and the properties of reduction release in multifunctional Pt(IV) compounds. This review provides a comprehensive summary of the design and synthesis strategies employed for Pt(II) derivatives that selectively target various enzymes (glucose receptor, folate, telomerase, etc.) or substances (mitochondria, oleic acid, etc.). Furthermore, it thoroughly examines and summarizes the rational design, anti-tumor mechanism of action, and reductive release capacity of novel multifunctional Pt(IV) compounds, such as those targeting p53-MDM2, COX-2, lipid metabolism, dual drugs, and drug delivery systems. Finally, this review aims to provide theoretical support for the rational design and development of new targeted Pt(IV) compounds.

PurposeCuproptosis is a newly discovered type of cell death. Little is known about the roles that cuproptosis related genes (CRGs) play in colorectal cancer (CRC). The aim of this study is to evaluate the prognostic value of CRGs and their relationship with tumor immune microenvironment.MethodsTCGA-COAD dataset was used as the training cohort. Pearson correlation was employed to identify CRGs and paired tumor-normal samples were used to identify those CRGs with differential expression pattern. A risk score signature was constructed using LASSO regression and multivariate Cox stepwise regression methods. Two GEO datasets were used as validation cohorts for confirming predictive power and clinical significance of this model. Expression patterns of seven CRGs were evaluated in COAD tissues. In vitro experiments were conducted to validate the expression of the CRGs during cuproptosis.ResultsA total of 771 differentially expressed CRGs were identified in the training cohort. A predictive model termed riskScore was constructed consisting of 7 CRGs and two clinical parameters (age and stage). Survival analysis suggested that patients with higher riskScore showed shorter OS than those with lower (P

There are increasing evidences that the biodilution effect can significantly reduce the biomagnification of mercury (Hg) in fish. The significant antagonism of selenium (Se) -Hg may have a potential diluting effect on Hg in fish; however, there is still lack of knowledge on such effect. To reveal the Se-Hg interaction and its role in controlling the biodilution effect of Hg, we investigated levels of Hg and Se in the muscle and liver of redlip mullet from Jiaozhou Bay, China, an urbanized semi-enclosed bay highly impacted by human activities. In general, Hg levels in fish muscle were significantly negatively correlated to the levels of Se in the liver and fish size for fish with a size of 200 mm, possibly because the normal metabolism of Hg in muscle was hindered by homeostatic regulation or physiological activities such as gonadal development in vivo. Furthermore, the molar ratio of Se in the liver/Hg in the muscle was significantly increasing with Se/Hg in the liver, suggesting that the liver may be the key organ involved in Se-Hg antagonism. Moreover, both ratios continued to decrease with increasing fish size, implying that the antagonistic effect weakens with fish growth. These results indicate that Hg sequestration by liver may be a key mechanism of Se-Hg antagonism in fish and function as a driver for the biodilution effect of Hg, especially at a size of

As an important research direction of swarm intelligence algorithm, particle swarm optimization (PSO) has become a popular evolutionary method and received extensive attention in the past decades. Despite many PSO variants have been proposed, how to maintain a good balance between the exploration and exploitation abilities, and how to jump out of the local optimal position are still challenges. In this article, based on empirical balance strategy, a new particle swarm optimization (EBPSO) algorithm is presented. Firstly, based on an adaptive adjustment mechanism, the algorithm can choose a better strategy from two search equations, which can maintain the balance between the exploration and exploitation abilities. Secondly, to utilize the information of individual historical optimal solution and the optimal solution of the current population, a weight for adjusting their influence is introduced into the search equation. Thirdly, by introducing the diversity of population, a moving equation for dynamically adjusting the search ability of the algorithm is proposed. Finally, to avoid falling into local optimum and to search the potential location, a dynamic random search mechanism is proposed, which is designed by using the information of the current optimal solution. Compared with some state-of-the-art algorithms, the experimental results show that EBPSO has excellent solution quality and convergence characteristic on almost all test problems.

This study aimed to compare the safety and efficacy of CyberKnife (CK) versus TomoTherapy for the treatment of brain metastases (BMs). Three cases of BM treated at our hospital – two with CK and one with TomoTherapy – were compared and analyzed. Both treatments showed good therapeutic effects, but CK was more effective. No radiation-related adverse reactions were observed in the three patients. It is concluded that both CK and TomoTherapy can effectively control target lesions by allowing a higher dose in a single treatment while minimizing damage to surrounding normal brain tissue. This can reduce the total number of treatments needed, improve the prognosis of patients, and save medical resources.

Extracellular vesicles are fundamentally significant in the communication between cells. Outer Membrane Vesicles(OMVs) are a special kind of EVs produced by Gram-negative bacteria, which are minute exosome-like particles budding from the outer membrane, which have been found to play essential roles in diverse bacterial life events, including regulation of microbial interactions, pathogenesis promotion, stress responses and biofilm formation. Recently, and more researches have explored the substantial potentials of EVs as natural functional nanoparticles in the bioengineering applications in infectious diseases, cardiovascular diseases, autoimmune diseases and neurological diseases, such as antibacterial therapy, cancer drugs and immunoadjuvants, with several candidates in clinical trials showing promising efficacy. However, due to the poor understanding of sources, membrane structures and biogenesis mechanisms of EVs, progress in clinical applications still remains timid. In this review, we summarize the latest findings of EVs, especially in gastrointestinal tract tumours, to provide a comprehensive introduction of EVs in tumorigenesis and therapeutics.

Objectives. To assess A-kinase anchor protein 95 (AKAP95), B-Raf, extracellular regulated protein kinases 1/2 (ERK1/2), and Elk-1 expression in colon cancer tissue, and characterize AKAP95 associations with B-Raf, ERK1/2, Elk-1, and colon cancer clinicopathological indices. Methods. The immunohistochemistry streptavidin-perosidase (SP) method was used to determine protein expression levels in 64 colon cancer and 32 para-carcinoma tissue specimens. Results. (1) Positive AKAP95 expression rates in colon cancer tissue were higher when compared with para-carcinoma tissue (92.19% vs. 59.38%, P0.05); however, in The Cancer Genome Atlas and Gene Expression Omnibus datasets, AKAP95 was closely related to immune infiltration, and highly expressed AKAP95 was negatively associated with overall survival and relapse free survival rates in colon cancer patients. (3) Correlations were observed between AKAP95 and ERK1/2, AKAP95 and Elk-1, B-Raf and ERK1/2, B-Raf and Elk-1, and ERK1/2 and Elk-1 (all P0.05). Conclusions. AKAP95 may affect immune infiltration levels in colon cancer by participating in ERK1/2–Elk-1 signal transduction.

Alzheimer disease (AD) is a progressive neurodegenerative disease resulting from the accumulation of extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles. There are currently no objective diagnostic measures for AD. The aim of this study was to identify potential diagnostic markers for AD and evaluate the role of immune cell infiltration in disease pathogenesis. AD expression profiling data for human hippocampus tissue (GSE48350 and GSE5281) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software and the Human Protein Atlas database was used to screen AD-related DEGs. We performed functional enrichment analysis and established a protein–protein interaction (PPI) network to identify disease-related hub DEGs. The fraction of infiltrating immune cells in samples was determined with the Microenvironment Cell Populations-counter method. The random forest algorithm was used to develop a prediction model and receiver operating characteristic (ROC) curve analysis was performed to validate the diagnostic utility of the candidate AD markers. The correlation between expression of the diagnostic markers and immune cell infiltration was also analyzed. A total of 107 AD-related DEGs were screened in this study, including 28 that were upregulated and 79 that were downregulated. The DEGs were enriched in the Gene Ontology terms GABAergic synapse, Morphine addiction, Nicotine addiction, Phagosome, and Synaptic vesicle cycle. We identified 10 disease-related hub genes and 20 candidate diagnostic genes. Synaptophysin (SYP) and regulator of G protein signaling 4 (RGS4) (area under the ROC curve = 0.909) were verified as potential diagnostic markers for AD in the GSE28146 validation dataset. Natural killer cells, B lineage cells, monocytic lineage cells, endothelial cells, and fibroblasts were found to be involved in AD; additionally, the expression levels of both SYP and RGS4 were negatively correlated with the infiltration of these immune cell types. These results suggest that SYP and RGS4 are potential diagnostic markers for AD and that immune cell infiltration plays an important role in AD development and progression.

BackgroundsAs a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass and bone microarchitectural damage. The global incidences of OP are high.MethodsData were retrieved from databases like Gene Expression Omnibus (GEO), GeneCards, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Gene Expression Profiling Interactive Analysis (GEPIA2), and other databases. R software (version 4.1.1) was used to identify differentially expressed genes (DEGs) and perform functional analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and random forest algorithm were combined and used for screening diagnostic markers for OP. The diagnostic value was assessed by the receiver operating characteristic (ROC) curve. Molecular signature subtypes were identified using a consensus clustering approach, and prognostic analysis was performed. The level of immune cell infiltration was assessed by the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. The hub gene was identified using the CytoHubba algorithm. Real-time fluorescence quantitative PCR (RT-qPCR) was performed on the plasma of osteoporosis patients and control samples. The interaction network was constructed between the hub genes and miRNAs, transcription factors, RNA binding proteins, and drugs.ResultsA total of 40 DEGs, eight OP-related differential genes, six OP diagnostic marker genes, four OP key diagnostic marker genes, and ten hub genes (TNF, RARRES2, FLNA, STXBP2, EGR2, MAP4K2, NFKBIA, JUNB, SPI1, CTSD) were identified. RT-qPCR results revealed a total of eight genes had significant differential expression between osteoporosis patients and control samples. Enrichment analysis showed these genes were mainly related to MAPK signaling pathways, TNF signaling pathway, apoptosis, and Salmonella infection. RT-qPCR also revealed that the MAPK signaling pathway (p38, TRAF6) and NF-kappa B signaling pathway (c-FLIP, MIP1β) were significantly different between osteoporosis patients and control samples. The analysis of immune cell infiltration revealed that monocytes, activated CD4 memory T cells, and memory and naïve B cells may be related to the occurrence and development of OP.ConclusionsWe identified six novel OP diagnostic marker genes and ten OP-hub genes. These genes can be used to improve the prognostic of OP and to identify potential relationships between the immune microenvironment and OP. Our research will provide insights into the potential therapeutic targets and pathogenesis of osteoporosis.

BackgroundHepatitis B surface antigen (HBsAg) loss is considered a functional cure for chronic hepatitis B (CHB), however, several factors influence HBsAg loss.Methods29 CHB patients who had achieved HBsAg loss, were selected and 58 CHB patients with persistent HBsAg were matched, according to gender and age (+/- 3 years). Logistic regression and restricted cubic spline (RCS) modelling were performed.ResultsMultivariate-adjusted logistic regression, based on stepwise selection, showed that baseline HBsAg levels negatively correlated with HBsAg loss (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.98-0.99). Interferon treatment positively related with HBsAg loss (OR = 7.99, 95%CI = 1.62-44.88). After adjusting for age, HBsAg level, ALT level, HBeAg status and interferon treatment, MMP-1 (OR = 0.66, 95%CI = 0.44-0.97), CXCL9 (OR = 0.96, 95%CI = 0.93-0.99) and TNF-R1 (OR = 0.97, 95%CI = 0.94-0.99) baseline levels all negatively correlated with HBsAg loss. Our multivariate-adjusted RCS model showed that baseline CXCL10 was associated with HBsAg loss although the relationship was “U-shaped”.ConclusionsCytokines such as MMP-1, CXCL9, CXCL10 and TNF-R1 are important factors which influence HBsAg loss. It may be possible to develop a nomogram which intercalates these factors; however, further research should consider immune processes involved in HBsAg loss.

Background and aimChronic hepatitis B (CHB) can be divided into immune tolerance (IT), immune clearance (IC), hepatitis B e antigen (HBeAg)-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. The conventional biomarkers used to distinguish these phases have limitations. We examined the clinical significance of hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) as novel biomarkers.MethodsOne hundred eighty-nine patients without treatment currently were categorized by CHB phase (IT = 46, IC = 45, ENQ = 49, ENH = 49). The associations of HBV RNA and HBcrAg with HBV DNA and alanine transaminase (ALT) were analyzed. The decision tree model was used to distinguish the four phases in the natural course of CHB.ResultsThe concentrations of HBV RNA and HBcrAg were highest in the IT and IC phases (P < 0.01). Serum HBV RNA was similar to HBcrAg in treatment-naïve patients. HBV RNA and HBcrAg correlated with HBV DNA in the HBeAg+ and HBeAg− status (HBV RNA: e+ r = 0.51, e− r = 0.62; HBcrAg: e+ r = 0.51, e− r = 0.71), but their association with HBV DNA differed among phases. The accuracy, sensitivity, and specificity of HBcrAg with ALT in distinguishing the CHB phases were 95.65%, 95.83%, and 95.55%, respectively.ConclusionSerum HBV RNA and HBcrAg may be useful to monitor CHB progression.

Abstract Background Pancreaticobiliary reflux (PBR) causes chronic inflammation of the gallbladder mucosa and changes in the bile components, which are known to promote gallstone formation. This study aimed to investigate the bile biochemistry changes in gallstone patients with PBR and provide new clues for research on the involvement of PBR in gallstone formation. Methods Patients undergoing surgery for gallstones between December 2020 and May 2021 were eligible for inclusion. The bile biochemistry (including amylase, lipase, triglyceride, cholesterol, free fatty acids [FFAs], alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and γ-glutamyl transferase [γ-GT]) of the included gallstone patients was analysed to determine correlations with PBR. Results In this study, 144 gallstone patients who underwent surgery were enrolled. Overall, 15.97 % of the patients had an increased bile amylase level, which was associated with older age and significantly higher bile levels of ALP, lipase, triglyceride, and FFAs. Positive correlations were observed between amylase and lipase, triglyceride, FFAs levels in the gallbladder bile. However, the bile levels of triglyceride, FFAs, and lipase were positively correlated with each other only in the PBR group and showed no significant correlation in the control (N) group. In addition, elevated bile FFAs levels were found to be an independent risk factor for gallbladder wall thickening. Conclusions In conclusion, PBR-induced increase in FFAs and triglyceride in the gallbladder bile is a cause of gallstone formation, and an increase in bile ALP suggests the presence of cholestasis in PBR.

Abstract Immune checkpoint blockade has dramatically altered the concept of cancer therapeutics over the past few years. Beyond the existing classical pathways, novel immune checkpoints, such as T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif (ITIM) structural domain (TIGIT), have also emerged in recent years and have promising therapeutic potential. Recent researches have provided ample evidence that TIGIT is extensively involved in various cancerous and noncancerous diseases such as chronic inflammation, autoimmune diseases, abnormal pregnancy status, and most recently coronavirus disease 2019. In contrast to the programmed cell death receptor 1 pathway which primarily affects T‐cell function, targeting TIGIT pathway regulates multiple types of immunocytes but has fewer immune‐related adverse events. Owing to its unique advantages and extensive involvement in diseases, extensive clinical trials blockade TIGIT or combine it with other targets are ongoing, and numerous phase II clinical trials have already seen promising results. In this review, we summarized the existing research on TIGIT in various diseases and discussed the perspective and challenges related to targeting this molecular for therapy, with an attempt to provide directions for subsequent studies.

G9P[8] became the predominant rotavirus A (RVA) genotype in China in 2012. To evaluate its genetic composition at the whole-genome level, 115 G9P[8] RVA strains isolated from children under 5 years old were sequenced and characterized. All 13 strains in 2016 and 2017 and an additional 54 strains in 2018 were genotyped as G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. The other 48 strains in 2018 were all genotyped as G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1, with the NSP4 gene characterized as a DS-1-like genotype. The time of the most recent common ancestor (tMRCA) and evolution rates of the VP7, VP4, and NSP4 (E1 and E2) genes of these strains were estimated by Bayesian evolutionary dynamics analysis. We estimated the evolution rates (nt substitutions per site per year) as 1.38 × 10–3 [the 95% highest posterior density (HPD) was 1.09–1.72 × 10–3] for VP7, 0.87 × 10–3 (95% HPD: 0.75–1.00 × 10–3) for VP4, 0.56 × 10–3 (95% HPD: 0.41–0.73 × 10–3) for NSP4-E1, and 1.35 × 10–3 (95% HPD: 0.92–1.86 × 10–3) for NSP4-E2. The tMRCA was estimated to be 1935.4 (95% HPD: 1892.4–1961.3) for VP7, 1894.3 (95% HPD: 1850.5–1937.8) for VP4, 1929.4 (95% HPD: 1892.4–1961.3) for NSP4-E1, and 1969.2 (95% HPD: 1942.2–1985.3) for NSP4-E2. The baseline genetic information in this study is expected to improve our understanding of the genomic and evolutionary characteristics of the rotavirus genome. Furthermore, it will provide a basis for the development of next-generation rotavirus vaccines for humans.

Abstract This paper is concerned with the existence of positive radial solutions of the following resonant elliptic system: { − Δ u = u v + f ( | x | , u ) , 0 < R 1 < | x | < R 2 , x ∈ R N , − Δ v = c g ( u ) − d v , 0 < R 1 < | x | < R 2 , x ∈ R N , ∂ u ∂ n = 0 = ∂ v ∂ n , | x | = R 1 , | x | = R 2 , $$ \textstyle\begin{cases} -\Delta u=uv+f( \vert x \vert ,u), & 0< R_{1}< \vert x \vert < R_{2}, x\in \mathbb{R}^{N}, \\ -\Delta v=cg(u)-dv, & 0< R_{1}< \vert x \vert < R_{2}, x\in \mathbb{R}^{N}, \\ \frac{\partial u}{\partial \textbf{n}}=0= \frac{\partial v}{\partial \textbf{n}},& \vert x \vert =R_{1}, \vert x \vert =R_{2}, \end{cases} $$ where R N $\mathbb{R}^{N}$ ( N ≥ 1 $N\geq 1$ ) is the usual Euclidean space, n indicates the outward unit normal vector, f ∈ C ( [ R 1 , R 2 ] × [ 0 , ∞ ) , R ) $f\in C([R_{1},R_{2}]\times [0,\infty ),\mathbb{R})$ , g ∈ C ( [ 0 , ∞ ) , [ 0 , ∞ ) ) $g\in C([0,\infty ),[0,\infty ))$ , and c and d are positive constants. By employing the classical fixed point theory we establish several novel existence theorems. Our main findings enrich and complement those available in the literature.

Leakage incidents on LNG bunker vessels will result in a serious degree of hazard. This paper investigates typical high-risk scenarios such as hose ruptures and valve joint leakages. The consequences of an LNG leakage accident during the simultaneous operation of a bunker vessel and a container carrier are simulated using the FLACS software, and the dispersion range of the combustible vapor cloud is quantitatively analyzed under both ballast and laden conditions. Under the ballast condition, the diffusion range of the combustible vapor cloud on the side of the bunker vessel is 58 × 15.5 m from the front wall of the cargo equipment room to the bow of the vessel, and 35 × 9.5 m between the cargo equipment room and the transom of the vessel. Under the laden condition, the diffusion range on the side of the bunker vessel is 58 × 15.5 m from the front wall of the cargo equipment room to the bow of the vessel, and 15 × 4 m between the rear end wall of the cargo equipment room and the front wall of the stern of the vessel. These results provide important technical guidance and reference values for the safe operation of LNG bunker vessels.

A microgrid cluster is composed of multiple interconnected microgrids and operates in the form of cluster, which can realize energy complementation between microgrids and significantly improve their renewable energy consumption capacity and system operation reliability. A microgrid optimal dispatch based on a distributed economic model predictive control algorithm is proposed in this paper. Firstly, the control task of the microgrid power generation system is defined, which is required to meet the load demand while reducing the economic loss of the system and realize dynamic economic optimization. The global objective function is designed based on the control task, and the detailed design method of the distributed economic model predictive controller is given. The control law is obtained by an iterative calculation using the Nash optimal method, which can effectively reduce the amount of data in the communication network. Finally, a microgrid group composed of four microgrids is used as an example for simulation verification. The simulation results show that the distributed economic model predictive control algorithm proposed in this paper has good economic benefits for microgrid dispatching.

Abstract Background Retroperitoneal fibrosis (RPF) is a rare disease with a poor prognosis characterized by systemic inflammation and fibroinflammatory tissue. Idiopathic RPF (IRPF) accounts for approximately two-thirds of RPF cases. Case presentation A 56-year-old female patient with abdominal distension was admitted to Changxing Hospital. Laboratory tests revealed mild anemia and elevated CA125, while IgG4 and autoantibodies were within the normal ranges. Computed tomography (CT) revealed a gallbladder-occupying lesion, pancreatic cyst and retroperitoneal mass, which may have contributed to bilateral ureteral compression and hydronephrosis. The initial diagnosis was gallbladder carcinoma with lymph node metastasis. Then, abdominal adhesiolysis, cholecystectomy and partial hepatectomy were performed. Histologically, there were fibrosis and inflammation in the retroperitoneal tissue without any malignant cells in the retroperitoneal or gallbladder tissue. Finally, we confirmed the diagnosis of idiopathic retroperitoneal fibrosis, chronic cholecystitis and pancreatic cyst. The patient recovered well following the CT scan, in which dilatation of the bile duct was reduced, and effusion of the bilateral upper ureter was no longer significant. Conclusion This atypical case illustrates that RPF can be combined with other biliary tract diseases. The coexistence of other diseases conceals the symptoms of RPF, which increases the difficulty of image identification. A high degree of suspicion is necessary for routine clinical work. As more cases are reported, further advances in the diagnosis and treatment of RPF can be expected.

Abstract Background Human Sapoviruses (SaVs) has been reported as one of the causative agents of acute gastroenteritis (AGE) worldwide. An outbreak of SaVs affected 482 primary school students during spring activities from February 24 to March 11, 2019 in Shenzhen City, China. Our study was aimed at determining the epidemiology of the outbreak, investigating its origins, and making a clear identification of the SaVs genetic diversity. Methods Epidemiological investigation was conducted for this AGE outbreak. Stool samples were collected for laboratory tests of causative agents. Real-time reverse-transcription polymerase chain reaction (rRT-PCR) and conventional RT-PCR were used for detecting and genotyping of SaVs. The nearly complete genome of GII.8 SaV strains were amplified and sequenced by using several primer sets designed in this study. Phylogenetic analysis was performed to characterize the genome of GII.8 SaV strains. Results The single factor analysis showed that the students who were less than 1.5 m away from the vomitus in classroom or playgroundwere susceptible (P

Although circulating tumor cells (CTCs) have shown promise as potential biomarkers for diagnostic and prognostic assessment in gastric cancer (GC), determining the predictive and prognostic value of programmed death‐ligand 1 (PD‐L1)‐positive CTCs in patients with GC is a challenge. Here, we identified that the expression of total vimentin (VIM) protein was positively correlated with PD‐L1 and inhibited CD8+ T‐cell activation in patients with GC according to bioinformatics analysis. Notably, coexpression of PD‐L1 and cell‐surface VIM (CSV) was detected by immunofluorescence and immunohistochemistry assay in locally advanced GC tumor specimens and metastatic lymph nodes. Likewise, CSV expression level was significantly decreased after transiently knocking down PD‐L1 in GC cell lines. Based on our established CTC detection platform, CTCs were isolated from peripheral blood samples collected from 70 patients (38 resectable and 32 unresectable) with GC using magnetic positive selection and a CSV‐specific monoclonal antibody, 84‐1. CSV+PD‐L1+CTCs were observed in 50 of 70 (71%) GC patient samples, ranging from 0 to 261 mL−1. A higher number of CSV+PD‐L1+CTCs were significantly associated with a short survival duration and poor therapeutic response. This study demonstrated that detection of PD‐L1+CTCs using a CSV‐enrichment method has promising value as a clinically relevant prognostic marker for GC.

CaliciNet China, a network of provincial, county, and city laboratories coordinated by the Chinese Centers for Disease Control and Prevention, was launched in October 2016 to monitor the epidemiology and genotype distribution of norovirus outbreaks in China. During October 2016–September 2018, a total of 556 norovirus outbreaks were reported, and positive fecal samples from 470 (84.5%) outbreaks were genotyped. Most of these outbreaks were associated with person-to-person transmission (95.1%), occurred in childcare centers or schools (78.2%), and were reported during November–March of each year (63.5%). During the 2-year study period, 81.2% of all norovirus outbreaks were typed as GII.2[P16]. In China, most norovirus outbreaks are reported by childcare centers or schools; GII.2[P16] is the predominant genotype. Ongoing surveillance by CaliciNet China will provide information about the evolving norovirus genotype distribution and outbreak characteristics important for the development of effective interventions, including vaccines.

In the present work, based on the generalized principal component analysis, we propose a new approach to decompose the subspace of fault deviations, which is used for reconstruction-based fault diagnosis through principal component analysis (PCA) monitoring system. The proposed method is advanced since it lightens the computational burden by eliminating the irrelavant information and simplifying the fault subspace. The fault effects are extracted through analyzing the generalized principal components of the normal operating data and the fault data. The significant fault deviations that cause the alarming monitoring statistic are calculated. This is achieved by designing a two-part feature decomposition procedure. In the first part, the normal operating subspace is extracted through analyzing the generalized principal components of both the historical normal data and fault data. The fault-free part of the data is eliminated by projecting the data into the normal operating subspace. In the second part, principal component analysis is performed on the remaining part of the data, where the largest fault deviation directions are decomposed in order. By the two-part decomposition, an integrated fault subspace for all monitoring statistic indices is obtained, which separates the measurement data into two different parts for fault reconstruction. One part is related to the normal operating subspace, which is deemed to follow normal rules, and thus insignificant to remove alarming monitoring statistics. The other is related to the fault subspace, which contributes to the out-of-control signals. Theoretical support is constructed and the related statistical characteristics are analyzed. Its feasibility and performance are illustrated with the data from the Tennessee Eastman (TE) benchmark process.

Thermostatically controlled loads (TCLs) have become a major tool for the demand response (DR) program when air conditioners cause peak loads in a day during the winter or summer. To solve the problem of a direct load control with TCL usually affecting user comfort and hardly considering responsiveness, a power retailer air-conditioning load aggregation operation control and demand response method was proposed in this research. From the perspective of a power retailer, a compensation mechanism for TCL was constructed, which was composed of a basic incentive program and an additional incentive program. The basic incentive program aimed to encourage users with a low response degree to increase the response capacity in order to participate in DR. An auxiliary service market control strategy based on a new compensation mechanism of the electricity retailer was detailed, which fully considered the enthusiasm of the user in mobilizing the response and reducing the load reduction fluctuation when using the state-queuing (SQ) model. Case studies were provided to verify the effectiveness of the proposed method. Compared with other compensation schemes, the simulation results showed that the compensation mechanism provided in this research was more reasonable, and it could smooth the load and reduce fluctuations. The compensation distribution among the user groups could effectively control the uniform distribution in the user groups in the temperature range, and it could mobilize users at different temperatures to participate in DR.

This article addresses the fault-tolerant control problem for high-speed trains (HSTs) with actuator faults under strong winds. For the healthy system, a non-singular fast terminal sliding mode surface is introduced into the controller, which ensures the system fast converge to the equilibrium point with finite time, and the radial basis function neural network (RBFNN) with the adaptive compensation term of the error is used to approximate the unknown nonlinear disturbances of the train system in strong winds and predict the time delay generated in the train communication network. Through the RBFNN observer established specifically for actuator failures, the real effective factors are identified. Combining with the identified effective factors and predicted time delay, an adaptive fault-tolerant sliding mode control method is established for train systems. With dynamic parameters and position update strategy guided by negative gradient thought, an improved particle swarm optimization algorithm is proposed to optimize the uncertain parameters of control method, which weakens the chattering phenomenon from the sliding mode controller and improves the control accuracy. Simulation results show that the proposed method has better tracking performance and real-time performance compared with other fault-tolerant control methods under various operating conditions, which ensures the running safety of HSTs under different strong winds.

ABSTRACT Accumulating evidence suggests that p53 is involved in viral infection. However, it remains elusive whether avian p53 orchestrates avian leukosis virus (ALV) replication. We showed that p53 recruits the histone deacetylase 1 and 2 (HDAC1/2) complex to the ALV promoter to shut off ALV's promoter activity and viral replication. HDAC1/2 binding to the ALV promoter was abolished in the absence of p53. Moreover, we collected samples in ALV-infected chickens and found that the acetylation status of ALV-bound H3 and H4 histones correlated with ALV viremia. HDAC inhibitors (HDACi) potently increase ALV replication, but HDACi-promoted viral replication is dramatically reduced in cells with p53 depletion. These data demonstrate that p53 is critical for inhibition ALV replication and suggest that future studies of ALV replication need to account for the potential effects of p53 activity. IMPORTANCE Rous sarcoma virus (RSV)/ALV was the first retrovirus to be discovered, which was really the first hint that cancer, or a tumor, could be transmitted by a virus. The specific mechanisms that regulate ALV replication during infection remain poorly understood. Here, we show that avian p53 and HDAC complex inhibit ALV promoter activity and replication, and p53 inhibits ALV replication through binding to the ALV promoter. We demonstrated that the acetylation status of ALV-bound H3 and H4 histones correlates with ALV viremia level using clinical samples collected from commercial poultry. These findings identify both p53-mediated inhibition on ALV replication and a potential role for virus-induced tumorigenesis.

Colocating workloads are commonly used in datacenters to improve server utilization. However, the unpredictable application performance degradation caused by the contention for shared resources makes the problem difficult and limits the efficiency of this approach. This problem has sparked research in hardware and software techniques that focus on enhancing the datacenters’ isolation abilities. There is still lack of a comprehensive benchmark suite to evaluate such techniques. To address this problem, we present SDCBench, a new benchmark suite that is specifically designed for workload colocation and characterization in datacenters. SDCBench includes 16 applications that span a wide range of cloud scenarios, which are carefully selected from the existing benchmarks using the clustering analysis method. SDCBench implements a robust statistical methodology to support workload colocation and proposes a concept of latency entropy for measuring the isolation ability of cloud systems. It enables cloud tenants to understand the performance isolation ability in datacenters and choose their best-fitted cloud services. For cloud providers, it also helps them to improve the quality of service to increase their revenues. Experimental results show that SDCBench can simulate different workload colocation scenarios by generating pressures on multidimensional resources with simple configurations. We also use SDCBench to compare the latency entropies in public cloud platforms such as Huawei Cloud and AWS Cloud and a local prototype system FlameCluster-II; the evaluation results show FlameCluster-II has the best performance isolation ability over these three cloud systems, with 0.99 of experience availability and 0.29 of latency entropy.

As an individual plant participating in the power market, the virtual power plant (VPP) is regarded as the ultimate configuration of the energy Internet, and effective dispatching is a challenge. This paper proposes a multi-agent optimal bidding strategy based on a self-adaptive global optimal harmony search algorithm (SGHSA) to solve the problem of multi-operator participation in virtual power station scheduling. The method takes multiple agents to simulate the bidding process in the VPPs and distributes the profits for the operators based on the market mechanism to optimize the distributed energy resources (DERs). Case studies are provided and show that the proposed method realizes the optimal distribution of power generation and demand level, which improves the comprehensive advantage of the VPP in electricity market transactions.

Amino-thiol bifunctional polysilsesquioxane/carbon nanotubes (PSQ/CNTs) magnetic composites were prepared by sol-gel method with two types of functional siloxanes coating on carboxyl CNTs simultaneously. The composites were served as efficient adsorbents for removing Hg(II) in aqueous solution and the adsorption properties were investigated systematically. The optimal pH of bifunctional composites for Hg(II) removal is at pH 4.5. The thermodynamic fitting curves are more consistent with the Langmuir model and the adsorption capacities of the bifunctional composites for Hg(II) varied from 1.63 to 1.94 mmol g−1 at 25°C according to the Langmuir model. The kinetics curves are more fitted to the pseudo-second-order model and the composites could selectively adsorb Hg(II) in a series of binary metal ions solution. The elution regeneration tests showed that the adsorption rate could still reach 78% after repeat cycle three times. It is expected that the bifunctional PSQ/CNTs magnetic composites can be potentially applied to remove low concentration Hg(II) from waste water.

The heat transfer enhancement of a jet issued from the circular cylinder placed in a three-dimensional microchannel at low Reynolds numbers were studied systematically by using the numerical simulation. The effects of the jet on thermal efficiency were evaluated by varying injection ratios (I) and jet angles (θ). The physical mechanism of heat transfer was revealed through the analyses of vorticity dynamic and temperature field. The results showed that the thermal efficiency was proportional to the injection ratio at Re = 100 and 200. However, at Re = 300, the thermal efficiency did not increase monotonically with the injection ratio, and the local maximum value of heat transfer efficiency, slightly less than the highest thermal efficiency, appeared at I = 1.5. This was a result of the jet inducing the vortex generated on the cylinder to become unstable. Furthermore, the change of jet angle had a better effect on heat transfer performance compared to the increase in the injection ratio. The separation point of the flow over cylinder and the vortices in the near field were adjusted by the change in jet angle. At the appropriate range of the jet angle, the wake vortices in the near field transitioned from quasi-steady to unsteady in the far field. The instability of wake vortices can disturb the thermal boundary layer near the wall so as to improve the heat transfer performance.

Dendrimers as commonly used metal ions adsorption materials have the advantages of good adsorption performance and high reuse rate, but the high cost limits its extensive use. Compared with dendrimers, hyperbranched dendrimers have similar physical and chemical properties and are more economical. Therefore, hyperbranched dendrimers are more suitable for industrial large-scale adsorption. The hyperbranched polyamidoamine (HPAMAM) gels were prepared by cross-linking hyperbranched polyamidoamine (HPAMAM-ECH-x and HPAMAM-EGDE-x) with different amounts of epichlorohydrin (ECH) and ethylene glycol diglycidyl ether (EGDE), respectively. The as-synthesized adsorbents were characterized by FT-IR, SEM and XPS. The prepared adsorbents were used to adsorb Hg(Ⅱ) in aqueous solution, and the effects of solution pH, contact time, temperature and initial concentration of metal ion on the adsorption capacity were investigated. The effect of solution pH indicated that the optimum condition to Hg(Ⅱ) removing was at pH 5.0. The adsorption kinetic curves of the two kinds of materials were in accordance with the pseudo-second-order model. For the HPAMAM-ECH samples, the adsorption thermodynamic curves fitted the Langmuir model, while for the HPAMAM-EGDE samples, both Langmuir and Freundlich equations fitted well. The maximum adsorption capacity of HPAMAM-ECH-3 obtained from Langmuir model toward Hg(Ⅱ) was 3.36 mmol/g at pH 5.0 and 35°C.

White matter hyperintensity (WMH) is common in healthy adults in their 60s and can be seen as early as in their 30s and 40s. Alterations in the brain structural and functional profiles in adults with WMH have been repeatedly studied but with a focus on late-stage WMH. To date, structural and functional MRI profiles during the very early stage of WMH remain largely unexplored. To address this, we investigated multimodal MRI (structural, diffusion, and resting-state functional MRI) profiles of community-dwelling asymptomatic adults with very early-stage WMH relative to age-, sex-, and education-matched non-WMH controls. The comparative results showed significant age-related and age-independent changes in structural MRI-based morphometric measures and resting-state fMRI-based measures in a set of specific gray matter (GM) regions but no global white matter changes. The observed structural and functional anomalies in specific GM regions in community-dwelling asymptomatic adults with very early-stage WMH provide novel data regarding very early-stage WMH and enhance understanding of the pathogenesis of WMH.