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As a crucial technique for identifying irregular samples or outlier patterns, anomaly detection has broad applications in many fields. Convex analysis (CA) is one of the fundamental methods used in anomaly detection, which contributes to the robust approximation of algebra and geometry, efficient computation to a unique global solution, and mathematical optimization for modeling. Despite the essential role and evergrowing research in CA-based anomaly detection algorithms, little work has realized a comprehensive survey of it. To fill this gap, we summarize the CA techniques used in anomaly detection and classify them into four categories of density estimation methods, matrix factorization methods, machine learning methods, and the others. The theoretical background, sub-categories of methods, typical applications as well as strengths and limitations for each category are introduced. This paper sheds light on a succinct and structured framework and provides researchers with new insights into both anomaly detection and CA. With the remarkable progress made in the techniques of big data and machine learning, CA-based anomaly detection holds great promise for more expeditious, accurate and intelligent detection capacities.

Lung squamous cell carcinoma (LUSC) remains as a major cause of cancer-associated mortality with few therapeutic options. Continued research on new driver genes is particularly important. FGF19, a fibroblast growth factor, is frequently observed as amplified in human LUSC, which is also associated with multiple genomic gains and losses. However, the importance of these associated changes is largely unknown. In this study, we aimed to clarify a novel mechanism that link neighboring oncogene co-amplification in the development of LUSC. We found that FGF19 was co-amplified and co-expressed with its neighboring gene CCND1 in a subset of LUSC patients and associated with poor prognosis. Moreover, FGF19 combined with CCND1 promoted the cell cycle progression of LUSC cells. Mechanistically, FGF19 also enhanced CCND1 expression by activating FGFR4-ERK1/2 signaling and strengthening CCND1-induced phosphorylation and inactivation of retinoblastoma (RB). In a murine model of lung orthotopic cancer, knockdown of CCND1 was found to prolong survival by attenuating FGF19-induced cell proliferation. Furthermore, the combination treatment of the FGFR4 inhibitor BLU9931 and the CDK4/6 inhibitor palbociclib potentiated the growth inhibition and arrested cells in G1 phase. In vivo, co-targeting FGFR4 and CDK4/6 also showed marked inhibition of tumor growth than single agent treatment. These findings further elucidate the oncogenic role of FGF19 in LUSC and provide insights into how the co-amplification of neighboring genes synergistically function to promote cancer growth, and combined inhibition against both FGF19 and CCND1 is more effective.

BackgroundInterstitial lung disease (ILD) is frequently observed in anti-melanoma differentiation-associated protein 5 (MDA5) antibody positive dermatomyositis (DM) and anti-synthetase syndrome (ASS), where they often develop a rapidly progressive ILD (RP-ILD) leading to poor prognosis.ObjectiveThe aim of this study was to construct multivariable prediction risk factors for rapid progressive ILD (RP-ILD) in anti-MDA5 positive DM (MDA5+DM) and ASS.Methods333 idiopathic inflammatory myopathy (IIM) associated ILD patients were studied retrospectively. Risk factors for RP-ILD in MDA5+DM and ASS patients were identified by univariate and multivariable logistic regression analysis. The mortality was assessed using Kaplan-Meier analysis.ResultsRP-ILD was more prevalent in MDA5+DM patients than ASS patients. MDA5+DM patients with RP-ILD had significantly lower survival rates than those in ASS patients. The independent risk factors for RP-ILD in MDA5+DM patients were fever (OR 3.67, 95% CI:1.79-7.52), lymphopenia (OR 2.14, 95% CI:1.01-4.53), especially decreased levels of CD3+T cells (OR 2.56, 95% CI:1.17-5.61), decreased levels of CD3+CD4+ T cells (OR 2.80, 95% CI:1.37-5.73), CD3+CD8+T cells (OR 2.18, 95% CI:1.05-4.50), elevated CD5-CD19+ B cells (OR 3.17, 95% CI:1.41-7.13), elevated ALT (OR 2.36, 95% CI:1.15-4.81), high lactate dehydrogenase (LDH) (OR 3.08, 95% CI:1.52-6.27), hyper-ferritin (OR 4.97, 95% CI:1.97-12.50), elevated CEA (OR 2.28, 95% CI:1.13-4.59), and elevated CA153 (OR 3.31, 95% CI:1.50-7.27). While the independent risk factors for RP-ILD in ASS patients were elevated CEA (OR 5.25, 95% CI: 1.73-15.93), CA125 (OR 2.79, 95% CI: 1.10-7.11) and NSE (OR 4.86, 95% CI: 1.44-16.37). Importantly, serum ferritin>2200ng/ml predicted patient’s death within half a year in MDA5+DM patients with RP-ILD, but not in ASS patients.ConclusionsThere were significant different mortality and multivariable risk factors for RP-ILD in MDA5+DM patients and ASS patients. Potential clinical benefits of using these different risk factors deserve assessment of severity and prognosis in IIM patients.

Abstract Background T cell Ig and ITIM domain (TIGIT)/CD226 pathway has a critical role in regulating T cell responses and has come to the forefront in cancer as a promising immunotherapeutic target. However, its role in autoimmune diseases is just beginning to be elucidated. Dermatomyositis (DM) is an autoimmune disease, in which T cell dysregulation plays a pivotal role, and importantly, it is a common immune-related adverse event in response to treatment of cancers with immune checkpoint inhibitors, but no studies have implicated the TIGIT/CD226 axis in DM. Methods We recruited 30 treatment-naïve DM patients and 26 healthy controls. Flow cytometry analysis was used to investigate the co-expression of TIGIT and CD226 on T cells in blood samples. Magnetic bead or FACS-based cell isolation, T cell proliferation assay, and intracellular cytokine staining were performed to analyze the functions of different TIGIT/CD226 phenotypes. Recombinant proteins CD155, CD112, and anti-CD226 antibodies were used to suppress the function of TIGIT/CD226-expressing CD4 T cells. Results Four distinct subsets of T cells based on TIGIT/CD226 co-expression, TIGIT+CD226−, TIGIT+CD226+, TIGIT−CD226+, and TIGIT−CD226−, were identified and characterized in DM patients. Our data showed that the function of CD4 T cell subset varied by the TIGIT/CD226 phenotype. An elevated TIGIT+CD226+ CD4 subset with enhanced effector function was observed in patients with DM, especially the patients complicated with interstitial lung disease. This subpopulation was closely related to DM activity and decreased significantly in DM remission after treatment. Furthermore, the effector function of TIGIT+CD226+ CD4 subset could be suppressed by blocking CD226. Conclusion Our data revealed that the TIGIT and CD226 expression profiles could be used to identify functionally distinct subsets of CD4 T cells and TIGIT+CD226+ CD4 T cells is a significant subset in DM with enhanced frequency and effector function. This abnormal subset could be suppressed by blocking CD226, providing insight into the therapeutic target of the TIGIT/CD226 axis.

Abstract Background The role of nicotinamide N-methyltransferase (NNMT) in ovarian cancer is still elusive. Our aim is to explore the expression of NNMT in ovarian cancer and to assess its association with patient prognosis and treatment response. Methods We first analyzed the differential expression of NNMT among fallopian tube epithelium, primary ovarian cancers, metastatic ovarian cancers, and recurrent ovarian cancers using Gene Expression Ominus (GEO) database (GSE10971, GSE30587, GSE44104 and TCGA datasets). Then, we assessed the association of NNMT expression with clinical and molecular parameters using CSIOVDB database and GSE28739 dataset. Next, we evaluate the association of NNMT expression with the prognosis of ovarian cancer patients in both GSE9891 dataset and TCGA dataset. Finally, GSE140082 dataset was used to explore the association of NNMT expression with bevacizumab response. Results NNMT expression was significantly elevated in lymphovascular space invasion (LVSI)-positive ovarian cancers compared with that in LVSI-negative ovarian cancers (TCGA dataset, P

While the number of highway tunnels is increasing, the current Chinese criteria and Uniform Traffic Control Equipment Manual (MUTCD) 2009 guidelines provide no clear method for setting exit advance guide signs in highway tunnels. To solve this problem, this paper proposes separate guide signs, consisting of location and distance signs. Location signs on the tops of tunnels use Chinese characters with a height of 40 cm and a width 20 cm. The distance signs are 62.6 m from the location signs with a character height and width of 1.5 m and a total sign length of 22.5 m. Four schemes were tested, in which the distance sign was on the left or right wall of the tunnel and the vehicle was in the left or right lane. At the “Perception” and “Recognition” stages, the pupil area change rate of the four schemes had a slight difference to no sign but were always less than the 20% threshold line. A Markov chain was employed to analyze the driver's eye movement characteristics to evaluate the effect of separate guide signs. The results are the following. In the left lane, when a distance sign on the left wall of the tunnel appeared, the driver's fixation points were relatively balanced, except in the left area. After the sign disappeared, the driver's fixation points were no different than before, except in the front area. However, when a distance sign appeared on the right wall, 77.84% of the driver's fixation points were concentrated in the front and right areas, which decreased the driving safety. Similar results were obtained in the right lane. Therefore, distance signs should be placed on the left wall of the highway tunnel. This study can forewarn a driver in a tunnel of the exit location and distance and help the driver to exit the highway safely.

The purpose of this article is to analyse the emotional evolution of the netizens in reaction to the events of the Anti-ELAB (Anti-Extradition Law Amendment Bill) movement in Hong Kong. We attempt to investigate evolving laws of large-scale Internet public opinion events and provide relevant agencies with a theoretical basis for a public opinion response mechanism. On the basis of improving the Bidirectional Encoder Representations from Transformers (BERT) pre-training task, we add in-depth pre-training tasks, and based on the optimisation results of the LDA topic embedding, we integrate deeply with the LDA model to dynamically present the fine-grained public sentiment of the event. Through the collection of large-scale text data related to the Anti-ELAB Movement from a well-known forum in Hong Kong, a BERT-LDA hybrid model for large-scale network public opinion analysis is constructed in a complex context. Through empirical analysis, we calculate and reveal the emotional change process of netizens and opinion leaders in the three transition stages of the Anti-ELAB Movement with the evolution of the topic word as the core by visualisation. We also analyse the emotional distribution and evolution trend of public opinion under the `text topic', and deeply analyse the character and role of opinion leaders in Anti-ELAB public opinion events. The improved BERT-LDA model or sentiment classification AUC value exceeds 99.6% in the sentiment classification task for the Anti-ELAB Movement.

In machine learning, observation features are measured in a metric space to obtain their distance function for optimization. Given similar features that are statistically sufficient as a population, a statistical distance between two probability distributions can be calculated for more precise learning. Provided the observed features are multi-valued, the statistical distance function is still efficient. However, due to its scalar output, it cannot be applied to represent detailed distances between feature elements. To resolve this problem, this paper extends the traditional statistical distance to a matrix form, called a statistical distance matrix. The proposed approach performs well in object recognition tasks and clearly and intuitively represents the dissimilarities between cat and dog images in the CIFAR dataset, even when directly calculated using the image pixels. By using the hierarchical clustering of the statistical distance matrix, the image pixels can be separated into several clusters that are geometrically arranged around a center like a Mandala pattern. The statistical distance matrix with clustering is called the Information Mandala.

AbstractBackground Studies have demonstrated the diagnostic efficiency of antibody testing in COVID-19 infection. There is limited data on the IgM/IgG changes in asymptomatic and discharged patients with reoccurring positive nucleic acid test (RPNAT). This study aims to investigate these IgM/IgG changes.Methods There were 111 patients with positive nucleic acid test (NAT) and 40 suspected patients enrolled in the study. The serum SARS-CoV-2 specific IgM/IgG antibody levels were retrospectively analysed with the disease progress in asymptomatic and RPNAT patients.Results The best overall performance was found by combining the IgM, IgG, and CT; 95.1% sensitivity and 75% specificity. This was tested in 111 RT-PCR positive cases. The median IgM and IgG levels were lower in the asymptomatic group compared to the symptomatic group (p

Abstract Background Understanding the geographic distribution of hidden population, such as men who have sex with men (MSM), sex workers, or injecting drug users, are of great importance for the adequate deployment of intervention strategies and public health decision making. However, due to the hard-to-access properties, e.g., lack of a sampling frame, sensitivity issue, reporting error, etc., traditional survey methods are largely limited when studying such populations. With data extracted from the very active online community of MSM in China, in this study we adopt and develop location inferring methods to achieve a high-resolution mapping of users in this community at national level. Methods We collect a comprehensive dataset from the largest sub-community related to MSM topics in Baidu Tieba, covering 628,360 MSM-related users. Based on users’ publicly available posts, we evaluate and compare the performances of mainstream location inference algorithms on the online locating problem of Chinese MSM population. To improve the inference accuracy, other approaches in natural language processing are introduced into the location extraction, such as context analysis and pattern recognition. In addition, we develop a hybrid voting algorithm (HVA-LI) by allowing different approaches to vote to determine the best inference results, which guarantees a more effective way on location inference for hidden population. Results By comparing the performances of popular inference algorithms, we find that the classic gazetteer-based algorithm has achieved better results. And in the HVA-LI algorithms, the hybrid algorithm consisting of the simple gazetteer-based method and named entity recognition (NER) is proven to be the best to deal with inferring users’ locations disclosed in short texts on online communities, improving the inferring accuracy from 50.3 to 71.3% on the MSM-related dataset. Conclusions In this study, we have explored the possibility of location inferring by analyzing textual content posted by online users. A more effective hybrid algorithm, i.e., the Gazetteer & NER algorithm is proposed, which is conducive to overcoming the sparse location labeling problem in user profiles, and can be extended to the inference of geo-statistics for other hidden populations.

The Devon Ice Cap (DIC) is one of the largest ice masses in the Canadian Arctic. Each summer, extensive supraglacial river networks develop on the DIC surface and route large volumes of meltwater from ice caps to the ocean. Mapping their extent and understanding their temporal evolution are important for validating runoff routing and melt volumes predicted by regional climate models (RCMs). We use 10 m Sentinel-2 images captured on 28 July and 10/11 August 2016 to map supraglacial rivers across the entire DIC (12,100 km2). Both dendritic and parallel supraglacial drainage patterns are found, with a total length of 44,941 km and a mean drainage density (Dd) of 3.71 km−1. As the melt season progresses, Dd increases and supraglacial rivers form at progressively higher elevations. There is a positive correlation between RCM-derived surface runoff and satellite-mapped Dd, suggesting that supraglacial drainage density is primarily controlled by surface runoff.

Background. Quinolones are commonly used for reducing the duration of diarrhea, infection severity, and limiting further transmission of disease related to Vibrio cholerae, but V. cholerae susceptibility to quinolone decreases over time. In addition to mutations in the quinolone-resistance determining regions (QRDRs), the presence of qnr and other acquired genes also contributes to quinolone resistance. Results. We determined the prevalence of quinolone resistance related genes among V. cholerae O139 strains isolated in China. We determined that eight strains carried qnrVC, which encodes a pentapeptide repeat protein of the Qnr subfamily, the members of which protect topoisomerases from quinolone action. Four qnrVC alleles were detected: qnrVC1, qnrVC5, qnrVC12, and qnrVC9. However, the strains carrying qnrVC1, qnrVC5, and qnrVC12 were ciprofloxacin (CIP)-sensitive. Contrastingly, the strain carrying qnrVC9 demonstrated high CIP resistance. qnrVC9 was carried by a small plasmid, which was conjugative and contributed to the high CIP resistance to the receptor V. cholerae strain. The same plasmid was also detected in V. vulnificus. The qnrVC1, qnrVC5, and qnrVC12 were cloned into expression plasmids and conferred CIP resistance on the host V. cholerae O139 strain. Conclusions. Our results revealed the contribution of quinolone resistance mediated by the qnrVC9 carried on the small plasmid and its active horizontal transfer among Vibrio species. The results also suggested the different effects of qnrVC alleles in different V. cholerae strains, which is possibly due to differences in sequences of qnrVC alleles and even the genetic characteristics of the host strains.

Objective: To detect the prevalence and characterize of Cryptosporidium spp., Giardia (G.) duodenalis, Enterocytozoon (E.) bieneusi and Blastocystis sp. of animals at a tropical wildlife park in Hainan Province, China, and to assess zoonotic risks and the potential threat of public health. Methods: Fecal specimens were collected from animals of 27 species at the wildlife park in Hainan Province, China, and detected these pathogens using polymerase chain reaction (PCR) amplifications and sequencing of gene fragments based on small subunit ribosomal RNA (SSU rRNA) gene, glutamate dehydrogenase (GDH), internal transcribed spacer (ITS) and SSU rRNA gene, respectively. Results: A total of 99 animals were studied, and 33 (33.3%) animals were found to harbor intestinal parasite, and the prevalence of Cryptosporidium spp., G. duodenalis, E. bieneusi and Blastocystis sp. were 9.1%, 2.0%, 5.1%, and 25.3%, respectively. Five Cryptosporidium species (C. parvum, C. ubiquitum, C. scrofarum, C. xiaoi and C. parvum-like), one G. duodenalis assemblages (E), four E. bieneusi ITS genotypes (CM1, HLJD-I, HNR-III and 1 novel genotype HNED-III) were detected, and seven subtypes of Blastocystis sp. (ST1, ST2, ST3, ST5, ST10, ST14 and ST15) were also identified. Conclusions: This is the first molecular detection and public health risk assessment of four intestinal protozoa species in Hainan Tropical Wildlife Park and Botanical Garden, China. Almost all species/genotypes/subtypes of four intestinal protozoa identified in this study have the potential of zoonosis and may cause public health risks.

Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan–Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16– group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20–0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07–0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression.

Meat quality has a close relationship with fat and connective tissue; therefore, screening and identifying functional genes related to lipid metabolism is essential for the production of high-grade beef. The transcriptomes of the Longissimus dorsi muscle in Wagyu and Chinese Red Steppe cattle, breeds with significant differences in meat quality and intramuscular fat deposition, were analyzed using RNA-seq to screen for candidate genes associated with beef quality traits. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the 388 differentially expressed genes (DEGs) were involved in biological processes such as short-chain fatty acid metabolism, regulation of fatty acid transport and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In addition, crystallin alpha B (CRYAB), ankyrin repeat domain 2 (ANKRD2), aldehyde dehydrogenase 9 family member A1 (ALDH9A1) and enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH) were investigated for their effects on intracellular triglyceride and fatty acid content and their regulatory effects on genes in lipogenesis and fatty acid metabolism pathways. This study generated a dataset from transcriptome profiling of two cattle breeds, with differing capacities for fat-deposition in the muscle, and revealed molecular evidence that CRYAB, ANKRD2, ALDH9A1 and EHHADH are related to fat metabolism in bovine fetal fibroblasts (BFFs). The results provide potential functional genes for maker-assisted selection and molecular breeding to improve meat quality traits in beef cattle.

Objective: This study aimed to explore the predictive value of the Injury Severity Score (ISS), Trauma Index (TI) and different types of shock indices (SI) on the early mortality risk of acute trauma patients. Methods: Clinical data of acute trauma patients who met the inclusion and exclusion criteria of this study and were treated in the hospital from January 2020 to December 2020 were retrospectively collected, including gender, age, trauma mechanism, severe injury site, ISS, TI, admission vital signs, different types of shock indices (SI), death within 7 days, length of hospital stay, and Glasgow Outcome Score (GOS). The predictive value of the Injury Severity Score, Trauma Index, and different types of shock indices on the risk of early mortality in patients with acute trauma were compared using relevant statistical methods. Results: A total of 283 acute trauma patients (mean age 54.0 ± 17.9 years, 30.74% female) were included, and 43 (15.19%) of the patients died during 7 days of hospitalization. The admission ISS, TI, SI, MSI, and ASI in the survival group were significantly lower than those in the death group, and the difference was statistically significant (p < 0.05). Meanwhile, different trauma assessment tools included in the study have certain predictive value for early mortality risk of trauma patients. Conclusions: The TI indicates a better capability to predict the risk of early death in patients with acute trauma. As the most sensitive predictor, the SI has the greatest reference value in predicting the risk of early death in patients with traumatic shock.

We report new dirhamnolipid ester forming reverse wormlike micelles in nonpolar solvents without the addition of any primer. Therefore, these compounds represent a rare case of a binary system showing this gel-like behavior. In this study, the influence of the concentration of the rhamnolipid ester and the ester alkyl chain length on the rheological properties of the reverse wormlike micelles in toluene was investigated in detail. Highly viscoelastic solutions were obtained even at a relatively low concentration of less than 1 wt %. The phase transition temperatures indicate that the formation of reverse wormlike micelles is favored for dirhamnolipid esters with shorter alkyl chain lengths. Oscillatory shear measurements for the viscoelastic samples reveal that the storage modulus (G') and the loss modulus (G'') cross each other and fit the Maxwell model very well in the low-ω region. As is typical for wormlike micelle systems, the normalized Cole–Cole plot of G''/G''max against G'/G''max was obtained as a semicircle centered at G'/G''max = 1. The formation of network structures was also verified by polarized light microscopy. The sample was birefringent at ambient temperature and anisotropic at an elevated temperature. Differential scanning calorimetry analysis yielded a transition enthalpy of about ΔHSG/GS = ±7.2 kJ/mol. This value corresponds to a strong dispersion energy and explains the formation of the highly viscous gels by the entanglement of wormlike micelles through the interaction of the alkyl chains.

Metastatic dissemination in breast cancer patients occurs early in malignant transformation, raising questions about how disseminated cancer cells (DCC) progress at distant sites. Here, the authors show that DCCs in bone marrow are activated via IL6-trans-signaling and thereby acquire stemness traits relevant for metastasis formation.

Abstract Background Serum lipids were reported to be the prognostic factors of various cancers, but their prognostic value in malignant biliary tumor (MBT) patients remains unclear. Thus we aim to assess and compare prognosis values of different serum lipids, and construct a novel prognostic nomogram based on serum lipids. Methods Patients with a confirmed diagnosis of MBT at our institute from 2003 to 2017 were retrospectively reviewed. Prognosis-related factors were identified via univariate and multivariate Cox regression analyses. Then the novel prognostic nomogram and a 3-tier staging system were constructed based on these factors and further compared to the TNM staging system. Results A total of 368 patients were included in this study. Seven optimal survival-related factors—TC/HDL > 10.08, apolipoprotein B > 0.9 g/L, lipoprotein> 72 mg/L, lymph node metastasis, radical cure, CA199 > 37 U/mL, and tumor differentiation —were included to construct the prognostic nomogram. The C-indexes in training and validation sets were 0.738 and 0.721, respectively. Besides, ROC curves, calibration plots, and decision curve analysis all suggested favorable discrimination and predictive ability. The nomogram also performed better predictive ability than the TNM system and nomogram without lipid parameters. And the staging system based on nomogram also presented better discriminative ability than TNM system (P

When biomaterials are implanted in the human body, the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation, causing peri-implant infection which frequently results in the failure of prosthetics and revision surgery. Ti–Mo alloy is one of the commonly used implant materials for load-bearing bone replacement, and the prevention of infection of Ti–Mo implants is therefore crucial. In this study, bacterial inhibitory copper (Cu) was added to Ti–Mo matrix to develop a novel Ti–Mo–Cu alloy with bacterial inhibitory property. The effects of Cu content on microstructure, tensile properties, cytocompatibility, and bacterial inhibitory ability of Ti–Mo–Cu alloy were systematically investigated. Results revealed that Ti–10Mo–1Cu alloy consisted of α and β phases, while there were a few Ti2Cu intermetallic compounds existed for Ti–10Mo–3Cu and Ti–10Mo–5Cu alloys, in addition to α and β phases. The tensile strength of Ti–10Mo-xCu alloy increased with Cu content while elongation decreased. Ti–10Mo–3Cu alloy exhibited an optimal tensile strength of 1098.1 MPa and elongation of 5.2%. Cytocompatibility study indicated that none of the Ti–10Mo-xCu alloys had a negative effect on MC3T3-E1 cell proliferation. Bacterial inhibitory rates against S. aureus and E. coli increased with the increase in Cu content of Ti–10Mo-xCu alloy, within the ranges of 20–60% and 15–50%, respectively. Taken together, this study suggests that Ti–10Mo–3Cu alloy with high strength, acceptable elongation, excellent cytocompatibility, and the bacterial inhibitory property is a promising candidate for biomedical implant applications.

The rice mutant ossac4 (starch accumulating 4) was raised from seeds of the rice (Oryza sativa L.) indica maintainer line Xinong 1B treated with ethyl methanesulfonate. The distal and medial portions of the second leaf displayed premature senescence in the ossac4 mutant at the four-leaf stage. Physiological and biochemical analysis, and cytological examination revealed that the ossac4 mutant exhibited the premature leaf senescence phenotype. At the four-leaf stage, the leaves of the ossac4 mutant exhibited significantly increased contents of starch compared with those of the wild type (WT). Quantitative real-time PCR analysis showed that the expression levels of photosynthesis-associated genes were down-regulated and the expression levels of glucose metabolism-associated genes were abnormal. Genetic analysis indicated that the ossac4 mutation was controlled by a single recessive nuclear gene. The OsSAC4 gene was localized to a 322.7-kb interval between the simple-sequence repeat marker XYH11-90 and the single-nucleotide polymorphism marker SNP5300 on chromosome 11. The target interval contained 20 annotated genes. The present results demonstrated that ossac4 represents a novel starch accumulation and premature leaf senescence mutant, and lays the foundation for cloning and functional analysis of OsSAC4.

Abstract Objective To assess the anti-tumor activity and side effects of different dosages of paclitaxel (albumin binding type) (hereinafter referred to as nab-P) combined with Apatinib (hereinafter referred to as AP) in platinum-resistant ovarian cancer cell line and xenograft models. Methods SKOV-3/DDP cell line was selected as the research object in cytology experiment. Firstly, we divided it into three groups for experiments to explore the individual effects of nab-P and AP. a): Control group, blank control, no drug intervention; b): nab-P group, nab-P 40 μmol/l; c): AP group, AP 50 μmol/l (Drug doses were IC-50 values that detected by MTT assay). Apoptosis related protein (Bax, bcl-2), vascular related protein(p-VEGFR-2), invasion related protein (MMP-2) expression were detected by Western blot and Cellular immunofluorescence, the invasion ability of tumor cells were detected by Transwell and Cell scratch test. Based on these dates, secondly, establishing different doses of nab-P combined with Ap to explore the curative effect of combination therapy. a): Control group, blank control, no drug intervention; b): Group-1, nab-P 5 μmol/l + AP 10 μmol/l, c): Group-2, nab-P 4.5 μmol/l + AP 10 μmol/l, d): Group-3, nab-P 4 μmol/l + AP 10 μmol/l, e): nab-P group, nab-P 5 μmol/l, f): AP group, AP 10 μmol/l (MTT assay). The combination index was analyzed by Compusyn software, Western blot, Immunofluescence, Transwell and Cell scratch test also were also chose to observe of inhibition effect. Thirdly, we used xenograft models to verify the results of cytological experiments. Tumor-forming BALB/c female nude mice were randomly divided into 4 groups, a): Control group, no drug intervention, only saline injection, b): nab-P 20 mg/kg + AP 150 mg/kg, c): nab-P 18 mg/kg + AP 150 mg/kg, d): nab-P 16 mg/kg + AP 150 mg/kg (The doses were guided by the pharmaceutical manufacturers). The tumor growth curve was analyzed during the experiment. And the apoptosis related protein (Bax, bcl-2), angiogenesis related protein (CD31, p-VEGFR-2) and invasion related protein (MMP-2) were observed by Western blot, Immunofluescence and Immunohistochemistry to analysis the ant-tumor effects. The quality of life in nude mice were observed to analysed the drug-induced side effects. Result In the separate medication section, (1) The IC-50 value of nab-P was 45.53 ± 4.06 μmol/l, while the AP was 50.66 ± 4.96 umol/L (48 h). (2) The expressions of bcl-2 (nab-P group, AP group), p-VEGFR-2 (AP group), MMP-2(nab-P group, AP group) were higher than Control group, while Bax (nab-P group, AP group) lower (P

In this study, corrosion, wear, and tribocorrosion of Ti-16Mo alloy manufactured by powder metallurgy (PM) in phosphate-buffered saline are investigated. The results indicate that the corrosion rate of Ti-16Mo alloy increases about 100 times from 0.00009 mm/yr to 0.00851 mm/yr under the tribocorrosion condition. Also, corrosion accelerates wear loss, and wear increment rate due to the corrosion (4.7715 mm/yr) of Ti-16Mo alloy is about 40% of pure mechanical wear rate (11.78 mm/yr). Compared with as-cast pure Ti (23.70999 mm/yr) and Ti-6Al-4 V (17.12003 mm/yr), Ti-16Mo alloy exhibits the lowest materials loss of 16.56001 mm/yr making it become a promising alloy for bone-tissue applications.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with increasing incidence in the last decades. Microvascular invasion (MVI) is a poor prognostic factor for patients with ICC, which correlates early recurrence and poor prognosis, and it can affect the selection of personalized therapeutic regime.PurposeThis study aimed to develop and validate a radiomics-based nomogram for predicting MVI in ICC patients preoperatively.MethodsA total of 163 pathologically confirmed ICC patients (training cohort: n = 130; validation cohort: n = 33) with postoperative Ga-DTPA-enhanced MR examination were enrolled, and a time-independent test cohort (n = 24) was collected for external validation. Univariate and multivariate analyses were used to determine the independent predictors of MVI status, which were then incorporated into the MVI prediction nomogram. Least absolute shrinkage and selection operator logistic regression was performed to select optimal features and construct radiomics models. The prediction performances of models were assessed by receiver operating characteristic (ROC) curve analysis. The performance of the MVI prediction nomogram was evaluated by its calibration, discrimination, and clinical utility.ResultsLarger tumor size (p = 0.003) and intrahepatic duct dilatation (p = 0.002) are independent predictors of MVI. The final radiomics model shows desirable and stable prediction performance in the training cohort (AUC = 0.950), validation cohort (AUC = 0.883), and test cohort (AUC = 0.812). The MVI prediction nomogram incorporates tumor size, intrahepatic duct dilatation, and the final radiomics model and achieves excellent predictive efficacy in training cohort (AUC = 0.953), validation cohort (AUC = 0.861), and test cohort (AUC = 0.819), fitting well in calibration curves (p > 0.05). Decision curve and clinical impact curve further confirm the clinical usefulness of the nomogram.ConclusionThe nomogram incorporating tumor size, intrahepatic duct dilatation, and the final radiomics model is a potential biomarker for preoperative prediction of the MVI status in ICC patients.

BackgroundChemotherapy generally causes serious diarrhea and oral mucositis in cancer patients, and subsequently affects treatment. Oral administration of probiotics provides a therapeutic choice to address these limitations. This study aims to conduct a systematic review and meta-analysis on the efficacy of oral probiotic use in the management of the chemotherapy-induced adverse reactions, and to summarize the mechanisms underlying the action.MethodsWe searched PubMed, Embase, ClinicalTrials.gov, and Web of Science from the start of the study to its completion on Dec. 31, 2021. Risk of bias was assessed using Cochrane Collaboration's Tool. Statistical analysis of the acquired data was performed via the RevMan and the Stata Statistical Software. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO registration number: CRD42020220650).ResultsTwelve randomized controlled trials including 1,013 patients were recruited and analyzed via the standard procedure of meta-analysis. In contrast to the control group, orally taking probiotics significantly decreased the risk of chemotherapy-induced diarrhea (≥ 1 grade) (RR = 0.70; 95% Cl: 0.56, 0.88; P = 0.002) and oral mucositis (≥ 1 grade) (RR: 0.84; 95% Cl: 0.78, 0.91; P < 0.00001) at all grades. Further analysis found that severe diarrhea (≥ 2 grades) (RR: 0.50; 95% Cl: 0.32, 0.78; P = 0.002) and severe oral mucositis also significantly declined (≥ 3 grades) (RR: 0.66; 95% Cl: 0.55, 0.79; P < 0.00001) after oral probiotic use. Interestingly, the beneficial effects of probiotics displayed statistically significant only in Asian patients. Importantly, the more species of bacteria they took, the lower the incidences of the adverse reactions occurred. We used Egger's test P value to confirm that there is no publication bias.ConclusionsThis meta-analysis demonstrated that orally administrated probiotics has a potential to decrease chemotherapy-induced diarrhea and oral mucositis incidences. However, the efficacy of oral probiotic use against the adverse reactions needs to be further verified through more clinical trials, and the species and number of probiotics have to be optimized and standardized prior to clinical applications.Systematic Review Registrationhttps://www.crd.york.ac.uk, identifier: 220650.

To study the influencing factors of liquid droplets on the cleaning effects of the scale layer, a three-dimensional droplet-impacting-a-blade model is constructed. The finite volume method and the volume of fluid method are used to numerically study the dynamic characteristics of a droplet impacting the fouling layer of a blade. The results show that under certain conditions, increased velocity and diameter of the droplet lead to an increase in the impact force of the droplet, and the greater the curvature of the blade surface, the smaller the vertical impact force of the droplet; likewise, the greater the impact force on cutting, the larger the corresponding spreading coefficient. The impact of liquid on the surface of the blade reduces the peak value of the droplet impact force. Finally, the increase in droplet diameter and velocity will improve the cleaning effect of the jet droplet. The larger the blade surface curvature, the wider the droplet cleaning area will be.

Immune-mediated necrotizing myopathy (IMNM) is characterized by manifestation of myonecrosis and regeneration of muscle fibers; however, the underlying pathogenesis remains unclear. This study aimed to investigate the role and mechanism of miR-18a-3p and its target RNA-binding protein HuR in IMNM. HuR and miR-18a-3p levels were detected in the skeletal muscles of 18 patients with IMNM using quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR) and western blotting analysis. Human myoblasts were transfected with small interfering RNA targeting HuR and miR-18a-3p mimic or inhibitor. Myogenic differentiation markers, myogenin and myosin heavy chain, were analyzed by qRT-PCR, western blotting analysis, and immunofluorescence staining. The results showed that miR-18a-3p was upregulated (p=0.0002), whereas HuR was downregulated (p=0.002) in the skeletal muscles of patients with IMNM. The expression of miR-18a-3p in patients with IMNM was negatively correlated with those of HuR (r = -0.512, p = 0.029). We also found that disease activity was positively correlated with HuR expression (r = 0.576, p = 0.012) but muscle activity was negatively correlated with miR-18a-3p expression (r = -0.550, p = 0.017). Besides, bioinformatics analysis and dual-luciferase reporter assays suggested that miR-18a-3p could directly target HuR. Cellular experiments showed that overexpression of miR-18a-3p inhibited myogenic differentiation by targeting HuR, whereas inhibition of miR-18a-3p led to opposite results. Therefore, miR-18a-3p and its target protein HuR may be responsible for modulating the myogenic process in IMNM and can thus be therapeutic targets for the same.

Acyl-CoA synthetase family member 3 (ACSF3) carries out the first step of mitochondrial fatty acid synthesis II, which is the linkage of malonate and, to a lesser extent, methylmalonate onto CoA. Malonyl-coenzyme A (malonyl-CoA) is a central metabolite in mammalian fatty acid biochemistry that is generated and utilized in the cytoplasm. In this research, we verified the relationship between expression of the ACSF3 and the production of triglycerides (TGs) at the cellular level by silencing and over-expressing ACSF3. Subsequently, through Sanger sequencing, five polymorphisms were found in the functional domain of the bovine ACSF3, and the relationship between ACSF3 polymorphism and the economic traits and fatty acid composition of Chinese Simmental cattle was analyzed by a means of variance analysis and multiple comparison. The results illustrated that the expression of ACSF3 promoted triglyceride synthesis in bovine mammary epithelial cells and bovine fetal fibroblast cells. Further association analysis also indicated that individuals with the AG genotype (g.14211090 G > A) of ACSF3 were significantly associated with the fatty acid composition of intramuscular fat (higher content of linoleic acid, α-linolenic acid, and arachidonic acid), and that CTCAG haplotype individuals were significantly related to the fatty acid composition of intramuscular fat (higher linoleic acid content). Individuals with the AA genotypes of g.14211055 A > G and g.14211090 G > A were substantially associated with a larger eye muscle area in the Chinese Simmental cattle population. ACSF3 played a pivotal role in the regulation of cellular triacylglycerol and long-chain polyunsaturated fatty acid levels, and polymorphism could serve as a useful molecular marker for future marker-assisted selection in the breeding of intramuscular fat deposition traits in beef cattle.

Huangjiu is a national alcoholic beverage in China. Millet has congenital advantages in development and utilization of nutrient. Brewing Huangjiu with millet can increase the value of millet. Microbial community plays crucial roles in millet Huangjiu fermentation. Flavor compounds reflect the quality and health function of Huangjiu. The flavor compounds of Huangjiu are complex and their formation is closely associated with microorganisms, but the relationship between them during fermentation has been unknown. In this research, this relationship during millet Huangjiu fermentation were deeply investigated. Totally 86 volatile compounds were detected. Bacillus, Weissella, Paenibacillus, Klebsiella, Prevotella was investigated as the dominant microbes through high-throughput sequencing. 537 correlations between major flavor compounds and microbes were established to reflect the dynamic change during millet Huangjiu fermentation. The top five dominant genus of flavor producing microbes were Chryseobacterium, Sporolactobacillus, Psychrobacter, Sphingobium and Anoxybacillus. The content of malic acid and citric acid was gradually improved all through the millet Huangjiu fermentation. Malic acid and citric acid generated from millet Huangjiu fermentation shows healthy properties as liver protection and eliminating fatigue. Our research provides essential information on microbial community succession and the flavor formation during millet Huangjiu fermentation, and beneficial for development of Huangjiu products.

Background: The measurement and identification of changes in the social structure in response to an exceptional event like COVID-19 can facilitate a more informed public response to the pandemic and provide fundamental insights on how collective social processes respond to extreme events.Objective: In this study, we built a generalized framework for applying social media data to understand public behavioral and emotional changes in response to COVID-19.Methods: Utilizing a complete dataset of Sina Weibo posts published by users in Wuhan from December 2019 to March 2020, we constructed a time-varying social network of 3.5 million users. In combination with community detection, text analysis, and sentiment analysis, we comprehensively analyzed the evolution of the social network structure, as well as the behavioral and emotional changes across four main stages of Wuhan's experience with the epidemic.Results: The empirical results indicate that almost all network indicators related to the network's size and the frequency of social interactions increased during the outbreak. The number of unique recipients, average degree, and transitivity increased by 24, 23, and 19% during the severe stage than before the outbreak, respectively. Additionally, the similarity of topics discussed on Weibo increased during the local peak of the epidemic. Most people began discussing the epidemic instead of the more varied cultural topics that dominated early conversations. The number of communities focused on COVID-19 increased by nearly 40 percent of the total number of communities. Finally, we find a statistically significant “rebound effect” by exploring the emotional content of the users' posts through paired sample t-test (P = 0.003).Conclusions: Following the evolution of the network and community structure can explain how collective social processes changed during the pandemic. These results can provide data-driven insights into the development of public attention during extreme events.

ObjectiveThis study aimed to analyze the clinical features of anti-PM/Scl antibodies in Chinese patients.MethodWe reviewed the clinical data of anti-PM/Scl antibody-positive patients, including their long-term follow-up.ResultsA total of 30 patients carried anti-PM/Scl antibodies, 21 (70%) were females, and the mean age was 55.4 years, 15 (50%) and 10 (33.3%) patients were positive for anti-PM/Scl-75 and anti-PM/Scl-100, respectively. Fifteen cases (50%) were diagnosed as inflammatory myopathy, namely, 11 dermatomyositis (DM) and 4 polymyositis (PM). Five (16.7%) patients were diagnosed with overlap syndrome, and only one (3.3%) was diagnosed as systemic sclerosis. The other 9 (30%) patients were classified as undifferentiated connective tissue disease. Twenty-six (86.7%) had interstitial lung disease (ILD) and was the sole manifestation in 8 (26.7%) patients, 15 (58.0%) showed non-specific interstitial pneumonia based on high-resolution CT or lung biopsy. The majority of patients (95%) with mild and moderate groups on basis of pulmonary function tests. Compared to the anti-PM/Scl-100 group, the occurrence of clinical characteristics was not significantly different from the anti-PM/Scl-75 group, except the levels of C-reactive protein and erythrocyte sedimentation rate in the anti-PM/Scl-75 antibody-positive group were higher (p < 0.05). All patients with positive Ro-52 antibodies had ILD and were more likely to develop skin rash in the group with Ro-52 (p = 0.024). With a follow-up of the present cohort, 70.8% improved with treatment, but 16.7% of patients are easy to relapse.ConclusionThe anti-PM/Scl antibody occurred frequently in DM/PM patients, ILD was the major clinical feature, especially in patients combined with Ro-52. Some patients may complicate with ILD alone without extrapulmonary manifestations. Anti-PM/Scl antibodies positive patients were responsive to treatment.

Sex differences in immune responses had been reported to correlate with different symptoms and mortality in the disease course of coronavirus disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection interferes with females’ fertility and causes different symptoms among pregnant and non-pregnant females remains unknown. Here, we examined the differences in viral loads, SARS-CoV-2-specific antibody titers, proinflammatory cytokines, and levels of T cell activation after SARS-CoV-2 sub-lethal infection between pregnant and non-pregnant human Angiotensin-Converting Enzyme II (ACE2) transgenic mouse models. Both mice showed elevated levels of viral loads in the lung at 4 days post-infection (dpi). However, viral loads in the pregnant group remained elevated at 7 dpi while decreased in the non-pregnant group. Consistent with viral loads, increased production of proinflammatory cytokines was detected from the pregnant group, and the IgM or SARS-CoV-2-specific IgG antibody in serum of pregnant mice featured delayed elevation compared with non-pregnant mice. Moreover, by accessing kinetics of activation marker expression of peripheral T cells after infection, a lower level of CD8+ T cell activation was observed in pregnant mice, further demonstrating the difference of immune-response between pregnant and non-pregnant mice. Although vertical transmission did not occur as SARS-CoV-2 RNA was absent in the uterus and fetus from the infected pregnant mice, a lower pregnancy rate was observed when the mice were infected before embryo implantation after mating, indicating that SARS-CoV-2 infection may interfere with mice’s fertility at a specific time window. In summary, pregnant mice bear a weaker ability to eliminate the SARS-CoV-2 virus than non-pregnant mice, which was correlated with lower levels of antibody production and T cell activation.

Objective. The present study investigated the clinical efficacy of percutaneous kyphoplasty (PKP) combined with calcitriol and calcium in the treatment of traumatic nonosteoporotic vertebral compression fractures (TNVCFs). Methods. The patients were equally divided into a control group and a treatment group by a random number table. The patients in the control group underwent PKP surgery, and the patients in the treatment group received calcitriol and calcium on the basis of PKP surgery. The visual analog scale (VAS) pain scores, Oswestry Disability Index (ODI) scores, the height of the anterior edge of the vertebral body, Cobb’s angle, and the level of the bone mineral density of the two groups of TNVCF patients before surgery were recorded and compared, one and six months after surgery. Results. Thirty-six inpatients with TNVCFs admitted to the trauma center of the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were recruited. There were no significant differences in the VAS and ODI scores, the height of the anterior edge of the injured vertebral body, Cobb’s angle, and bone mineral density between the two groups before surgery (P>0.05). The VAS scores, ODI scores, the height of the anterior edge of the injured vertebral body, and Cobb’s angle of the two groups of patients after surgery were significantly better than those before surgery. One and six months after surgery, the VAS and ODI scores, the height of the anterior edge of the injured vertebral body, Cobb’s angle, and the bone mineral density of the patients in the treatment group improved significantly compared to those in the control group (P

Exploring the spatiotemporal variation in vegetation net primary productivity (NPP) and evaluating the impact of different drivers on NPP are vital for vegetation protection and restoration in Guizhou Province, which is a typical karst area in China. In this study, Cox–Stuart test, linear regression and spatial statistics were used to analyze the spatiotemporal variation in vegetation NPP in Guizhou. Random Forest combined with local spatial autocorrelation analysis was applied to quantify the effects of eight drivers from climate, topography, human activities and vegetation growth status on the NPP from different clusters in different years based on the NPP product from the Global Production Efficiency Model (GLO-PEM). The following results were obtained. (1) The average annual NPP in Guizhou during 2000–2010 showed no significant increasing or decreasing trend. (2) The annual mean NPP in the west was the lowest in the period, but the NPP per year had a rising tendency in the west and a declining one in the east from 2000 to 2010. (3) The NPP in Guizhou showed a significant clustering trend across each year in the period, whereas the clustering degree reflected a downward trend over time. The statistically significant clusters of high values (HH) and clusters of low values (LL) of NPP were mainly distributed in the east and west, respectively, in 2000, 2005 and 2010. (4) The accuracy of the driver analysis of the three NPP cluster types combined (HH + LL, HL + LH, and HH + HL + LH + LL) was higher than that of the other cluster types in Guizhou in 2000, 2005 and 2010. Vegetation growth and human activities show greater effect on the NPP of the three combined types than climate and topography. These findings are valuable in refining the results of the driver analysis and improving their accuracy. This study provides a deeper insight into the effect of different drivers on the NPP from different spatial clusters in Guizhou. Our results indicate that implementing appropriate silvicultural measures and formulating effective management policies are essential to improve the NPP and reduce the adverse effects of human activities on NPP in Guizhou.

Abstract Background Tea plant is one of the most important non-alcoholic beverage crops worldwide. While potassium (K+) is an essential macronutrient and greatly affects the growth and development of plants, the molecular mechanism underlying K+ uptake and transport in tea plant root, especially under limited-K+ conditions, is still poorly understood. In plants, HAK/KUP/KT family members play a crucial role in K+ acquisition and translocation, growth and development, and response to stresses. Nevertheless, the biological functions of these genes in tea plant are still in mystery, especially their roles in K+ uptake and stress responses. Results In this study, a total of 21 non-redundant HAK/KUP/KT genes (designated as CsHAKs) were identified in tea plant. Phylogenetic and structural analysis classified the CsHAKs into four clusters (I, II, III, IV), containing 4, 8, 4 and 5 genes, respectively. Three major categories of cis-acting elements were found in the promoter regions of CsHAKs. Tissue-specific expression analysis indicated extremely low expression levels in various tissues of cluster I CsHAKs with the exception of a high root expression of CsHAK4 and CsHAK5, a constitutive expression of clusters II and III CsHAKs, and a moderate cluster IV CsHAKs expression. Remarkably, the transcript levels of CsHAKs in roots were significantly induced or suppressed after exposure to K+ deficiency, salt and drought stresses, and phytohormones treatments. Also notably, CsHAK7 was highly expressed in all tissues and was further induced under various stress conditions. Therefore, functional characterization of CsHAK7 was performed, and the results demostrated that CsHAK7 locates on plasma membrane and plays a key role in K+ transport in yeast. Taken together, the results provide promising candidate CsHAKs for further functional studies and contribute to the molecular breeding for new tea plants varieties with highly efficient utilization of K+. Conclusion This study demonstrated the first genome-wide analysis of CsHAK family genes of tea plant and provides a foundation for understanding the classification and functions of the CsHAKs in tea plants.

Abstract Background Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. DTI was applied to assess fiber in liver disorders in previous studies. However, the data obtained have been insufficient in determining if DTI can be used to exactly stage chronic hepatitis. This study assessed the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A) and steatosis (S) with chronic hepatitis in rats. Methods Seventy male Sprague-Dawley rats were divided into a control group(n = 10) and an experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All of the rats underwent 3.0 T MRI. Regions of interest (ROIs) were subjected to DTI to estimate the MR parameters (rADC value and FA value). Histopathology was used as the reference standard. Multiple linear regression was used to analyze the associations between the MR parameters and pathology. The differences in the MR parameters among the pathological stages were evaluated by MANOVA or ANOVA. The LSD test was used to test for differences between each pair of groups. ROC analysis was also performed. Results The count of each pathology was as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r = − 0.392, P = 0.008) and inflammation (r = − 0.359, P = 0.015). The FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in the FA values between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). The AUC of the FA value differentiating F4 from F0 ~ F3 was 0.909 (p

Abstract Myeloid‐derived suppressor cells with polymorphonuclear morphology (PMN‐MDSCs) contribute to the progression and immune evasion of prostate cancer. However, the spatial distribution of tumor‐infiltrating PMN‐MDSCs in primary and metastatic prostate cancer, especially in the context of comparison between the epithelial and stromal compartments of the tumor, has not been characterized. Here, we describe a multicolor immunofluorescence staining study of 90 primary tumors, 37 lymph node metastases (all with matched primary tumors) and 35 bone metastases using archived samples. CD11b+ CD15+ cells were identified as PMN‐MDSCs and pan‐cytokeratin+ cells were identified as prostate epithelial cells. We found that, in both primary tumor and metastases, PMN‐MDSCs infiltrate much more readily in the stromal area compared with the epithelial area of the tumor regions. In comparison to the stromal area of primary tumors, the stromal area of either lymph node metastases or bone metastases was infiltrated with more PMN‐MDSCs. In primary tumors, stromal PMN‐MDSCs were associated with vascularization, segmented neutrophils, patient age and close juxtaposition to neoplastic epithelial cells. These results reveal the stroma rather than the epithelia of prostate cancer as the major hotbed for PMN‐MDSCs and support the role of PMN‐MDSCs in the metastatic progression of prostate cancer.

This paper attempts to disclose the damage mechanism of reinforced concrete plate-column structures under room temperature and fire. Several tests were carried out to record the law of crack development on the plate surface under room temperature. The infrared detection technology was adopted to observe how cracks develop under fire. The acoustic emission (AE) signals at different positions of the specimen were monitored by the AE techniques. Coupled with the macroscopic test phenomena, several characteristic parameters collected by the AE system, namely, cumulative number of events, event rate, energy rate and b-value, were analyzed in details. The results show that: the cumulative number of events was active in the loading, heating and cooling stages; the crack density and the change of internal forces could be derived from the trend of event rate; the local energy changes of the specimen could be deciphered from the curves of energy rate and b-value, making it possible to judge if a component has reached the failure state; the specimen suffered the most severe damage, when the AE parameters suddenly changed; AE monitoring enables the early warning of fire to reinforced concrete plate-column structure; infrared detection technology is suitable for real-time monitoring of crack development under high temperature.

Abstract Background Deregulation of integrins signaling had been documented to participate in multiple fundamental biological processes, and the aberrant expression of integrin family members were linked to the prognosis of various cancers. However, the role of integrins in predicting progression and prognosis of ovarian cancer patients are still largely elusive. This study is aimed to explore the prognostic values of ITGA and ITGB superfamily members in high grade serous ovarian cancers (HGSOC). Methods GSE26712 dataset was used to determine the differential expression of ITGA and ITGB superfamily member between HGSOC and normal counterparts. The Cancer Genome Altas (TGGA) and GSE9891 datasets were used to determine the prognostic values of ITGA and ITGB superfamily members in HGSOC, followed by the development of nomograms predictive of recurrence free survival (RFS) and overall survival (OS). Results ITGA6 and ITGB5 expression were significantly downregulated in HGSOC compared with that in normal counterparts. In contrast, ITGA2, ITGA5, ITGA7, ITGA8, ITGA9, ITGA10, ITGB3, ITGB4, ITGB6, and ITGB8 were all significantly upregulated in HGSOC compared with that in normal counterparts. Both univariable and multivariable analysis indicated that ITGB1 was associated with extended RFS. The ITGB1-related nomogram indicated that ITGB1 had the largest contribution to RFS, followed by FIGO stage and debulking status. The C-index for predicting RFS was 0.55 (95% CI 0.50–0.59) in TCGA dataset (training dataset) and 0.65 (95% CI 0.59–0.72) in GSE9891 dataset (validation dataset), respectively. Regarding OS, ITGB8 was associated with reduced survival suggested by both univariable and multivariable analysis. ITGA7 appeared to be associated with improved survival though without reaching statistical significance. The ITGA7/ITGB8-based nomogram showed that age at initial diagnosis had the largest contribution to OS, followed by ITGB8 and ITGA7 expression. The C-index for predicting OS was 0.65 (95% CI 0.60–0.69) in TCGA dataset (training dataset) and 0.59 (95% CI 0.51–0.66) in GSE9891 dataset (validation dataset), respectively. Conclusion In conclusion, ITGB1, ITGA7 and ITGB8 added prognostic value to the traditional clinical risk factors used to assess the clinical outcomes of HGSOC.

Penile squamous cell carcinoma (PSCC) is a cancer that is associated with significant mortality. Here, the authors develop a mouse model of PSCC by co-deletion of Smad4 and Apc in the androgen-responsive penile epithelium, and show synergistic efficacy of checkpoint therapy with cabozantinib or celecoxib in their model.

Post-transcriptional regulation by miRNAs plays an important role in the pathogenesis of rheumatoid arthritis (RA), however, the roles of specific miRNAs in RA pathogenesis remain largely unclear. This study performed dual-omics (miRNA and mRNA) integration analysis and in-depth cellular and molecular functional exploration to identify novel RA-associated miRNAs and to understand their underlying pathogenic mechanism. Based on the miRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from a discovery sample set (25 RA cases and 18 healthy controls), 18 differentially expressed miRNAs (DEMIRs) (|Fold-change|>2 and P

Abstract Background von Hippel-Lindau (VHL) disease is a familial neoplasia syndrome that results from the germline mutation of VHL. Pathogenic VHL mutations include deletion, frameshift, nonsense and missense mutations. Synonymous mutations are expected to be phenotypically silent and their role in VHL disease remains poorly understood. Case presentation We report a Caucasian male with a family history of pheochromocytoma and the synonymous VHL mutation c.414A > G (p.Pro138Pro). At 47-years, MRI revealed pheochromocytoma in the left adrenal gland and hemangioblastomas in the spine and brain. Pheochromocytoma was treated by adrenalectomy. Radiotherapy, followed by craniotomy and resection were needed to reduce hemangioblastomas to residual lesions. Two of three of the proband’s children inherited the mutation and both presented with retinal hemangioblastomas without pheochromocytoma at age 7: one twin needed four laser treatments. Primary skin fibroblasts carrying the heterozygous mutation or wild type VHL were established from the family. Mutant fibroblasts downregulated full-length VHL mRNA and protein, and upregulated the short VHL mRNA isoform (a result of exon 2 skipping in splicing) at the mRNA level but not at the protein level. Conclusions Our study shows that the synonymous VHL mutation c.414A > G can within 7 years induce pediatric retinal hemangioblastoma in absence of pheochromocytoma. This highlights the need to include splicing-altering synonymous mutations into the screening for VHL disease. This is also the first report on detecting and validating a synonymous VHL mutation using patient-derived fibroblasts. The mutation c.414A > G translates to p.Pro138Pro, yet it is not functionally silent, because it causes aberrant splicing by skipping exon 2. The reduced but not completely abolished pVHL protein in a loss-of-heterozygosity genetic backdrop may underlie the etiology of VHL disease.

Abstract Background Many studies have found that the hippocampus plays a very important role in major depressive disorder (MDD). The hippocampus can be divided into three subfields: the cornu ammonis (CA), dentate gyrus (DG) and subiculum. Each subfield of the hippocampus has a unique function and are differentially associated with the pathological mechanisms of MDD. However, no research exists to describe the resting state functional connectivity of each hippocampal subfield in MDD. Methods Fifty-five patients with MDD and 25 healthy controls (HCs) matched for gender, age and years of education were obtained. A seed-based method that imposed a template on the whole brain was used to assess the resting-state functional connectivity (rsFC) of each hippocampal subfield. Results Patients with MDD demonstrated increased connectivity in the left premotor cortex (PMC) and reduced connectivity in the right insula with the CA seed region. Increased connectivity was reported in the left orbitofrontal cortex (OFC) and left ventrolateral prefrontal cortex (vlPFC) with the DG seed region. The subiculum seed region revealed increased connectivity with the left premotor cortex (PMC), the right middle frontal gyrus (MFG), the left ventrolateral prefrontal cortex (vlPFC) and reduced connectivity with the right insula. ROC curves confirmed that the differences between groups were statistically significant. Conclusion The results suggest that the CA, DG and subiculum have significant involvement with MDD. Specifically, the abnormal functional connectivity of the CA may be related to bias of coding and integration of information in patients with MDD. The abnormal functional connectivity of the DG may be related to the impairment of working memory in patients with MDD, and the abnormal functional connectivity of the subiculum may be related to cognitive impairment and negative emotions in patients with MDD.

Neutrophils, the most abundant leukocytes in human blood, are essential fighter immune cells against microbial infection. Based on the finding that neutrophils can either restrict or promote cancer progression, tumor-associated neutrophils (TAN) are classified into anti-tumor N1 and pro-tumor N2 subsets. One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells, in particular, cytotoxic T lymphocytes. Currently, no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells (G/PMN-MDSC). In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy, as established from data obtained with diverse cancer models, therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy. Here, we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories: (1) depletion of existing PMN-MDSCs, (2) blockade of the development of PMN-MDSCs, (3) blockade of PMN-MDSC recruitment, (4) inhibition of immunosuppressive function. Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier, neutrophils are outstanding candidate carriers in nanoparticle-based therapies. Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery. In the second part of the review, we have highlighted recent advances in the field of neutrophil-based cancer drug delivery. Overall, we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.

In the cloud environment, owing to the large-scale sharing of the upper application instance and the underlying virtual machine resources, the tenants' information flow boundary in the shared virtual machine is fuzzy and difficult to identify. In addition, protection of tenant information flow between processes is inadequate, resulting in the leakage of sensitive information of tenants. Therefore, a dynamic control method for tenants' sensitive information flow based on virtual boundary recognition is proposed. By analyzing the behavior and operation log of tenants, the behavior feature vectors of tenants are constructed, and an automatic recognition algorithm of tenant virtual boundary based on the dynamic spiking neural network is designed. This algorithm can realize dynamic identification of the tenant virtual security boundary when the application service demand changes dynamically. Further, combined with the concept of centralized and decentralized information flow control, a dynamic control method of sensitive information flow is established. The security label is formally defined by using the lattice structure, and the control rules of tenants' information flow and the rules of tenant label encryption-declassification are designed. Thus, the independent, dynamic and secure control of tenants' information flow inside and outside the tenant virtual boundary. Finally, the detailed design of a dynamic security control application system for cloud tenants' sensitive information flow is provided. Experiments confirm that the proposed algorithm can identify the security boundary of tenants more accurately and efficiently than the traditional spiking neural network classification methods. Further, the security and effectiveness of the method is verified by the intransitive noninterference theory and the experiment of information flow control.

Abstract Background The clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer. Methods Since lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases. Results We observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer. Conclusions Our findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.

The collected end-of-life (EoL) silicon wafers from the discharged photovoltaic (PV) panels are easily contaminated by impurities such as doping elements and attached materials. In this study, the thermodynamic criteria for EoL silicon wafers refining using three most typical metallurgical refining processes: oxidation refining, evaporation refining, and solvent refining were systemically and quantitatively evaluated. A total of 42 elements (Ag, Al, Au, B, Be, Bi, C, Ca, Ce, Co, Cr, Cu, Fe, Ga, Gd, Ge, Hf, In, La, Mg, Mn, Mo, Na, Nb, Ni, Os, P, Pb, Pd, Pt, Re, Ru, Sb, Sn, Ta, Ti, U, V, W, Y, Zn, Zr) that are likely to be contained in the collected EoL silicon-based PV panels were considered. The principal findings are that the removal of aluminum, beryllium, boron, calcium, gadolinium, hafnium, uranium, yttrium, and zirconium into the slag, and removal of antimony, bismuth, carbon, lead, magnesium, phosphorus, silver, sodium, and zinc into vapor phase is possible. Further, solvent refining process using aluminum, copper, and zinc as the solvent metals, among the considered 14 potential ones, was found to be efficient for the EoL silicon wafers refining. Particularly, purification of the phosphorus doped n-type PV panels using solvent metal zinc and purification of the boron doped p-type PV panels using solvent metal aluminum are preferable. The efficiency of metallurgical processes for separating most of the impurity elements was demonstrated, and to promote the recycling efficiency, a comprehensive management and recycling system considering the metallurgical criteria of EoL silicon wafers refining is critical.

Abstract Background Dual-purpose cattle are more adaptive to environmental challenges than single-purpose dairy or beef cattle. Balance among milk, reproductive, and mastitis resistance traits in breeding programs is therefore more critical for dual-purpose cattle to increase net income and maintain well-being. With dual-purpose Xinjiang Brown cattle adapted to the Xinjiang Region in northwestern China, we conducted genome-wide association studies (GWAS) to dissect the genetic architecture related to milk, reproductive, and mastitis resistance traits. Phenotypic data were collected for 2410 individuals measured during 1995–2017. By adding another 445 ancestors, a total of 2855 related individuals were used to derive estimated breeding values for all individuals, including the 2410 individuals with phenotypes. Among phenotyped individuals, we genotyped 403 cows with the Illumina 150 K Bovine BeadChip. Results GWAS were conducted with the FarmCPU (Fixed and random model circulating probability unification) method. We identified 12 markers significantly associated with six of the 10 traits under the threshold of 5% after a Bonferroni multiple test correction. Seven of these SNPs were in QTL regions previously identified to be associated with related traits. One identified SNP, BovineHD1600006691, was significantly associated with both age at first service and age at first calving. This SNP directly overlapped a QTL previously reported to be associated with calving ease. Within 160 Kb upstream and downstream of each significant SNP identified, we speculated candidate genes based on functionality. Four of the SNPs were located within four candidate genes, including CDH2, which is linked to milk fat percentage, and GABRG2, which is associated with milk protein yield. Conclusions These findings are beneficial not only for breeding through marker-assisted selection, but also for genome editing underlying the related traits to enhance the overall performance of dual-purpose cattle.

Abstract Background To examine the microbial profiles in parenchyma tissues in bladder cancer. Methods Tissue samples of cancerous bladder mucosa were collected from patients diagnosed with bladder cancer (22 carcinoma tissues and 12 adjacent normal tissues). The V3‐V4 region of the bacterial 16S rRNA gene was PCR amplified, followed by sequencing on an Illumina MiSeq platform. Bioinformatics analysis for microbial classification and functional assessment was performed to assess bladder microbiome diversity and variations. Results The predominant phylum in both tissues was Proteobacteria. The cancerous tissues exhibited lower species richness and diversity. Beta diversity significantly differed between the cancerous and normal tissues. Lower relative abundances of the microbial genera Lactobacillus, Prevotella_9, as well as Ruminococcaceae were observed, whereas those of Cupriavidus spp., an unknown genus of family Brucellaceae, and Acinetobacter, Anoxybacillus, Escherichia‐Shigella, Geobacillus, Pelomonas, Ralstonia, and Sphingomonas were higher in the cancerous tissues. These findings indicate that these genera may be potentially utilized as biomarkers for bladder cancer. PICRUSt analysis revealed that several pathways involved in the metabolism of harmful chemical compounds were enriched in the cancer tissues, thereby providing evidence that environmental factors are strongly associated with bladder cancer etiology. Conclusion This is the first study that has described and analyzed the dysbiotic motifs of urinary microbiota in the parenchymatous tissues of bladder cancer via 16S rRNA gene sequencing. Our results suggest that changes in the bladder microbiome may serve as biomarkers for bladder cancer, possibly assisting in disease screening and monitoring.