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Most of the existing remote sensing image super-resolution (SR) methods based on deep learning tend to learn the mapping from low-resolution (LR) images to high-resolution (HR) images directly. But they ignore the potential structure and texture consistency of LR and HR spaces, which cause the loss of high-frequency information and produce artifacts. A structure-texture dual preserving method is proposed to solve this problem and generate pleasing details. Specifically, we propose a novel edge prior enhancement strategy that uses the edges of LR images and the proposed interactive supervised attention module (ISAM) to guide SR reconstruction. First, we introduce the LR edge map as a prior structural expression for SR reconstruction, which further enhances the SR process with edge preservation capability. In addition, to obtain finer texture edge information, we propose a novel ISAM in order to correct the initial LR edge map with high-frequency information. By introducing LR edges and ISAM-corrected HR edges, we build LR–HR edge mapping to preserve the consistency of LR and HR edge structure and texture, which provides supervised information for SR reconstruction. Finally, we explore the salient features of the image and its edges in the ascending space, and restored the difference between LR and HR images by residual and dense learning. A large number of experimental results on Draper and NWPU-RESISC45 datasets show that our model is superior to several advanced SR algorithms in both objective and subjective image quality.

Abstract Background Prostate cancer with bone metastasis has significant invasiveness and markedly poorer prognosis. The purpose of this study is to establish two nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of prostate cancer patients with bone metastasis. Methods From January 2000 to December 2018, a total of 2683 prostate adenocarcinoma with bone metastasis patients were identified from the Surveillance, Epidemiology, and End Results Program (SEER) database. These patients were then divided into a training cohort and a validation cohort, with OS and CSS as the study endpoints. Correlation analyses were employed to assess the relationship between variables. Univariate and multivariate Cox analyses were utilized to ascertain the independent prognostic factors. Calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were employed to evaluate discrimination and calibration of the nomogram. DCA was applied to examine accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Lastly, the risk stratifications of the nomogram and the AJCC Stage System were compared. Results There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that seven variables (age, surgery, brain metastasis, liver metastasis, lung metastasis, Gleason score, marital status) and six variables (age, surgery, lung metastasis, liver metastasis, Gleason score, marital status) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System. Conclusion Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of PABM patients.

Summary: The major histocompatibility complex class I (MHC class I)-mediated tumor antigen processing and presentation (APP) pathway is essential for the recruitment and activation of cytotoxic CD8+ T lymphocytes (CD8+ CTLs). However, this pathway is frequently dysregulated in many cancers, thus leading to a failure of immunotherapy. Here, we report that activation of the tumor-intrinsic Hippo pathway positively correlates with the expression of MHC class I APP genes and the abundance of CD8+ CTLs in mouse tumors and patients. Blocking the Hippo pathway effector Yes-associated protein/transcriptional enhanced associate domain (YAP/TEAD) potently improves antitumor immunity. Mechanistically, the YAP/TEAD complex cooperates with the nucleosome remodeling and deacetylase complex to repress NLRC5 transcription. The upregulation of NLRC5 by YAP/TEAD depletion or pharmacological inhibition increases the expression of MHC class I APP genes and enhances CD8+ CTL-mediated killing of cancer cells. Collectively, our results suggest a crucial tumor-promoting function of YAP depending on NLRC5 to impair the MHC class I APP pathway and provide a rationale for inhibiting YAP activity in immunotherapy for cancer.

Abstract Background After the introduction of cisplatin-based chemotherapy, the survival time of testicular cancer (TC) patients has improved dramatically. However, the overall risk of death in patients with TC remains significantly higher than in the general population. The aim of this study was to assess and quantify the causes of death after TC diagnosis. Method In total, 44,975 men with TC in the United States diagnosed and registered by the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2018 were studied. In this study, standardized mortality rates (SMRs) were calculated for each cause of death in TC individuals and further analyzed in strata according to age and race. Result Of the included participants, 3,573 (7.94%) died during the follow-up period. The greatest proportion of deaths (38.20%) occurred within 1 to 5 years after diagnosis. Most deaths occurred from TC itself and other cancers. For non-malignant conditions, the most common causes of death within 1 years after diagnosis were accidents and adverse effects (53, 4.75%) followed by diseases of heart (45, 4.04%). However, > 1 years after diagnosis, the most common noncancer causes of death were heart diseases. Results of stratified analysis show that non-Hispanic White TC participants have a lower SMR (0.68, 95% CI, 33.39–38.67) from Cerebrovascular Diseases than the general U.S. population. Conclusions Although TC remains the most common cause of death after TC diagnosis, other non-TC causes of death represent a significant number of deaths among TC men. These findings help TC survivors understand the various health risks that may occur at different follow-up periods.

This review discusses the variety, chemical composition, pharmacological effects, toxicology, and clinical research of corals used in traditional medicine in the past two decades. At present, several types of medicinal coral resources are identified, which are used in 56 formulas such as traditional Chinese medicine, Tibetan medicine, Mongolian medicine, and Uyghur medicine. A total of 34 families and 99 genera of corals are involved in medical research, with the Alcyoniidae family and Sarcophyton genus being the main research objects. Based on the structural types of compounds and the families and genera of corals, this review summarizes the compounds primarily reported during the period, including terpenoids, steroids, nitrogen-containing compounds, and other terpenoids dominated by sesquiterpene and diterpenes. The biological activities of coral include cytotoxicity (antitumor and anticancer), anti-inflammatory, analgesic, antibacterial, antiviral, immunosuppressive, antioxidant, and neurological properties, and a detailed summary of the mechanisms underlying these activities or related targets is provided. Coral toxicity mostly occurs in the marine ornamental soft coral Zoanthidae family, with palytoxin as the main toxic compound. In addition, nonpeptide neurotoxins are extracted from aquatic corals. The compatibility of coral-related preparations did not show significant acute toxicity, but if used for a long time, it will still cause toxicity to the liver, kidneys, lungs, and other internal organs in a dose-dependent manner. In clinical applications, individual application of coral is often used as a substitute for orthopedic materials to treat diseases such as bone defects and bone hyperplasia. Second, coral is primarily available in the form of compound preparations, such as Ershiwuwei Shanhu pills and Shanhu Qishiwei pills, which are widely used in the treatment of neurological diseases such as migraine, primary headache, epilepsy, cerebral infarction, hypertension, and other cardiovascular and cerebrovascular diseases. It is undeniable that the effectiveness of coral research has exacerbated the endangered status of corals. Therefore, there should be no distinction between the advantages and disadvantages of listed endangered species, and it is imperative to completely prohibit their use and provide equal protection to help them recover to their normal numbers. This article can provide some reference for research on coral chemical composition, biological activity, chemical ecology, and the discovery of marine drug lead compounds. At the same time, it calls for people to protect endangered corals from the perspectives of prohibition, substitution, and synthesis.

AbstractInhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3Kα and a panel of PI3Kα-addicted cancer cells. Among them, compound 35 was identified as a PI3Kα inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed 35 induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable in vitro ADME properties. The design, synthesis, and SAR exploration of 35 are described within.

Abstract In the repair of maxillofacial bone defects, autogenous craniofacial bone can often provide superior clinical results over long bone grafts. Most current studies have focused on the osteogenic differences between alveolar bone marrow (ABM) and long bone marrow (LBM), however, studies about the angiogenic differences between the two are currently lacking. We downloaded single-cell RNA sequencing (scRNA-seq) of mouse ABM and LBM respectively from the public database, and the data were processed by using Seurat package. CellphoneDB2 results showed that macrophages had the strongest interaction with mesenchymal stem cells (MSCs) and endothelial cells (ECs). ELISA results confirmed that ABM macrophages secreted a higher level of vascular endothelial growth factor A (Vegfa) compared to LBM macrophages, which further promoted angiogenesis of ECs and MSCs. Using SCENIC package, six key transcription factors (TFs) were identified to regulate the difference between ABM and LBM macrophages, and activating transcription factor 4 (Atf4) was confirmed to be more expressed in ABM macrophages by polymerase chain reaction (PCR) and western blot (WB), with predicted target genes including Vegfa. Besides, the result of scRNA-seq implied ABM macrophages more in M1 status than LBM macrophages, which was confirmed by the following experiments. From the results of another assay for transposase accessible chromatin sequencing (ATAC-seq) and RNA-seq about M1 macrophages, Atf4 was also confirmed to regulate the M1 polarization. So, we suspected that Atf4 regulated the different expression of Vegfa between ABM and LBM macrophages by activating M1 polarization. After knocking down Atf4, the expression of M1 polarization markers and Vegfa were downregulated and vasculogenic differences were eliminated, which were subsequently reversed by the addition of LPS/IFN-γ. Our study might provide a new idea to improve the success rate of autologous bone grafting and treatment of oral diseases.

Abstract Background Renal clear cell carcinoma (ccRCC) is the most prevalent tumors worldwide. Discovering effective biomarkers is essential to monitor the prognosis and provide alternative clinical options. SPTBN1 is implicated in various cancerous processes. However, its role in ccRCC remains unelucidated. This study intends to explore the biological function and mechanism of SPTBN1 in ccRCC. Methods Single-cell and bulk RNA-seq, tissue microarray, real-time quantitative PCR, and western blotting were applied to verify the expression and predictive value of SPTBN1 in ccRCC. Gain or loss of functional ccRCC cell line models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Actinomycin D experiment, RNA immunoprecipitation (RIP), specific inhibitors, and rescue experiments were carried out to define the molecular mechanisms. Results SPTBN1 was down-regulated in ccRCC and knockdown of SPTBN1 displayed a remarkably oncogenic role both in vitro and in vivo; while overexpressing SPTBN1 reversed this effect. SPTBN1 mediated ccRCC progression via the pathway of glutamate pyruvate transaminase 2 (GPT2)-dependent glycolysis. The expression of GPT2 was significantly negatively correlated with that of SPTBN1. As an RNA binding protein SPTBN1, regulated the mRNA stability of GPT2. Conclusion Our research demonstrated that SPTBN1 is significantly down-regulated in ccRCC. SPTBN1 knockdown promotes ccRCC progression via activating GPT2-dependent glycolysis. SPTBN1 may serve as a therapeutic target for the treatment of ccRCC.

Proline accumulation has been shown to occur in plants in response to various environmental stresses. Although proline metabolism-related genes have been functionally characterized, the inter-organ transport of proline in stressed plants remains unclear. In this study, free proline was detected with significant accumulations in the roots, stems, and leaves of watermelon drought-tolerant germplasm M08 and drought-susceptible line Y34 under drought stress. Expression profiling and enzyme activity measurements revealed that ClP5CS1 gene, rather than its paralog ClP5CS2, mainly contributes to the proline synthesis in leaves via the Glu pathway. Additionally, over-expression of the ClP5CS genes significantly enhanced the drought tolerance of transgenic Arabidopsis lines. Furthermore, we confirmed that proline is mainly synthesized in leaves and transported to roots in watermelon under drought stress. Transcriptome and expression analyses revealed that the genes involved in proline metabolism exhibited different expression levels. Specifically, ClP5CS1 was upregulated in leaves and roots, while ClP5CS2 was downregulated under drought stress. Also, 415 and 362 differently expressed TFs were identified in roots and leaves, respectively, with the majority upregulated in the former. Ultimately, a model for proline metabolism was proposed. The findings of this study provided new insights into the biosynthesis, transport, and regulatory mechanism of drought-induced proline in plants.

Sexual differentiation is an important developmental phenomenon in cucurbits that directly affects fruit yield. The natural existence of multiple flower types in melon offers an inclusive structure for studying the molecular basis of sexual differentiation. The current study aimed to identify and characterize the molecular network involved in sex determination and female development in melon. Male and female pools separated by the F2 segregated generation were used for sequencing. The comparative multi-omics data revealed 551 DAPs and 594 DEGs involved in multiple pathways of melon growth and development, and based on functional annotation and enrichment analysis, we summarized four biological process modules, including ethylene biosynthesis, flower organ development, plant hormone signaling, and ubiquitinated protein metabolism, that are related to female development. Furthermore, the detailed analysis of the female developmental regulatory pathway model of ethylene biosynthesis, signal transduction, and target gene regulation identified some important candidates that might have a crucial role in female development. Two CMTs ((cytosine-5)-methyltransferase), one AdoHS (adenosylhomocysteinase), four ACSs (1-aminocyclopropane-1-carboxylic acid synthase), three ACOs (ACC oxidase), two ARFs (auxin response factor), four ARPs (auxin-responsive protein), and six ERFs (Ethylene responsive factor) were identified based on various female developmental regulatory models. Our data offer new and valuable insights into female development and hold the potential to offer a deeper comprehension of sex differentiation mechanisms in melon.

The continuously improving performance of mass-market global navigation satellite system (GNSS) chipsets is enabling the prospect of high-precision GNSS positioning for smartphones. Nevertheless, a substantial portion of Android smartphones lack the capability to access raw carrier phase observations. Therefore, this paper introduces a precise code positioning (PCP) method, which utilizes Doppler-smoothed pseudo-range and inter-satellite single-difference methods. For the first time, the results of a quality investigation involving BDS-3 B1C/B2a/B1I, GPS L1/L5, and Galileo E1/E5a observed using smartphones are presented. The results indicated that Xiaomi 11 Lite (Mi11) exhibited a superior satellite data decoding performance compared to Huawei P40 (HP40), but it lagged behind HP40 in terms of satellite tracking. In the static open-sky scenario, the carrier-to-noise ratio (CNR) values were mostly above 25 dB-Hz. Additionally, for B1C/B1I/L1/E1, they were approximately 8 dB-Hz higher than those for B2a/L5/E5a. Second, various PCP models were developed to address ionospheric delay. These models include the IF-P models, which combine traditional dual-frequency IF pseudo-ranges with single-frequency ionosphere-corrected pseudo-ranges using precise ionospheric products, and IFUC models, which rely solely on single-frequency ionosphere-corrected pseudo-ranges. Finally, static and dynamic tests were conducted using datasets collected from various real-world scenarios. The static tests demonstrated that the PCP models could achieve sub-meter-level accuracy in the east (E) and north (N) directions, while achieving meter-level accuracy in the upward (U) direction. Numerically, the root mean square error (RMSE) improvement percentages were approximately 93.8%, 75%, and 82.8% for HP40 in the E, N, and U directions, respectively, in both open-sky and complex scenarios compared to single-point positioning (SPP). In the open-sky scenario, Mi11 showed an average increase of about 85.6%, 87%, and 16% in the E, N, and U directions, respectively, compared to SPP. In complex scenarios, Mi11 exhibited an average increase of roughly 68%, 75.9%, and 90% in the E, N, and U directions, respectively, compared to SPP. Dynamic tests showed that the PCP models only provided an improvement of approximately 10% in the horizontal plane or U direction compared to SPP. The triple-frequency IFUC (IFUC123) model outperforms others due to its lower noise and utilization of multi-frequency pseudo-ranges. The PCP models can enhance smartphone positioning accuracy.

Watermelon is a crucial horticultural crop worldwide but its genetic base has become extremely narrow owing to long-term cultivation. Induced mutagenesis can create a range of variations with distinctive agricultural characteristics. To broaden the genetic diversity of watermelon, we established a mutagenesis library containing over 4000 M1 seeds from an inbred line ‘M08’, which was irradiated by 350 Gy of 60Co γ-rays for 3 h. The rates of germination, emergence, and survival of the M1 seeds were reduced by 5.88%, 18.66%, and 41.96%, respectively. After phenotypic screening, 20 and 10 types of morphological changes were observed in the M1 and M2 generations, with approximately 10.57% and 14.17% mutation frequencies, respectively. Six mutants with desirable horticultural alterations were selected for additional presentation, including the leaf color mutant C1-NO.1, the yellow peel mutant C1-NO.2, the pericarp thickening mutant C1-NO.3, the pericarp thinning mutant C1-NO.4, the seedless mutant C1-NO.5, and the C2-No.1 mutant with normal female flowers and malformed male flowers. Moreover, the three mutants M1-3, M2-1, and M1-5 were identified from our EMS-induced M2 library, exhibiting the fusiform fruit, the dark green peel, and the yellow leaves, respectively. Compared to the wild type (WT), the photosynthetic pigments and parameters were negatively impacted in the yellow-leaf mutant M1-5. For example, the total chlorophyll was 1.22 and 2.22 mg/g in the young and mature leaves of M1-5, respectively, which were significantly lower than those in the WT (2.58 and 2.90 mg/g, respectively). Notably, some mutagenesis phenotypes could be stably inherited, including traits such as yellow leaf color, fusiform fruit shape, and thickening and thinning pericarp. Taken together, these results indicate that these two mutant libraries serve as essential resources to discover new phenotypic germplasms, thereby facilitating the genetic breeding and functional gene exploration in watermelon.

tRNA methylations, including base modification and 2’-O-methylation of ribose moiety, play critical roles in the structural stabilization of tRNAs and the fidelity and efficiency of protein translation. These modifications are catalyzed by tRNA methyltransferases (TRMs). Some of the TRMs from yeast can fully function only by a single subunit. In this study, after performing the primary bioinformatic analyses, the progress of the studies of yeast single-subunit TRMs, as well as the studies of their homologues from yeast and other types of eukaryotes and the corresponding TRMs from other types of organisms was systematically reviewed, which will facilitate the understanding of the evolutionary origin of functional diversity of eukaryotic single-subunit TRM.

PurposeTo systematically evaluate the potential of radiomics coupled with machine-learning algorithms to improve the predictive power for overall survival (OS) of renal cell carcinoma (RCC).MethodsA total of 689 RCC patients (281 in the training cohort, 225 in the validation cohort 1 and 183 in the validation cohort 2) who underwent preoperative contrast-enhanced CT and surgical treatment were recruited from three independent databases and one institution. 851 radiomics features were screened using machine-learning algorithm, including Random Forest and Lasso-COX Regression, to establish radiomics signature. The clinical and radiomics nomogram were built by multivariate COX regression. The models were further assessed by Time-dependent receiver operator characteristic, concordance index, calibration curve, clinical impact curve and decision curve analysis.ResultThe radiomics signature comprised 11 prognosis-related features and was significantly correlated with OS in the training and two validation cohorts (Hazard Ratios: 2.718 (2.246,3.291)). Based on radiomics signature, WHOISUP, SSIGN, TNM Stage and clinical score, the radiomics nomogram has been developed. Compared with the existing prognostic models, the AUCs of 5 years OS prediction of the radiomics nomogram were superior to the TNM, WHOISUP and SSIGN model in the training cohort (0.841 vs 0.734, 0.707, 0.644) and validation cohort2 (0.917 vs 0.707, 0.773, 0.771). Stratification analysis suggested that the sensitivity of some drugs and pathways in cancer were observed different for RCC patients with high-and low-radiomics scores.ConclusionThis study showed the application of contrast-enhanced CT-based radiomics in RCC patients, creating novel radiomics nomogram that could be used to predict OS. Radiomics provided incremental prognostic value to the existing models and significantly improved the predictive power. The radiomics nomogram might be helpful for clinicians to evaluate the benefit of surgery or adjuvant therapy and make individualized therapeutic regimens for patients with renal cell carcinoma.

This paper presents a computational impact angle control guidance law based on the energy cost weighted by arbitrary functions in order to shape the acceleration command as desired. The optimal guidance problem is established in the impact angle frame and is solved by the Gauss orthogonal collocation method. The proposed guidance law is formulated from the generalized optimal control framework, thus a new guidance law that allows achieving a specific guidance goal can be easily obtained in the way of devising a proper weighting function (smooth, piecewise, nonsmooth, or even discontinuous). This property provides more degrees of freedom in the guidance law design to accomplish a specified guidance objective. A hardware experiment is conducted to evaluate the real-time computational capacity of the proposed computational guidance law. Illustrative examples with several types of weighting functions, including smooth, piecewise, nonsmooth, and discontinuous functions, are provided to demonstrate the advantages and capacity of the proposed guidance law.

Yield and fruit quality loss by powdery mildew (PM) fungus is a major concern in cucurbits, but early-stage resistance mechanisms remain elusive in the majority of cucurbits. Here, we explored the comparative transcriptomic dynamics profiling of resistant line ZXG1755 (R) and susceptible line ZXG1996 (S) 48 h post-inoculation in watermelon seedlings to check precise expression changes induced by Podosphaera. xanthii race ‘2F’. Phenotypic responses were confirmed by microscopy and endogenous levels of defense and signaling related phytochromes were detected higher in resistant lines. In total, 7642 differently expressed genes (DEGs) were detected, and 57.27% of genes were upregulated in four combinations. DEGs were predominantly abundant in the KEGG pathway linked with phenylpropanoid biosynthesis, plant hormone and transduction, and phenylalanine metabolism, whereas GO terms of defense response, response to fungus, and chitin response were predominant in resistant lines, evidencing significant defense mechanisms and differences in the basal gene expression levels between these contrasting lines. The expression of selected DEGs from major pathways (hormonal, lignin, peroxidase, sugar) were validated via qRT-PCR. Detailed analysis of DEGs evidenced that along with other DEGs, genes including PR1 (Cla97C02G034020) and PRX (Cla97C11G207220/30, Cla97C02G045100 and Cla97C02G049950) should be studied for their potential role. In short, our study portrayed strong evidence indicating the important role of a complex network associated with lignin biosynthesis and phytohormone related downstream mechanisms that are responsible for incompatible interaction between PM and watermelon resistance line.

Purpose: This study aimed to investigate the relationship between phthalate metabolites and renal function. Methods: We analyzed data from 9989 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Renal function was reflected by estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and hypertension. We used generalized linear regression to estimate the correlation between covariate-adjusted creatinine-normalized phthalate metabolites and renal function. In addition, subgroup analysis was used to further compare the effect differences between various populations. Results: In the adjusted model, we found differential associations between phthalates and plasticizers metabolites and renal function. We found that Mono-benzyl phthalate, Mono-(3-carboxypropyl) phthalate, and Mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with lower eGFR with odds ratios (95% confidence intervals) of 1.38 (1.14, 1.67), 1.30 (1.09, 1.57), and 1.27 (1.04, 1.53). While Mono-ethyl phthalate, Mono-(2-ethyl)-hexyl phthalate, Mono-isononyl phthalate and Mono-isobutyl phthalate were negatively associated with lower eGFR with OR values of 0.79 (0.69, 0.90), 0.64 (0.52, 0.78), 0.65 (0.51, 0.82) and 0.80 (0.63, 1.00), respectively. In addition, we found that Mono(carboxyoctyl) phthalate and Mono-isobutyl phthalate were negatively associated with hypertension with ORs of 0.86 (0.78, 0.96) and 0.84 (0.72, 0.98). But phthalates and plasticizers metabolites were not associated with UACR. Conclusion: This study found differences in the effects of phthalates and plasticizers metabolites on kidney function, which may raise concerns about possible changes in kidney function resulting from exposure to current levels of plasticizers.

Abstract Upregulation of transmembrane protein 97 (TMEM97) has been associated with progression and poor outcome in multiple human cancers, including breast cancer. Recent studies suggest that TMEM97 may be involved in the activation of the Wnt/β-catenin pathway. However, the molecular mechanism of TMEM97 action on Wnt/β-catenin signaling is completely unclear. In the current study, TMEM97 was identified as an LRP6-interacting protein. TMEM97 could interact with LRP6 intracellular domain and enhance LRP6-mediated Wnt signaling in a CK1δ/ε-dependent manner. The binding of TMEM97 to LRP6 facilitated the recruitment of CK1δ/ε to LRP6 complex, resulting in LRP6 phosphorylation at Ser 1490 and the stabilization of β-catenin. In breast cancer cells, knockout of TMEM97 attenuated the Wnt/β-catenin signaling cascade via regulating LRP6 phosphorylation, leading to a decrease in the expression of Wnt target genes AXIN2, LEF1, and survivin. TMEM97 deficiency also suppressed cell viability, proliferation, colony formation, migration, invasion, and stemness properties in breast cancer cells. Importantly, TMEM97 knockout suppressed tumor growth through downregulating the Wnt/β-catenin signaling pathway in a breast cancer xenograft model. Taken together, our results revealed that TMEM97 is a positive modulator of canonical Wnt signaling. TMEM97-mediated Wnt signaling is implicated in the tumorigenesis of breast cancer, and its targeted inhibition may be a promising therapeutic strategy for breast cancer.

Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed.

Recent research has demonstrated the diverse relationship between tumour metabolism and the tumour microenvironment (TME), for example, abnormal serine metabolism. This study investigated the role of serine metabolism in papillary renal cell carcinoma (pRCC) focusing on the prognostic value and regulatory mechanisms. Gene expression profiles and clinical data of patients with pRCC were obtained from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Kaplan–Meier curves were used for survival analysis and consensus clustering for tumour serine metabolic signatures extraction. Functional analysis, including the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA), was applied to explore the biological characteristics. The gene set variation analysis (GSVA), single-sample GSEA (ssGSEA), and Estimation of Stromal and Immune cells in Malignant Tumour tissues using Expression data (ESTIMATE) methods were utilised to estimate the immune infiltration in the various subtypes. Five serine metabolic genes (SMGs) were used to classify patients with pRCC, with four clusters identified with diverse prognoses and immune features based on these survival-related SMGs. Further analysis of the best and worst clusters (B and D clusters) revealed variations in survival, clinical progression, oncogenic pathways, and TME, which included immune infiltration scores, immunosuppressive cell infiltration, and expression of immune checkpoints. In addition, SMGs, especially SHMT2, exacerbated the carcinogenesis and immunosuppressive cells in pRCC, thus promoting tumour proliferation. In conclusion, higher SHMT2 gene expression and higher serine metabolism in tumour cells are associated with poorer clinical outcomes in pRCC. SHMT2 is a potential novel target gene for targeted therapy and immunotherapy in pRCC.

Circular RNAs (circRNAs) are a special type of endogenous RNAs with extensive roles in multiple human diseases. They are formed by back-splicing of partial sequences of the parental precursor mRNAs. Unlike linear RNAs, their covalently closed loop structure without a 5′ cap and a 3′ polyadenylated tail confers on them high stability and they are difficult to be digested by RNase R. Increasing evidence has proved that aberrant expressions of many circRNAs are detected and that circRNAs exert essential biological functions in disease development and progression via acting as a molecular sponge of microRNA, interacting with proteins as decoys or scaffolds, or self-encoding small peptides. Circular RNA zinc finger protein 609 (circ-ZNF609) originates from exon2 of ZNF609, which is located at chromosome 15q22.31, and it has recently been proved that it can translate into a protein. Being aberrantly upregulated in various diseases, it could promote malignant progression of human tumors, as well as tumor cell proliferation, migration, and invasion. Here in this review, we concluded the biological functions and potential mechanisms of circ-ZNF609 in multiple diseases, which could be further explored as a targetable molecule in future accurate diagnosis and prognosis.

Bedaquiline (BDQ), a new antitubercular agent, has been used to treat drug-resistant tuberculosis (TB). Although mutations in atpE, rv0678, and pepQ confer major resistance to BDQ, the mechanisms of resistance to BDQ in vitro and in clinical settings have not been fully elucidated. We selected BDQ-resistant mutants from 7H10 agar plates containing 0.5 mg/L BDQ (the critical concentration) and identified mutations associated with BDQ resistance through whole genome sequencing and Sanger sequencing. A total of 1,025 mutants were resistant to BDQ. We randomly selected 168 mutants for further analysis and discovered that 157/168 BDQ-resistant mutants harbored mutations in rv0678, which encodes a transcriptional regulator that represses the expression of the efflux pump, MmpS5–MmpL5. Moreover, we found two mutations with high frequency in rv0678 at nucleotide positions 286–287 (CG286–287 insertion; accounting for 26.8% [45/168]) and 198–199 (G198, G199 insertion, and G198 deletion; accounting for 14.3% [24/168]). The other mutations were dispersed covering the entire rv0678 gene. Moreover, we found that one new gene, glpK, harbors a G572 insertion; this mutation has a high prevalence (85.7%; 144/168) in the isolated mutants, and the minimum inhibitory concentration (MIC) assay demonstrated that it is closely associated with BDQ resistance. In summary, we characterized 168/1,025 mutants resistant to BDQ and found that mutations in rv0678 confer the primary mechanism of BDQ resistance. Moreover, we identified a new gene (glpK) involved in BDQ resistance. Our study offers new insights and valuable information that will contribute to rapid identification of BDQ-resistant isolates in clinical settings.

Ovarian sensitivity could affect the outcome of in vitro fertilization and embryo transfer (IVF-ET). The objective of this study was to explore the relationship between the ovarian sensitivity index (OSI) and traditional ovarian response makers and observe the relationship between OSI and insulin resistance (IR). The patients enrolled in this study included 131 patients with polycystic ovary syndrome (PCOS) with IR (PCOS-IR), 52 patients with PCOS without IR (PCOS-N), 164 patients with control with IR (control-IR), 133 patients with control without IR (control-N), 295 patients with IR, 184 patients with non-IR, 183 patients with PCOS, and 297 patients with control (patients with non-PCOS). All patients received standard long protocol or the gonadotropin-releasing hormone (GnRH) antagonist protocol to induce follicular development. The two protocols downregulated the pituitary function or blocked the pituitary luteinizing hormone (LH) secretion with a GnRH antagonist. Both protocols can block premature LH surges because premature luteinization is not conducive to follicular development. All patients underwent IVF or intracytoplasmic sperm injection (ICSI). Embryo transfer was carried out according to the specific situation of each patient. The OSI was significantly reduced in patients with IR. The OSI had a significant positive relationship with anti-Müllerian hormone (AMH), antral follicle count (AFC), basal LH/follicle-stimulating hormone (FSH), dominant follicle number on trigger day, retrieved oocytes, embryo number, and high-quality embryo number. OSI had a significant negative relationship with age, body mass index (BMI), basal FSH, initial dose of Gn, and total dose of Gn. The receiver operating characteristic (ROC) curve of OSI demonstrated a better accuracy in distinguishing patients with positive pregnancy and clinical pregnancy, with an area under the curve (AUC) of 0.662 (95% CI, 0.598–0.727) and 0.636 (95% CI, 0.577–0.695), respectively. Patients could get a higher rate of dominant follicle count (p < 0.0001) through the treatment of standard long protocol when compared with GnRH antagonist protocol. The OSI has a significant correlation with traditional ovarian response markers and could be a good predictor of positive pregnancy and clinical pregnancy for patients with IR.

Recently a large number of 3D object tracking methods have been extensively investigated and applied in a variety of applications using convolutional neural networks. Although most of them have made great progress in partial occlusion, the intricate interweaving of moving agents (e.g. pedestrians and vehicles) may lead to inferior performance of 3D object tracking in complex traffic scenes. To boost the performance of 3D object tracking in cases of severe occlusions, we present an end-to-end deep learning framework with a driving behavior-aware model that takes full advantage of spatial-temporal details in consecutive frames and learns the driving behavior from object variations in 2D center point, depth, rotation and translation in parallel. In contrast to prior work, our novelty formulates driving behavior that reasons about the possible motion trajectories of the investigated target for autonomous systems. We show in experiments that our method outperforms state-of-the-art approaches on 3D object tracking in the challenging nuScenes dataset.

Massive green tides caused by Ulva prolifera have annually occurred in the Yellow Sea since 2007, which has attracted much attention from the government and society. There are associations between the green tides in the Yellow Sea and social response in the social media (i.e., Sina Weibo), which are bidirectional and could be captured by the bidirectional neural network. For instance, how to detect daily U. prolifera green tides by fusing remote sensing data with social media data, and how to use the observed U. prolifera green tides to infer the social response are two challenges of State Oceanic Administration, China. This article first illustrated that there are bidirectional associations between green tides and Sina Weibo data. Then, this article introduced a bidirectional spatio-temporal associative memory neural network (BSAMNN) model for modeling this bidirectional association from the spatio-temporal perspective. BSAMNN first extracted six characteristics from green tides and nine characteristics from the social responses in 2016–2019. Second, these characteristics were split by year, and the characteristics in 2016–2018 were, respectively, put into the bidirectional associative memory neural network (BAM), which is a two-layer artificial neural network. Based on the BAM results and the observed data, the residual network was constructed. Third, BSAMNN extracted the spatio-temporal rules from the characteristics in 2016–2018 as the constraints through the mining rule algorithm and modify the results via sea surface wind and ocean surface current. Last, BSAMNN put the characteristics in 2019 into BAM and used the residual network to modify the results, which was constrained by the spatio-temporal rules. The feasibility and reliability of our approach were demonstrated by using the U. prolifera green tides in 2019. The average accuracy, false alarm rate, and missing alarm rate of BSAMNN results were 0.69, 0.25, and 0.31, respectively, which was 0.11 higher, 0.10 lower, and 0.11 lower than that of the traditional BAM. The results indicated that our method is an effective alternative of linking the U. prolifera green tides and its public sentiments on social media.

A novel series of triazoloquinazolinone derivatives were designed, synthesised, and evaluated for their in vitro biological activities against the SHP2 protein. Moreover, some compounds were evaluated against A375 cells. The results revealed that target compounds possessed moderate to excellent inhibitory activity against SHP2 protein, whereas compounds 12f, 12l, 12j, 17e, and 17f have strong antiproliferative activity on A375 cells. The compound 12l showed remarkable cytotoxicity against A375 cells and a strong inhibitory effect against SHP2 protein when compared with SHP244. The structure-activity relationships (SARs) indicated that electron-donating groups (EDGs) on phenyl rings are beneficial for improving the antitumor activity; compounds with a hydroxyl substituent at the 2-position of phenyl ring exhibited superior activities than compounds with a substituent at the 4-position. In addition, compound 12l displayed improved physicochemical properties as well as metabolic stability compared to SHP244. Our efforts identified 12l as a promising SHP2 protein inhibitor, warranting its further investigation.

Election forecasting has been traditionally dominated by subjective surveys and polls or methods centered upon them. We have developed a novel platform for forecasting elections based on agent-based modeling (ABM), which is entirely independent from surveys and polls. The platform uses statistical results from objective data along with simulation models to capture how voters have voted in past elections and how they are likely to vote in an upcoming election. We screen for models that can reproduce results that are very close to the actual results of historical elections and then deploy these selected models to forecast an upcoming election with simulations by combining extrapolated data from historical demographic record and more updated data on economic growth, employment, shock events, and other factors. Here, we report the results of two recent experiments of real-time election forecasting: the 2020 general election in Taiwan and six states in the 2020 general election in the United States. Our mostly objective method using ABM may transform how elections are forecasted and studied.

The host immune system plays a pivotal role in the containment of Mycobacterium tuberculosis (Mtb) infection, and host-directed therapy (HDT) is emerging as an effective strategy to treat tuberculosis (TB), especially drug-resistant TB. Previous studies revealed that expression of sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, was downregulated in macrophages after Mycobacterial infection. Inhibition of SIRT7 with the pan-sirtuin family inhibitor nicotinamide (NAM), or by silencing SIRT7 expression, promoted intracellular growth of Mtb and restricted the generation of nitric oxide (NO). Addition of the exogenous NO donor SNAP abrogated the increased bacterial burden in NAM-treated or SIRT7-silenced macrophages. Furthermore, SIRT7-silenced macrophages displayed a lower frequency of early apoptotic cells after Mycobacterial infection, and this could be reversed by providing exogenous NO. Overall, this study clarified a SIRT7-mediated protective mechanism against Mycobacterial infection through regulation of NO production and apoptosis. SIRT7 therefore has potential to be exploited as a novel effective target for HDT of TB.

The currently available triple-frequency signals give rise to new prospects for precise point positioning (PPP). However, they also bring new bias, such as time-varying parts of the phase bias in the hardware of receivers and satellites due to the fact that dual-frequency precise clock products cannot be directly applied to triple-frequency observation. These parameters generate phase-based inter-frequency clock bias (PIFCB), which impacts the PPP. However, the PIFCBs of satellites are not present in all GNSSs. In this paper, various IF1213 PPP models are constructed for these parts, namely, the triple-frequency PIFCB (TF-C) model with PIFCB estimation, the TF inter-frequency bias (IFB) (TF-F) model ignoring the PIFCB, and the TF-PIFCB-IFB (TF-CF) model with one system PIFCB estimation. Additionally, this study compares these IF1213 PPP models with the dual-frequency ionosphere-free (DF) model. We conducted single system static PPP, dual-system static and kinematic PPP experiments based on BDS/GPS observation data. The GPS static PPP experiment demonstrates the reliability of the TF-C model, as well as the non-negligibility of the GPS PIFCB. The BDS static PPP experiment demonstrates the reliability of the TF-F and TF-CF models, and that the influence of the BDS-2 PIFCB can be neglected in BDS. The BDS/GPS PPP experimental results show that the third frequency does not significantly improve the positioning accuracy but shortens the convergence time. The positioning accuracy of TF-C and TF-CF for static PPP is better than 1.0 cm, while that for kinematic PPP is better than 2.0 cm and 4.0 cm in the horizontal and vertical components, respectively. Compared with the DF model, the convergence time of the TF-C and TF-CF models for static PPP is improved by approximately 23.5%/18.1%, 13.6%/9.7%, and 19.8%/12.1%, while that for kinematic PPP is improved by approximately 46.2%/49.6%, 33.5%/32.4%, and 35.1%/36.1% in the E, N and U directions, respectively. For dual-system PPP based on BDS/GPS observations, the TF-C model is recommended.

How to deal with data sets in high-dimensional space is the focus of image processing. At present, subspace clustering method is one of the most commonly used methods for processing high-dimensional data sets. Traditional subspace clustering assumes that the data comes from different linear subspaces, and the different subspace regions do not overlap. However, the real data often does not satisfy these two constraints, which affects the effect of subspace clustering. In order to deal with these two problems, we first introduce the consensus Hilbert space to solve the nonlinear problem of subspace data, that is, a method that can learn the best consensus Hilbert space from a given set of kernel space; The second-order neighbors of the subspace coefficient matrix are used to deal with overlapping subspace problems. The second-order neighbors can effectively optimize the sparseness and connectivity of the self-representation. Subsequently, in order to effectively handle the above complex iterative optimization steps, an alternating direction multiplier method was developed. Finally, the designed multiple kernel subspace clustering algorithm is tested on a total of sixteen real data sets of four types, including face, handwritten, UCI and biomedical data sets. It can be seen from the experimental results that our proposed method has improved clustering accuracy, normalized mutual information and adjusted rand index compared to the latest algorithms.

Background: Multidrug-resistant pulmonary tuberculosis (MDR-PTB) has become a major cause of high morbidity and mortality related to TB. Conventional drug regimens are ineffective for the treatment of MDR-PTB patients with cavities. This study aimed to evaluate the clinical efficacy and safety of one-way endobronchial valves (EBVs) for the treatment of cavities in MDR-PTB patients. Methods: MDR-PTB patients with positive sputum cultures, sputum smears, and cavities were treated with EBVs in the drainage bronchus of the pulmonary cavity between November 2013 and March 2018. The participants comprised those who had failed previous anti-tuberculosis therapy, as determined by drug susceptibility testing. Results: Thirty-five MDR-PTB patients were included, three of whom were lost during follow-up. The size of the lung cavity was reduced in all of the patients after EBV implantation, including the three lost to follow-up. In the remaining 32 patients, the sputum culture conversion (SCC) rate reached 100%, and the cavity closure rate was 68.8%. There were no significant differences in the cavity closure rate between patients aged ≤40 and >40 years, between the upper and lower lobes, or between the use and non-use of linezolid groups (p > 0.05). Interestingly, the cavity closure rate was higher in women than in men (p = 0.005). Moreover, the cavity closure rate correlated with the time to SCC (correlation coefficient, 0.8933; p < 0.0001). There were no severe adverse events in the patients treated with EBV implantation. Conclusion: EBV installation is effective and safe for the treatment of cavities in MDR-PTB patients. The efficacy of EBV treatment may not be affected by age, disease course, or the location of the lung lobe in the cavity.

We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic–clonic seizures (IGE-GTCS) via MRI volumetry and vertex-based shape analysis and to evaluate the relationships between MRI measures and drug responses. In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D T1WI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates [age, sex, and intracranial volume (ICV)]. Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs (p = 0.004, false discovery rate corrected) and SF patients (p = 0.029, uncorrected). Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC (p < 0.05, FWE corrected). There were significant correlations between the volume changes and seizure frequency (r = −0.324, p = 0.030) and between shape (r = −0.438, p = 0.003) changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency (r = −0.689, p = 0.006). The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.

The problem of three-dimensional impact time control guidance considering field-of-view constraints and time-varying velocity is investigated in this study. First, considering the effect of gravity and aerodynamic forces on velocity, a simplified numerical estimation algorithm of flight time with a three-dimensional proportional navigation guidance law is derived. Then, based on the structure of the biased proportional navigation guidance law, the effect of the biased term on flight time is analyzed. The biased term is then designed to achieve impact time and field-of-view constraints considering time-varying velocity. Finally, numerical simulations are performed to demonstrate the effectiveness and superiority of the proposed guidance law.

This paper suggests an online solution for the optimal tracking control of robotic systems based on a single critic neural network (NN)-based reinforcement learning (RL) method. To this end, we rewrite the robotic system model as a state-space form, which will facilitate the realization of optimal tracking control synthesis. To maintain the tracking response, a steady-state control is designed, and then an adaptive optimal tracking control is used to ensure that the tracking error can achieve convergence in an optimal sense. To solve the obtained optimal control via the framework of adaptive dynamic programming (ADP), the command trajectory to be tracked and the modified tracking Hamilton-Jacobi-Bellman (HJB) are all formulated. An online RL algorithm is the developed to address the HJB equation using a critic NN with online learning algorithm. Simulation results are given to verify the effectiveness of the proposed method.

Background. Recent research found that N5-methylcytosine (m5C) was involved in the development and occurrence of numerous cancers. However, the function and mechanism of m5C RNA methylation regulators in clear cell renal cell carcinoma (ccRCC) remains undiscovered. This study is aimed at investigating the predictive and clinical value of these m5C-related genes in ccRCC. Methods. Based on The Cancer Genome Atlas (TCGA) database, the expression patterns of twelve m5C regulators and matched clinicopathological characteristics were downloaded and analyzed. To reveal the relationships between the expression levels of m5C-related genes and the prognosis value in ccRCC, consensus clustering analysis was carried out. By univariate Cox analysis and last absolute shrinkage and selection operator (LASSO) Cox regression algorithm, a m5C-related risk signature was constructed in the training group and further validated in the testing group and the entire cohort. Then, the predictive ability of survival of this m5C-related risk signature was analyzed by Cox regression analysis and nomogram. Functional annotation and single-sample Gene Set Enrichment Analysis (ssGSEA) were applied to further explore the biological function and potential signaling pathways. Furthermore, we performed qRT-PCR experiments and measured global m5C RNA methylation level to validate this signature in vitro and tissue samples. Results. In the TCGA-KIRC cohort, we found significant differences in the expression of m5C RNA methylation-related genes between ccRCC tissues and normal kidney tissues. Consensus cluster analysis was conducted to separate patients into two m5C RNA methylation subtypes. Significantly better outcomes were observed in ccRCC patients in cluster 1 than in cluster 2. m5C RNA methylation-related risk score was calculated to evaluate the prognosis of ccRCC patients by seven screened m5C RNA methylation regulators (NOP2, NSUN2, NSUN3, NSUN4, NSUN5, TET2, and DNMT3B) in the training cohort. The AUC for the 1-, 2-, and 3-year survival in the training cohort were 0.792, 0.675, and 0.709, respectively, indicating that the risk signature had an excellent prognosis prediction in ccRCC. Additionally, univariate and multivariate Cox regression analyses revealed that the risk signature could be an independent prognostic factor in ccRCC. The results of ssGSEA suggested that the immune cells with different infiltration degrees between the high-risk and low-risk groups were T cells including follicular helper T cells, Th1_cells, Th2_cells, and CD8+_T_cells, and the main differences in immune-related functions between the two groups were the interferon response and T cell costimulation. In addition, qRT-PCR experiments confirmed our results in renal cell lines and tissue samples. Conclusions. According to the seven selected regulatory factors of m5C RNA methylation, a risk signature associated with m5C methylation that can independently predict prognosis in patients with ccRCC was developed and further verified the predictive efficiency.

The carotenoid cleavage dioxygenase (CCD) gene family in plants comprises two subfamilies: CCD and 9-cis-epoxycarotenoid dioxygenase (NCED). Genes in the NCED subfamily are mainly involved in plant responses to abiotic stresses such as salt, low temperature, and drought. Members of the NCED subfamily are the most important rate-limiting enzymes in the biosynthesis of abscisic acid (ABA). In the present study, genome-wide analysis was performed to identify CCD gene members in six Cucurbitaceae species, including watermelon (Citrullus lanatus), melon (Cucumis melo), cucumber (C.sativus), pumpkin (Cucurbita moschata), bottle gourd (Lagenaria siceraria), and wax gourd (Benincasa hispida). A total of 10, 9, 9, 13, 8, 8 CCD genes were identified in the six species, respectively, and these genes were unevenly distributed in different chromosomes. Phylogenetic analysis showed that CCD genes of the six species clustered into two subfamilies: CCD and NCED, with five and three independent clades, respectively. The number of exons ranged from 1 to 15, and the number of motifs were set to 15 at most. The cis-acting elements analysis showed that a lot of the cis-acting elements were implicated in stress and hormone response. Melon seedlings were treated with salt, low temperature, drought, and ABA, and then tissue-specific analysis of CCDs expression were performed on the root, stem, upper leaf, middle leaf, female flower, male flower, and tendril of melon. The results showed that genes in CCD family exhibited various expression patterns. Different CCD genes of melon showed different degrees of response to abiotic stress. This study presents a comprehensive analysis of CCD gene family in six species of Cucurbitaceae, providing a strong foundation for future studies on specific genes in this family.

Abstract Background Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a member of microfilament-related formins and mediates cell motility in breast cancer (BrCa). However, the genetic mutation status of DAAM1 mRNA and its correlation with pathological characteristics are still unclearly. Methods A patient cohort and BrCa cells were recruited to demonstrate the role of functional SNP in microRNA-208a-5p binding site of DAAM1 3′-UTR and underlying mechanism in BrCa metastasis. Results The expression and activation of DAAM1 increased markedly in lymphnode metastatic tissues. A genetic variant (rs79036859 A/G) was validated in the miR-208a-5p binding site of DAAM1 3′-UTR. The G genotype (AG/GG) was a risk genotype for the metastasis of BrCa by reducing binding affinity of miR-208a-5p for the DAAM1 3′-UTR. Furthermore, the miR-208a-5p expression level was significantly suppressed in lymphnode metastatic tissues compared with that in non-lymphnode metastatic tissues. Overexpression of miR-208a-5p inhibited DAAM1/RhoA signaling pathway, thereby leading to the decrease of the migratory ability. Conclusion Overall, the rs79036859 G variant of DAAM1 3′-UTR was identified as a relevant role in BrCa metastasis via the diversity of miR-208a-5p binding affinity.

With the increasing amount of HD or even UHD video, the video streaming transmission over the mobile network is confronted with various quality of experience issues. To facilitate the delivery of compressed video over the network, it is extremely helpful to further compress the coded video bit stream without any information loss, so-called lossless recompression. However, the existing lossless video/image compression algorithms aim to remove the pixel-domain (e.g., lossless coding mode of HEVC) or the coefficient-domain (e.g., entropy coding) redundancy rather than the bit-stream-domain redundancy. To this end, we propose a novel lossless recompression approach to eliminate statistical redundancy in the coded video bit stream. The core idea is to increase the probability of this repetitive pattern of continuous “0” or “1” symbol strings in the binary symbol sequence by rearranging the sequence, including value mapping and position aggregation. In particular, Fibonacci-based mapping rule is used to convert the original sequence (those binary symbols in Fibonacci positions) into a new one with more continuous “0” or “1.” Besides, we aggregate as many identical symbols as possible together to further increase the probability of the occurrence of repetitive patterns. Finally, the lossless compression algorithm and the asymptotic lossless compression scheme are designed to achieve a compact representation of the rearranged symbol sequence. We also regulate formal syntactic structures for the proposed mapping rule, aggregation algorithm, and recompression scheme so as to deterministically revert from the recoded version to the original bit stream. The experimental results on compressed H.264/AVC and H.265/HEVC video data show that our approach can considerably reduce the bit rate of streaming video.

Semantic segmentation domain adaptation is used to deal with segmentation problems in a new domain even without pixel-level labels. Highly precise boundaries are the major indicator of segmentation performance, but the previous methods mainly have focused on global representation rather than on local representation, leading to an inferior performance of object boundaries in domain adaptation. In this paper, we propose weighted boundary constraint to refine those segmentation predictions and incorporate it into a generative adversarial network (GAN)-based network for domain adaption to achieve further significant improvement. The boundary constraint loss is designed as the cross-entropy between the intermediate result and the refined result. In addition, confidence from discriminator of GAN is used to constrain the boundary constraint loss to reduce the negative impact from inaccurate object boundaries. The entire network can be learned in an end-to-end manner. Both quantitative and qualitative experiments demonstrate the benefits of our approach which shows the competitive performance with the state-of-the-art methods.

Ulva prolifera (U. prolifera), a seaweed species in the family Ulvaceae, has been causing green tides in the Yellow Sea, China, every year since 2008. This has attracted the attention of the government and the scientific community because of its influence on the region's marine economy and coastal zone environment. Remote sensing, surveillance ships, and airplanes are three common surveillance approaches used by the State Oceanic Administration (SOA) for U. prolifera detection in the Yellow Sea. However, improving the accuracy and convenience of daily U. prolifera detection by fusing the data from these sources, and obtaining the coverage area and distribution of U. prolifera without human intervention, are two challenges that need to be addressed. To this end, this study proposes an improved multi-source evidence fusion method based on Dempster-Shafer evidence theory to detect the distribution and coverage area of U. prolifera using data from multiple sources (MODIS images, Sentinel-2A images, and surveillance ship data). This improved approach can handle the conflicts caused by differences in image characteristics and spatial resolutions as well as differences between surveillance ship data and remote sensing data. The capability of the improved method to extract the distribution and coverage area of U. prolifera was tested experimentally. The results agree with the reference data supplied by SOA in terms of spatial position and geometry. The fusion of multi-source data demonstrates better results in the detection of U. prolifera coverage area and spatial distribution compared with those from individual data sources. The improved approach can be applied to daily and emergent monitoring tasks for U. prolifera detection.

Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Renal tubular injury plays an important role in the development and progression of DN. And apoptosis of renal tubular epithelial cells (RTEC) contribute to the loss of renal function, increased levels of serum creatinine (SCr), blood urea nitrogen (BUN), urine total protein to urine creatinine and microalbuminuria and reduction of creatinine clear rate (CCr). Moreover, recent findings suggested that endoplasmic reticulum (ER) stress may lead to apoptosis of renal cells. Astragalosides IV (AS-IV) has a variety of pharmacological effects such as anti-apoptosis. Thus, in this study we investigated the effects and mechanisms of AS-IV on apoptosis of RTEC in high-fat diets (HFD) and low-dose streptozotocin (STZ)-induced type 2 DN rats. The results showed that AS-IV (40, 80 mg/kg) could alleviate RTEC apoptosis in DN rats. Furthermore, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney were also improved by AS-IV. And AS-IV could reduce the expression of apoptosis-related proteins cleaved caspase-3, Bax/Bcl-2 ratio. ER stress-related proteins GRP78, p-PERK, ATF4 and CHOP were also inhibited by AS-IV in kidney of DN rats. Taken together, our study suggests that the protective effects of AS-IV may be related to inhibit ER stress-induced apoptosis through down-regulating the expression of p-PERK, ATF4 and CHOP. And our study provides a new theoretical basis for the clinical treatment of patients with kidney diseases.

Recently, context learning networks have shown promise in filling large holes in natural images. These networks can decorate the predicted contents with high-frequency details by borrowing or copying neural information from the known region. However, this operation might introduce undesired content change in the synthesized region, especially when similar neural patterns cannot be found in the known region. To solve this problem, we present a network named Artist-Net to decompose an image into the content code and style code explicitly. The Artist-Net completes a corrupted image following the way an artist restores a damaged picture. It can produce more detailed content by inferring the content code of the corrupted images in the latent space since the dimension of the content space is lower than the original image. The Artist-Net can also keep style consistent over the entire image by decorating the inferred content code with the style code extracted from the known region. The experiments on multiple datasets, including structural and natural images demonstrate that the proposed network out-performs the existing ones in terms of content accuracy as well as texture details.

It has been an important objective in China’s energy development strategy to accelerate the promotion of natural gas utilization, cultivate main sources of natural gas, and increase the proportion of natural gas consumption. Based on the analysis of the development of natural gas utilization in China over the past 3 decades by means of classified and comparative research, this paper reveals the shift in the development pattern of China’s natural gas utilization structure from the domination of industrial gas and chemical gas to a relative balance among industrial fuel, urban gas, and power generation gas. Sustained and steadily growing natural gas is an important basis for the rapid growth of natural gas utilization. Maintaining moderate growth in the natural gas transmission and distribution network is an important guarantee for the rapid growth of natural gas utilization. The slowdown in the world’s economic growth has not caused any significant adverse impact on the rapid growth in China’s electricity generation gas. The natural gas utilization policy has no effect on the adjustment of industrial fuel gas any longer. Industrial fuels and chemical gas are greatly subject to natural gas prices. Based on China’s energy consumption targets for 2020 and 2030, this paper estimates the gas consumption of major gas areas and their development position, namely, more development space for industrial fuels, still rapid growth in urban gas but hardly major breakthroughs in gas proportion, rapid growth in power generation gas and a more prominent role in peak shaving, sustained high growth in transportation gas and challenges from new energy and low oil prices, and a significant decline but still a large scale in chemicalgas. Keywords: Natural gas utilization, Structure distribution, Influencing factors, Development trends, Development positioning

Diabetic cardiomyopathy (DCM) is one of the main complications of type 2 diabetes mellitus (T2DM), and it is also one of the main causes of heart failure and death in advanced diabetes. The myocardial lipotoxic injury induced by abnormal lipid metabolism plays an important role in the occurrence and development of DCM, such as myocardial inflammation and fibrosis, ultimately leading to myocardial remodeling and cardiac insufficiency. Astragaloside IV (AS-IV) has many pharmacological effects such as anti-oxidation, anti-inflammatory, immune regulation, and anti-ischemic brain damage. This study was performed to investigate whether AS-IV could prevent T2DM-induced cardiomyopathy and regulate the abnormal myocardial lipid metabolism in diabetes. In this study, the T2DM model was induced by feeding with high-fat food and injected with low-dose STZ in rats. Then the model rats were treated with AS-IV and metformin (Met) for 8 weeks. The results showed that AS-IV improved cardiac systolic and diastolic function, and ameliorated the cardiac histopathological changes in the T2DM rats. Moreover, AS-IV significantly improved circulating TC, TG and HDL levels and cardiac lipid accumulation in T2DM rats as well as in high-fat diet (HFD) rats. Furthermore, AS-IV significantly inhibited the expressions of TNF-α, IL-6 and IL-1β and myocardial fibrosis in T2DM rats, which might be attributed to the improvement of myocardial lipid metabolism, ultimately improving cardiac function in T2DM rats. Taken together, these data suggested that AS-IV has protective effects on T2DM-induced myocardial injury in rats, and its mechanism may be related to the improvement of lipid metabolism in cardiomyocytes.

The use of rejuvenators has enhanced the workability of asphalt mixtures containing the reclaimed asphalt pavement (RAP). This conclusion is based on the determination of viscosity of asphalt binders, while not validated from reclaimed asphalt mixtures. In this study, the effect of two rejuvenators (ordinary and emulsified rejuvenator) on the workability of reclaimed asphalt mixtures was evaluated by measuring the mixing torque and determining the air void content of reclaimed mixtures. In addition, their effects on the performances of reclaimed mixture were studied via the three indexes tests, rutting test and freeze-thaw splitting tests. The experimental results show that mixing torque and air void content of reclaimed mixtures with the emulsified rejuvenator is 4% and 6% lower than that with the ordinary rejuvenator, respectively. This indicates that improvement of the workability of reclaimed mixtures can be achieved by using an emulsified rejuvenator, but not by an ordinary rejuvenator. That is also the reason that at least 20% greater high-temperature stability is found for reclaimed mixtures by using the emulsified rejuvenator than using the ordinary rejuvenator. In addition, reclaimed mixtures with the emulsified rejuvenator show similar moisture susceptibility to that with the ordinary rejuvenator. This study provides a feasible method to assess the workability effect of rejuvenators on reclaimed mixtures directly and recommends the use of an emulsified rejuvenator to improve the workability and high-temperature stability of reclaimed mixtures.

The problem of impact time control guidance with field-of-view constraint is addressed based on time-varying sliding mode control. The kinematic conditions that satisfy the impact time control with field-of-view constraint are defined, and then a novel time-varying sliding surface is constructed to achieve the defined conditions. The sliding surface contains two unknown coefficients: one is tuned to achieve the global sliding surface to satisfy the impact time constraint and zero miss distance, and the other is tuned to guarantee the field-of-view constraint. The guidance law is designed to ensure the realization of the global sliding mode. On this basis, the guidance law is modified to a closed-loop structure, and the maximum detection capability of the seeker is utilized to a greater extent. Under the proposed guidance law, neither the small angle assumption nor time-to-go estimation is needed. The guidance command is continuous and converges to 0 at the desired impact time. Simulation results demonstrate the effectiveness and superiority of the proposed guidance law.

Because the data volume of news videos is increasing exponentially, a way to quickly browse a sketch of the video is important in various applications, such as news media, archives and publicity. This paper proposes a news video summarization method based on SURF features and an improved clustering algorithm, to overcome the defects in existing algorithms that fail to account for changes in shot complexity. Firstly, we extracted SURF features from the video sequences and matched the features between adjacent frames, and then detected the abrupt and gradual boundaries of the shot by calculating similarity scores between adjacent frames with the help of double thresholds. Secondly, we used an improved clustering algorithm to cluster the color histogram of the video frames within the shot, which merged the smaller clusters and then selected the frame closest to the cluster center as the key frame. The experimental results on both the public and self-built datasets show the superiority of our method over the alternatives in terms of accuracy and speed. Additionally, the extracted key frames demonstrate low redundancy and can credibly represent a sketch of news videos.

Abstract Background Homoharringtonine (HHT) is a natural alkaloid with potent antitumor activity, but its precise mechanism of action is still poorly understood. Methods We examined the effect of HHT on alternative splicing of Bcl-x and Caspase 9 in various cells using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The mechanism of HHT-affected alternative splicing in these cells was investigated by treatment with protein phosphatase inhibitors and overexpression of a protein phosphatase. Results Treatment with HHT downregulated the levels of anti-apoptotic Bcl-xL and Caspase 9b mRNA with a concomitant increase in the mRNA levels of pro-apoptotic Bcl-xS and Caspase 9a in a dose- and time-dependent manner. Calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), significantly inhibited the effects of HHT on the alternative splicing of Bcl-x and Caspase 9, in contrast to okadaic acid, a specific inhibitor of PP2A. Overexpression of PP1 resulted in a decrease in the ratio of Bcl-xL/xS and an increase in the ratio of Caspase 9a/9b. Moreover, the effects of HHT on Bcl-x and Caspase 9 splicing were enhanced in response to PP1 overexpression. These results suggest that HHT-induced alternative splicing of Bcl-x and Caspase 9 is dependent on PP1 activation. In addition, overexpression of PP1 could induce apoptosis and sensitize MCF7 cells to apoptosis induced by HHT. Conclusion Homoharringtonine regulates the alternative splicing of Bcl-x and Caspase 9 through a PP1-dependent mechanism. Our study reveals a novel mechanism underlying the antitumor activities of HHT.

Abstract Background Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has been shown to have promising therapeutic potential against cancer cells, but its mechanism of action remains unclear. Methods The inhibitory effect of gigantol on Wnt/β-catenin signaling was evaluated with the SuperTOPFlash reporter system. The levels of phosphorylated low-density lipoprotein receptor related protein 6 (LRP6), total LRP6 and cytosolic β-catenin were determined by Western blot analysis. The expression of Wnt target genes was analyzed using real-time PCR. Cell viability was measured with a MTT assay. The effect of gigantol on cell migration was examined using scratch wound-healing and transwell migration assays. Results Gigantol decreased the level of phosphorylated LRP6 and cytosolic β-catenin in HEK293 cells. In breast cancer MDA-MB-231 and MDA-MB-468 cells, treatment with gigantol reduced the level of phosphorylated LRP6, total LRP6 and cytosolic β-catenin in a dose-dependent manner, resulting in a decrease in the expression of Wnt target genes Axin2 and Survivin. We further demonstrated that gigantol suppressed the viability and migratory capacity of breast cancer cells. Conclusion Gigantol is a novel inhibitor of the Wnt/β-catenin pathway. It inhibits Wnt/β-catenin signaling through downregulation of phosphorylated LRP6 and cytosolic β-catenin in breast cancer cells.