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Supplementary Figure S1; Supplementary Table S1.

Purpose: High-motility group AT-hook gene 1 (HMGA1) is a non-histone nuclear binding protein that is developmentally regulated. HMGA1 is significantly overexpressed in and associated with high grade and advance stage of prostate cancer (PC). The oncogenic role of HMGA1 is at least mediated through chromosomal instability and structural aberrations. However, regulation of HMGA1 expression is not well understood. Identification of microRNA-mediated HMGA1 regulation will provide a promising therapeutic target in treating PC.Experimental Design: In this study, we examined the functional relation between miR-296 and HMGA1 expression in several PC cell lines and a large PC cohort. We further examined the oncogenic property of HMGA1 regulated by miR-296.Results: Here we report that miR-296, a microRNA predicted to target HMGA1, specifically represses HMGA1 expression by promoting degradation and inhibiting HMGA1translation. Repression of HMGA1 by miR-296 is direct and sequence specific. Importantly, ectopic miR-296 expression significantly reduced PC cell proliferation and invasion, in part through the downregulation of HMGA1. Examining PC patient samples, we found an inverse correlation between HMGA1 and miR-296 expression: high levels of HMGA1 were associated with low miR-296 expression and strongly linked to more advanced tumor grade and stage.Conclusions: Our results indicate that miR-296 regulates HMGA1 expression and is associated with PC growth and invasion. Clin Cancer Res; 17(6); 1297–305. ©2010 AACR.

Wind tunnel test is a critical way to investigate flutter characteristics of aircraft, particularly in identifying the transonic dip phenomenon in the aeroelastic design. The continuous wind tunnel has advantages over the blow-down wind tunnel in long running time, wide bandwidth of dynamic pressure, and stable flow field. Thus, the continuous wind tunnel is more suitable for transonic flutter tests. Flutter test techniques are studied for FL-62 wind tunnel, the first large-scale continuous transonic wind tunnel in China. A protection system and a real-time signal processing are developed to ensure the safety and efficiency. Flutter boundaries of a horizontal-tail model are investigated in FL-62 wind tunnel in the Mach number regime between 0.65 and 0.98. In the test, structural vibrations are measured via strain gauges, deformations and pressure distributions are measured via non-contact optical techniques, and flutter boundaries are predicted via a modal identification method.

This paper investigates the problems of the observer-based fault estimation (FE) and fault-tolerant control (FTC) for nonlinear systems subjected to external disturbances by the T–S fuzzy model method with local nonlinear models. Firstly, an FE strategy is proposed based on the unknown input observer technology, where the local nonlinear terms can be decoupled from the FE error system for relaxing the design of observer. Then, by using the FE information, a fuzzy fault-tolerant controller is designed to guarantee the stability of the system. Additionally, in the design schemes of the FE observer and the fault-tolerant controller, the $${L_\infty }$$ method is used to deal with the problems of FE and FTC for the system with persistent disturbance such that the robustness of the system against the persistent external disturbance can be increased. Compared with the traditional $${H_\infty }$$ method which is only applicable for dealing with the energy bounded signals, the $${L_\infty }$$ FTC strategy proposed in this paper can deal with the persistent disturbance such that the shortcomings of the traditional $${H_\infty }$$ approach are overcome. Finally, the effectiveness of the proposed method is verified by simulation results.

Nasopharyngeal carcinoma (NPC), a neoplasm of the head and neck, has high incidence and mortality rates in East and Southeast Asia.The active ingredients of Evodia and targets in NPC were obtained from multiple databases, and an interaction network was constructed via the Cytoscape and STRING databases. The key biological processes and signalling pathways were predicted using Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses. Molecular docking technology was used to identify the affinity and activity of target genes, and The Cancer Genome Atlas and Human Protein Atlas databases were used to analyse differential expression. Cell Counting Kit-8 (CCK-8) and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) dual-fluorescence staining were used for experimental verification.Active Evodia compounds included quercetin, isorhamnetin, and evodiamine, and important NPC targets included MAPK14, AKT1, RELA, MAPK1, JUN, and p53, which were enriched in lipid and atherosclerosis signalling pathways. Additionally, we verified the high affinity and activity of the active compounds through molecular docking, and the target proteins were verified using immunohistochemistry and differential expression analyses. Furthermore, CCK-8 assays and Annexin V-FITC/PI dual-fluorescence staining showed that isorhamnetin inhibited the proliferation of NPC cells and induced apoptosis.Our results identified the molecular mechanisms of Evodia and demonstrated its ability to alter the proliferation and apoptosis of NPC cells through multiple targets and pathways, thereby providing evidence for the clinical application of Evodia.

This paper focuses on the observer-based fault-tolerant control problem for the discrete-time nonlinear systems with the perturbation and the fault signals. First, the nonlinear term with perturbation is put into the local nonlinear part so that the nonlinear system with perturbation can be described as an interval type-1 (IT1) T-S fuzzy system. Then, based on the unknown input observer technology, the IT1 T-S fuzzy fault estimation (FE) observer scheme is presented to obtain the real-time FE information and decouple the local nonlinear part from the estimation error system, where the design complexity and the computational burden are reduced simultaneously. Second, based on the real-time FE information, an FE-based interval type-2 (IT2) T-S fuzzy fault-tolerant control scheme is presented to achieve the compensation for the influence of the fault signal and the stabilization for the system. Different from the traditional methods, a mixed design scheme, which is based on the IT1 T-S fuzzy fault estimation observer method and the IT2 T-S fuzzy fault-tolerant controller method, is proposed in this paper. This strategy can not only reduce the computational burden, but also obtain a less conservative result. Finally, the effectiveness of the mixed design approach is illustrated by an example.

Since China implemented a comprehensive two-child policy in October 2015, it has not reached the expected peak birth rate. Therefore, birth willingness, determining factors and policy optimization have become key topics of discussion and analysis. This study examined the factors influencing childbearing intentions among female employees of Department M in the Public Sector in China under the “Two-child” Policy Using a questionnaire survey and interview guide both capturing three dimensions that are individual basic information, actual marital status and family structure characteristics, data were collected from female employees of Department M in the Public Sector in China. Data were collected from 280 female employees. Logistic binary regression was carried out for quantitative data using SAS software while qualitative data were analysed using content analysis. The findings revealed that the influencing factors of the current female employees’ willingness to bear children in the Department M were marital factors, birth and support costs, growth environment, family conditions and external conditions. Therefore, it was concluded that the severe cost of childbirth and its own development situation will affect the willingness of female employees to bear children. And the recommendations of this study are that the government should pay more attention to the fertility environment of the whole society.

Background: Nasopharyngeal carcinoma (NPC) is a neoplasm of the head and neck, with the highest incidence and mortality rates occurring in East and Southeast Asia. Evodia rutaecarpa is a tree that is native to Korea and China, and its fruit (hereafter referred to as Evodia) exhibits remarkable antitumor properties. However, little is known about its mechanism of action in NPC. In this study, we employed network pharmacology to identify targets of the active Evodia compounds in nasopharyngeal carcinoma and generate an interaction network.Methods: The active ingredients of Evodia and the targets for nasopharyngeal carcinoma were obtained from multiple databases, and an interaction network was constructed via the Cytoscape and STRING databases. The key biological processes and signaling pathways were predicted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Molecular docking technology was used to identify the affinity and activity of target genes, while The Cancer Genome Atlas and Human Protein Atlas databases were used to analyze differential expression. Cell Counting Kit (CCK)-8 and Annexin V-FITC/PI dual fluorescence staining were used for experimental verification.Results: Active Evodia compounds included quercetin, isorhamnetin, and evodiamine, and important nasopharyngeal carcinoma targets included MAPK14, AKT1, RELA, MAPK1, JUN, and p53, whose content in the lipid and atherosclerosis signaling pathways was also high. Additionally, we verified the high affinity and activity of the active compounds through molecular docking, and the target proteins were verified using immunohistochemistry and differential expression analyses. Furthermore, Cell Counting Kit-8 assays and Annexin V-FITC/propidium iodide dual-fluorescence staining verified that isorhamnetin inhibited the proliferation of nasopharyngeal carcinoma cells and induced apoptosis, respectively.Conclusion: These results elucidated the molecular mechanism of Evodia and demonstrated its ability to alter the proliferation and apoptosis of nasopharyngeal carcinoma cells through multiple targets and pathways, thereby providing evidence for its clinical application.

In point cloud generation and completion, previous methods for transforming latent features to point clouds are generally based on fully connected layers (FC-based) or folding operations (Folding-based). However, point clouds generated by FC-based methods are usually troubled by outliers and rough surfaces. For folding-based methods, their data flow is large, convergence speed is slow, and they are also hard to handle the generation of non-smooth surfaces. In this work, we propose AXform, an attention-based method to transform latent features to point clouds. AXform first generates points in an interim space, using a fully connected layer. These interim points are then aggregated to generate the target point cloud. AXform takes both parameter sharing and data flow into account, which makes it has fewer outliers, fewer network parameters, and a faster convergence speed. The points generated by AXform do not have the strong 2-manifold constraint, which improves the generation of non-smooth surfaces. When AXform is expanded to multiple branches for local generations, the centripetal constraint makes it has properties of self-clustering and space consistency, which further enables unsupervised semantic segmentation. We also adopt this scheme and design AXformNet for point cloud completion. Considerable experiments on different datasets show that our methods achieve state-of-the-art results., 9 pages, 7 figures, AAAI 2022

Triassic granitic magmatism is widespread in the Eastern Kunlun Orogenic Belt (EKOB), northern Tibetan Plateau. Some of the granitoids are characterized by high Sr and low Y contents, and consequently high Sr/Y ratios. These high Sr/Y-ratio granitoids are often interpreted as adakitic rocks, originating from the thickened continental lower crust. However, studies have shown that granitoids with high Sr/Y ratios may have formed via other geological processes. This paper reports U–Pb ages, geochemical and Sr–Nd–Hf isotopic data for newly discovered granodiorite porphyries in the Kunlun River area of the Eastern Kunlun Orogenic Belt, and discusses whether the EKOB experienced crustal thickening during the Triassic. The granodiorite porphyries crystallized at 205 Ma. They have some adakitic characteristics with SiO2 = 66.96–69.68 wt.%, Sr/Y ratios = 31–43, La/Yb = 26.9–57.9, Y = 8.47–11.3, Yb = 0.75–1.30, and MgO = 0.44–0.99 wt.%. However, the relatively flat heavy rare earth element patterns indicate that garnet was not the main residue in the magma source. In addition, combined with Nd–Hf isotopic data, these results indicate that the timing of the original generation of the crustal sources of the granodiorites should be Mesoproterozoic, with the involvement of older (Paleoproterozoic) components. The granodiorite porphyries were emplaced in a post-collisional environment after the northward subduction of Paleo-Tethyan oceanic lithosphere, and without thickening of the continental crust.

Petrology, whole-rock geochemistry, in situ zircon U–Pb ages, and Lu–Hf isotopic data are reported for granodiorite and monzonitic granite samples from the Harizha Region in the eastern section of the East Kunlun Orogenic Belt. The results of the LA-ICP-MS zircon dating indicate that the granodiorite and monzonitic granite were emplaced at 447.9 ± 3.0 Ma and 443.8 ± 3.5 Ma, respectively, i.e., in the Late Ordovician–Early Paleozoic periods. The granodiorite is characterized by relatively high MgO (4.52–5.91 wt%), Sr (541–712 ppm), Cr (218–357 ppm), Ni (56.7–80.7 ppm) and V (66.8–94.7 ppm), with low Y (10.40–13.60 ppm) and Yb (1.05–1.45) contents. This results in elevated Mg# (65–68), Sr/Y (39.78–58.84), and (La/Yb)N (10.21–18.30) ratios, common features for adakitic high-Mg andesite (HMA). The granodiorite is metaluminous to weakly peraluminous and high-K calc-alkaline in composition. In addition, the granodiorite is enriched in light rare-earth elements (LREE) and large ion lithophile elements (LILEs, Rb, K, Sr, and Pb) U, and Nd; and depleted in high-field strength elements (HFSEs, Nb, Ta, Zr, Hf, Ti) and P. The zircon grains from the granodiorites have eHf(t) values of − 5.5 to + 4.7, with two-stage Hf model ages (tDM2) ranging from 0.92 to 1.71 Ga. These features suggest that the granodiorites were formed by mixing processes of crustal melts and magma from a metasomatized mantle in a subduction setting. The monzonitic granite possesses high normative corundum values (2.34–4.10 wt%), is strongly peraluminous (A/CNK ratios of 1.16–1.32, with minor mineral muscovite), with high-K calc-alkaline affinity. Furthermore, enrichments in large ion lithophile elements (Rb, K, and Pb), U, Th, and Nd, depletions in high-field strength elements (Nb, Ta, and Ti) and Ba and P, and mainly right-inclined REE patterns with negative Eu anomalies, exhibits an S-type granite affinity. The magmatic zircons from the monzonitic granite yielded eHf(t) values between − 4.9 and − 2.7, corresponding to two-stage Hf model ages of 1.60–1.73 Ga. Therefore, this study suggests that the monzonitic granite magma was derived from crustal material (metagreywacke) in a syn-collision setting. Subsequently, by combining these findings with the previous research results, this study propose that a transverse diachronism closure model which entailed an “earlier on the sides–later in the middle” in an East–West direction in the East Kunlun Orogenic Belt for the Proto-Tethys Ocean’s evolution process.

This study aimed to evaluate whether the whole powder (SRPW) and polysaccharide (SRPS) from Sporisorium reilianum could modulate the gut microbiota in mice with dextran sulfate sodium (DSS) induced colitis. The results showed that the disease and structure of colon tissue were improved, and the balance of colonic mucosal related factors was restored. Compared to ulcerative colitis (UC) mice, the composition and diversity of gut microbiota were significantly increased. Specifically, the abundance of Bacteroidetes, TM7, and Proteobacteria at the phylum level and Bacteroides, Coprobacillus, Streptococcus, and Lactobacillus at the genus level were restored to normal levels. Furthermore, functional analysis revealed that carbohydrate, amino acid, and energy metabolism were regulated by S. reilianum, thus promoting the recovery of the intestinal mucosal structure. These findings indicated the possibility of S. reilianum as a functional food to prevent colitis through the gut microbiota.

Pinus koraiensis nut-coated film is a kind of by-product of nut processing, which has been shown to contain flavonoids, polyphenols, and other substances that can be used to produce natural antioxidant extracts. In this study, response surface methodology (RSM) was used to optimize the extraction process of flavonoids of P. koraiensis nut-coated film (PNF), and macroporous resin HPD600 was used to purify PNF (P-PNF). Its antioxidant activity was examined by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging capacity, oxygen free radical absorption capacity (ORAC), total oxygen radical capture (TRAP), and iron ion reduction capacity. Under the ideal extraction conditions comprising a cellulase dosage of 90 U/g, a material/liquid ratio of 1:20 (g/mL), and an extraction time of 2 h, the PNF yield was 3.37%. Purification conditions were sample concentration of 2.0 mg/mL, pH of 5, water washing volume of 3 bed volume (BV), eluent ethanol concentration of 50%, and volume of 2 BV. The P-PNF recovery was 84.32%, and purity increased from 33.80% to 61.70%. Additionally, P-PNF showed increased antioxidant activity compared to PNF. Cumulatively, this study obtained the optimal values for the process parameters in order to achieve the maximum rates of extraction of PNF for economically optimal production at an industrial scale.

The present study aimed to identify the expression of key mRNAs as prognostic factors for papillary thyroid cancer (PTC) using integrated bioinformatic analyses and in vitro assays. Using mRNA sequencing data from The Cancer Genome Atlas, we found that alpha-1 type I collagen (COL1A1), an extracellular matrix protein, was significantly overexpressed in PTC, and its expression was correlated with a lower probability of disease-free survival and clinical characteristics of PTC patients by applying Kaplan-Meier curves and logistic regression analysis. Furthermore, we performed in vitro assays, including cell proliferation, colony formation, transwell, and wound healing assays, to validate the role of COL1A1 in the progression and metastasis of PTC. Downregulation of COL1A1 with siRNA inhibited cell proliferation, invasion, and migration. COL1A1 is a potential prognostic biomarker and target for preventing the recurrence of PTC.

This study investigated lipid metabolism regulation by anthocyanins from Aronia melanocarpa (AAM) in 3T3-L1 preadipocytes and high fat diet (HFD) mice. Ultra-performance liquid chromatography/ion mobility quadrupole time-of-flight mass spectrometry analysis identified the constituents of AAM, which decreased lipid content and inflammation in 3T3-L1 cells without cytotoxicity. Meanwhile, taking normal diet and orlistat mice as references, AAM supplementation improved blood lipid levels and adipocyte degeneration, promoted beneficial gut microbial growth, and maintained lipid metabolism in HFD mice. Furthermore, AAM activated the AMP-activated protein kinase (AMPK) signaling pathway, accompanied by the regulation of adipogenic transcription factors and their target genes in vitro and in vivo. Collectively, our data demonstrated that AAM exhibits anti-adipogenic activities that were partially mediated by the AMPK pathway and gut microbiota regulation. This study provides new insight into the regulation of lipid metabolism by AAM and suggests that AAM has potential therapeutic effects on hyperlipidemia.

Introduction Estrogen receptor β (ERβ) always lacks expression in estrogen-dependent tumors, which may result from gene inactivation by methylation. In this study, we aimed to determine whether aberrant methylation of the ERβ promoter is associated with decreased ERβ gene expression in breast cancer. Material and methods ERβ methylation status was determined for 132 pairs of breast cancer and adjacent normal tissues via the MethyLight method. Additionally, mRNA relative expression was quantified by real-time polymerase chain reaction (RT-PCR) to determine whether aberrant methylation had a negative correlation with expression. The correlation of ERβ promoter methylation and clinical parameters is also discussed. Results Methylation was observed in 96 (72.7%) breast cancer samples, and the median percentage of fully methylated reference (PMR) among methylated tissues was 0.83. Meanwhile, 94 (71.2%) adjacent normal tissues were methylated and the median PMR was 0.48. Compared to adjacent normal tissues, the methylation level of breast cancer was significantly higher (p < 0.001) and mRNA expression was much lower (p < 0.001). There was a significant correlation between ERβ methylation and mRNA expression in adjacent normal breast tissues (p = 0.004). In addition, the methylation rate of cancer tissues whose maximum diameter < 3 cm was significantly higher than those > 3 cm (p = 0.025). Conclusions ERβ promoter methylation level varies between cancerous and adjacent normal breast tissues. There was significant downregulation of ERβ methylation expression in pre-cancerous stages of breast cancer. Therefore, demethylation drugs may offer a potential strategy for preventing the development of pre-cancerous cells.

Background: To investigate the cooling and healing effect of different modalities: Hydrogel dressing® was compared with targeted artery injection of low temperature liquid as a coolant following application to a fresh deep partial thickness hot water scald in a rabbit hind limb model. Materials and methods: Fifty five rabbits were randomly divided into 5 groups. Treatment group received femoral artery injection of low temperature liquid and hydrogel dressing post burn 30 min or 1 hour. Control group were just scalded. Subcutaneous (Tu) and deep mussel temperatures (Tm) were continually monitored in all wounds. After scald the rectal temperature were detected within 6 hours. The wounds were biopsied for histological assessment at 72 h and 3 weeks. Results: Effective cooling of the burn wound and an increased rate of wound healing was achieved by both treatment methods. The final temperature at 1h decreased to the preburn temperature. Compared with hydrogel dressing group (Tm decreased by 1.3 ± 0.4°C), Tm decreased by 2.8 ± 0.3°C in femoral artery injection group, showing significant difference (P < 0.05). Artery injection of low temperature liquid and hydrogel dressing almost exert no influence on rabbit core temperature. Clinical and histological assessment at 21 days indicated more rapid healing in both the 30 min hydrogel dressing and artery injection burns compared with the controls and the 60 minutes intervention groups. Conclusion: This result indicates artery injection of low temperature liquid earlier to cooling limb is an effective means to reduce residual heat damage tissue without affect core temperature and increase wound healing.

Glomerular sparing (GS) is defined as a unique growth pattern in which tumor cells replace the majority of renal tubes and overrun intact glomeruli. This phenomenon has been well recognized by pathologists as a typical infiltrative pattern and some studies suggested it was an independent risk factor. Here, we study the clinical, pathological, and immunohistochemical features of primary kidney neoplasms with glomerular sparing pattern. We searched the archives of our pathology department for nephrectomy specimens and reviewed all pathology reports from 2009-2013. We selected cases with tumor and collected clinicopathological information, focusing on re-evaluation of cases with glomerular sparing pattern. To facilitate our study we performed immunohistochemical stains of PAX-8, p63, and InI-1 on selected cases. We selected a total of 204 nephrectomy cases in this study, including 163 cases of renal cell carcinoma; 37 cases of urothelial carcinoma; 4 cases from other categories (Wilms tumor, primary diffuse large B-cell lymphoma, angiolipoma, rhabdoid tumor). Finally, we identified 7 cases of primary kidney tumors with glomerular sparing pattern: 2 cases of clear cell renal cell carcinomas (ccRCC), 1 case of collecting duct carcinoma, 2 cases of urothelial carcinoma (UC), 1 case of diffuse large B-cell lymphoma and 1 case of malignant rhabdoid tumor. The primary kidney tumors with glomerular sparing pattern are rare and incidence in our study is