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In this study, analytical solutions are developed to assess the hydraulic and structure responses of underwater tunnels by considering the tidal loading in conjunction with water ingress. Two scenarios are considered, that is, the surface water fluctuation (SWF) and groundwater variation (GWV). A single-step scheme is put forward to obtain the exact horizontal displacement developed at the springline with high efficiency. The proposed analytical method is verified by comparing the result from numerical simulations. A detailed parameter analysis is presented to investigate the effect of soil properties on the ground and tunnel behaviors as well as the discrepancies between these two hydraulic loadings. This study reveals that the underwater tunnel tends to act as drainage in the SWF condition whereas blockage for GWV. Much more intensive hydraulic and structure responses are observed under SWF than GWV, but both cases lead to slight tunnel deformations.

This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer.A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not.The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status.The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis

This paper proposes Attribute-Decomposed GAN (ADGAN), a novel generative model for arbitrary image synthesis, which can produce realistic images with desired controllable attributes provided in various source inputs. The core idea of the proposed model is to embed attributes into the latent space as independent codes and achieve flexible and continuous control of attributes via mixing and interpolation operations in explicit style representations. Specifically, a new network architecture consisting of two encoding pathways with style block connections is proposed to decompose the original hard mapping into multiple more accessible subtasks. Since the original ADGAN fails to handle the image synthesizing task where the number of attribute categories is huge, this paper also proposes ADGAN++, which uses serial encoding of different attributes to generate attributes of wild images and residual blocks with segmentation guided instance normalization to combine the separated attributes and refine the original synthesis results. The two-stage ADGAN++ is designed to alleviate the massive computational resources introduced by wild images with numerous attributes while maintaining the disentanglement of different attributes to enable flexible control of arbitrary semantic parts of the images. Experimental results demonstrate the proposed methods' superiority over the state of the art in various image synthesis tasks.

Introduction: Senile osteoporosis is one of the most common age-related diseases worldwide. Glucagon like peptide-2 (GLP-2), a naturally occurring gastrointestinal peptide, possesses therapeutic effects on bone loss in postmenopausal women and ovariectomized rats. However, the role of GLP-2 in senile osteoporosis and underlying mechanisms has not been explored. Methods: GLP-2 was subcutaneously injected into the 6-month-old male senile osteoporosis model of senescence-accelerated mouse prone 6 (SAMP6) mice for 6 weeks. SAMP6 subjected to normal saline and senescence-accelerated mouse resistant 1 served as control groups. Micro-computed tomography was performed to evaluate the bone mass and microarchitecture of the mice. Osteoblastic and osteoclastic activities were determined by biochemical, quantitative real-time PCR, histological, and histomorphometric analyses combined with hematoxylin-eosin, toluidine blue, and tartrate-resistant acid phosphatase staining. We also examined the proteins and structure of intestinal tight junction using immunohistochemical assay as well as a transmission electron microscope. Serum inflammation marker levels were measured using ELISA. Additionally, anti-oxidative enzymes GPX-4 and SOD-2 and receptors of GLP-2 and vitamin D expression in the ileum and colon were detected under immunofluorescence staining. Results: Six-week GLP-2 treatment attenuated bone loss in SAMP6 mice, as evidenced by increased bone mineral density, improved microarchitecture in femora, and enhanced osteogenic activities. In contrast, the activity of osteoclastic activity was not obviously inhibited. Moreover, GLP-2 ameliorated tight junction structure and protein expression in the intestinal barrier, which was accompanied by the reduction of TNF-α level. The expression of receptors of intestinal GLP-2 and vitamin D in the ileum was elevated. Furthermore, the oxidative stress in the intestines was improved by increasing the GPX-4 and SOD-2 signaling. Conclusion: Our findings suggest that GLP-2 could ameliorate age-associated bone loss, tight junction structure, and improved antioxidant enzyme activity in the gut in SAMP6 mice. Amelioration of gut barrier dysfunction may potentially contribute to improving bone formation and provide evidence for targeting the entero-bone axis in the treatment of senile osteoporosis.

The secreted products of cells drive many functions in vivo; however, methods to link this functional information to surface markers and transcriptomes have been lacking. By accumulating secretions close to secreting cells held within cavity-containing hydrogel nanovials, we demonstrate workflows to analyze the amount of IgG secreted from single human B cells and link this information to surface markers and transcriptomes from the same cells. Measurements using flow cytometry and imaging flow cytometry corroborate the association between IgG secretion and CD38/CD138. By using oligonucleotide-labeled antibodies we find that upregulation of pathways for protein localization to the endoplasmic reticulum and mitochondrial oxidative phosphorylation are most associated with high IgG secretion, and uncover surrogate plasma cell surface markers (e.g., CD59) defined by the ability to secrete IgG. Altogether, this method links quantity of secretion with single-cell sequencing (SEC-seq) and enables researchers to fully explore the links between genome and function, laying the foundation for discoveries in immunology, stem cell biology, and beyond.

Previously, 36 TEAM benchmark problems have been established, used to verify the numerical calculation methods of electromagnetic fields. Among them, there is only one problem related to the magnetic field considering magnetic hysteresis, which is problem 32. The results of it are obtained by experimental measurement. In this paper, a same kind of benchmark problem is proposed, in which the field results are obtained by using analytical method. This benchmark problem can be used to verify both 2D and 3D numerical calculation methods. The analytical solving process of the problem is that H is obtained by using Ampere’s law, then B is calculated based on the hysteresis model of the material, so that the field distribution results are formed. The required hysteresis model could be any kind, such as Preisach model, J–A model, etc. As long as the same kind of model is used both in the benchmark problem and in the numerical method, the numerical method can be verified through the proposed benchmark problem. Considering the form of J–A hysteresis model required by the benchmark problem does not exist, which is the field separation-based forward dynamic J–A model, it is derived based on the forward static J–A model.

The effect of vanadium nitride (VN) particles additives on microstructure and mechanical properties of the extruded AZ31 Mg alloy was systematically investigated. The experimental results revealed that the addition of 0.5 wt% VN decreased the average grain size of AZ31 Mg alloy from 6.4 to 4.9 µm. With the increase in VN content, the refining effect would weaken because excessive VN particles would negatively affect the dynamic recrystallization process of the alloys. The scanning electron microscopy and energy-dispersive spectroscopy indicated that AlN, VN and Al–V–N particles with different morphologies were distributed in the streamline along the extrusion direction during the extrusion process. The mechanical properties of AZ31 Mg alloy vary with the addition of VN. The extruded AZ31 + 0.5 wt% VN Mg alloy possesses an excellent combination of high strength and ductility. The yield strength and ultimate tensile strength of the extruded AZ31 + 0.5 wt% VN Mg alloy were increased without sacrificing ductility. This is mainly due to the grain refinement caused by double-heterogeneous nucleation particles. With a further increase in VN content, the presence of excessive VN particles increases the stress concentration, and the initiation source of microcracks in the alloy during alloy deformation makes the cracks more easily propagated and results in a decrease in the ductility of the extruded alloy.

Patients with prostate-specific membrane antigen (PSMA)-positive tumors can benefit from PSMA-targeted therapy; thus, we have constructed a phage-displayed synthetic antibody library for the production of novel PSMA antibodies with superior PSMA-targeting ability, favoring clinical management. The binding affinities of anti-PSMA antibodies were verified by an enzyme-linked immunosorbent assay (ELISA). Several in vitro and in vivo experiments, including cellular uptake, internalization, and cytotoxicity studies, micro single photon emission computed tomography (microSPECT)/CT, and biodistribution studies, were performed to select the most promising antibody among six different antibodies. The results showed the target affinities of our antibodies in the ELISA assays (7A, 8C, 8E, and 11A) were comparable to the existing antibodies (J591). The half-maximal effective concentrations of 7A, 8C, 8E, 11A, and J591 were 2.95, 6.64, 5.50, 2.08, and 4.79, respectively. The radiochemical yield of

A growing number of environmental professionals are realizing that equitable and meaningful engagement of local community members in the development of programming is essential for catalyzing the durable, long-term action needed to conserve wildlife. Many who attempt to codesign programs with (not for) communities find that choosing the most effective strategies to accomplish this task is crucial and can oftentimes feel daunting. In this paper, a validated psychometric instrument called the Five Factors of Sustained Engagement (Five Factors) was used to analyze community engagement projects from two AZA-accredited institutions, highlighting how the leaders of each project believe they have fostered each factor in their projects. Professionals can use the Five Factors as guideposts and evaluation criteria to increase the long-term motivation of community members to engage in conservation efforts over time. The discussion offers strategies that psychological research has shown to increase long-term motivation for wildlife conservation and suggest how to implement them in the codesign of conservation programming with the communities that are impacted by it the most. Together, this synthesis offers an innovative, psychology-based approach to fostering and evaluating the success of sustainable community engagement for conservation Wildlife conservation projects are rarely su long-term engagement from the humans who are most impacted by those projects.

Metallic magnesium is a promising high-capacity anode material for energy storage technologies beyond lithium-ion batteries. However, most reported Mg metal anodes are only cyclable under shallow cycling (≤1 mAh cm

Leakage-induced hydraulic and ground responses in a twin-tunnel system are analyzed via the proposed analytical solution on the seepage field. The seepage continuity conditions are rigorously satisfied at the interface between the ground and the tunnel lining, in terms of both water pressure and seepage velocity. The analytical solution is verified by comparing the results of numerical simulations. A detailed parametric analysis is carried out to explore the effect of tunnels’ spatial layouts and degraded waterproof facilities on leakage-induced hydraulic and ground response, including head decline, water inflow and ground surface settlement. Our results show that the often used single tunnel model tends to overestimate the pore pressure on the lining along with water inflow into the tunnel, and underestimate the leakage-induced ground settlement.

AimAccurate preoperative prediction of cervical lymph node metastasis (LNM) in patients with mPTMC provides a basis for surgical decision making and the extent of tumor resection. This study aimed to develop and validate an ultrasound radiomics nomogram for the preoperative assessment of LN status.MethodsA total of 450 patients pathologically diagnosed with mPTMC were enrolled, including 348 patients in the modeling group and 102 patients in the validation group. Univariate and multivariate logistic regression analyses were performed on the basic information, ultrasound characteristics, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) scores of the patients in the modeling group to identify independent risk factors for LNM in mPTMC and to construct a logistic regression equation and nomogram to predict the risk of LNM. The validation group data were used to evaluate the predictive performance of the nomogram.ResultsMale sex, age 0.5 cm, capsular invasion, a maximum ACR score >9 points, and a total ACR score >19 points were independent risk factors for the development of cervical LNM in mPTMC. Both the area under the curve (AUC) and concordance index (C-index) of the prediction model constructed from the above six factors were 0.838. The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, decision curve analysis (DCA) demonstrated a significantly greater net benefit of the model. The external validation demonstrated the reliability of the prediction nomogram.ConclusionsThe presented radiomics nomogram, which is based on ACR TI-RADS scores, shows favorable predictive value for the preoperative assessment of LNs in patients with mPTMC. These findings may provide a basis for surgical decision making and the extent of tumor resection.

Although the potent antibacterial ability of radezolid against Staphylococcus aureus has been widely reported worldwide, its antibacterial and anti-biofilm activity against the S. aureus clinical isolates from China remains elusive. In this study, the minimum inhibitory concentration (MIC) of radezolid was determined in S. aureus clinical isolates from China using the agar dilution method, and the relationship between radezolid susceptibility and ST distribution was also investigated. The anti-biofilm activity of radezolid against S. aureus was determined by a crystal violet assay and compared with that of linezolid and contezolid. The quantitative proteomics of S. aureus treated with radezolid was analyzed, and the genetic mutations in radezolid-induced resistant S. aureus were determined by whole-genome sequencing. The dynamic changes in transcriptional expression levels of several biofilm-related genes were analyzed by quantitative RT-PCR. Our data showed that radezolid MIC ranged from ≤0.125 to 0.5 mg/L, which was almost 1/4 × MIC of linezolid against S. aureus, indicating the greater antibacterial activity of radezolid than linezolid. The S. aureus clinical isolates with radezolid MICs of 0.5 mg/L were most widely distributed in ST239 of MRSA and ST7 of MSSA. Moreover, the more robust anti-biofilm activity of radezolid with subinhibitory concentrations (1/8 × MIC and 1/16 × MIC) was demonstrated against S. aureus when compared with that of contezolid and linezolid. Genetic mutations were found in glmS, 23S rRNA, and DUF1542 domain-containing protein in radezolid-induced resistant S. aureus selected by in vitro induction of drug exposure. Quantitative proteomic analysis of S. aureus indicated that the global expression of some biofilm-related and virulence-related proteins was downregulated. Quantitative RT-PCR further confirmed that the expressions of some downregulated biofilm-related proteins, including sdrD, carA, sraP, hlgC, sasG, spa, sspP, fnbA, and oatA, were decreased after 12 h and 24 h of exposure to radezolid. Conclusively, radezolid shows robust antibacterial and anti-biofilm activity against S. aureus clinical isolates from China when compared with contezolid and linezolid.

PDF file - 146K, Figure S1. Analysis of microRNA profiles in various MLL-associated leukemias. Figure S2. Analysis of MLL-AF9 expression cells transformed from bone marrow stem/progenitors. Figure S3. Phenotypic analysis of leukemia from mice transplanted with MLL-AF9 cells. Figure S4. Quantitative PCR analysis of miR-150 expression in various cell types. Figure S5. Wild type and mutated binding sites of miR-150 in Myb luciferase constructs. Figure S6. Wild type and mutated binding sites of miR-150 in CBL and Egr2 luciferase constructs.

The microRNA miR-150, a critical regulator of hematopoiesis, is downregulated in mixed-lineage leukemia (MLL). In this study, miR-150 acts as a potent leukemic tumor suppressor by blocking the oncogenic properties of leukemic cells. By using MLL-AF9–transformed cells, we demonstrate that ectopic expression of miR-150 inhibits blast colony formation, cell growth, and increases apoptosis in vitro. More importantly, ectopic expression of miR-150 in MLL-AF9–transformed cells completely blocked the development of myeloid leukemia in transplanted mice. Furthermore, gene expression profiling revealed that miR-150 altered the expression levels of more than 30 “stem cell signature” genes and many others that are involved in critical cancer pathways. In addition to the known miR-150 target Myb, we also identified Cbl and Egr2 as bona fide targets and shRNA-mediated suppression of these genes recapitulated the pro-apoptotic effects observed in leukemic cells with miR-150 ectopic expression. In conclusion, we demonstrate that miR-150 is a potent leukemic tumor suppressor that regulates multiple oncogenes.Implications: These data establish new, key players for the development of therapeutic strategies to treat MLL-AF9–related leukemia. Mol Cancer Res; 11(8); 912–22. ©2013 AACR.

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Supplementary Figure 1 from E2F8 Contributes to Human Hepatocellular Carcinoma via Regulating Cell Proliferation

The E2F family member of transcription factors includes the atypical member E2F8, which has been little studied in cancer. We report that E2F8 is strongly upregulated in human hepatocellular carcinoma (HCC), where it was evidenced to contribute to oncogenesis and progression. Ectopic overexpression of E2F8 promoted cell proliferation, colony formation, and tumorigenicity, whereas E2F8 knockdown inhibited these phenotypes, as documented in Huh-7, Focus, Hep3B, and YY-8103 HCC cell lines. Mechanistic analyses indicated that E2F8 could bind to regulatory elements of cyclin D1, regulating its transcription and promoting accumulation of S-phase cells. Together, our findings suggest that E2F8 contributes to the oncogenic potential of HCC and may constitute a potential therapeutic target in this disease. Cancer Res; 70(2); 782–91

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Hundreds of members have been synthesized and versatile applications have been promised for endofullerenes (EFs) in the past 30 y. However, the formation mechanism of EFs is still a long-standing puzzle to chemists, especially the mechanism of embedding clusters into charged carbon cages. Here, based on synthesis and structures of two representative vanadium–scandium–carbido/carbide EFs, VSc 2 C@ I h (7)-C 80 and VSc 2 C 2 @ I h (7)-C 80 , a reasonable mechanism—C 1 implantation (a carbon atom is implanted into carbon cage)—is proposed to interpret the evolution from VSc 2 C carbido to VSc 2 C 2 carbide cluster. Supported by theoretical calculations together with crystallographic characterization, the single electron on vanadium (V) in VSc 2 C@ I h (7)-C 80 is proved to facilitate the C 1 implantation. While the V=C double bond is identified for VSc 2 C@ I h (7)-C 80 , after C 1 implantation the distance between V and C atoms in VSc 2 C 2 @ I h (7)-C 80 falls into the range of single bond lengths as previously shown in typical V-based organometallic complexes. This work exemplifies in situ self-driven implantation of an outer carbon atom into a charged carbon cage, which is different from previous heterogeneous implantation of nonmetal atoms (Group-V or -VIII atoms) driven by high-energy ion bombardment or high-pressure offline, and the proposed C 1 implantation mechanism represents a heretofore unknown metal–carbon cluster encapsulation mechanism and can be the fundamental basis for EF family genesis.

ObjectiveThe purpose of the study was to investigate the abnormality both of static spontaneous brain activity and dynamic temporal variances following a pontine infarction.MethodsForty-six patients with chronic left pontine infarction (LPI), thirty-two patients with chronic right pontine infarction (RPI), and fifty healthy controls (HCs) were recruited for the study. The static amplitude of low-frequency fluctuations (sALFF), static regional homogeneity (sReHo), dynamic ALFF (dALFF), and dynamic ReHo (dReHo) were employed to detect the alterations in brain activity induced by an infarction. The Rey Auditory Verbal Learning Test and Flanker task were used to evaluate the verbal memory and visual attention function, respectively. Receiver operating characteristic curve analysis was used to reveal the potential capacity of these metrics to distinguish the patients from HCs.ResultsThere were significant variations of these static and dynamic metrics in patients with chronic pontine infarction. The altered regions involved the supratentorial regions, including cortex and subcortical. Moreover, the altered metrics were significantly correlated with verbal memory and visual attention. In addition, these static and dynamic metrics also showed potential in distinguishing stroke patients with behavior deficits from HCs.ConclusionThe pontine infarction-induced cerebral activation changes are observed in both motor and cognitive systems, indicating the functional damage and reorganization across the global cerebral level in these patients with subtentorial infarction, and there is a reciprocal effect between motor and cognitive impairment and repair.

ObjectiveThe objective of this research is to investigate the clinical application value of cerebrospinal fluid (CSF) cytology and circulating tumor DNA (ctDNA) in lung adenocarcinoma (LUAD) meningeal metastasis-meningeal carcinomatosis (MC), and to further explore the possible molecular mechanisms and drug treatment targets of LUAD meningeal metastasis by next-generation sequencing (NGS).MethodsWe retrospectively analyzed LUAD with MC in 52 patients. CSF cytology was carried out using the slide centrifugation precipitation method and May-Grüwald-Giemsa (MGG) staining. Tumor tissue, plasma and CSF ctDNA of some MC patients were detected by NGS.ResultsOf the 52 MC patients, 46 (88.46%) were positive for CSF cytology and 34 (65.38%) were positive for imaging, with statistically significant differences in diagnostic positivity (P < 0.05). In 32 of these patients, CSF cytology, cerebrospinal fluid ctDNA, plasma ctDNA and MRI examination were performed simultaneously, and the positive rates were 84.38, 100, 56.25, and 62.50% respectively, the difference was statistically significant (P < 0.001). Analysis of the NGS profiles of tumor tissues, plasma and CSF of 12 MC patients: the mutated gene with the highest detection rate was epidermal growth factor receptor (EGFR) and the detection rate were 100, 58.33, and 100% respectively in tumor tissues, plasma and CSF, and there were 6 cases of concordance between plasma and tissue EGFR mutation sites, with a concordance rate of 50.00%, and 12 cases of concordance between CSF and tissue EGFR mutation sites, with a concordance rate of 100%. In addition, mutations not found in tissue or plasma were detected in CSF: FH mutation, SETD2 mutation, WT1 mutation, CDKN2A mutation, CDKN2B mutation, and multiple copy number variants (CNV), with the most detected being CDKN2A mutation and MET amplification.ConclusionCSF cytology is more sensitive than traditional imaging in the diagnosis of meningeal carcinomatosis and has significant advantages in the early screening and diagnosis of MC patients. CSF ctDNA can be used as a complementary diagnostic method to negative results of CSF cytology and MRI, and CSF ctDNA can be used as an important method for liquid biopsy of patients with MC, which has important clinical significance in revealing the possible molecular mechanisms and drug treatment targets of meningeal metastasis of LUAD.

Haemophagocytic lymphohistiocytosis (HLH) is a cytokine-driven inflammatory syndrome caused by uncontrolled hypersecretion of inflammatory cytokines. Conventional first-line treatment for HLH included HLH-94 and HLH-2004 regimens. However, quite a few patients do not respond to treatment or cannot tolerate intensive chemotherapy. We reported two cases of HLH, one caused by natural killer (NK)/T-cell lymphoma and another associated with missense variants in the perforin 1 gene. They both received the ruxolitinib plus dexamethasone protocol and had a rapid response to treatment without obvious adverse effects. Our report indicates that treatment with ruxolitinib plus dexamethasone might be a potential option for HLH, and clinical trials warrant further investigation. In addition, the detection of HLH-related genes is necessary for the identification of late-onset familial HLH in certain settings.