Geometallurgy and Gold Mineralization of the Monument Bay Project, Stull Lake Greenstone Belt, Manitoba, Canada

The Monument Bay Project is located in the Archean Stull Lake Greenstone Belt, in Northern Manitoba, Canada. This thesis focuses on the geometallurgy and gold mineralization of the Monument Bay Deposit in order to better understand the multiple gold mineralizing events and provide a pathfinder to gold mineralization. Traditional microscopy is used in combination with geochemical and mineralogical analytical techniques (Electron Probe Microanalysis (EPMA) and Energy-dispersive X-ray Spectroscopy (EDS)/(WDS) element map) and synchrotron geochemical techniques (synchrotron X-ray Diffraction (SR-XRD), synchrotron micro X-ray fluorescence (SR-µXRF) mapping, X-ray Absorption Near-edge Structure (XANES) Spectroscopy). Metallic gold (Au0) exists as free gold and inclusion gold, and no refractory gold (Au+1) has been found in the selected samples. As-1, which is the non-toxic form of arsenic, occurs in arsenopyrite and is the only form of arsenic in the samples. Free gold and inclusion gold have been found in porphyritic dacite and metasediments. Only free gold exhibit in metavolcanic rocks. Microscopic gold distribution is related to sulphide morphology. There is evidence for four sulphide generations identified from microscopy and EDS/WDS element maps: Ⅰ. Arsenopyrite 1 (Apy1); Ⅱ. Pyrite 1 (Py1) and Arsenopyrite 2 (Apy2); Ⅲ. Chalcopyrite (Ccp), Galena (Gn), and Sphalerite (Sp); Ⅳ. Pyrite 2 (Py2) and Arsenopyrite 3 (Apy3). The various Au/Ag and Au/Sb ratios identified using EDS point analysis suggest an episode of Au remobilization during sulphide formation because of changes in temperature and pressure. The spatial distribution of different types of sulphides in different veining events suggests there were three main gold mineralizing events. The majority of the gold was deposited as metallic gold in episode Ⅱ. This information is being applied by Yamana to understand the multi-episodic fluid history and environmental characterization of the Monument Bay project and will lead to a better understanding of the mineralogical expression of gold mineralization and geometallurgy at the Monument Bay Project

MFAP3L activation promotes colorectal cancer cell invasion and metastasis

AbstractAn abundance of microfibril-associated glycoprotein 3-like (MFAP3L) significantly correlates with distant metastasis in colorectal cancer (CRC), although the mechanism has yet to be explained. In this study, we observed that MFAP3L knock-down resulted in reduced CRC cell invasion and hepatic metastasis. We evaluated the cellular location and biochemical functions of MFAP3L and found that this protein was primarily localized in the nucleus of CRC cells and acted as a protein kinase. When EGFR translocated into the nucleus upon stimulation with EGF, MFAP3L was phosphorylated at Tyr287 within its SH2 motif, and the activated form of MFAP3L phosphorylated ERK2 at Thr185 and Tyr187. Moreover, the metastatic behavior of CRC cells in vitro and in vivo could be partially explained by activation of the nuclear ERK pathway through MFAP3L phosphorylation. Hence, we experimentally demonstrated for the first time that MFAP3L likely participates in the nuclear signaling of EGFR and ERK2 and acts as a novel nuclear kinase that impacts CRC metastasis

Q-Refine: A Perceptual Quality Refiner for AI-Generated Image

With the rapid evolution of the Text-to-Image (T2I) model in recent years, their unsatisfactory generation result has become a challenge. However, uniformly refining AI-Generated Images (AIGIs) of different qualities not only limited optimization capabilities for low-quality AIGIs but also brought negative optimization to high-quality AIGIs. To address this issue, a quality-award refiner named Q-Refine is proposed. Based on the preference of the Human Visual System (HVS), Q-Refine uses the Image Quality Assessment (IQA) metric to guide the refining process for the first time, and modify images of different qualities through three adaptive pipelines. Experimental shows that for mainstream T2I models, Q-Refine can perform effective optimization to AIGIs of different qualities. It can be a general refiner to optimize AIGIs from both fidelity and aesthetic quality levels, thus expanding the application of the T2I generation models.Comment: 6 pages, 5 figure

Promoted Photocharge Separation in 2D Lateral Epitaxial Heterostructure for Visible‐Light‐Driven CO2 Photoreduction

Photocarrier recombination remains a big barrier for the improvement of solar energy conversion efficiency. For 2D materials, construction of heterostructures represents an efficient strategy to promote photoexcited carrier separation via an internal electric field at the heterointerface. However, due to the difficulty in seeking two components with suitable crystal lattice mismatch, most of the current 2D heterostructures are vertical heterostructures and the exploration of 2D lateral heterostructures is scarce and limited. Here, lateral epitaxial heterostructures of BiOCl @ Bi2O3 at the atomic level are fabricated via sonicating‐assisted etching of Cl in BiOCl. This unique lateral heterostructure expedites photoexcited charge separation and transportation through the internal electric field induced by chemical bonding at the lateral interface. As a result, the lateral BiOCl @ Bi2O3 heterostructure demonstrates superior CO2 photoreduction properties with a CO yield rate of about 30 µmol g−1 h−1 under visible light illumination. The strategy to fabricate lateral epitaxial heterostructures in this work is expected to provide inspiration for preparing other 2D lateral heterostructures used in optoelectronic devices, energy conversion, and storage fields

Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression

Psoriasin (S100A7) is an 11-kDa small calcium binding protein initially isolated from psoriatic skin lesions. It belongs to the S100 family of proteins which play an important role in a range of cell functions including proliferation, differentiation, migration and apoptosis. Aberrant Psoriasin expression has been implicated in a range of cancers and is often associated with poor prognosis. This study examined the role of Psoriasin on pancreatic cancer cell functions and the implication in progression of the disease. Expression of Psoriasin was determined in a cohort of pancreatic tissues comprised of 126 pancreatic tumours and 114 adjacent non-tumour pancreatic tissues. Knockdown and overexpression of Psoriasin in pancreatic cancer cells was performed using specifically constructed plasmids, which either had anti-Psoriasin ribozyme transgene or the full length human Psoriasin coding sequence. Psoriasin knockdown and overexpression was verified using conventional RT-PCR and qPCR. The effect of manipulating Psoriasin expression on pancreatic cancer cell functions was assessed using several in vitro cell function assays. Local invasive pancreatic cancers extended beyond the pancreas expressed higher levels of Psoriasin transcripts compared with the cancers confined to the pancreas. Primary tumours with distant metastases exhibited a reduced expression of Psoriasin. Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, Psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Overexpression of Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Taken together, higher expression of Psoriasin was associated with local invasion in pancreatic cancers. Psoriasin expression is associated with pancreatic cancer cell growth, migration, cell-matrix adhesion, and invasion via regulation of MMPs. As such, the proposed implications of Psoriasin in invasion, disease progression and as a potential therapeutic target warrant further investigation

Activated leukocyte cell adhesion molecule (ALCAM)/CD166 in pancreatic cancer, a pivotal link to clinical outcome and vascular embolism

Activated leukocyte cell adhesion molecule (ALCAM, or CD166) is a cell adhesion molecule and one of potential tumour metastasis ‘soil’ receptors that via homotypic and heterotypic interactions, mediates cancer cell adhesion. The present study investigated clinical, pathological and prognostic values of ALCAM in patients with pancreatic cancer. Human pancreatic cancer (PANC-1 and Mia PaCa-2) and human vascular endothelial cell lines were used to construct cell models differentially expressing levels of ALCAM. Tumour-endothelial interaction and tumour migration were assessed by a DiI-based method and electric cell-substrate impedance sensing (ECIS) assay. Pancreatic cancer tissues (n=223), collected immediately after surgery, were analysed for levels of the ALCAM transcripts, which were also analysed against clinical, pathological and clinical outcomes of the patients. ALCAM protein was assessed by immunohistochemistry on a tissue array. Our study demonstrate that pancreatic cancer tissues had significantly higher levels of ALCAM transcripts than normal tissues (P<0.00001). There were no significant differences with staging, differentiation and tumour locations. Tumours from patients who died of pancreatic cancer had significantly high levels of ALCAM compared with those who lived (P=0.018), and this finding was further supported by ROC analysis (P=0.016). Multivariant analysis showed that ALCAM is an independent prognosis factor for overall survival (HR=5.485), with both nodal status and TNM staging contributing to the model (HR=2.578 and 3.02, respectively). A surprising finding was the relationship between ALCAM expression and microvessel embolism of tumour cells (P=0.021, with vs without tumour embolism). Levels of ALCAM were found to be a determinant factor to adherence of the pancreatic cancer cells to vascular endothelial cells, as demonstrated by pancreatic cancer cell models genetically engineered to express differential levels of ALCAM. The tumour-endothelial interaction mediated by ALCAM was readily blocked by addition of soluble ALCAM. Our data supports the conclusion that ALCAM expression is aberrant in pancreatic cancer and its raised expression is an independent prognostic factor for the survival of the patients and the microvascular embolism by cancer cells. Our results suggest that ALCAM plays a key role in mediating tumour-endothelial cell interactions and enhancing tumour embolism in pancreatic cancer, and targeting ALCAM represents a potential therapeutic strategy for treating human pancreatic cancer

Activated leukocyte cell adhesion molecule (ALCAM)/CD166 in pancreatic cancer, a pivotal link to clinical outcome and vascular embolism.

Activated leukocyte cell adhesion molecule (ALCAM, or CD166) is a cell adhesion molecule and one of potential tumour metastasis 'soil' receptors that via homotypic and heterotypic interactions, mediates cancer cell adhesion. The present study investigated clinical, pathological and prognostic values of ALCAM in patients with pancreatic cancer. Human pancreatic cancer (PANC-1 and Mia PaCa-2) and human vascular endothelial cell lines were used to construct cell models differentially expressing levels of ALCAM. Tumour-endothelial interaction and tumour migration were assessed by a DiI-based method and electric cell-substrate impedance sensing (ECIS) assay. Pancreatic cancer tissues (n=223), collected immediately after surgery, were analysed for levels of the ALCAM transcripts, which were also analysed against clinical, pathological and clinical outcomes of the patients. ALCAM protein was assessed by immunohistochemistry on a tissue array. Our study demonstrate that pancreatic cancer tissues had significantly higher levels of ALCAM transcripts than normal tissues (P<0.00001). There were no significant differences with staging, differentiation and tumour locations. Tumours from patients who died of pancreatic cancer had significantly high levels of ALCAM compared with those who lived (P=0.018), and this finding was further supported by ROC analysis (P=0.016). Multivariant analysis showed that ALCAM is an independent prognosis factor for overall survival (HR=5.485), with both nodal status and TNM staging contributing to the model (HR=2.578 and 3.02, respectively). A surprising finding was the relationship between ALCAM expression and microvessel embolism of tumour cells (P=0.021, with vs without tumour embolism). Levels of ALCAM were found to be a determinant factor to adherence of the pancreatic cancer cells to vascular endothelial cells, as demonstrated by pancreatic cancer cell models genetically engineered to express differential levels of ALCAM. The tumour-endothelial interaction mediated by ALCAM was readily blocked by addition of soluble ALCAM. Our data supports the conclusion that ALCAM expression is aberrant in pancreatic cancer and its raised expression is an independent prognostic factor for the survival of the patients and the microvascular embolism by cancer cells. Our results suggest that ALCAM plays a key role in mediating tumour-endothelial cell interactions and enhancing tumour embolism in pancreatic cancer, and targeting ALCAM represents a potential therapeutic strategy for treating human pancreatic cancer

Implication of capillary morphogenesis gene 2 (CMG2) in the disease progression and peritoneal metastasis of pancreatic cancer

Simple Summary: Pancreatic cancer remains as one of the most life-threatening cancers with a 5-year overall survival rate less than 6%. As a transmembrane protein, capillary formation gene 2 (CMG2) mediates cell–matrix adhesion and migration. Recent studies have revealed emerging roles of CMG2 in various cancers. This study aimed to evaluate expression of CMG2 in pancreatic cancer and its implication in the disease progression and distant metastasis. Interestingly, the significant upregulation of CMG2 was seen in pancreatic cancer, which was associated with poor survival and distant metastases highlighting the potential of targeting this molecule for the prevention of dissemination of pancreatic cancer cells. Abstract: Capillary morphogenesis gene 2 (CMG2) mediates cell–matrix interactions to facilitate cell adhesion and migration. CMG2 has been implicated in the disease progression of breast cancer, prostate cancer and gastric cancer. The present study aims to determine the role of CMG2 in the disease progression and peritoneal metastasis of pancreatic cancer. Pancreatic tumour samples were collected from Peking University Cancer Hospital. CMG2 expression was determined using quantitative PCR. After the creation of knockdown and overexpression of CMG2 in pancreatic cancer cells, the effect of CMG2 on several cell functions and adhesion to the peritoneum was examined. Potential pathways regulated by CMG2 were found via proteomics analysis and drug tests. CMG2 was upregulated in pancreatic cancer tissues and associated with a poor prognosis. CMG2 was increased in metastatic lesions and those primary tumours with distant metastases. CMG2 promotes cell–cell, cell–matrix and cell–hyaluronic acid adhesion, which may be mediated by epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) pathway activation

Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells in vitro and in vivo, respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling

Image_2_Astragaloside IV Inhibits Triglyceride Accumulation in Insulin-Resistant HepG2 Cells via AMPK-Induced SREBP-1c Phosphorylation.TIF

<p>Objective: Insulin resistance (IR) is a risk factor for non-alcoholic fatty liver disease (NAFLD), which is characterized by lipid accumulation in hepatocytes. AMP-activated protein kinase (AMPK)-induced sterol regulatory element binding protein-1c (SREBP-1c) phosphorylation is crucial for proper regulation of lipid metabolism in the liver. Astragaloside IV (AST-IV) was found to decrease lipid accumulation in hepatocytes by activating AMPK, which is required to regulate lipid metabolism in liver tissue by inducing SREBP-1c phosphorylation.</p><p>Method: To evaluate the direct effect of AST on lipid accumulation in hepatocytes with IR and elucidate the underlying mechanisms, we induced IR in HepG2 cells, and used compound C and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) (an AMPK inhibitor and agonist, respectively) as control substances. We evaluated glucose, triglyceride (TG), and non-esterified fatty acid (NEFA) production, as well as SREBP-1c transcription, SREBP-1c protein expression, and downstream gene expression with or without the presence of AST. We also investigated whether phosphorylation of SREBP-1c at Ser372 was required for AST function.</p><p>Results: We found that AST attenuated IR and lipid accumulation in HepG2 cells. As an AMPK activator, AST promoted gene expression and activation of AMPK by increasing phosphorylation of AMPKa. AST also inhibited translocation of SREBP-1c into the nucleus of insulin-resistant HepG2 cells by inducing phosphorylation of SREBP-1c at Ser372.</p><p>Conclusion: This study demonstrated that AST attenuates IR and lipid accumulation in HepG2 cells by regulating AMPK-dependent phosphorylation of SREBP-1c at Ser372, suggesting AST as a promising drug for treating hepatic steatosis.</p