Proc Natl Acad Sci U S A
December 2024
Oxidation of the sub-arc mantle driven by slab-derived fluids has been hypothesized to contribute to the formation of gold deposits in magmatic arc environments that host the majority of metal resources on Earth. However, the mechanism by which the infiltration of slab-derived fluids into the mantle wedge changes its oxidation state and affects Au enrichment remains poorly understood. Here, we present the results of a numerical model that demonstrates that slab-derived fluids introduce large amounts of sulfate (S) into the overlying mantle wedge that increase its oxygen fugacity by up to 3 to 4 log units relative to the pristine mantle.
View Article and Find Full Text PDFPhanerozoic orogenic gold mineralization at craton margins is related to the metasomatism of the lithospheric mantle by crustal material. Slab subduction transfers Au from the crust to the metasomatized mantle and oxidizes the latter to facilitate the mobilization of Au into mantle melts. The role of volatiles in the mobilization of Au in the mantle is unclear because of the absence of direct geochemical evidence relating the mantle source of Au to Au mineralization in the overlying crust.
View Article and Find Full Text PDFPIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells.
View Article and Find Full Text PDFMetastasis causes breast cancer-related mortality. Tumor-infiltrating neutrophils (TINs) inflict immunosuppression and promote metastasis. Therapeutic debilitation of TINs may enhance immunotherapy, yet it remains a challenge to identify therapeutic targets highly expressed and functionally essential in TINs but under-expressed in extra-tumoral neutrophils.
View Article and Find Full Text PDFChemotherapy prior to immune checkpoint blockade (ICB) treatment appears to improve ICB efficacy but resistance to ICB remains a clinical challenge and is attributed to highly plastic myeloid cells associating with the tumor immune microenvironment (TIME). Here we show by CITE-seq single-cell transcriptomic and trajectory analyses that neoadjuvant low-dose metronomic chemotherapy (MCT) leads to a characteristic co-evolution of divergent myeloid cell subsets in female triple-negative breast cancer (TNBC). Specifically, we identify that the proportion of CXCL16 + myeloid cells increase and a high STAT1 regulon activity distinguishes Programmed Death Ligand 1 (PD-L1) expressing immature myeloid cells.
View Article and Find Full Text PDFPurpose Of Review: It is well described that tumor-directed aberrant myelopoiesis contributes to the generation of various myeloid populations with tumor-promoting properties. A growing number of recent studies have revealed the importance of the previously unappreciated roles of erythroid progenitor cells (EPCs) in the context of cancer, bringing the updated concept that altered erythropoiesis also facilitates tumor growth and progression. Better characterization of EPCs may provide attractive therapeutic opportunities.
View Article and Find Full Text PDFThis study, via combined analysis of geophysical and geochemical data, reveals a lithospheric architecture characterized by crust-mantle decoupling and vertical heat-flow conduits that control orogenic gold mineralization in the Ailaoshan gold belt on the southeastern margin of Tibet. The mantle seismic tomography indicates that the crust-mantle decoupled deformation, defined from previous seismic anisotropy analysis, was formed by upwelling and lateral flow of the asthenosphere, driven by deep subduction of the Indian continent. Our magnetotelluric and seismic images show both a vertical conductor across the Moho and high Vp/Vs anomalies both in the uppermost mantle and lowest crust, suggesting that crust-mantle decoupling promotes ponding of mantle-derived basic melts at the base of the crust via a heat-flow conduit.
View Article and Find Full Text PDFBackground: Mechanically gated PIEZO channels lead to an influx of cations, activation of additional Ca channels, and cell depolarization. This study aimed to investigate PIEZO2's role in breast cancer.
Methods: The clinical relevance of expression in breast cancer patient was analyzed in a publicly available dataset.
To explore the molecular mechanism of Georgi in treating gastric cancer by network pharmacological analysis and molecular docking. Taking Georgi as the object, the active components and corresponding potential drug targets in Georgi were obtained from the database of TCM Pharmacological System Analysis Platform (TCMSP). GeneCards/OMIM/DrugBank and other databases were used to collect gastric cancer-related genes, and the obtained genes were intersected with drug targets to obtain the target genes of Georgi on gastric cancer.
View Article and Find Full Text PDFHigh dimensional compositional and transcriptional profiling of heterogeneous brain-infiltrating leukocytes can lead to novel biological and therapeutic discoveries. High-quality single-cell leukocyte preparations are a prerequisite for optimal single cell profiling. Here, we describe a protocol for epitope and RNA-preserving dissociation of adult mouse brains and subsequent leukocyte purification and staining, which is adaptable to homeostatic and pathogenic brains.
View Article and Find Full Text PDFIEEE Trans Biomed Eng
November 2021
Goal: Typical SRUS images are reconstructed by localizing ultrasound microbubbles (MBs) injected in a vessel using normalized 2-dimensional cross-correlation (2DCC) between MBs signals and the point spread function of the system. However, current techniques require isolated MBs in a confined area due to inaccurate localization of densely populated MBs. To overcome this limitation, we developed the ℓ1-homotopy based compressed sensing (L1H-CS) based SRUS imaging technique which localizes densely populated MBs to visualize microvasculature in vivo.
View Article and Find Full Text PDFThe majority of women with ovarian cancer are diagnosed with metastatic disease, therefore elucidating molecular events that contribute to successful metastatic dissemination may identify additional targets for therapeutic intervention and thereby positively impact survival. Using two human high grade serous ovarian cancer cell lines with inactive TP53 and multiple rounds of serial in vivo passaging, we generated sublines with significantly accelerated intra-peritoneal (IP) growth. Comparative analysis of the parental and IP sublines identified a common panel of differentially expressed genes.
View Article and Find Full Text PDFRapidly proliferating tumor and immune cells need metabolic programs that support energy and biomass production. The amino acid glutamine is consumed by effector T cells and glutamine-addicted triple-negative breast cancer (TNBC) cells, suggesting that a metabolic competition for glutamine may exist within the tumor microenvironment, potentially serving as a therapeutic intervention strategy. Here, we report that there is an inverse correlation between glutamine metabolic genes and markers of T cell-mediated cytotoxicity in human basal-like breast cancer (BLBC) patient data sets, with increased glutamine metabolism and decreased T cell cytotoxicity associated with poor survival.
View Article and Find Full Text PDFPhenotypic and functional plasticity of brain immune cells contribute to brain tissue homeostasis and disease. Immune cell plasticity is profoundly influenced by tissue microenvironment cues and systemic factors. Aging and gut microbiota dysbiosis that reshape brain immune cell plasticity and homeostasis has not been fully delineated.
View Article and Find Full Text PDFBrain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid cells (BMDMs) cooperatively regulate brain immunity. The phenotypic heterogeneity and specific roles of these myeloid subsets in shaping the br-met niche to regulate br-met outgrowth have not been fully revealed.
View Article and Find Full Text PDFA tumor blood vessel is a key regulator of tissue perfusion, immune cell trafficking, cancer metastasis, and therapeutic responsiveness. mTORC1 is a signaling node downstream of multiple angiogenic factors in the endothelium. However, mTORC1 inhibitors have limited efficacy in most solid tumors, in part due to inhibition of immune function at high doses used in oncology patients and compensatory PI3K signaling triggered by mTORC1 inhibition in tumor cells.
View Article and Find Full Text PDFAcquired resistance to targeted cancer therapy is a significant clinical challenge. In parallel with clinical trials combining CDK4/6 inhibitors to treat HER2+ breast cancer, we sought to prospectively model tumor evolution in response to this regimen in vivo and identify a clinically actionable strategy to combat drug resistance. Despite a promising initial response, acquired resistance emerges rapidly to the combination of anti-HER2/neu antibody and CDK4/6 inhibitor Palbociclib.
View Article and Find Full Text PDFYolk-shell nanostructures have received great attention for boosting the performance of lithium-ion batteries because of their obvious advantages in solving the problems associated with large volume change, low conductivity, and short diffusion path for Li ion transport. A universal strategy for making hollow transition metal oxide (TMO) nanoparticles (NPs) encapsulated into B, N co-doped graphitic nanotubes (TMO@BNG (TMO = CoO, Ni O , Mn O ) through combining pyrolysis with an oxidation method is reported herein. The as-made TMO@BNG exhibits the TMO-dependent lithium-ion storage ability, in which CoO@BNG nanotubes exhibit highest lithium-ion storage capacity of 1554 mA h g at the current density of 96 mA g , good rate ability (410 mA h g at 1.
View Article and Find Full Text PDFBackground: The 14-3-3 family of proteins have been reported to play an important role in development in various mouse models, but the context specific developmental functions of 14-3-3ζ remain to be determined. In this study, we identified a context specific developmental function of 14-3-3ζ.
Results: Targeted deletion of 14-3-3ζ in the C57Bl/6J murine genetic background led to neonatal lethality due to respiratory distress and could be rescued by out-breeding to the CD-1 or backcrossing to the FVB/NJ congenic background.
Most bauxite in China is located upon the karst surface, yet the relation between karstification process and bauxite formation is barely known. Here we discuss how the relation affects the karst and bauxite evolution through analyzing distributions of orebody parameters from 9,007 exploration wells (434 orebodies) in western Guangxi, South China block. In high-elevation karst terrain dominated by peaks, orebodies have greater average thickness, lower AlO and higher FeO than those in low-elevation region dominated by depressions.
View Article and Find Full Text PDFThe 14-3-3ζ protein belongs to the 14-3-3 family of regulatory eukaryotic proteins that modulate signaling by binding to wide variety of signaling molecules. 14-3-3ζ expression is amplified in over 40% breast cancer patients and is associated with a poor prognosis. Various and xenograft models have suggested that attenuating 14-3-3ζ expression may provide therapeutic benefits but there has been no study looking at tumor onset and metastasis in breast cancer mouse models with a targeted deletion of 14-3-3ζ.
View Article and Find Full Text PDFTo cater for the demands of electrochemical energy storage system, the development of cost effective, durable and highly efficient electrode materials is desired. Here, a novel electrode material based on redox active β-Co(OH) and B, N co-doped graphene nanohybrid is presented for electrochemical supercapacitor by employing a facile metal-organic frameworks (MOFs) route through pyrolysis and hydrothermal treatment. The Co(OH) could be firmly stabilized by dual protection of N-doped carbon polyhedron (CP) and B/N co-doped graphene (BCN) nanosheets.
View Article and Find Full Text PDFThe effect of the different forms of titanium salt coagulant conditioning on sludge dewatering performance was studied. The result showed that the sludge dewaterability was the best and the specific resistance to filtration (SRF), the compressibility and the content of organic content in EPS were the lowest when =0.5 compared with others.
View Article and Find Full Text PDFMetastatic microenvironments are spatially and compositionally heterogeneous. This seemingly stochastic heterogeneity provides researchers great challenges in elucidating factors that determine metastatic outgrowth. Herein, we develop and implement an integrative platform that will enable researchers to obtain novel insights from intricate metastatic landscapes.
View Article and Find Full Text PDFThis work successfully demonstrates metal-organic framework (MOF) derived strategy to prepare nanoporous carbon (NPC) with or without Fe3O4/Fe nanoparticles by the optimization of calcination temperature as highly active electrode materials for asymmetric supercapacitors (ASC). The nanostructured Fe3O4/Fe/C hybrid shows high specific capacitance of 600 F/g at a current density of 1 A/g and excellent capacitance retention up to 500 F/g at 8 A/g. Furthermore, hierarchically NPC with high surface area also obtained from MOF gels displays excellent electrochemical performance of 272 F/g at 2 mV/s.
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