As a class of non-Newtonian fluids with yield stresses, Bingham fluids possess both solid and liquid phases separated by implicitly defined non-physical yield surfaces, which makes the standard ...numerical discretization challenging. The variational reformulation established by Duvaut and Lions, coupled with an augmented Lagrange method (ALM), brings about a finite element approach, whereas the inevitable local mesh refinement and preconditioning of the resulting large-scaled ill-conditioned linear system can be involved. Inspired by the mesh-free feature and architecture flexibility of physics-informed neural networks (PINNs), an ALM-PINN approach to steady-state Bingham fluid flow simulation, with dynamically adaptable weights, is developed and analyzed in this work. The PINN setting enables not only a pointwise ALM formulation but also the learning of families of (physical) parameter-dependent numerical solutions through one training process, and the incorporation of ALM into a PINN induces a more feasible loss function for deep learning. Numerical results obtained via the ALM-PINN training on one- and two-dimensional benchmark models are presented to validate the proposed scheme. The efficacy and limitations of the relevant loss formulation and optimization algorithms are also discussed to motivate some directions for future research.
•Excellent adsorption performance of aqueous As(V) by MSW biochars.•2M KOH activated MSW biochars were more favorable for As(V) adsorption.•Second-order model and Langmuir equation for better ...description of adsorption.•Porosity and functional group changes promoted As(V) adsorption on MSW biochars.
Biochar converted from waste products is being considered as an alternative adsorbent for removal of aqueous heavy metal(loid)s. In this work, experimental and modeling investigations were conducted to examine the effect of biochars pyrolytically produced from municipal solid wastes on removing aqueous As(V) before and after activated by 2M KOH solution. Results showed that the highest adsorption capacity of pristine biochars was 24.49mg/g. The pseudo-second-order model and Langmuir adsorption isotherm model can preferably describe the adsorption process. The activated biochar showed enhanced As(V) adsorption ability with an adsorption capacity of 30.98mg/g, which was more than 1.3times of pristine biochars, and 2–10times of modified biochars reported by other literatures. Increase of surface area and changes of porous texture, especially the functional groups on the surface of activated biochars are the major contributors to its more efficient adsorption of As(V).
Tendons are traditionally thought to consist of tenocytes only, the resident cells of tendons; however, a recent study has demonstrated that human and mouse tendons also contain stem cells, referred ...to as tendon stem/progenitor cells (TSCs). However, the differential properties of TSCs and tenocytes remain largely undefined. This study aims to characterize the properties of these tendon cells derived from rabbits.
TSCs and tenocytes were isolated from patellar and Achilles tendons of rabbits. The differentiation potential and cell marker expression of the two types of cells were examined using histochemical, immunohistochemical, and qRT-PCR analysis as well as in vivo implantation. In addition, morphology, colony formation, and proliferation of TSCs and tenocytes were also compared.
It was found that TSCs were able to differentiate into adipocytes, chondrocytes, and osteocytes in vitro, and form tendon-like, cartilage-like, and bone-like tissues in vivo. In contrast, tenocytes had little such differentiation potential. Moreover, TSCs expressed the stem cell markers Oct-4, SSEA-4, and nucleostemin, whereas tenocytes expressed none of these markers. Morphologically, TSCs possessed smaller cell bodies and larger nuclei than ordinary tenocytes and had cobblestone-like morphology in confluent culture whereas tenocytes were highly elongated. TSCs also proliferated more quickly than tenocytes in culture. Additionally, TSCs from patellar tendons formed more numerous and larger colonies and proliferated more rapidly than TSCs from Achilles tendons.
TSCs exhibit distinct properties compared to tenocytes, including differences in cell marker expression, proliferative and differentiation potential, and cell morphology in culture. Future research should investigate the mechanobiology of TSCs and explore the possibility of using TSCs to more effectively repair or regenerate injured tendons.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We study an augmented Lagrangian approach to Bingham fluid flows in a lid-driven square cavity. The piecewise linear equal-order finite element spaces for both the velocity and the pressure ...approximations, proposed and analyzed by Latché and Vola
18, are applied. Based on the resulting regularity of the numerical solutions, a mesh adaptive strategy is proposed to render the yield surfaces of desired resolution. The corresponding numerical scheme is formulated for general Herschel–Bulkley models, and its validity is verified on the benchmark model: Bingham fluid flows in a lid-driven square cavity.
Daratumumab and its use in combination with other agents is becoming a new standard of care for the treatment of multiple myeloma. We mechanistically studied how daratumumab acts on natural killer ...(NK) cells.
Quantities of NK cells in peripheral blood and/or bone marrow of patients with multiple myeloma or healthy donors were examined by flow cytometry. NK-cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded
using feeder cells. Combination treatment of daratumumab and expanded NK cells was performed using an MM.1S xenograft animal model.
CD38
NK cells survived, whereas CD38
NK cells were almost completely eliminated, in peripheral blood and bone marrow of daratumumab-treated multiple myeloma patients. NK-cell depletion occurred due to daratumumab-induced NK-cell fratricide via antibody-dependent cellular cytotoxicity. Consequently, CD38
NK cells were more effective for eradicating multiple myeloma cells than were CD38
NK cells in the presence of daratumumab. Blockade of CD38 with the F(ab)
fragments of daratumumab inhibited the antibody-mediated NK-cell fratricide. CD38
NK cells displayed a significantly better potential for expansion than CD38
NK cells, and the expanded NK cells derived from the former population were more cytotoxic than those derived from the latter against multiple myeloma cells. Therefore, infusion of
-expanded autologous NK cells from daratumumab-treated patients may improve the antibody therapy.
We unravel a fratricide mechanism for daratumumab-mediated NK-cell depletion and provide a potential therapeutic strategy to overcome this side effect in daratumumab-treated patients with multiple myeloma.
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Blockade of PD-L1 expression on tumor cells via anti-PD-L1 monoclonal antibody (mAb) has shown great promise for successful cancer treatment by overcoming T-cell exhaustion; however, the function of ...PD-L1 on natural killer (NK) cells and the effects of anti-PD-L1 mAb on PD-L1
NK cells remain unknown. Moreover, patients with PD-L1
tumors can respond favorably to anti-PD-L1 mAb therapy for unclear reasons. Here, we show that some tumors can induce PD-L1 on NK cells via AKT signaling, resulting in enhanced NK-cell function and preventing cell exhaustion. Anti-PD-L1 mAb directly acts on PD-L1
NK cells against PD-L1
tumors via a p38 pathway. Combination therapy with anti-PD-L1 mAb and NK cell-activating cytokines significantly improves the therapeutic efficacy of human NK cells against PD-L1
human leukemia when compared with monotherapy. Our discovery of a PD-1-independent mechanism of antitumor efficacy via the activation of PD-L1
NK cells with anti-PD-L1 mAb offers new insights into NK-cell activation and provides a potential explanation as to why some patients lacking PD-L1 expression on tumor cells still respond to anti-PD-L1 mAb therapy. SIGNIFICANCE: Targeting PD-L1 expressed on PD-L1
tumors with anti-PD-L1 mAb successfully overcomes T-cell exhaustion to control cancer, yet patients with PD-L1
tumors can respond to anti-PD-L1 mAb. Here, we show that anti-PD-L1 mAb activates PD-L1
NK cells to control growth of PD-L1
tumors
, and does so independent of PD-1.
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A growing body of evidence suggests that long non‐coding RNA (lncRNA) is aberrantly expressed in human cancer and linked to cancer initiation and development. We previously identified Homo sapiens ...PGM5 antisense RNA 1 (PGM5‐AS1) as a novel esophageal squamous cell carcinoma (ESCC)‐related lncRNA by performing high‐throughput RNA sequencing. However, its clinical implication and biological function in ESCC are still uncharacterized. In the present study, we found that PGM5‐AS1 was frequently downregulated in ESCC tissues, plasma, and cell lines, and low PGM5‐AS1 expression was positively correlated with poor differentiation, advanced tumor node metastasis (TNM) stage, and lymph node metastasis. Importantly, PGM5‐AS1 was identified to be an effective diagnostic and prognostic biomarker for ESCC patients. Functional experiments revealed that exogenous expression of PGM5‐AS1 significantly suppressed the proliferation, migration, and invasion of ESCC cells in vitro as well as tumor growth in vivo. Mechanistically, PGM5‐AS1 was transcriptionally activated by p53 and it could directly interact with and sequester miR‐466 to elevate PTEN expression, thereby inhibiting ESCC progression. Overall, our data indicate that PGM5‐AS1 is a novel tumor suppressor in ESCC and restoration of PGM5‐AS1 may be a promising avenue for treatment of ESCC patient.
The co-existence of organic pollutants and nanoparticles in the environment may lead to combined biological effects. The joint toxicity of pollutants and nanoparticles has been receiving increasing ...attention from researchers, but few studies have focused on soil biota due to the complexity of soil matrices. This study investigated the effects of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) at 0, 5, and 25 mg/kg and nanoparticulate TiO2 (nTiO2) at 0, 500, and 2500 mg/kg in a 3 × 3 factorial arrangement of treatments for 28 days (d) on Eisenia fetida (earthworm). Compared with the control group (the 0 mg/kg TDCIPP + 0 mg/kg nTiO2 treatment), all other single (TDCIPP or nTiO2) and binary (TDCIPP + nTiO2) treatments except for the single 500 mg/kg nTiO2 treatment significantly reduced the weight gain rate of E. fetida. The binary treatments had significantly greater such effect than their corresponding single treatments, exhibiting a synergistic toxicity between TDCIPP and nTiO2 on the growth of E. fetida. Since TDCIPP and nTiO2 had no significant effect on their concentrations in the soil or in E. fetida during binary exposure, the synergistic toxicity could be a result of the superimposition of the toxicity pathways of TDCIPP and nTiO2. Transcriptomic analysis of E. fetida intestinal region revealed that exposure to 25 mg/kg TDCIPP or 2500 mg/kg nTiO2 affected nutrient-related or cell apoptosis and DNA damage related genes, respectively; their co-exposure greatly inhibited genes related to nutrient digestion and absorption, while causing abnormal transcription of genes related to the development and maintenance of E. fetida’s muscles, leading to synergistic toxicity. These findings provide new insights into the environmental risks of organophosphorus flame retardants, nanoparticles, and their co-exposure.
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•Co-exposure to TDCIPP and nTiO2 synergistically inhibited earthworm growth.•The two analytes did not alter the concentration of each other in soil or earthworms.•TDCIPP inhibited expression of genes related to nutrient digestion and absorption.•nTiO2 affected cell apoptosis and DNA damage related genes.•The synergistic effect could be caused by the superimposition of toxic pathways.
As one of the most described epigenetic marks in human cancers, DNA methylation plays essential roles in gene expression regulation and has been implicated in the prognosis and therapeutics of many ...cancers. We are motivated in this study to explore DNA methylation profiles capturing breast cancer heterogeneity to improve breast cancer prognosis at the epigenetic level.
Through comparisons on differentially methylated CpG sites among breast cancer subtypes followed by a sequential validation and functional studies using computational approaches, we propose 313 CpG, corresponding to 191 genes, whose methylation pattern identifies the triple negative breast cancer subtype, and report cell migration as represented by extracellular matrix organization and cell proliferation as mediated via MAPK and Wnt signalings are the primary factors driving breast cancer subtyping.
Our study offers novel CpGs and gene methylation patterns with translational potential on triple negative breast cancer prognosis, as well as fresh insights from the epigenetic level on breast cancer heterogeneity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alterations and personal variations of RNA interactions have been mechanistically coupled with disease etiology and phenotypical variations. RNA biomarkers, RNA mimics, and RNA antagonists have been ...developed for diagnostic, prognostic, and therapeutic uses. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are two major types of RNA molecules with regulatory roles, deregulation of which has been implicated in the initiation and progression of many human malignancies. Accumulating evidence indicated the clinical roles of regulatory RNAs in cancer control, stimulating a surge in exploring the functionalities of regulatory RNAs for improved understanding on disease pathogenesis and management. In this review, we highlight the critical roles of lncRNAs and miRNAs played in tumorigenesis, scrutinize their potential functionalities as diagnostic/prognostic biomarkers and/or therapeutic targets in clinics, outline opportunities that ncRNAs may bring to complement current clinical practice for improved cancer management and identify challenges faced by translating frontier knowledge on non-coding RNAs (ncRNAs) to bedside clinics as well as possible solutions.
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