Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of ...< 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors. However, clinical outcomes are far from satisfying for pancreatic cancer patients receiving anti-angiogenic therapies. In this review, we summarize the current status of angiogenesis in pancreatic cancer research and explore the reasons for the poor efficacy of anti-angiogenic therapies, aiming to identify some potential therapeutic targets that may enhance the effectiveness of anti-angiogenic treatments.
Analytical relations between the critical buckling load of a functionally graded material (FGM) Timoshenko beam and that of the corresponding homogeneous Euler–Bernoulli beam subjected to axial ...compressive load have been derived for clamped–clamped (C–C), simply supported–simply supported (S–S) and clamped–free (C–F) edges. However, no such relation is found for clamped–simply supported (C–S) beams. For C–S beams, the transcendental equation has been derived to find the critical buckling load for the FGM Timoshenko beam which is similar to that for a homogeneous Euler–Bernoulli beam. For the FGM beams Young’s modulus, E, and Poisson’s ratio, ν, are assumed to vary through the thickness. The significance of this work is that for the C–C, S–S and C–F FGM Timoshenko beams, the critical buckling load can be easily found from that of the corresponding homogeneous Euler–Bernoulli beam and two constants whose values depend upon the through-the-thickness variations of E and ν. For the C–S FGM Timoshenko beam the transcendental equation for the determination of the critical buckling load is similar to that for the corresponding homogeneous Euler–Bernoulli beam.
Exact correspondence relations between the bending solutions of a simply supported rectangular functionally graded material plate based on the four variable refined higher-order shear deformation ...theory and those of the corresponding reference homogenous Kirchhoff plate based on the classical plate theory are derived analytically for the material properties varying continuously in the thickness direction. The deflection, stress components, the resultant forces and bending moments of a thick functionally graded material plate are expressed analytically in terms of the deflection of the reference homogenous Kirchhoff plate with the same geometry, loadings and boundary constraints. Consequently, the bending solution of a functionally graded material plate based on the higher-order shear deformation theory is simplified as calculations of three scaling factors which can be easily determined analytically for the specified material gradient profile, the shear stress shape function and the aspect ratio of the functionally graded material plate, because the solution of the reference homogenous Kirchhoff plate can be easily found even in the text book. As examples, particular solutions for a functionally graded material plate subjected to both uniformly and sinusoidally distributed loads are presented, which illustrate the validity of this new approach. Accuracy of the present solutions are demonstrated by comparing them with those obtained by different palate theories with different shear stress shape functions available in the literature. The analytical solutions can be used as benchmarks to check numerical solutions of static bending of functionally graded material plates based on different higher-order shear deformation theories.
A novel photo-triggered self-catalyzed fluoroalkylation/cyclization of quinazolinones containing unactivated alkenes with various fluoroalkyl bromides has been developed. This transformation exhibits ...excellent substrate generality with respect to both the coupling partners. Of note is that this is the first example describing the Csp3–Br bond homolysis of alkyl bromides via a substrate (quinazolinones) induced energy transfer process. Additionally, the mild conditions, tolerance to a wide range of functional groups and operational simplicity make this protocol practical for the synthesis of fluorine-containing ring-fused quinazolinones.
Abstract
Context
Programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), ...and T-cell immunoglobulin and ITIM domain (TIGIT) are considered major immune co-inhibitory receptors (CIRs) and the most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in medullary thyroid carcinoma (MTC).
Objective
We aimed to provide the first evidence regarding the expression profiles and clinical significance of CIRs in a large cohort of MTC patients.
Design and Patients
In total, 200 MTC patients who received initial surgery in our hospital were included. Immunohistochemistry was performed to evaluate CIR expressions in tissue microarrays (TMAs). Combined with the results of our previous programmed cell death ligand-1 (PD-L1) study, clinicopathologic and prognostic correlations of these proteins were retrospectively analyzed.
Results
TIM-3, PD-1, CTLA-4, LAG-3, and TIGIT positivity was detected in 96 (48.0%), 27 (13.5%), 25 (12.5%), 6 (3.0%), and 6 (3.0%) patients, respectively, in whom TIM-3, PD-1, and CTLA-4 expressions were positively correlated. Log-rank tests and multivariate Cox analyses both indicated that TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression were associated with worse structural recurrence-free survival. In addition, among 20 patients who developed advanced disease during follow-up, 12 (60%) showed TIM-3 positivity, among whom 6 cases also had concurrent moderate to strong PD-1, PD-L1, or CTLA-4 expression.
Conclusions
Using the currently largest TMA cohort of this rare cancer, we delineated the CIR expression profiles in MTC, and identified TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression as promising biomarkers for tumor recurrence. Furthermore, a subset of advanced MTCs are probably immunogenic, for which single or combined immunotherapy including TIM-3, PD-1, PD-L1, or CTLA-4 blockade may be potential therapeutic approaches in the future.
In this paper, thermoelastic damping (TED) in free vibrating functionally graded material (FGM) micro beams with rectangular cross sections is investigated. The material properties of the micro beams ...are assumed to be varied continuously in the thickness direction. Based on the classical beam theory and coupled thermo-elastic dynamics, governing equations coupled with the thermal effects derived in terms of the deflection and temperature rise filed. A layer-wise homogenization method is proposed to solve the one-way coupled heat conduction equation with variable coefficients. By using the mathematical similarity between the vibration equation of the FGM beam and that of the reference homogenous beam, complex frequency of the FGM beam including TED is expressed in the terms of that of the reference homogenous beam without TED. Numerical results of TED are obtained for the specific material constituents and the power law gradient profile. The effects of the material gradient index, beam thickness, vibration modes and boundary conditions on the TED of the FGM micro beams are studied in detail.
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•A new MEOR approach by bioaugmenting indigenous biosurfactant producer was studied.•Pseudomonas was one of dominant genera in Daqing oil reservoirs.•P. aeruginosa DQ3 that can ...anaerobically produce biosurfactant at 42 °C was isolated.•P. aeruginosa DQ3 in situ produced biosurfactant at stimulated reservoir conditions.•Bioaugmenting strain DQ3 effectively controlled SRB and well enhanced oil recovery.
Considering the anoxic conditions within oil reservoirs, a new microbial enhanced oil recovery (MEOR) technology through in-situ biosurfactant production without air injection was proposed. High-throughput sequencing data revealed that Pseudomonas was one of dominant genera in Daqing oil reservoirs. Pseudomonas aeruginosa DQ3 which can anaerobically produce biosurfactant at 42 °C was isolated. Strain DQ3 was bioaugmented in an anaerobic bioreactor to approximately simulate MEOR process. During bioaugmentation process, although a new bacterial community was gradually formed, Pseudomonas was still one of dominant genera. Culture-based data showed that hydrocarbon-degrading bacteria and biosurfactant-producing bacteria were activated, while sulfate reducing bacteria were controlled. Biosurfactant was produced at simulated reservoir conditions, decreasing surface tension to 33.8 mN/m and emulsifying crude oil with EI24 = 58%. Core flooding tests revealed that extra 5.22% of oil was displaced by in-situ biosurfactant production. Bioaugmenting indigenous biosurfactant producer P. aeruginosa without air injection is promising for in-situ MEOR applications.
Employing theranostic nanoparticles, which combine both therapeutic and diagnostic capabilities in one dose, has promise to propel the biomedical field toward personalized medicine. Here we ...investigate the theranostic properties of topological insulator bismuth selenide (Bi2Se3) in in vivo and in vitro system for the first time. We show that Bi2Se3 nanoplates can absorb near-infrared (NIR) laser light and effectively convert laser energy into heat. Such photothermal conversion property may be due to the unique physical properties of topological insulators. Furthermore, localized and irreversible photothermal ablation of tumors in the mouse model is successfully achieved by using Bi2Se3 nanoplates and NIR laser irradiation. In addition, we also demonstrate that Bi2Se3 nanoplates exhibit strong X-ray attenuation and can be utilized for enhanced X-ray computed tomography imaging of tumor tissue in vivo. This study highlights Bi2Se3 nanoplates could serve as a promising platform for cancer diagnosis and therapy.
This paper presents a theoretical investigation on the response of free vibration of functionally graded material (FGM) micro-plates with thermoelastic damping (TED). Continuous through thickness ...variation of the mechanical and thermal properties of the FGM plate is considered. By employing the simplified one-way coupled heat conduction equation and Kirchhoff’s plate theory, governing equations for the free vibration of the FGM micro-plates with thermoelastic coupling effect are established, in which stretching-bending coupling produced by the material inhomogeneity in the thickness direction is also considered. The heat conduction equation with variable coefficients is solved effectively by a layer-wise homogenization approach. Harmonic responses of the FGM micro-plates with complex frequency are obtained from the mathematical similarity between the eigenvalue problems of the FGM micro-plate with TED and that of the homogenous one without TED. The presented analytical solutions are suitable for evaluating TED in FGM micro-plates with arbitrary through-thickness material gradient, geometry and boundary conditions. Numerical results of TED for a ceramic-metal composite FGM micro-plate with power-law material gradient profile are illustrated to quantitatively show the effects of the material gradient index, the plate thickness, and the boundary conditions on the TED. The results indicate that by adjusting the physical and geometrical parameters of the FGM micro- plate, one can get the minimum of the TED which is even smaller than that of the pure ceramic resonator.
Thermoelastic damping (TED) in a simply supported functionally graded material (FGM) micro rectangular plate is investigated analytically based on the higher-order shear deformation plate theory. The ...equations of motion for the thermo-elastic coupled transverse free vibration and the heat conduction equation coupled are derived based on the Levinson plate theory and the one-way coupled heat conduction theory. A semi-analytical solution of the heat conduction equation with variable coefficients is obtained by using a layer-wise homogenization approach. The complex frequency of the micro plate including TED is determined in terms of the frequency of the corresponding isothermal homogenous Kirchhoff plate by using the mathematical similarity between the eigenvalue problems for the two types of plates. The effects of the shear deformation, the material gradient and the geometry on the TED are examined in detail for the FGM micro plate made of ceramic–metal constituents with the power-law gradient profile. The numerical results show that the TED evaluated by the Levinson plate theory is smaller than that by the Kirchhoff plate theory. Therefore, for a thick or moderately thick micro plate the Levinson plate theory can provide a more accurate prediction of the TED than the Kirchhoff plate theory.
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