5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

Photodynamic therapy (PDT) has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) signaling cascades are activated following 5-aminolevulinic acid (ALA)-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy

Comparative Study of Some Population-based Optimization Algorithms on Inverse Scattering of a Two-Dimensional Perfectly Conducting Cylinder in Slab Medium

[[abstract]]The application of four techniques for the shape reconstruction of a 2-D metallic cylinder buried in dielectric slab medium by measured the cattered fields outside is studied in the paper. The finite-difference time-domain (FDTD) technique is employed for electromagnetic analyses for both the forward and inverse scattering problems, while the shape reconstruction problem is transformed into optimization one during the course of inverse scattering. Then, four techniques including asynchronous particle swarm optimization (APSO), PSO, dynamic differential evolution (DDE) and self-adaptive DDE (SADDE) are applied to reconstruct the location and shape of the 2-Dmetallic cylinder for comparative purposes. The statistical performances of these algorithms are compared. The results show that SADDE outperforms PSO, APSO and DDE in terms of the ability of exploring the optima. However, these results are considered to be indicative and do not generally apply to all optimization problems in electromagnetics.[[incitationindex]]SCI[[incitationindex]]EI[[booktype]]紙本[[booktype]]電子

A Gell-Mann & Low Theorem Perspective on Quantum Computing: New Paradigm for Designing Quantum Algorithm

The Gell-Mann & Low theorem is a cornerstone of Quantum Field Theory (QFT) and condensed matter physics, and many-body perturbation theory is a foundational tool for treating interactions. However, their integration into quantum algorithms remains a largely unexplored area of research, with current quantum simulation algorithms predominantly operating in the Schr\"odinger picture, leaving the potential of the interaction picture largely untapped. Our Variational Interaction-Picture S-matrix Ansatz (VIPSA) now fills this gap, specifically in the context of the Fermi-Hubbard model -- a canonical paradigm in condensed matter physics which is intricately connected to phenomena such as high-temperature superconductivity and Mott insulator transitions. This work offers a new conceptual perspective for variational quantum computing based upon the Gell-Mann & Low theorem. We achieve this by employing an innovative mathematical technique to explicitly unfold the normalized S-matrix, thereby enabling the systematic reconstruction of the Dyson series on a quantum computer, order by order. This method stands in contrast to the conventional reliance on Trotter expansion for adiabatic time evolution, marking a conceptual shift towards more sophisticated quantum algorithmic design. We leverage the strengths of the recently developed ADAPT-VQE algorithm, tailoring it to reconstruct perturbative terms effectively. Our simulations indicate that this method not only successfully recovers the Dyson series but also exhibits robust and stable convergence. We believe that our approach shows great promise in generalizing to more complex scenarios without increasing algorithmic complexity.Comment: 12 pages, 10 figure

Device Integrity of Drug-eluting Depot Stent for Smart Drug Delivery

Atherosclerosis, or hardening of the arteries, is a condition in which plaque, made of cholesterol, fatty substances, cellular waste products, calcium, and fibrin, builds up inside the arteries. A metallic stent is a small mesh tube that is used to treat these narrowed arteries such as coronary artery diseases. The drug-eluting stent has a metallic stent platform coated with drug-polymer mix and has been shown to be superior to its metallic stent counterpart in reducing restenosis. In the past few years, a novel variation of the drug-eluting stent with micro-sized drug reservoirs (depot stent) has been introduced to the market. It allows smart programmable drug delivery with spatial/temporal control and has potential advantages over conventional stents. The drug-polymer mix compound can be altered from one reservoir to the next, allowing a highly-controlled release of different medications. For example, this depot stent concept can be applied in the renal indication for potential treatment of both renal artery stenosis (upstream) and its associated kidney diseases (downstream) simultaneously. However, the creation of such drug reservoirs on the stent struts inevitably compromises its mechanical integrity. In this study, the effects of these drug reservoirs on stent key clinical attributes were systematically investigated. We developed finite element models to predict the mechanical integrity of a balloon-expandable stent at various stages of its function life such as manufacturing and acute deployment, as well as the stent radial strength and chronic fatigue life. Simulation results show that (1) creating drug reservoirs on a stent strut could impact the stent fatigue resistance to certain degrees; (2) drug reservoirs on the high stress concentration regions led to much greater loss in all key clinical attributes than reservoirs on other locations; (3) reservoir shape change resulted in little differences in all key clinical attributes; and (4) for the same drug loading capacity, larger and fewer reservoirs yielded higher fatigue safety factor. These results can help future stent designers to achieve the optimal balance of stent mechanical integrity and smart drug delivery, thereby opening up a wide variety of new opportunities for disease treatments. We also proposed an optimized depot stent with tripled drug capacity and acceptable marginal trade-off in key clinical attributes when compared to the current drug-eluting stents. This depot stent prototype was manufactured for the demonstration of our design concept

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

<p>Abstract</p> <p>Background</p> <p>This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1) expression on response to cisplatin-based induction chemotherapy (IC) followed by concurrent chemoradiation (CCRT) in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) patients.</p> <p>Methods</p> <p>Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records.</p> <p>Results</p> <p>The 12-month progression-free survival (PFS) and 2-year overall survival (OS) rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p < 0.001) and 2-year OS (74.2 vs. 44.4%, p = 0.023) rates. Multivariate analysis showed that for patients who did not chew betel nuts and had low expression of ERCC1 were independent predictors for prolonged survival.</p> <p>Conclusions</p> <p>Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.</p