To determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin in ...tumors.
Comparisons in vitro and in vivo were carried out between non-thermosensitive liposomes (NTSL) and low temperature-sensitive liposomes (LTSL). Liposomes were incubated in vitro over a range of temperatures and durations, and the amount of doxorubicin released was measured. For in vivo experiments, liposomes and free doxorubicin were injected i.v. in mice followed by pulsed-HIFU exposures in s.c. murine adenocarcinoma tumors at 0 and 24 h after administration. Combinations of the exposures and drug formulations were evaluated for doxorubicin concentration and growth inhibition in the tumors.
In vitro incubations simulating the pulsed-HIFU thermal dose (42 degrees C for 2 min) triggered release of 50% of doxorubicin from the LTSLs; however, no detectable release from the NTSLs was observed. Similarly, in vivo experiments showed that pulsed-HIFU exposures combined with the LTSLs resulted in more rapid delivery of doxorubicin as well as significantly higher i.t. concentration when compared with LTSLs alone or NTSLs, with or without exposures. Combining the exposures with the LTSLs also significantly reduced tumor growth compared with all other groups.
Combining low-temperature heat-sensitive liposomes with noninvasive and nondestructive pulsed-HIFU exposures enhanced the delivery of doxorubicin and, consequently, its antitumor effects. This combination therapy could potentially produce viable clinical strategies for improved targeting and delivery of drugs for treatment of cancer and other diseases.
Discriminating between Higgs production mechanisms can play a crucial role in determining the couplings of Higgs to gauge bosons, probing the nature of electroweak symmetry breaking. We propose a ...novel method to distinguish the Higgs production mechanisms at the LHC by utilizing the jet charge asymmetry of the two leading forward jets in Higgs plus two jets production. This novel observable provides a way to disentangle the W fusion from the Z fusion and gluon fusion processes for the first time, due to the electric charge correlation of the two leading jets in the events. We show that the Higgs couplings to gauge bosons can be well constrained, and its conclusion does not depend on the other possible new physics effects which modify the Higgs total or partial width. We also discuss the complementary roles between the proposed jet charge asymmetry measurement and the Higgs signal strength measurements at the high luminosity LHC (HL-LHC) in determining the Higgs couplings.
Epithelial-mesenchymal transition (EMT) is an essential component of metastasis. Our previous study demonstrated that cancer-associated fibroblasts (CAFs) induce EMT in lung cancer cells. In recent ...years, many studies have demonstrated that CAFs induce metastasis and drug resistance in cancer cells via exosomes.
We sought to discover the mechanism underlying how CAFs induce EMT in lung cancer cells, unveiling the role of exosomes in lung cancer progression.
We cultured lung cancer cell (i) with control medium, normal fibroblasts (NFs) or CAFs; (ii) with SNAI1-transfected or NC (negative control)-transfected CAFs; (iii) with exosomes extracted from NF- or CAF-conditioned medium; (iv) with exosomes released by SNAI1 or NC-transfected CAFs; (v) with CAF-conditioned medium or exosome-depleted CAF-conditioned medium.
qRT-PCR was conducted to examine the expression of CDH1 (gene of E-cadherin) and VIM (gene of Vimentin), western blotting was conducted to examine E-cadherin and vimentin levels in lung cancer cells.
Exosomes released by CAFs-promoted EMT in lung cancer cells. Interestingly, SNAI1 levels in exosomes secreted from CAFs were correlated with SNAI1 expression in CAFs. Furthermore, the level of SNAI1 in exosomes was crucial for inducing EMT in lung cancer cells. Finally, treatment of CAFs with GW4869, an inhibitor of exosome release, noticeably inhibited their EMT-inducing effect on recipient epithelial cells.
The molecular mechanism underlying how CAFs induce EMT in cancer cells may be that CAFs deliver SNAI1 to recipient cancer cells via exosomes.
Even though perovskite solar cells have reached 22% efficiency within a very short span, the presence of lead is a major bottleneck to its commercial application. Tin and germanium based perovskites ...failed to be viable replacements due to the instability of their +2 oxidation states. Antimony could be a possible replacement, forming perovskites with structure A3M2X9. However, solution processing of Cs, organic ammonium based Sb perovskites result in the formation of the dimer phase with poor charge transport properties. Here we demonstrate that Rb can template the formation of the desired layered phase irrespective of processing methodologies, enabling the demonstration of efficient lead-free perovskite solar cells.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It ...was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.
•This article provides ESMO expert recommendations adapted for the treatment of localised colon cancer in Asian patients.•The aim was to provide guidance for the optimisation of the management of such patients across Asia.•The availability and applicability of certain procedures as they relate to certain of the recommendations are discussed.
Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment significantly influence cancer growth and metastasis. Transforming growth factor-β (TGF-β) is ...known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN-) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-β1 to mediate adoption of the CAF phenotype. This OPN-TGF-β1 pathway requires the transcription factor, myeloid zinc finger 1 (MZF1). In vivo studies with xenotransplant models in NOD-scid mice showed that OPN expression increases cancer growth and metastasis by mediating MSC-to-CAF transformation in a process that is MZF1 and TGF-β1 dependent. We conclude that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN-MZF1-TGF-β1 pathway.
Construction is a high hazard industry which involves many factors that are potentially dangerous to workers. Safety has always been advocated by many construction companies, and they have been ...working hard to make sure their employees are protected from fatalities and injuries. With the advent of Virtual and Augmented Reality (VR/AR), there has been a witnessed trend of capitalizing on sophisticated immersive VR/AR applications to create forgiving environments for visualizing complex workplace situations, building up risk-preventive knowledge and undergoing training. To better understand the state-of-the-art of VR/AR applications in construction safety (VR/AR-CS) and from which to uncover the related issues and propose possible improvements, this paper starts with a review and synthesis of research evidence for several VR/AR prototypes, products and the related training and evaluation paradigms. Predicated upon a wide range of well-acknowledged scholarly journals, this paper comes up with a generic taxonomy consisting of VR/AR technology characteristics, application domains, safety scenarios and evaluation methods. According to this taxonomy, a number of technical features and types that could be implemented in the context of construction safety enhancement are derived and further elaborated, while significant application domains and trends regarding the VR/AR-CS research are generalized, i.e., hazards recognition and identification, safety training and education, safety instruction and inspection, and so on. Last but not least, this study sets forth a list of gaps derived from the in-depth review and comes up with the prospective research works. It is envisioned that the outcomes of this paper could assist both researchers and industrial practitioners with appreciating the research and practice frontier of VR/AR-CS and soliciting the latest VR/AR applications.
•90 VR/AR-CS related articles from 2000 to 2017 are reviewed•The review taxonomy was consolidated by technology characteristics, application domains, safety enhancement mechanisms, and safety assessment and evaluation•The top three application domains include hazards identification, safety education and training, and safety inspection and instruction
Abstract
ASASSN-V J205543.90+240033.5 (ASJ2055) is a possible post-common-envelope binary system. Its optical photometric data show an orbital variation of about 0.52 days and a fast period ...modulation of
P
0
∼ 9.77 minutes, whose origin is unknown. In this Letter, we report evidence of the stellar oscillation of the companion star as the origin of the fast period modulation. We analyze the photometric data taken by the Transiting Exoplanet Survey Satellite, the Liverpool Telescope, and the Lulin One-meter Telescope. It is found that the period of the 9.77 minutes signal measured in 2022 August is significantly shorter than that in 2021 July/August, and the magnitude of the change is of the order of ∣△
P
0
∣/
P
0
∼ 0.0008(4). Such a large variation will be incompatible with the scenario of the white dwarf (WD) spin as the origin of the 9.77 minutes periodic modulation. We suggest that the fast periodic signal is related to the emission from the irradiated companion star rather than that of the WD. Using existing photometric data covering a wide wavelength range, we estimate that the hot WD in ASJ2055 has a temperature of
T
eff
∼ 80,000 K and is heating the oscillating M-type main-sequence star with
T
eff
∼ 3500 K on its unirradiated surface. The stellar oscillation of the M-type main-sequence star has been predicted in theoretical studies, but no observational confirmation has been done. ASJ2055, therefore, has the potential to be a unique laboratory for investigating the stellar oscillation of an M-type main-sequence star and the heating effect on stellar oscillation.
Diabet. Med. 27, 54–60 (2010)
Aims Increased dietary fish‐oil consumption is associated with a reduced risk of coronary heart events and has pronounced effects on dyslipidaemia. However, the effects ...of fish‐oil supplement on vascular function and metabolic profile in patients with Type 2 diabetes mellitus (DM) are unclear.
Methods In a double‐blind placebo‐controlled trial, we randomized 97 Type 2 DM patients without prior cardiovascular disease to fish‐oil (4 g/day, n = 49) or olive‐oil (with equivalent calories, as placebo, n = 48) supplements for 12 weeks. Assessment of vascular function with brachial artery flow‐mediated dilation (FMD) and circulating levels of endothelial progenitor cells (EPCs), and metabolic parameters, high‐sensitivity C‐reactive protein (hsCRP), oxidative stress markers and renal function were examined before and after the supplement.
Results Despite a significant reduction in serum triglycerides (−0.47 mmol/l, P < 0.01), 12‐week supplement of fish oil did not improve vascular function as determined by FMD (+0.16%, P = 0.83) and circulating EPC count (+4 cells/μl, P = 0.78). Furthermore, fish‐oil supplement did not have any significant treatment effects on hsCRP, oxidative stress, low‐ and high‐density lipoprotein and glycated haemoglobin (HbA1c) (all P > 0.05). In contrast, serum creatinine was lower (−4.5 μmol/l, P = 0.01) in fish‐oil‐treated patients as compared with control subjects.
Conclusions This study demonstrated that 12 weeks of fish‐oil supplement had no significant beneficial effect on vascular endothelial function, but improved renal function without changes in endothelial function, metabolic profiles, blood pressure, inflammation or oxidative stress in patients with Type 2 DM.
Noninvasive genotyping using plasma cell-free DNA (cfDNA) has the potential to obviate the need for some invasive biopsies in cancer patients while also elucidating disease heterogeneity. We sought ...to develop an ultra-deep plasma next-generation sequencing (NGS) assay for patients with non-small-cell lung cancers (NSCLC) that could detect targetable oncogenic drivers and resistance mutations in patients where tissue biopsy failed to identify an actionable alteration.
Plasma was prospectively collected from patients with advanced, progressive NSCLC. We carried out ultra-deep NGS using cfDNA extracted from plasma and matched white blood cells using a hybrid capture panel covering 37 lung cancer-related genes sequenced to 50000× raw target coverage filtering somatic mutations attributable to clonal hematopoiesis. Clinical sensitivity and specificity for plasma detection of known oncogenic drivers were calculated and compared with tissue genotyping results. Orthogonal ddPCR validation was carried out in a subset of cases.
In 127 assessable patients, plasma NGS detected driver mutations with variant allele fractions ranging from 0.14% to 52%. Plasma ddPCR for EGFR or KRAS mutations revealed findings nearly identical to those of plasma NGS in 21 of 22 patients, with high concordance of variant allele fraction (r=0.98). Blinded to tissue genotype, plasma NGS sensitivity for de novo plasma detection of known oncogenic drivers was 75% (68/91). Specificity of plasma NGS in those who were driver-negative by tissue NGS was 100% (19/19). In 17 patients with tumor tissue deemed insufficient for genotyping, plasma NGS identified four KRAS mutations. In 23 EGFR mutant cases with acquired resistance to targeted therapy, plasma NGS detected potential resistance mechanisms, including EGFR T790M and C797S mutations and ERBB2 amplification.
Ultra-deep plasma NGS with clonal hematopoiesis filtering resulted in de novo detection of targetable oncogenic drivers and resistance mechanisms in patients with NSCLC, including when tissue biopsy was inadequate for genotyping.
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