Thiacalix4arenes as a family of promising ligands have been widely used to construct polynuclear metal clusters, but scarcely employed in silver nanoclusters. Herein, an anion-templated Ag
...nanocluster (SD/Ag88a) built from p-tert-butylthiacalix4arene (H
TC4A) is reported. Single-crystal X-ray diffraction reveals that C
-symmetric SD/Ag88a resembles a metal-organic super calix comprised of eight TC4A
as walls and 88 silver atoms as base, which can be deconstructed to eight CrO
@Ag
(TC4A)(EtS)
(OAc) secondary building units arranged in an annulus encircling a CrO
in the center. Local and global anion template effects from chromates are individually manifested in SD/Ag88a. The solution stability and hierarchical assembly mechanism of SD/Ag88a are studied by using electrospray mass spectrometry. The Ag
nanocluster represents the highest nuclearity metal cluster capped by TC4A
. This work not only exemplify the specific macrocyclic effects of TC4A
in the construction of silver nanocluster but also realize the shape heredity of TC4A
to overall silver super calix.
ABSTRACT
Geotechnical seismic isolation (GSI) system involves the dynamic interaction between structure and low‐modulus foundation material, such as rubber‐soil mixtures (RSM). Whilst numerical ...studies have been carried out to demonstrate the potential benefits of GSI‐RSM system, experimental research is indispensable for confirming its isolation mechanism and effectiveness in reducing structural demand. In this regard, centrifuge modelling with an earthquake shaker under an acceleration field of 50 g adopted in this study can mimic the actual nonlinear dynamic response characteristics of RSM and subsoil in a coupled soil‐foundation‐structure system. This is the first time the performance of GSI‐RSM system was examined in a geotechnical centrifuge. It was found that an average of 40‐50% reduction of structural demand can be achieved. The increase in both the horizontal and rotation responses of the foundation was also evidenced. The unique augmented rocking mechanism with reversible foundation rotation was highlighted.
We present a blueprint for aromatic C–H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. ...Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities.
International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan ...National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV.
A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios.
Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty.
At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.
Gelatin-methacryloyl (GelMa) is a very versatile biomaterial widely used in various biomedical applications. The addition of methacryloyl makes it possible to have hydrogels with varying mechanical ...properties due to its photocuring characteristics. In addition, gelatin is obtained and derived from natural material; thus, it retains various cell-friendly motifs, such as arginine-glycine-aspartic acid, which then provides implanted cells with a friendly environment for proliferation and differentiation. In this study, we fabricated human dermal fibroblast cell (hDF)-laden photocurable GelMa hydrogels with varying physical properties (5%, 10%, and 15%) and assessed them for cellular responses and behavior, including cell spreading, proliferation, and the degree of extracellular matrix remodeling. Under similar photocuring conditions, lower concentrations of GelMa hydrogels had lower mechanical properties than higher concentrations. Furthermore, other properties, such as swelling and degradation, were compared in this study. In addition, our findings revealed that there were increased remodeling and proliferation markers in the 5% GelMa group, which had lower mechanical properties. However, it was important to note that cellular viabilities were not affected by the stiffness of the hydrogels. With this result in mind, we attempted to fabricate 5-15% GelMa scaffolds (20 × 20 × 3 mm
) to assess their feasibility for use in skin regeneration applications. The results showed that both 10% and 15% GelMa scaffolds could be fabricated easily at room temperature by adjusting several parameters, such as printing speed and extrusion pressure. However, since the sol-gel temperature of 5% GelMa was noted to be lower than its counterparts, 5% GelMa scaffolds had to be printed at low temperatures. In conclusion, GelMa once again was shown to be an ideal biomaterial for various tissue engineering applications due to its versatile mechanical and biological properties. This study showed the feasibility of GelMa in skin tissue engineering and its potential as an alternative for skin transplants.
Adequate stress on the Endoplasmic Reticulum (ER) with the Unfolded Protein Response (UPR) could maintain glioma malignancy. Uncontrolled ER stress, on the other hand, predisposes an ...apoptosis-dominant UPR program. We studied here the proapoptotic actions of the Epidermal Growth Factor Receptor (EGFR) inhibitor gefitinib, with the focus on ER stress. The study models were human H4 and U87 glioma cell lines. We found that the glioma cell-killing effects of gefitinib involved caspase 3 apoptotic cascades. Three branches of ER stress, namely Activating Transcription Factor-6 (ATF6), Protein Kinase R (PKR)-Like ER Kinase (PERK), and Inositol-Requiring Enzyme 1 (IRE1), were activated by gefitinib, along with the elevation of intracellular free Ca
, Reactive Oxygen Species (ROS), and NADPH Oxidase2/4 (NOX2/4). Specifically, elevated IRE1 phosphorylation, Tumor Necrosis Factor (TNF) Receptor-Associated Factor-2 (TRAF2) expression, Apoptosis Signal-Regulating Kinase-1 (Ask1) phosphorylation, c-Jun N-Terminal Kinase (JNK) phosphorylation, and Noxa expression appeared in gefitinib-treated glioma cells. Genetic, pharmacological, and biochemical studies further indicated an active ROS/ER stress/Ask1/JNK/Noxa axis causing the glioma apoptosis induced by gefitinib. The findings suggest that ER-stress-based therapeutic targeting could be a promising option in EGFR inhibitor glioma therapy, and may ultimately achieve a better patient response.
Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), the mammalian ortholog of yeast vesicular protein sorting 34 (Vps34), belongs to the phosphoinositide 3-kinase (PI3K) family. PIK3C3 ...can phosphorylate phosphatidylinositol (PtdIns) to generate phosphatidylinositol 3-phosphate (PI3P), a phospholipid central to autophagy. Inhibition of PIK3C3 successfully inhibits autophagy. Autophagy maintains cell survival when modifications occur in the cellular environment and helps tumor cells resist metabolic stress and cancer treatment. In addition, PIK3C3 could induce oncogenic transformation and enhance tumor cell proliferation, growth, and invasion through mechanisms independent of autophagy. This review addresses the structural and functional features, tissue distribution, and expression pattern of PIK3C3 in a variety of human tumors and highlights the underlying mechanisms involved in carcinogenesis. The implications in cancer biology, patient prognosis prediction, and cancer therapy are discussed. Altogether, the discovery of pharmacological inhibitors of PIK3C3 could reveal novel strategies for improving treatment outcomes for PIK3C3-mediated human diseases.
Graphene, with cracks filled with gold nanoparticles, is grown by chemical vapor deposition on a Cu substrate. The crack‐filled graphene not only exhibits superior electrical properties but also ...forms a better junction with other semiconductors. A high‐quality crack‐filled graphene/Si Schottky junction solar cell is achieved, demonstrating the highest fill factor (0.79) and best efficiency (12.3%).
Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The ...extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. This study delves into the designing and fabrication of three-dimensional (3D)-printed scaffolds that were made out of calcium silicate (CS), polycaprolactone (PCL), and decellularized ECM (dECM) from MG63 cells, generating a promising bone tissue engineering strategy that revolves around the concept of enhancing osteogenesis by creating an osteoinductive microenvironment with osteogenesis-promoting dECM. We cultured MG63 on scaffolds to obtain a dECM-coated CS/PCL scaffold and further studied the biological performance of the dECM hybrid scaffolds. The results indicated that the dECM-coated CS/PCL scaffolds exhibited excellent biocompatibility and effectively enhanced cellular adhesion, proliferation, and differentiation of human Wharton's Jelly mesenchymal stem cells by increasing the expression of osteogenic-related genes. They also presented anti-inflammatory characteristics by showing a decrease in the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Histological analysis of in vivo experiments presented excellent bone regenerative capabilities of the dECM-coated scaffold. Overall, our work presented a promising technique for producing bioscaffolds that can augment bone tissue regeneration in numerous aspects.
The future trend in achieving precision medicine involves the development of non-invasive cancer biomarker sensors that offer high accuracy, low cost, and time-saving benefits for risk clarification, ...early detection, disease detection, and therapeutic monitoring. A facile approach for the synthesis of MoO3 nanosheets was developed by thermally oxidizing MoS2 nanosheets in air followed by thermal annealing. Subsequently, Au@MnO2 nanocomposites were prepared using a combined hydrothermal process and in situ chemical synthesis. In this study, we present a novel immunosensor design strategy involving the immobilization of antiHSP70 antibodies on Au@MnO2/MoO3 nanocomposites modified on a screen-printed electrode (SPE) using EDC/NHS chemistry. This study establishes HSP70 as a potential biomarker for monitoring therapeutic response during anticancer therapy. Impedance measurements of HSP70 on the Au@MnO2/MoO3/SPE immunosensor using EIS showed an increase in impedance with an increase in HSP70 concentration. The electrochemical immunosensor demonstrated a good linear response in the range of 0.001 to 1000 ng mL−1 with a detection limit of 0.17 pg mL−1 under optimal conditions. Moreover, the immunosensor was effective in detecting HSP70 at low concentrations in a lung adenocarcinoma cell line following Paclitaxel treatment, indicating its potential for early detection of the HSP70 biomarker in organ-on-a-chip and clinical applications.
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