Abstract Poly( para ‐xylylene) (PPX) is a robust and biocompatible coating material that is widely used in various applications, including electronics, aerospace and defense materials, automotive ...materials, and biomaterials. In this progress report, recent developments in PPX technology ranging from the advancement of physical chemistry properties and structural properties for device integration to the transformation of 3D monolith materials of PPX with controls in outer and inner structures at the micro‐ and nanometer scales are highlighted. Based on emerging chemistry studies on 2.2paracyclophanes, which are primarily used precursors to synthesize PPX via vapor deposition polymerization, functionalization, and the creation of a wide variety of functional PPX derivatives are demonstrated without resistance. Widely used as an interface coating material, PPX is processed to form integrated structural materials and has already been found to be useful in the market as part of electronic and medical implant products. Using a newly innovated transformation to fabricate PPX through templates (metal‐organic frameworks, liquid crystal, ice crystal), 3D monoliths, nanoscale particles, hierarchical and gradient interior structures, and dynamically transformable shapes at the nanoscale are demonstrated. A vast landscape of novel applications and device products is expected based on the already established R&D and market maturity of PPX.
Among kidney cancers, clear cell renal cell carcinoma (ccRCC) has the highest incidence rate in adults. The survival rate of patients diagnosed as having metastatic ccRCC drastically declines even ...with intensive treatment. We examined the efficacy of simvastatin, a lipid-lowering drug with reduced mevalonate synthesis, in ccRCC treatment. Simvastatin was found to reduce cell viability and increase autophagy induction and apoptosis. In addition, it reduced cell metastasis and lipid accumulation, the target proteins of which can be reversed through mevalonate supplementation. Moreover, simvastatin suppressed cholesterol synthesis and protein prenylation that is essential for RhoA activation. Simvastatin might also reduce cancer metastasis by suppressing the RhoA pathway. A gene set enrichment analysis (GSEA) of the human ccRCC GSE53757 data set revealed that the RhoA and lipogenesis pathways are activated. In simvastatin-treated ccRCC cells, although RhoA was upregulated, it was mainly restrained in the cytosolic fraction and concomitantly reduced Rho-associated protein kinase activity. RhoA upregulation might be a negative feedback effect owing to the loss of RhoA activity caused by simvastatin, which can be restored by mevalonate. RhoA inactivation by simvastatin was correlated with decreased cell metastasis in the transwell assay, which was mimicked in dominantly negative RhoA-overexpressing cells. Thus, owing to the increased RhoA activation and cell metastasis in the human ccRCC dataset analysis, simvastatin-mediated Rho inactivation might serve as a therapeutic target for ccRCC patients. Altogether, simvastatin suppressed the cell viability and metastasis of ccRCC cells; thus, it is a potentially effective ccRCC adjunct therapy after clinical validation for ccRCC treatment.
Designing a successful biological interface for a biomaterial requires the application of concepts from multiple fields, including materials science, surface science, nanoscience, physics, and ...biochemistry. With current biomaterials, such as polymers, ceramics, and natural materials, the original inherent properties of these materials no longer suffice for the needs of advanced and stringent biotechnological and medical applications that require controlled precision of physical and biochemical properties. Thus, the development of surface modifications to provide coatings that alter the interface properties of the original materials is pursued with much success to render desired and sophisticated interfacial properties. With acknowledging the available processing materials and fabrication techniques of the biointerface coatings, perspectives from advanced achievements in both physical and biochemical properties of the coating interfaces, and anisotropic presentations of these properties such as gradient of specific properties, the control of interface properties in confined micro/nanodomains and/or in introduced topographical geometries to mimic relevant biological activities is discussed in depth. The mentioned interface properties and the intended interactions toward biological microenvironments in vitro and in vivo are reviewed. Future prospective biointerface coatings with combinatorial and complementary properties from the discussed disciplines are suggested by the authors’ opinions. Last, challenges of current works demonstrating practical and important applications are discussed.
This article is a review of biointerface coatings including discussions from structural and biochemical perspectives to provide a future development of an advanced biointerface coating with combinatorial and complementary properties from the discussed disciplines.
•Ent2 plays an important role in adenosine homeostasis in the brain.•Ent2 KO ameliorates LPS-induced neuroinflammation.•Ent2 KO decreases LPS-induced downregulation of tight junctions and pericyte ...injury.•Ent2 KO protects against LPS-induced blood-brain barrier leakage and neurotoxicity.
Neuroinflammation is a common pathological feature of many brain diseases and is a key mediator of blood-brain barrier (BBB) breakdown and neuropathogenesis. Adenosine is an endogenous immunomodulator, whose brain extracellular level is tightly controlled by equilibrative nucleoside transporters-1 (ENT1) and ENT2. This study was aimed to investigate the role of ENTs in the modulation of neuroinflammation and BBB function. The results showed that mRNA level of Ent2 was significantly more abundant than that of Ent1 in the brain (hippocampus, cerebral cortex, striatum, midbrain, and cerebellum) of wild-type (WT) mice. Ent2-/- mice displayed higher extracellular adenosine level in the hippocampus than their littermate controls. Repeated lipopolysaccharide (LPS) treatment induced microglia activation, astrogliosis and upregulation of proinflammatory cytokines, along with aberrant BBB phenotypes (including reduced tight junction protein expression, pericyte loss, and immunoglobulin G extravasation) and neuronal apoptosis in the hippocampus of WT mice. Notably, Ent2-/- mice displayed significant resistance to LPS-induced neuroinflammation, BBB breakdown, and neurotoxicity. These findings suggest that Ent2 is critical for the modulation of brain adenosine tone and deletion of Ent2 confers protection against LPS-induced neuroinflammation and neurovascular-associated injury.
The current standard therapy of epithelial ovarian cancer (EOC) is the combination of surgery (primary cytoreductive surgery or interval cytoreductive surgery) and platinum-based chemotherapy (mainly ...using paclitaxel and carboplatin either by neoadjuvant chemotherapy and/or by postoperative adjuvant chemotherapy) with/without adding targeted therapy (mainly using anti-angiogenesis agent- bevacizumab). After front-line chemotherapy, the advanced-stage EOC can be successfully controlled and three-quarters of patients can achieve a complete clinical remission. Unfortunately, nearly all patients will recur and progression-free survival (PFS) of these patients is seldom more than 3 years with a dismal median PFS of 12–18 months. With each recurrence, patients finally develop resistance to standard chemotherapy regimen, contributing to fewer than half of women who survive for more than 5 years after diagnosis with a median overall survival (OS) of 40.7 months. Due to the lower PFS and OS, particularly for those advanced-stage patients, novel therapeutic options during the front-line therapy are desperately needed to decrease the occurrence of recurrence, and the majority of them are still under investigation. It is well-known that overexpression of CA125 has been associated with attenuated cellular apoptosis, platinum chemotherapy resistance, tumor proliferation and disease progression, suggesting that anti-CA125 may play a role in the management of patients with EOC. The current review is a Part I which will focus on development of anti-CA125 monoclonal antibody, hoping that alternation of the front-line therapy by chemo-immunotherapy will be beneficial for prolonged survival of patients with EOC.
The homeostasis of intracellular pH (pHi) affects many cellular functions. Our previous study has established a functional and molecular model of the active pHi regulators in human induced ...pluripotent stem cells (hiPSCs). The aims of the present study were to further quantify passive pHi buffering power (β) and to investigate the effects of extracellular pH and Na+–H+ exchanger 1 (NHE1) activity on pluripotency in hiPSCs. pHi was detected by microspectrofluorimetry with pH‐sensitive dye‐BCECF. Western blot, immunofluorescence staining, and flow cytometry were used to detect protein expression and pluripotency. Our study in hiPSCs showed that (a) the value of total (βtot), intrinsic (βi), and CO2‐dependent (βCO2) buffering power all increased while pHi increased; (b) during the spontaneous differentiation for 4 days, the β values of βtot and βCO2 changed in a tendency of decrease, despite the absence of statistical significance; (c) an acidic cultured environment retained pluripotency and further upregulated expression and activity of NHE1 during spontaneous differentiation; (d) inhibition on NHE1 activity promoted the loss of pluripotency. In conclusion, we, for the first time, established a quantitative model of passive β during differentiation and demonstrated that maintenance of NHE1 at a higher level was of critical importance for pluripotency retention in hiPSCs.
Characterization of Buffering Power, and Effect of pH and NHE1 on Pluripotency.
In this paper we demonstrate the use of low-temperature-solution-processable bismuth iodide (BiI3) nanosheets as hole transport layers in organic photovoltaics with an active layer comprising ...poly(3-hexylthiophene) (P3HT) mixed with a fullerene derivative. The performance of the resulting devices was comparable with that of corresponding conventionally used systems incorporating polyethylenedioxythiophene:polystyrenesulfonate (PEDOT:PSS). UV–vis spectroscopy revealed that the transparency of a BiI3 layer in the visible (>620nm) and near-infrared range is greater than that of a PEDOT:PSS layer. X-ray photoemission spectroscopy of a BiI3 film revealed signals at 158.8, 164, 618.6, and 630eV—characteristic of Bi 4f7/2, Bi 4f5/2, I 3d5/2, and I 3d3/2, respectively—that indicated a stoichiometric BiI3 film. Wet milling of BiI3 crystals resulted in the formation of nanosheets, the presence of which we confirmed using scanning electron microscopy. The resultant power conversion efficiency of the device was approximately 3.5%, with an open-circuit voltage of 0.56V, a short-circuit current density of 10.4mAcm–2, and a fill factor of 60.1% under AM1.5G irradiation (100mWcm−2).
•BiI3 nanosheets prepared using a low-cost homemade wet grinder.•XPS confirmed the formation of stoichiometric BiI3 films on the substrates.•BiI3 has been used as low-temperature-solution-processable hole transport layer.•Performance of devices incorporating BiI3 as HTLs is comparable with that of devices featuring PEDOT:PSS layers.
