Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade.

Background: Adenine exhibits potential anticancer activity against several types of malignancies. However, whether adenine has anticancer effects on hepatocellular carcinoma (HCC) cells is incompletely explored. Methods: Human HCC cell lines HepG2 and SK-Hep-1 (p53-wild type) and Hep3B (p53-deficient) were used as cell model. Cell growth and cell cycle distribution were determined using MTT assay and flow cytometric analysis, respectively. Protein expression and phosphorylation were assessed by Western blot. Involvement of AMP-activated protein kinase (AMPK) was evaluated using specific inhibitor and small inhibitory RNA (siRNA). Results: Adenine treatments (0.5 - 2 mM) clearly decreased the cell growth of Hep G2 and SK-Hep-1 cells to 72.5 ± 3.4% and 71.3 ± 4.6% of control, respectively. In parallel, adenine also induced sub-G1 and S phase accumulation in both HCC cells. However, adenine did not affect the cell growth and cell cycle distribution of Hep3B cell. Western blot analysis showed that adenine reduced expression of cyclin A/D1 and cyclin-dependent kinase (CDK)2 and upregulated p53, p21, Bax, PUMA, and NOXA in HepG2 cell. Moreover, adenine induced AMPK activation that was involved in the p53-associated apoptotic cascade in HepG2 cells. Inhibition of AMPK activation or knockdown of AMPK restored the decreased cell growth of HepG2 and SK-Hep-1 cells in response to adenine. Conclusions: These findings reveal that adenine reduces the cell growth of HepG2 and SK-Hep-1 but not Hep3B cells, attributing to the AMPK/p53-mediated S phase arrest and apoptosis. It suggests that adenine has anticancer potential against p53-wild type HCC cells and may be beneficial as an adjuvant for HCC treatment.

Re-entrant transition as a bridge of broken ergodicity in confined monolayers of hexagonal prisms and cylinders.

The entropy-driven monolayer assembly of hexagonal prisms and cylinders was studied under hard slit confinement. At the conditions investigated, the particles have two distinct and dynamically disconnected rotational states: unflipped and flipped, depending on whether their circular/hexagonal face is parallel or perpendicular to the wall plane. Importantly, these two rotational states cast distinct projection areas over the wall plane that favor either hexagonal or tetragonal packing. Monte Carlo simulations revealed a re-entrant melting transition where an intervening disordered Flipped-Unflipped (FUN) phase is sandwiched between a fourfold tetratic phase at high concentrations and a sixfold triangular solid at intermediate concentrations. The FUN phase contains a mixture of flipped and unflipped particles and is translationally and orientationally disordered. Complementary experiments were conducted with photolithographically fabricated cylindrical microparticles confined in a wedge cell. Both simulations and experiments show the formation of phases with comparable fraction of flipped particles and structure, i.e., the FUN phase, triangular solid, and tetratic phase, indicating that both approaches sample analogous basins of particle-orientation phase-space. The phase behavior of hexagonal prisms in a soft-repulsive wall model was also investigated to exemplify how tunable particle-wall interactions can provide an experimentally viable strategy to dynamically bridge the flipped and unflipped states.

Processing-Structure-Performance Relationships of Microporous Metal-Organic Polymers for Size-Selective Separations.

Small-molecule impurities, such as N-nitrosodimethylamine (NDMA), have infiltrated the generic drug industry, leading to recalls in commonly prescribed blood pressure and stomach drugs in over 43 countries since 2018 and directly affecting tens of millions of patients. One promising strategy to remove small-molecule impurities like NDMA from drug molecules is by size exclusion, in which the contaminant is removed by selective adsorption onto a (micro)porous material due to its smaller size. However, current solution-phase size-exclusion separations are primarily limited by the throughput-selectivity trade-off. Here, we report a bioinspired solution to conquer these critical challenges by leveraging the assembly of atomically precise building blocks into hierarchically porous structures. We introduce a bottom-up approach to form micropores, mesopores, and macroscopic superstructures simultaneously using functionalized oxozirconium clusters as building blocks. Further, we leverage recent advances in photopolymerization to design macroscopic flow structures to mitigate backpressure. Based on these multiscale design principles, we engineer simple, inexpensive devices that are able to separate NDMA from contaminated drugs. Beyond this urgent model system, we expect this design strategy to open up hitherto unexplored avenues of nanomaterial superstructure fabrication for a range of size-exclusion purification strategies.

Porous cage-derived nanomaterial inks for direct and internal three-dimensional printing.

The convergence of 3D printing techniques and nanomaterials is generating a compelling opportunity space to create advanced materials with multiscale structural control and hierarchical functionalities. While most nanoparticles consist of a dense material, less attention has been payed to 3D printing of nanoparticles with intrinsic porosity. Here, we combine ultrasmall (about 10 nm) silica nanocages with digital light processing technique for the direct 3D printing of hierarchically porous parts with arbitrary shapes, as well as tunable internal structures and high surface area. Thanks to the versatile and orthogonal cage surface modifications, we show how this approach can be applied for the implementation and positioning of functionalities throughout 3D printed objects. Furthermore, taking advantage of the internal porosity of the printed parts, an internal printing approach is proposed for the localized deposition of a guest material within a host matrix, enabling complex 3D material designs.

A novel technique for closed-chamber iridodialysis repair.

PURPOSE: We introduce a novel technique for closed chamber iridodialysis repair. MATERIALS AND METHODS: We use a 2.8-mm paracentesis knife to penetrate into the anterior chamber and create interrupted incisions in the sclera. The wounds are 1.5 mm distant from the limbus, at consistent 2.8-mm intervals along the dialysis area. After injecting viscocohesive ophthalmic viscosurgical device through a side port to relieve the synechia and to push the iris toward the incisions, the iris is then grasped by Kelman forceps through the sclera, dragged carefully, and incarcerated. After adjusting the tension of the iris according to the pupil shape, the sclera and the incarcerated iris tissue were sutured together with 10-0 nylon. RESULTS: The technique was effective in six patients with traumatic iridodialysis. CONCLUSION: Our surgical technique repairs the iris, restores the shape of pupil, as well as avoids creating a large incision in the limbus in patients suffering from iridodialysis.

Bilateral corneal keloids after eyelid compression.

The purpose of this study is to present a case of bilateral corneal keloids after performing eyelid compression for half a year. This study was a retrospective case report. Visual acuity, as well as detailed high-resolution images of external eye photography, anterior segment optical coherence tomography (ASOCT), and topography were documented. Initially, the best-corrected visual acuities were 20/20 (OD) and 20/32 (OS). ASOCT revealed a characteristic irregular hyperplastic epithelium, a disrupted Bowman's layer, and an edematous stroma for both eyes. Topography exposed an irregular astigmatism of 2.1 diopters for the left eye, while the right eye had a relatively smooth surface. After 1 year of conservative treatment, the best-corrected visual acuity improved to 20/20 (OU), and astigmatism also decreased. Corneal keloid may be induced after long-term eyelid compression. ASOCT and topography are useful for detecting and monitoring disease progression. Conservative treatments are suggested as the first line of therapy, while the size, depth, and location of the lesions are tolerable.

Toxic Keratopathy Following the Use of Alcohol-Containing Antiseptics in Nonocular Surgery.

IMPORTANCE: Corneal abrasion is the most common ocular complication associated with nonocular surgery, but toxic keratopathy is rare. OBSERVATION: Three patients developed severe toxic keratopathy after orofacial surgery on the left side with general anesthesia. All patients underwent surgery in the right lateral tilt position with ocular protection but reported irritation and redness in their right eyes after the operation. Alcohol-containing antiseptic solutions were used for presurgical preparation. Ophthalmic examination showed decreased visual acuity ranging from 20/100 to 20/400, corneal edema and opacity, anterior chamber reaction, or stromal neovascularization in the patients' right eyes. Confocal microscopy showed moderate to severe loss of corneal endothelial cells in all patients. Despite prompt treatment with topical corticosteroids, these 3 patients eventually required cataract surgery, endothelial keratoplasty, or penetrating keratoplasty, respectively. After the operation, the patients' visual acuity improved to 20/30 or 20/40. Data analysis was conducted from December 6, 2010, to June 15, 2015. CONCLUSIONS AND RELEVANCE: Alcohol-containing antiseptic solutions may cause severe toxic keratopathy; this possibility should be considered in orofacial surgery management. Using alcohol-free antiseptic solutions in the periocular region and taking measures to protect the dependent eye in the lateral tilt position may reduce the risk of severe corneal injury.