I-GLAD: a new strategy for fabricating antibacterial surfaces.

The paper uses inverted glancing angle deposition (I-GLAD) for creating antibacterial surfaces. Antibacterial surfaces are found in nature, such as on insect wings, eyes, and plant leaves. Since the bactericidal mechanism is purely physical for these surfaces, the antimicrobial resistance of bacteria to traditional chemical antibiotics can be overcome. The technical problem is how to mimic, synthesize, and scale up the naturally occurring antibacterial surfaces for practical applications, given the fact that most of those surfaces are composed of three-dimensional hierarchical micro-nano structures. This paper proposes to use I-GLAD as a novel bottom-up nanofabrication technique to scale up bio-inspired nano-structured antibacterial surfaces. Our innovative I-GLAD nanofabrication technique includes traditional GLAD deposition processes alongside the crucial inverting process. Following fabrication, we explore the antibacterial efficacy of I-GLAD surfaces using two types of bacteria: Escherichia coli (E. coli), a gram-negative bacterium, and Staphylococcus aureus (S. aureus), a gram-positive bacterium. Scanning electron microscopy (SEM) shows the small tips and flexible D/P (feature size over period) ratio of I-GLAD nanoneedles, which is required to achieve the desired bactericidal mechanism. Antibacterial properties of the I-GLAD samples are validated by achieving flat growth curves of E. coli and S. aureus, and direct observation under SEM. The paper bridges the knowledge gaps of seeding techniques for GLAD, and the control/optimization of the I-GLAD process to tune the morphologies of the nano-protrusions. I-GLAD surfaces are effective against both gram-negative and gram-positive bacteria, and they have tremendous potentials in hospital settings and daily surfaces.

Targeting Ferroptosis-Elicited Inflammation Suppresses Hepatocellular Carcinoma Metastasis and Enhances Sorafenib Efficacy.

Triggering ferroptosis, an iron-dependent form of cell death, has recently emerged as an approach for treating cancer. A better understanding of the role and regulation of ferroptosis is needed to realize the potential of this therapeutic strategy. Here, we observed extensive activation of ferroptosis in hepatoma cells and human hepatocellular carcinoma (HCC) cases. Patients with low to moderate activation of ferroptosis in tumors had the highest risk of recurrence compared to patients with no or high ferroptosis. Upon encountering ferroptotic liver cancer cells, aggregated macrophages efficiently secreted proinflammatory IL1ß to trigger neutrophil-mediated sinusoidal vascular remodeling, thereby creating favorable conditions for aggressive tumor growth and lung metastasis. Mechanistically, hyaluronan fragments released by cancer cells acted via an NF-κB-dependent pathway to upregulate IL1ß precursors and the NLRP3 inflammasome in macrophages, and oxidized phospholipids secreted by ferroptotic cells activated the NLRP3 inflammasome to release functional IL1ß. Depleting either macrophages or neutrophils or neutralizing IL1ß in vivo effectively abrogated ferroptosis-mediated liver cancer growth and lung metastasis. More importantly, the ferroptosis-elicited inflammatory cellular network served as a negative feedback mechanism that led to therapeutic resistance to sorafenib in HCC. Targeting the ferroptosis-induced inflammatory axis significantly improved the therapeutic efficacy of sorafenib in vivo. Together, this study identified a role for ferroptosis in promoting HCC by triggering a macrophage/IL1ß/neutrophil/vasculature axis. SIGNIFICANCE: Ferroptosis induces a favorable tumor microenvironment and supports liver cancer progression by stimulating an inflammatory cellular network that can be targeted to suppress metastasis and improve the efficacy of sorafenib.

Andrographolide inhibits the proliferation and migration of vascular smooth muscle cells via PI3K/AKT signaling pathway and amino acid metabolism to prevent intimal hyperplasia.

Andrographolide (AGP) exerts pharmacological effects when used for the treatment of cardiovascular disease, but the molecular mechanisms underlying its inhibitory effects on the proliferation and migration of vascular smooth muscle cells (VSMCs) and intimal hyperplasia (IH) are unknown. The proliferation and migration of VSMCs treated with AGP were examined using the CCK-8, flow cytometry, and wound healing assays. Expression levels of proteins related to cell proliferation and apoptosis were quantified. Multi-omics analysis with RNA-seq and metabolome was used to explore the potential molecular mechanism of AGP treatment. Additionally, an in vivo model was established through ligation of the left common carotid artery to identify the therapeutic potential of AGP in IH. Molecular docking and western blotting were performed to verify the mechanism discovered with multi-omics analysis. The results showed that AGP inhibited the proliferation and migration of cultured VSMCs in a dose-dependent manner and alleviated IH-related vascular stenosis. AGP significantly downregulated the protein levels of CDK1, CCND1, and BCL2 and upregulated the protein level of BAX. Gene expression profiles showed a total of 3,298 differentially expressed genes (DEGs) after AGP treatment, of which 1,709 DEGs had upregulated expression and 1,589 DEGs had downregulated expression. KEGG enrichment analysis highlighted the PI3K/AKT signaling pathway, verified with the detection of the activation of PI3K and AKT phosphorylation. Further GO enrichment combined with metabolomics analysis showed that AGP inhibition in cultured VSMCs involved the amino acid metabolic process, and the expression levels of the two key factors PRDM16 and EZH2, identified with PPI and docking analysis, were significantly inhibited by AGP treatment. In conclusion, our study showed that AGP inhibited VSMCs proliferation and migration by suppressing the PI3K/AKT signaling pathway and amino acid metabolism, which, in turn, improved IH.

Bio-inspired antimicrobial surfaces fabricated by glancing angle deposition.

This paper describes the fabrication of cicada-wing-inspired antimicrobial surfaces using Glancing Angle Deposition (GLAD). From the study of an annual cicada (Neotibicen Canicularis, also known as dog-day cicada) in North America, it is found that the cicada wing surfaces are composed of unique three-dimensional (3D) nanofeature arrays, which grant them extraordinary properties including antimicrobial (antifouling) and antireflective. However, the morphology of these 3D nanostructures imposes challenges in artificially synthesizing the structures by utilizing and scaling up the template area from nature. From the perspective of circumventing the difficulties of creating 3D nanofeature arrays with top-down nanofabrication techniques, this paper introduces a nanofabrication process that combines bottom-up steps: self-assembled nanospheres are used as the bases of the features, while sub-100 nm pillars are grown on top of the bases by GLAD. Scanning electron micrographs show the resemblance of the synthesized cicada wing mimicry samples to the actual cicada wings, both quantitatively and qualitatively. The synthetic mimicry samples are hydrophobic with a water contact angle of 125˚. Finally, the antimicrobial properties of the mimicries are validated by showing flat growth curves of Escherichia coli (E. coli) and by direct observation under scanning electron microscopy (SEM). The process is potentially suitable for large-area antimicrobial applications in food and biomedical industries.

Direct-write microsphere photolithography of hierarchical infrared metasurfaces.

A direct-write configuration of microsphere photolithography (MPL) is investigated for the patterning of IR metasurfaces at large scales. MPL uses a self-assembled hexagonal close-packed array of microspheres as an optical element to generate photonic nanojets within a photoresist layer. The photonic jets can be positioned within the microsphere-defined unit cells by controlling the illumination's angle of incidence (AOI). This allows the definition of complex antenna elements. A digital micromirror device is used to provide spatial modulation across the microsphere arrays and coordinated with a set of stages providing AOI control. This provides hierarchical patterning at the sub- and super-unit cell levels and is suitable for a range of metasurfaces. The constraints of this approach are analyzed and demonstrated with a polarization-dependent infrared perfect absorber/emitter, which agrees well with modeling.

Modeling of microsphere photolithography.

Microsphere photolithography (MPL) is a fabrication technique that combines the ability to self-assemble arrays of microspheres with the ability of a microsphere to focus light to a photonic jet, in order to create highly ordered nanoscale features in photoresist. This paper presents a model of photoresist exposure with the photonic jet, combining a full-wave electromagnetic model of the microsphere/photoresist interaction with the sequential removal of exposed photoresist by the developer. The model is used to predict the dose curves for the MPL process based on the photoresist thickness, illumination conditions, and development time. After experimental validation, the model provides insight into the process including the resolution, sensitivity, and effects of off-normal illumination. This guides the fabrication of sub-100 nm hole/disk arrays using lift-off, and superposition is shown to predict the geometry for split-ring resonators created using multiple exposures. This model will assist synthesizing fabrication parameters to create large area scalable metasurfaces with sensing and energy management applications.

Fabrication and verification of a glass-silicon-glass micro-/nanofluidic model for investigating multi-phase flow in shale-like unconventional dual-porosity tight porous media.

Unconventional shale or tight oil/gas reservoirs that have micro-/nano-sized dual-scale matrix pore throats with micro-fractures may result in different fluid flow mechanisms compared with conventional oil/gas reservoirs. Microfluidic models, as a potential powerful tool, have been used for decades for investigating fluid flow at the pore-scale in the energy field. However, almost all microfluidic models were fabricated by using etching methods and very few had dual-scale micro-/nanofluidic channels. Herein, we developed a lab-based, quick-processing and cost-effective fabrication method using a lift-off process combined with the anodic bonding method, which avoids the use of any etching methods. A dual-porosity matrix/micro-fracture pattern, which can mimic the topology of shale with random irregular grain shapes, was designed with the Voronoi algorithm. The pore channel width range is 3 µm to 10 µm for matrices and 100-200 µm for micro-fractures. Silicon is used as the material evaporated and deposited onto a glass wafer and then bonded with another glass wafer. The channel depth is the same (250 nm) as the deposited silicon thickness. By using an advanced confocal laser scanning microscopy (CLSM) system, we directly visualized the pore level flow within micro/nano dual-scale channels with fluorescent-dyed water and oil phases. We found a serious fingering phenomenon when water displaced oil in the conduits even if water has higher viscosity and the residual oil was distributed as different forms in the matrices, micro-fractures and conduits. We demonstrated that different matrix/micro-fracture/macro-fracture geometries would cause different flow patterns that affect the oil recovery consequently. Taking advantage of such a micro/nano dual-scale 'shale-like' microfluidic model fabricated by a much simpler and lower-cost method, studies on complex fluid flow behavior within shale or other tight heterogeneous porous media would be significantly beneficial.

The research of synthesis and bioactivity of the novel indanedione anticoagulant rodenticides.

Three new anticoagulant rodenticides R1, R2, and R3 were designed. The containing fluorine acute toxicity groups was added to 1,3-indandione derivative. Analysis method of synthesized anticoagulant rodenticides were IR, 1H NMR. Acute bioactivity of the new rodenticides was evaluated, including the coefficient of absorb food and median lethal dose (LD50). Average coefficient of absorbed food for R1 was 0.54 and LD50 of R1 was 2.15 mg/kg. Average coefficient of absorbed food for R2 was 0.59 and the acute oral LD50 of R2 was 2.65 mg/kg. Average feeding coefficient of R3 was 0.68 and the acute oral LD50 of R3 was 3.12 mg/kg. Experiments showed that rat's death peak was at about 72 h and rodenticides had good characteristics of acute medicine. The LD50 of three new fluoride anticoagulant rodenticides showed that they had good palatability for big white rats, and they had a strong poison effect on rodent. The result of all experiments proved that the synthesis of 1,3-indan diketone used as parent compound of new anticoagulant rodenticides could replace the current 4-hydroxyl coumarin as parent compound of the second-generation anticoagulant rodenticides. 1,3-Indan diketone would be widely used as parent compound of anticoagulant rodenticides.

Identification of an HLA-A2-restricted CD147 epitope that can induce specific CTL cytotoxicity against drug resistant MCF-7/Adr cells.

Cluster of differentiation (CD)147 is highly expressed in drug-resistant tumor cell lines and is involved in the formation of tumor drug resistance. Therefore, immunotherapy utilizing CD147 epitope peptides is a promising approach for the elimination of drug-resistant tumor cells. However, like most tumor-associated antigens (TAAs), CD147 belongs to the autoantigen category, and T cells that recognize high affinity, immunodominant epitopes from autoantigens are deleted though thymic negative selection. Furthermore, wild-type autoantigen peptides cannot effectively activate and expand T lymphocytes with lower affinity T cell receptors in vivo. However, mutations of TAA peptides have been demonstrated to increase the affinity of major histocompatibility complex molecules and their binding to T cell receptor molecules, leading to activation of T lymphocytes in vitro. In the present study, a high-affinity point mutation peptide, CD147126-134L2, was predicted by the human leukocyte antigen (HLA) binding prediction algorithm and its affinity was testified using a T2 binding assay. In addition, when peptide-specific cytotoxic T lymphocytes (CTLs) were stimulated with dendritic cells loaded with the CD147126-134L2 peptide under HLA-A*02:01 restriction, interferon-γ release and cytotoxicity assays showed that peptide-specific CTLs effectively cross-recognized and lysed T2 target cells loaded either with the wild-type (CD147126-134) or mutated peptide (CD147126-134L2). Moreover, the CD147126-134L2 peptide-specific CTLs exerted strong cytotoxic activity against drug-resistant MCF-7/Adr cells, which express a high level of CD147 and are HLA-A*02:01-positive, but not against normal MCF-7 cells. Thus, this suggests that the wild-type peptide (CD147126-134) is naturally presented on HLA-A*02:01 of CD147-expressing MCF-7/Adr cells and is cross-recognized by CTLs. In conclusion, an HLA-A*02:01-restricted CD147-point mutant epitope peptide was identified that induces CTLs to efficiently lyse drug-resistant MCF-7 cells that highly express CD147. Therefore, this immunotherapeutic approach should be explored as a potential treatment for drug-resistant tumors.

Infrared metasurfaces created with off-normal incidence microsphere photolithography.

Fabricating metasurfaces over large areas at low costs remains a critical challenge to their practical implementation. This paper reports on the use of microsphere photolithography (MPL) to create infrared metasurfaces by changing the angle-of-incidence of the illumination to steer the photonic jet. The displacement of the photonic jet is shown to scale with the diameter of the microsphere while the exposure dose scales with the square of the microsphere diameter. This process is robust in the presence of local defects in the microsphere lattice. The paper demonstrates patterning split ring resonators and tripole based metasurfaces using MPL, which are fabricated and characterized with FTIR. The combination of bottom-up and top-down approaches in off-normal incidence microsphere photolithography technique provides cost-effective, flexible, and high-throughput fabrication of infrared metasurfaces.

Polycrystalline metasurface perfect absorbers fabricated using microsphere photolithography.

Microsphere photolithography (MPL) is a practical, cost-effective nanofabrication technique. It uses self-assembled microspheres in contact with the photoresist as microlenses. The microspheres focus incident light to a sub-diffraction limited array of photonic jets in the photoresist. This Letter explores the MPL technique to pattern metal-insulator-metal metasurfaces with near-perfect absorption at mid-wave infrared (MWIR) frequencies. Experimental results are compared to electromagnetic simulations of both the exposure process and the metasurface response. The microsphere self-assembly technique results in a polycrystalline metasurface; however, the metal-insulator-metal structure is shown to be defect tolerant. While the MPL approach imposes geometric constraints on the metasurface design, once understood, the technique can be used to create functional devices. In particular, the ability to tune the resonant wavelength with the exposure dose raises the potential of hierarchical structures.

Is vaginal mucosal graft the excellent substitute material for urethral reconstruction in female-to-male transsexuals?

PURPOSE: Construction of a neourethra is always considered to be a difficult part in phalloplasty, especially for the female-to-male (FTM) transsexual patients. We report our experience with prefabricated pars pendulans urethrae using vaginal mucosal graft for phalloplasty in FTM transsexuals. MATERIALS AND METHODS: We retrospectively reviewed notes on the 22 FTM patients treated with pedicled-flap phalloplasty with prefabricated pars pendulans urethrae using vaginal mucosal graft between January 2008 and December 2012. Surgical outcome, urological function, and complications were recorded. Histological difference between normal mucosa and skin, and pathological changes of vaginal mucosal graft were also observed. RESULTS: All the reconstructive penis survived, and patients could void in a standing position finally at a median follow-up of 25.4 ± 6.0 months. Urethral fistula and urethral stricture rates were 31.8 % (7/22 patients) and 4.5 % (1/22 patients), respectively. The occurrence of the urethral stricture was remarkably low compared with previous reports. Our histological results also showed a pronounced similarity between vaginal and buccal mucosa. Morphologically, they resembled urethral epithelium more closely than the forearm skin. Following the free transfer, the vaginal mucosal graft also showed a good revascularization and the inflammatory reaction and the extent of fibrosis of the mucosa decreased to the normal level after a 6-month prefabrication. CONCLUSION: With prefabrication of vaginal mucosal graft, we reconstruct a competent phallic neourethra in these FTM transsexuals. According to its histological similarities and source character, the vaginal mucosa is the excellent substitute material for promising urethral reconstruction in FTM transsexuals.

Low-frequency electrotherapy for female patients with detrusor underactivity due to neuromuscular deficiency.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to assess the efficacy of low-frequency electrotherapy (LFE) for female patients with early-stage detrusor underactivity (DUA) due to neuromuscular deficiency. METHODS: A total of 102 female patients were divided randomly into four groups: LFE-NC (normal compliance), LFE-LC (low compliance), CON (control)-NC and CON-LC. Patients in the LFE-NC and LFE-LC groups received LFE, and those in the CON-NC and CON-LC groups received conservative treatment. Urodynamic evaluation was performed before and after treatment. RESULTS: After treatment, 82 % of the LFE-NC regained detrusor contractility, whereas only 2 (8 %) of the CON-NC had normal detrusor contraction. None of LFE-LC or CON-LC regained detrusor contractility (p < 0.01). The per cent of LFE-NC who relied on catheterization for bladder emptying decreased by 43 % (p < 0.01). Those in the LFE-LC, CON-NC and CON-LC groups decreased by only 4, 12 or 0 % (p > 0.05). CONCLUSIONS: LFE was more effective for DUA patients with normal compliance; these patients benefited from LFE, but DUA patients with low compliance did not.

Impact of tension-free vaginal tape procedure on dysfunctional voiding in women with stress urinary incontinence.

OBJECTIVES: To determine the prevalence of dysfunctional voiding (DV) in female stress urinary incontinence (SUI) and its modification after tension-free vaginal tape (TVT) procedure. METHODS: Three hundred and sixty women with SUI were enrolled and underwent urodynamics from 2002 to 2008. DV was determined when non-neurogenic detrusor-sphincter dyssynergia occurred during voluntary voiding. It was further quantitatively analyzed using the tense/loose value, a parameter derived from external anal sphincter electromyogram. The distribution of other urodynamic variables was also evaluated. One hundred and fifty patients underwent the TVT procedure and forty of them were studied with urodynamics after surgery during follow up. RESULTS: Overall, DV was diagnosed in ninety-nine patients, with a prevalence of 27.5%. The functional profile length in SUI women with DV was significantly shorter than that in SUI women without DV (3.13 +/- 0.76 vs 3.32 +/- 0.65, P = 0.017). After the TVT procedure, the recovery of SUI between cases with and without DV showed no significant difference. The rate of DV state change after the surgery, namely from with to without DV or from without to with DV, significantly differed between the female patients with and without DV (66.7% vs 3.6%, P < 0.05) during follow up. The DV improved after the surgery in SUI women with DV. CONCLUSIONS: DV might represent a coexistent finding in women with SUI. The main difference of women with SUI and DV, as compared with those without DV, is a shortened functional profile length. In such cases, TVT procedure can improve DV along with the treatment of SUI.