Effect of Sample Geometry on Graphitization of Polyacrylonitrile.

In this study, it is analyzed how sample geometry (spheres, nanofibers, or films) influences the graphitization behavior of polyacrylonitrile (PAN) molecules. The chemical bonding and changes in the composition of these three geometries are studied at the oxidation, carbonization, and graphitization stages via scanning electron microscopy (SEM), in situ thermogravimetric-infrared (TGA-IR) analysis, elemental analysis, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The influence of molecular alignment on the graphitization of the three sample geometries is investigated using synchrotron wide-angle X-ray diffraction (WAXD) and transmission electron microscopy (TEM). The effects of molecular alignment at different draw rates during spinning are explored in detail.

Blocking Microglial Proliferation by CSF-1R Inhibitor Does Not Alter the Neuroprotective Effects of Adoptive Regulatory T Cells in 3xTg Alzheimer's Disease Mice.

Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes cognitive impairment. Neuroinflammation induced by activated microglia exacerbates AD. Regulatory T cells (Tregs) play roles in limiting neuroinflammation by converting microglial polarization. Therefore, adoptive Treg therapy is considered an attractive option for neurodegenerative disorders. However, the mechanism underlying Treg therapy via microglial modulation is not fully understood. In this study, we sought to determine whether adoptively transferred Tregs were effective when microglia proliferation was inhibited by using GW2580, which is an inhibitor of CSF1R. We found that inhibition of microglial proliferation during Treg transfer did not alter the therapeutic effects of Tregs on cognitive deficits and the accumulation of Aß and pTAU in 3xTg-AD mice. The expression of pro- and anti-inflammatory markers in the hippocampus of 3xTg mice showed that GW2580 did not affect the inhibition of neuroinflammation by Treg transfer. Additionally, adoptively transferred Tregs were commonly detected in the brain on day 7 after transfer and their levels decreased slowly over 100 days. Our findings suggest that adoptively transferred Tregs can survive longer than 100 days in the brain, suppressing microglial activation and thus alleviating AD pathology. The present study provides valuable evidence to support the prolonged efficacy of adoptive Treg therapy in AD.

Chemisorption of silicon tetrachloride on silicon nitride: a density functional theory study.

We studied the chemisorption of silicon tetrachloride (SiCl4) on the NH2/NH-terminated silicon nitride slab model using density functional theory (DFT) for atomic layer deposition (ALD) of silicon nitride. Initially, two reaction pathways were compared, forming HCl or NH3+Cl- as a byproduct. The NH3+Cl- complex formation was more exothermic than the HCl formation, with an activation energy of 0.26 eV. The -NH2* reaction sites are restored by desorption of HCl from the NH3+Cl- complexes at elevated temperatures of 205 °C or higher. Next, three sequential ligand exchange reactions forming Si-N bonds were modeled and simulated. The reaction energies became progressively less exothermic as the reaction progressed, from -1.31 eV to -0.30 eV to 0.98 eV, due to the stretching of Si-N bonds and the distortion of the N-Si-N bond angles. Also, the activation energies for the second and third reactions were 2.17 eV and 1.55 eV, respectively, significantly higher than the 0.26 eV of the first reaction, mainly due to the additional dissociation of the N-H bond. The third Si-N bond formation is unfavorable due to the endothermic reaction and higher activation energy. Therefore, the chemisorbed species would be -SiCl2* when the surface is exposed to SiCl4.

The semaphorin 3A/neuropilin-1 pathway promotes clonogenic growth of glioblastoma via activation of TGF-ß signaling.

Glioblastoma (GBM) is the most lethal brain cancer with a dismal prognosis. Stem-like GBM cells (GSCs) are a major driver of GBM propagation and recurrence; thus, understanding the molecular mechanisms that promote GSCs may lead to effective therapeutic approaches. Through in vitro clonogenic growth-based assays, we determined mitogenic activities of the ligand molecules that are implicated in neural development. We have identified that semaphorin 3A (Sema3A), originally known as an axon guidance molecule in the CNS, promotes clonogenic growth of GBM cells but not normal neural progenitor cells (NPCs). Mechanistically, Sema3A binds to its receptor neuropilin-1 (NRP1) and facilitates an interaction between NRP1 and TGF-ß receptor 1 (TGF-ßR1), which in turn leads to activation of canonical TGF-ß signaling in both GSCs and NPCs. TGF-ß signaling enhances self-renewal and survival of GBM tumors through induction of key stem cell factors, but it evokes cytostatic responses in NPCs. Blockage of the Sema3A/NRP1 axis via shRNA-mediated knockdown of Sema3A or NRP1 impeded clonogenic growth and TGF-ß pathway activity in GSCs and inhibited tumor growth in vivo. Taken together, these findings suggest that the Sema3A/NRP1/TGF-ßR1 signaling axis is a critical regulator of GSC propagation and a potential therapeutic target for GBM.

Assessing the associations between known genetic variants and substance use in people with HIV in the United States.

BACKGROUND: The prevalence of substance use in people with HIV (PWH) in the United States is higher than in the general population and is an important driver of HIV-related outcomes. We sought to assess if previously identified genetic associations that contribute to substance use are also observed in a population of PWH. METHODS: We performed genome-wide association studies (GWAS) of alcohol, smoking, and cannabis use phenotypes in a multi-ancestry population of 7,542 PWH from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We conducted multi-ancestry GWAS for individuals of African (n = 3,748), Admixed American (n = 1,334), and European (n = 2,460) ancestry. Phenotype data were self-reported and collected using patient reported outcomes (PROs) and three questions from AUDIT-C, an alcohol screening tool. We analyzed nine phenotypes: 1) frequency of alcohol consumption, 2) typical number of drinks on a day when drinking alcohol, 3) frequency of five or more alcoholic drinks in a 30-day period, 4) smoking initiation, 5) smoking cessation, 6) cigarettes per day, 7) cannabis use initiation, 8) cannabis use cessation, 9) frequency of cannabis use during the previous 30 days. For each phenotype we considered a) variants previously identified as associated with a substance use trait and b) novel associations. RESULTS: We observed evidence for effects of previously reported single nucleotide polymorphisms (SNPs) related to alcohol (rs1229984, p = 0.001), tobacco (rs11783093, p = 2.22E-4), and cannabis use (rs2875907, p = 0.005). We also report two novel loci (19p13.2, p = 1.3E-8; and 20p11.21, p = 2.1E-8) associated with cannabis use cessation. CONCLUSIONS: Our analyses contribute to understanding the genetic bases of substance use in a population with relatively higher rates of use compared to the general population.

The varied influence of ocular Demodex infestation on dry eye disease and meibomian gland dysfunction across different age groups.

This study aimed to investigate the impact of ocular demodicosis on dry eye disease (DED) and meibomian gland dysfunction (MGD) across different age populations: young (20 to < 40), middle-aged (40 to < 60), and elderly (≥ 60), based on the retrospective medical chart review. In each age subgroup, Demodex infestation and its count were correlated with clinical parameters of DED and MGD. Among the total of 351 subjects, 52.7% had ocular demodicosis, with a mean of 2.31 ± 1.39 mites per four eyelashes (0.58 per lash) in a unilateral eye. In the age subgroup 1 (age < 40; N = 44), subjects with Demodex had significantly higher meibum quality grades. In subgroup 2 (40 ≤ age < 60; N = 122), subjects with Demodex had higher ocular surface disease index scores and higher MG expressibility grades. However, in subgroup 3 (age ≥ 60; N = 185), demographics and all parameters did not differ according to Demodex infestation. Moreover, the number of mites did not correlate with MGD severity in any of the subgroups. In conclusion, age may act as a significant confounding factor in the relationship between ocular Demodex infestation and clinical features of DED and MGD, despite older patients aged 60 years and above being at a higher risk of Demodex infestation and experiencing more severe MGD.

Neural network application for assessing thyroid-associated orbitopathy activity using orbital computed tomography.

This study aimed to propose a neural network (NN)-based method to evaluate thyroid-associated orbitopathy (TAO) patient activity using orbital computed tomography (CT). Orbital CT scans were obtained from 144 active and 288 inactive TAO patients. These CT scans were preprocessed by selecting eleven slices from axial, coronal, and sagittal planes and segmenting the region of interest. We devised an NN employing information extracted from 13 pipelines to assess these slices and clinical patient age and sex data for TAO activity evaluation. The proposed NN's performance in evaluating active and inactive TAO patients achieved a 0.871 area under the receiver operating curve (AUROC), 0.786 sensitivity, and 0.779 specificity values. In contrast, the comparison models CSPDenseNet and ConvNeXt were significantly inferior to the proposed model, with 0.819 (p = 0.029) and 0.774 (p = 0.04) AUROC values, respectively. Ablation studies based on the Sequential Forward Selection algorithm identified vital information for optimal performance and evidenced that NNs performed best with three to five active pipelines. This study establishes a promising TAO activity diagnosing tool with further validation.

A theoretical study on the surface reaction of tetrakis(dimethylamino)titanium on titanium oxide.

Tetrakis(dimethylamino)-titanium (TDMAT, Ti(NMe2)4) has been used for the low-temperature atomic layer deposition (ALD) process of titanium oxide (TiO2) films. In this study, the chemisorption of TDMAT on a titanium oxide surface using a slab model was simulated by density functional theory (DFT) calculation. We calculated the activation energy for the chemisorption and predicted the final chemisorbed species. A TiO2 slab model was constructed with the optimized number of -OH surface groups. Three serial ligand exchange reactions between a TDMAT molecule and the TiO2 slab were exothermic with low activation energies of 0.16-0.46 eV, which can explain the low processing temperatures of the ALD TiO2 processes. Our DFT calculation showed that three NMe2 ligands of TDMAT would be released and the surface species of -TiNMe2 would be formed, which is in good agreement with the experimental observation in the literature.

Genetic differences according to onset age and lung function in asthma: A cluster analysis.

BACKGROUND: The extent of differences between genetic risks associated with various asthma subtypes is still unknown. To better understand the heterogeneity of asthma, we employed an unsupervised method to identify genetic variants specifically associated with asthma subtypes. Our goal was to gain insight into the genetic basis of asthma. METHODS: In this study, we utilized the UK Biobank dataset to select asthma patients (All asthma, n = 50,517) and controls (n = 283,410). We excluded 14,431 individuals who had no information on predicted values of forced expiratory volume in one second percent (FEV1%) and onset age, resulting in a final total of 36,086 asthma cases. We conducted k-means clustering based on asthma onset age and predicted FEV1% using these samples (n = 36,086). Cluster-specific genome-wide association studies were then performed, and heritability was estimated via linkage disequilibrium score regression. To further investigate the pathophysiology, we conducted eQTL analysis with GTEx and gene-set enrichment analysis with FUMA. RESULTS: Clustering resulted in four distinct clusters: early onset asthmanormalLF (early onset with normal lung function, n = 8172), early onset asthmareducedLF (early onset with reduced lung function, n = 8925), late-onset asthmanormalLF (late-onset with normal lung function, n = 12,481), and late-onset asthmareducedLF (late-onset with reduced lung function, n = 6508). Our GWASs in four clusters and in All asthma sample identified 5 novel loci, 14 novel signals, and 51 cluster-specific signals. Among clusters, early onset asthmanormalLF and late-onset asthmareducedLF were the least correlated (rg  = 0.37). Early onset asthmareducedLF showed the highest heritability explained by common variants (h2  = 0.212) and was associated with the largest number of variants (71 single nucleotide polymorphisms). Further, the pathway analysis conducted through eQTL and gene-set enrichment analysis showed that the worsening of symptoms in early onset asthma correlated with lymphocyte activation, pathogen recognition, cytokine receptor activation, and lymphocyte differentiation. CONCLUSIONS: Our findings suggest that early onset asthmareducedLF was the most genetically predisposed cluster, and that asthma clusters with reduced lung function were genetically distinct from clusters with normal lung function. Our study revealed the genetic variation between clusters that were segmented based on onset age and lung function, providing an important clue for the genetic mechanism of asthma heterogeneity.

Feasibility of microencapsulated phytochemical as disinfectant for inhibition of Candida albicans proliferation on denture base produced by digital light processing.

BACKGROUNDS: A proper disinfection of denture is vital to prevent a fungal infection. A study on the feasibility of microencapsulated phytochemical as complementary disinfectant and its interaction with effervescent tablet immersion on denture base resin is lacking. OBJECTIVES: The aim of this study was to examine the feasibility of phytochemical-filled microcapsules as disinfectant for the inhibition of Candida albicans (C. albicans) attachment on the denture base produced by digital light processing (DLP). METHODS: 54 denture base specimens uniformly mixed with or without 5wt% phytochemical-filled microcapsules were prepared using DLP. Fungal cells were inoculated onto the surfaces of the specimens, which were divided into three different disinfection treatment groups (n = 9): 1) none, 2) sterile tap water immersion for 15 min, and 3) effervescent tablet immersion for 15 min. After each treatment, the biofilm on denture surface was stained with a crystal violet solution to measure the absorbance. The number of fungal colonies was counted as colony-forming units (CFU) per mL. Morphological changes were examined by microscopy. An aligned rank transform analysis of variance was performed to analyze the interaction of presence of microcapsule and disinfection condition, with statistical significance set at P < 0.05. RESULTS: Both for the absorbance and CFU, there was no significant interaction between the presence of microcapsules and disinfection conditions (P = 0.543 and P = 0.077, respectively). The presence of microcapsules was statistically significant (both P < 0.001), while the effect of disinfection condition was not significant (P = 0.165 and P = 0.189, respectively). Morphological changes in fungi were detected in the groups containing microcapsules, whereas undamaged hyphal structures were found in those without microcapsules, irrespective of disinfection treatments. CONCLUSIONS: The presence of phytochemical-filled microcapsules significantly reduced the adhesion of C. albicans and inhibited its proliferation on denture surfaces, regardless of disinfection conditions.

Effect of build angle, resin layer thickness and viscosity on the surface properties and microbial adhesion of denture bases manufactured using digital light processing.

OBJECTIVES: To investigate differences in the surface properties and microbial adhesion of denture base resins for digital light processing (DLP) with varying resin layer thicknesses (LT), build angles (BA), and resin viscosities. METHODS: Two denture base resins for DLP with different viscosities (high and low) were used to prepare disk specimens applying two manufacturing parameters: 1) LT (50 or 100 µm) and 2) BA (0-, 45-, and 90-degree). Surface roughness and contact angle values were measured on the test surfaces (n=10 per group). Streptococcus oralis and Candida albicans absorbance was measured to assess microorganism attachment (n=6 per group). A three-way analysis of variance (ANOVA) was conducted, considering the main effects and their interactions (viscosity, LT, and BA). Post-hoc multiple pairwise comparisons were performed. All data were analyzed at a level of significance (P) of 0.05. RESULTS: LT and BA significantly affected the surface roughness and contact angle of the specimens, depending on resin viscosity (P<.001). Absorbance measurement showed no significant interaction between the three factors (P>.05). However, significant interactions were observed between viscosity and BA (P<.05) and between LT and BA (P<.05). CONCLUSIONS: Regardless of the viscosity and LT, discs with a 0-degree BA showed the least roughness. High-viscosity specimens fabricated with a 0-degree BA had the lowest contact angle. Regardless of the LT and viscosity, discs with a 0-degree BA showed the lowest S. oralis attachment. Attachment of C. albicans was the least on the disk with 50 µm LT, irrespective of the viscosity. CLINICAL SIGNIFICANCE: Clinicians should consider the effects of LT and BA on surface roughness, contact angle, and microbial adhesion of DLP-generated dentures, which can differ depending on resin viscosity. A 50 µm LT and 0-degree BA can be used with a high-viscosity resin to fabricate denture bases with less microbial adhesion.

Tissue factor is a critical regulator of radiation therapy-induced glioblastoma remodeling.

Radiation therapy (RT) provides therapeutic benefits for patients with glioblastoma (GBM), but inevitably induces poorly understood global changes in GBM and its microenvironment (TME) that promote radio-resistance and recurrence. Through a cell surface marker screen, we identified that CD142 (tissue factor or F3) is robustly induced in the senescence-associated ß-galactosidase (SA-ßGal)-positive GBM cells after irradiation. F3 promotes clonal expansion of irradiated SA-ßGal+ GBM cells and orchestrates oncogenic TME remodeling by activating both tumor-autonomous signaling and extrinsic coagulation pathways. Intratumoral F3 signaling induces a mesenchymal-like cell state transition and elevated chemokine secretion. Simultaneously, F3-mediated focal hypercoagulation states lead to activation of tumor-associated macrophages (TAMs) and extracellular matrix (ECM) remodeling. A newly developed F3-targeting agent potently inhibits the aforementioned oncogenic events and impedes tumor relapse in vivo. These findings support F3 as a critical regulator for therapeutic resistance and oncogenic senescence in GBM, opening potential therapeutic avenues.

Effect of layer thickness, build angle, and viscosity on the mechanical properties and manufacturing trueness of denture base resin for digital light processing.

OBJECTIVES: To investigate effects of layer thickness, build angle, and viscosity on the mechanical properties and trueness of denture base resins used for digital light processing (DLP). METHODS: Two denture base resins for DLP in different viscosity (high and low) were tested by using two manufacturing parameters:1) layer thickness (LT) (50- or 100-µm) and 2) build angle (BA) (0-, 45-, and 90-degree). disk- and bar-shaped specimens were used to evaluate hardness and flexural strength, respectively. Denture base specimens were used to examine trueness, and the deviation was calculated as the root mean square. Three-way analysis of variance (ANOVA) was conducted to determine the interaction among the three factors (viscosity, LT, and BA). Statistical significance was set at P < .05. RESULTS: Effects of LT and BA on hardness differed according to viscosity, with significant interactions among three factors (P=.027). Regardless of LT or BA, the low-viscosity group had higher hardness than the high-viscosity group (P<.001). In terms of flexural strength, no significant interaction was detected between the factors (P=.212), however, the effects of LT and BA were significant (P=.003 and P<.001, respectively). Regarding trueness, a significant interaction was observed between viscosity and BA (P=.001). Low-viscosity group had higher trueness than high-viscosity group when the 45- and 90-degree BA were applied (P<.001). CONCLUSIONS: LT and BA significantly affected the mechanical properties and trueness of the 3DP denture base, depending on the viscosity. For hardness and trueness, using low-viscosity resin and manufacturing with 50-µm LT and 45-degree BA are recommended. CLINICAL SIGNIFICANCE: Resin viscosity affects the influence of LT and BA on the hardness, flexural strength, and trueness of DLP-generated denture bases. A 50-µm LT and 45-degree BA can be used with a low-viscosity resin to fabricate denture bases with higher hardness and trueness.

Influence of postpolymerization time and atmosphere on the mechanical properties, degree of conversion, and cytotoxicity of denture bases produced by digital light processing.

STATEMENT OF PROBLEM: Studies on the effects of postprocessing conditions on the physical properties, degree of conversion (DC), and biocompatibility of denture bases produced by digital light processing are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the effects of the atmosphere during postpolymerization and of postpolymerization time on the flexural strength, Vickers hardness, DC, cytotoxicity, and residual monomer content of denture bases. MATERIAL AND METHODS: Six different groups of bar- and disk-shaped specimens from the denture base resin were produced, considering 2 different atmospheres (air and nitrogen) and 3 different postpolymerization times (5, 10, and 20 minutes). To determine the physical properties, the flexural strength and Vickers hardness were measured. Fourier transform infrared spectrometry was used to calculate DC. Cytotoxicity was assessed from the effect on human gingival fibroblasts. The residual monomer content was determined by using high-performance liquid chromatography. Based on the normality test by the Shapiro-Wilk method, a nonparametric factorial analysis of variances was conducted (α=.05). RESULTS: A significant interaction was detected between the atmosphere and postpolymerization time for hardness (P<.001) but no interaction for strength, DC, or cytotoxicity (P=.826, P=.786, and P=.563, respectively). Hardness was significantly affected by the postpolymerization time in the groups with the nitrogen atmosphere (P<.001). DC was significantly affected by the atmosphere (P=.012), whereas strength and cytotoxicity were not (P=.500 and P=.299, respectively). Cytotoxicity was significantly affected by the postpolymerization time (P<.001), but strength and DC were not (P=.482 and P=.167, respectively). Residual monomers were not detected after ≥10-minute postpolymerization time. CONCLUSIONS: The atmosphere significantly affected hardness and DC, whereas the postpolymerization time significantly affected hardness, DC, cytotoxicity, and residual monomer content. Denture bases produced in a nitrogen atmosphere and with the 10-minute postpolymerization time showed sufficient hardness, DC, and no cytotoxicity.

Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV.

BACKGROUND: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. METHODS: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. RESULTS: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. CONCLUSIONS: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.

The Encapsulation of Natural Organic Dyes on TiO2 for Photochromism Control.

Titanium dioxide (TiO2) plays a pivotal role in photocatalytic reactions and holds great promise for the cosmetic and paint industries due to its white color and high refractive index. However, the original color of TiO2 changes gradually to blue or yellow with UV irradiation, which affects its color realization. We encapsulated TiO2 with several natural organic dye compounds, including purpurin, curcumin, and safflower, to control its photochromism and realize a range of different colors. The chemical reaction between TiO2 and dyes based on their functional group was investigated, and the light absorption was tested via FTIR and UV-Vis spectroscopy. The changes in morphology and size distribution additionally supported their successful encapsulation. The discoloration after UV irradiation was evaluated by measuring the color difference (ΔE) of control TiO2 and dye encapsulated TiO2. The unique structure utilized natural dyes to preserve photochromism based on the physical barrier and automatically controlled the electronic transition of core TiO2. In particular, the color difference values of purpurin and curcumin were 4.05 and 3.76, which is lower than the 5.36 of the control TiO2. Dye encapsulated TiO2 was manipulated into lipstick to verify its color realization and retention.

The Influence of Cellulose Nanocrystal Characteristics on Regenerative Silk Composite Fiber Properties.

Cellulose nanocrystals (CNCs), obtained from natural resources, possess great potential as a bioderived reinforcement for natural-fiber-reinforced composites (NFRPs) due to their superior crystallinity and high aspect ratio. To elucidate the specific parameters of CNCs that significantly affect their mechanical performance, various CNCs were investigated to fabricate high-performance nanocomposite fibers together with regenerated silk fibroin (RSF). We confirmed that the high aspect ratio (~9) of the CNCs was the critical factor to increase the tensile strength and stiffness rather than the crystallinity. At a 1 vol% of CNCs, the strength and stiffness reached ~300 MPa and 10.5 GPa, respectively, which was attributed not only to a stable dispersion but also to alignment. This approach has the potential to evaluate the parameters of natural reinforcement and may also be useful in constructing high-performance NFRPs.

Dopamine receptor D2 regulates glioblastoma survival and death through MET and death receptor 4/5.

Recent studies indicate that signaling molecules traditionally associated with central nervous system function play critical roles in cancer. Dopamine receptor signaling is implicated in various cancers including glioblastoma (GBM) and it is a recognized therapeutic target, as evidenced by recent clinical trials with a selective dopamine receptor D2 (DRD2) inhibitor ONC201. Understanding the molecular mechanism(s) of the dopamine receptor signaling will be critical for development of potent therapeutic options. Using the human GBM patient-derived tumors treated with dopamine receptor agonists and antagonists, we identified the proteins that interact with DRD2. DRD2 signaling promotes glioblastoma (GBM) stem-like cells and GBM growth by activating MET. In contrast, pharmacological inhibition of DRD2 induces DRD2-TRAIL receptor interaction and subsequent cell death. Thus, our findings demonstrate a molecular circuitry of oncogenic DRD2 signaling in which MET and TRAIL receptors, critical factors for tumor cell survival and cell death, respectively, govern GBM survival and death. Finally, tumor-derived dopamine and expression of dopamine biosynthesis enzymes in a subset of GBM may guide patient stratification for DRD2 targeting therapy.

Influence of 0.002% Omidenepag Isopropyl on Intraocular Pressure and the Cornea in Normal Tension Glaucoma.

PRCIS: Although Omidenepag isopropyl drops elicited stable intraocular pressure reductions in NTG patients, transient changes in refraction and corneal endothelial cells, significant increase of central corneal thickness, and corneal erosion should be considered. PURPOSE: To analyze the efficacy and safety of 0.002% omidenepag Isopropyl (OMDI) eye drops in patients with normal tension glaucoma (NTG). METHODS: Medical records for 62 eyes treated with OMDI for ≥6 months were analyzed. Intraocular pressure (IOP), refraction, keratometry, central corneal thickness (CCT), endothelial cell count, coefficient of variation of endothelial cell area (CV), corneal erosion, and central retinal thickness were compared at baseline and 1, 3, and 6 months. RESULTS: IOP significantly decreased from 13.4±3.8 to 11.9±3.0, 11.7±2.9, and 12.2±3.3 mm Hg at each follow-up ( P <0.001). Endothelial cell count did not change, but CV transiently increased from 12.6 to 17.0 at 1 month, CCT increased from 531.5 to 538.4 µm, myopia changed from -1.5 to -1.9 D, and keratometry changed from 44.5 to 44.7 D. CV, myopia, and keratometry recovered to baseline at 6 months; however, CCT remained high. Significant corneal erosion was observed at 6 months. Central retinal thickness changes were not observed. There were improvements in prostaglandin-associated skin pigmentation (86.7%), eyelash elongation (40.0%), and deepening of the upper eyelid sulcus and ptosis (~30%) at 3 months after exchange to OMDI. Adverse reactions were corneal erosion (27.4%), corneal thickening (21.0%), conjunctival hyperemia (11.3%), photophobia (5.7%), blurred vision (5.7%), and anterior chamber cells (4.8%). CONCLUSIONS: OMDI eye drops elicited significant and stable IOP reductions after 6 months in NTG patients with low IOP. However, transient myopic and corneal endothelial cell changes, development of corneal thickening, and corneal erosion should be considered when using OMDI.

Selective etching mechanism of silicon oxide against silicon by hydrogen fluoride: a density functional theory study.

Selective etching of silicon oxide (SiO2) against silicon (Si) using anhydrous hydrogen fluoride (HF) vapor has been used for semiconductor device fabrication. We studied the underlying mechanism of the selective etching by density functional theory (DFT) calculation. We constructed surface slab models of SiO2 or Si with different degrees of fluorination and simulated the four steps of fluorination. The calculations show relatively low activation energies of 0.72-0.79 eV for the four steps of fluorination of SiO2, which are close to ∼0.69 eV observed in the experiment. The four-membered ring structure of -Si-O-H-F- in all transition states stabilized the system, resulting in relatively low activation energies. Thus, continuous etching of SiO2 by HF is plausible at near-room temperature. In contrast, the fluorinations of Si showed relatively high activation energies ranging from 1.22 to 1.56 eV due to the less stable transition state geometries. Thus, negligible etching of silicon by HF is expected by the near-room temperature process. Our calculation results explain well the experimental observation of the selective etching of SiO2 against Si by HF vapor.