Low-Dose Exposure of WS₂ Nanosheets Induces Differential Apoptosis in Lung Epithelial Cells

Escalating the production and application of tungsten disulfide (WS2) nanosheets inevitably increases environmental human exposure and warrants the necessity of studies to elucidate their biological impacts. Herein, we assessed the toxicity of WS2 nanosheets and focused on the impacts of low doses (≤10 μg/mL) on normal (BEAS-2B) and tumorigenic (A549) lung epithelial cells. The low doses, which approximate real-world exposures, were found to induce cell apoptosis, while doses ≥ 50 μg/mL cause necrosis. Focused studies on low-dose exposure to WS2 nanosheets revealed more details of the impacts on both cell lines, including reduction of cell metabolic activity, induction of lipid peroxidation in cell membranes, and uncoupling of mitochondrial oxidative phosphorylation that led to the loss of ATP production. These phenomena, along with the expression situations of a few key proteins involved in apoptosis, point toward the occurrence of mitochondria-dependent apoptotic signaling in exposed cells. Substantial differences in responses to WS2 exposure between normal and tumorigenic lung epithelial cells were noticed as well. Specifically, BEAS-2B cells experienced more adverse effects and took up more nanosheets than A549 cells. Our results highlight the importance of dose and cell model selection in the assessment of nanotoxicity. By using doses consistent with real-world exposures and comparing normal and diseased cells, we can gain knowledge to guide the development of safety precautions for mitigating the adverse impacts of nanomaterial exposure on human health

Screening of candidate genes at GLC3B and GLC3C loci in Chinese primary congenital glaucoma patients with targeted next generation sequencing

Primary congenital glaucoma (PCG) is characterized by developmental abnormalities of the anterior chamber angle. Although several genes have been associated with PCG, pathogenic mutations could only be detected in about 20% of Chinese patients. GLC3B (1p36.2–36.1) and GLC3C (14q24.3) loci were previously identified in PCG pedigrees via linkage analysis. However, no causative genes were reported in these loci. This study was designed to search for novel PCG-related genes in these genetic regions. DNA samples from 100 PCG patients and 200 normal controls were pooled and sequenced using a customized panel of 133 positional candidate genes located around GLC3B and GLC3C loci (±1Mb). PCG-related genes were prioritized by the distribution of variants between patients and controls. Confirmation of selected variants and co-segregation analysis were performed using Sanger sequencing. Patient and control group contained 116 and 147 rare variants respectively after screening. Three genes (ZC2HC1C, VPS13D, and PGF) were prioritized according to the distribution of variants between the two groups. Rare variants of PGF were only identified in PCG patients. To the best of our knowledge, this is the first study aiming at exploring novel PCG-related genes at GLC3B and GLC3C loci. Our preliminary results suggest that there are potential associations between ZC2HC1C, VPS13D, PGF, and PCG. However, larger cohort studies and functional assays are required to provide further evidence for the proposed genotype-phenotype association.</p

Differences between fellow eyes of acute and chronic primary angle closure (glaucoma): An ultrasound biomicroscopy quantitative study

<div><p>Purpose</p><p>To compare various biometric parameters between fellow eyes of acute primary angle closure (glaucoma) [APAC(G)] and fellow eyes of chronic primary angle closure (glaucoma) [CPAC(G)].</p><p>Methods</p><p>Ultrasound biomicroscopy examinations were performed on 47 patients with unilateral APAC(G) and 41 patients with asymmetric CPAC(G) before laser peripheral iridotomy and pilocarpine treatment. Anterior chamber depth and width (ACD and ACW), lens vault (LV), iris curvature (IC), iris root distance (IRD), trabecular-ciliary process distance (TCPD), iris-ciliary process distance (ICPD), trabecular-ciliary angle (TCA), and other biometric parameters were compared between fellow eyes of APAC(G) and fellow eyes of CAPC(G).</p><p>Results</p><p>Compared with fellow eyes of CPAC(G), fellow eyes of APAC(G) had smaller ACD (<i>P</i> < 0.001), ACW (<i>P</i> = 0.007), TCPD (<i>P</i> = 0.016), ICPD (<i>P</i> = 0.008), and TCA (<i>P</i> = 0.006), as well as larger LV (<i>P</i> = 0.002), IC (<i>P</i> = 0.012), and IRD (<i>P</i> = 0.003). On multivariate logistic regression analyses, a 0.1 mm decrease in ACD (odds ratio [OR]: 0.705, 95%CI: 0.564–0.880, <i>P</i> = 0.002), ICPD (OR: 0.557, 95%CI: 0.335–0.925, <i>P</i> = 0.024), and a 0.1 mm increase in IRD (OR: 2.707, 95%CI: 1.025–7.149, <i>P</i> = 0.045), was significantly associated with occurrence of acute angle closures.</p><p>Conclusions</p><p>Fellow eyes of APAC(G) had smaller anterior segment dimensions, higher LV, more posterior iris insertion, greater IC, and more anteriorly rotated ciliary body compared with fellow eyes of CPAC(G). ACD, ICPD, and IRD were the three most important parameters that distinguish eyes predisposed to APAC(G) or CPAC(G).</p></div

The determination of the parameters on an ultrasound biomicroscopy image of the horizontal perpendicular full view scans at the nasal-temporal position centered over the pupil.

<p>ACD = anterior chamber depth; ACW = anterior chamber width; LV = lens vault; PD = pupil diameter; SS = scleral spur.</p

Ultrasound biomicroscopy images of two patients (patient A and B).

<p>A, The fellow eye of a patient with acute primary angle closure (APAC). B, The fellow eye of a patient with chronic primary angle closure (CPAC). Note that the fellow eye of APAC has smaller anterior segment dimensions (anterior chamber depth [ACD] and anterior chamber width [ACW]), higher lens vault (LV) (A1 vs. B1), greater iris curvature (IC), more posterior iris insertion (longer iris root distance [IRD]), and more anteriorly positioned ciliary body (shorter trabecular-ciliary process distance [TCPD] and iris-ciliary process distance [ICPD], and smaller trabecular-ciliary angle [TCA]) (A2 vs. B2). Scale bar: 1mm.</p

Intra-observer and Inter-observer intra-class coefficients of the ultrasound biomicroscopy parameters.

<p>Intra-observer and Inter-observer intra-class coefficients of the ultrasound biomicroscopy parameters.</p

Comparison of ultrasound biomicroscopy parameters in fellow eyes of acute primary angle closure (Glaucoma) and chronic primary angle closure (Glaucoma).

<p>Comparison of ultrasound biomicroscopy parameters in fellow eyes of acute primary angle closure (Glaucoma) and chronic primary angle closure (Glaucoma).</p

Relationship of biometric and ultrasound biomicroscopy parameters with presence of acute angle closures.

<p>Relationship of biometric and ultrasound biomicroscopy parameters with presence of acute angle closures.</p

The determination of the parameters on an ultrasound biomicroscopy diagram of the radial scans centered over the limbus.

<p>A circle with a radius of 500 μm centered on the scleral spur (SS) is drawn. Angle-opening distance at 500 μm (AOD500) is the distance between the posterior corneal surface and the anterior iris surface on a line perpendicular to the trabecular meshwork 500 μm from the SS. Trabecular-iris space area at 500 μm (TISA500) is the area bounded anteriorly by AOD500 as determined, posteriorly by a line drawn from the SS perpendicular to the plane of the inner scleral wall to the iris, superiorly by the inner corneoscleral wall, and inferiorly by the iris surface. Trabecular-anterior iris surface angle (TAIA) is the angle between the posterior corneal surface and the anterior iris surface (angle of “a-SS-b”). Trabecular-posterior iris surface angle (TPIA) is the angle between the posterior corneal surface and the posterior iris surface (angle of “a-SS-c”). Iris thickness at 500 μm (IT500) is iris thickness at 500 μm from the SS. Iris curvature (IC) is the perpendicular distance from a line between the most central to the most peripheral points of the iris pigment epithelium to the posterior iris surface at the point of greatest convexity. Iris root distance (IRD): the distance from the SS to the insertion location of the iris into the ciliary body (line of “SS-e”). Trabecular-ciliary process distance (TCPD) is a line extending from the corneal endothelium 500 μm anterior to the SS toward the ciliary processes (line of “ad”). Iris-ciliary process distance (ICPD) is the posterior surface of the iris 500 μm anterior to the SS toward the ciliary processes (line of “cd”). Trabecular-ciliary angle (TCA) is the angle between the posterior corneal surface and the anterior surface of the ciliary body (angle of “a-SS-f”). Maximum ciliary body thickness (CBTmax) is the distance from the most inner point of the ciliary body to the inner wall of sclera or its extended line. Ciliary body thicknesses at the point of the SS (CBT0) and at a distance of 500 μm (CBT500) are also measured.</p

Decoupling the Interfacial Catalysis of CeO₂‑Supported Rh Catalysts Tuned by CeO₂ Morphology and Rh Particle Size in CO₂ Hydrogenation

Metal–oxide interfaces play a crucial role in catalyzing CO2 conversion, while comprehensively decoupling interfacial catalysis is challenging due to their structural complexity. Herein, Rh/CeO2 catalysts, whose interfacial structures are finely tuned by altering the CeO2 morphologies and Rh particle sizes, were employed for CO2 hydrogenation. The results reveal that the density of interfacial oxygen vacancies that varies with the CeO2 morphologies determines the catalytic activity, while the product selectivity strongly depends on the nature of supported Rh species. With a decrease in Rh particle size, the weakened metallicity results in the suppression of the Sabatier reaction and thus the low CH4 selectivity. Meanwhile, the enhanced reverse water–gas shift process that is more easily catalyzed than the Sabatier reaction contributes to the promotion of catalytic CO2 efficiency. Interestingly, the CH4 selectivity increases with the reaction temperature rise at fine Rh particles, which could be ascribed to the enhanced H-spillover effect at high temperatures. Spectroscopic results confirm CO2 hydrogenation proceeding through a redox mechanism to generate an adsorbed CO intermediate that either is further hydrogenated into CH4 with strong CO adsorption capacity/H-spillover effect or desorbs directly into CO