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The rapid growth of nanomaterial applications has raised safety concerns for human health. A number of studies have been conducted to assess the toxicokinetics, toxicology, dose-response, and risk assessment of different nanomaterials using in vitro and in vivo animal and human models. However, current studies cannot meet the demand for efficient assessment of toxicokinetics, dose-response relationships, or the toxicological risk arising from the rapidly increasing number of newly synthesized nanomaterials. In this article, we review the methods for conducting toxicokinetics, hazard identification, dose-response, exposure, and risk assessment studies of nanomaterials, identify the knowledge gaps, and discuss the challenges remaining. We provide the rationale behind the appropriate design of nanomaterial plasma toxicokinetic and tissue distribution studies, including caveats on the interpretation and correlation of in vitro and in vivo toxicology studies. The potential of using physiologically based pharmacokinetic (PBPK) models to extrapolate toxicokinetic and toxicity findings from in vitro to in vivo and from animals to humans is discussed, and the knowledge gaps of PBPK modeling for nanomaterials are identified. While challenges still exist, there has been progress in the toxicokinetics, hazard identification, and risk assessment of nanomaterials in the past two decades. Recent advancements in the field are highlighted with relevant examples. We also share latest guidelines as well as our perspectives on future studies needed to characterize the toxicokinetics, toxicity, and dose-response relationship in support of nanomaterial risk assessment. This article is categorized under: Toxicology and Regulatory Issues in NanomedicineToxicology of Nanomaterials Toxicology and Regulatory Issues in NanomedicineRegulatory and Policy Issues in Nanomedicine.

KDM6B-mediated epigenetic modification of the testicular regulator Dmrt1 has previously been identified as the primary switch of the male pathway in a temperature-dependent sex-determination (TSD) system; however, the molecular network of the female pathway has not yet been established. Here, we have functionally characterized for the first time an upstream regulator of the female pathway, the forkhead transcription factor FOXL2, in Trachemys scripta, a turtle species with a TSD system. FOXL2 exhibited temperature-dependent female-specific expression patterns before the onset of gonadal differentiation and was preferentially localized in ovarian somatic cells. Foxl2 responded rapidly to temperature shifts and estrogen. Importantly, forced expression of Foxl2 at the male-producing temperature led to male-to-female sex reversal, as evidenced by the formation of an ovary-like structure, and upregulation of the ovarian regulators Cyp19a1 and R-spondin1. Additionally, knockdown of Foxl2 caused masculinization at the female-producing temperature, which was confirmed by loss of the female phenotype, development of seminiferous tubules, and elevated expression of Dmrt1 and Sox9. Collectively, we demonstrate that Foxl2 expression is necessary and sufficient to drive ovarian determination in T. scripta, suggesting a crucial role of Foxl2 in female sex determination in the TSD system.

Toxicogenomics and physiologically based pharmacokinetic (PBPK) models are useful approaches in chemical risk assessment, but the methodology to incorporate toxicogenomic data into a PBPK model to inform risk assessment remains to be developed. This study aimed to develop a probabilistic human health risk assessment approach by integrating toxicogenomic dose-response data and PBPK modeling using perfluorooctane sulfonate (PFOS) as a case study. Based on the available human

The size effect on the electronic structure and optical properties of cubic CsPbBr3 perovskite quantum dots is investigated by using an 8-band ${k}\cdot{p} $ model based on effective-mass envelope function theory with exciton binding energy consideration. Quantum dots with smaller size have larger bandgaps due to quantum confinement. The transition matrix element (TME) is also influenced by the size. The optical gain of such material is calculated by considering TME, Fermi factor, injected carrier density, quantum dot size, and dephasing rate. Higher density of injected carrier is needed for smaller quantum dot to get a positive optical gain. The peak of optical gain has a blue shift as the size of quantum dot decreases. When the carrier density increases for a quantum dot with certain size, a blue shift in emission peak position can be observed due to band filling effect. Smaller quantum dots have higher differential optical gain at carrier densities within certain range.

Retinoic acid (RA) plays various embryogenesis and post-embryogenesis roles in vertebrates. As exposure of metamorphosing flounder larvae to RA has teratogenic effects on skin color and vertebral column development, harmonized RA synthesis and catabolism are likely essential in metamorphic development. To approach understanding of the roles of RA in flounder metamorphic development, we here examined the tissue mRNA expression of RA synthases (aldh1a1, aldh1a2, aldh1a3) and catabolic enzymes (cyp26a1, cyp26b1, cyp26c1) in newly hatched and metamorphosing larvae, and three-month-old juveniles by in situ hybridization (ISH). No ISH signal was detected for any genes from the skin and vertebral column susceptible to the teratogenic effects by RA. Since the intestine expressed aldh1a2 at high level in larvae but not in juvenile, it is a possibility that the larval intestine serves as a source of RA, and RA catabolic enzymes function at the level below sensitivity of ISH at vertebral column and skin development. We found that aldh1a2 and aldh1a3 were expressed along the margin of the tectum and the neurohypophysis of pituitary, respectively, both in contact with the cerebrospinal fluid (CSF), and cyp26b1 at the posterior tectum and cerebellum. We hypothesize that RA is supplied from the tectum and pituitary via the CSF for brain growth and maintenance, and cyp26b1 locally regulates RA contents in the brain.

Our objective was to investigate the association between herbal/botanic supplement use and perceived quality of life (QoL), cancer recurrence, and all-cause mortality in colon cancer patients.Patients (n = 453) newly diagnosed with stage II adenocarcinoma of the colon between 2009 and 2011 were recruited from the North Carolina Central Cancer Registry. Data including demographic variables, herbal medicine use and frequency, lifestyle, diet, cancer treatment, and QoL were collected by interviews at diagnosis (baseline) and 1 and 2 y after diagnosis. Mortality information was obtained via the National Death Index. The Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and Medical Outcomes Short Form 12 (SF-12) were used to evaluate QoL.At baseline, herbal/botanic supplement users were more likely to have a healthier lifestyle than non-users, including more physical activity (P 0.01), more fruit and vegetable consumption (P = 0.01), less smoking (P 0.01), and less energy intake from fat (P = 0.02). After adjustment for potential confounders, no significant association was found between herbal/botanic supplement use and QoL assessed by FACT-C and SF-12. Similarly, herbal/botanic supplement use was not associated with the risk of recurrence, all-cause mortality or the combined.In this study, patients with stage II colon cancer using herbal/botanic supplements had no significant improvement in their QoL and no difference in odds of colon cancer recurrence and all-cause mortality over 2 y after diagnosis compared with those who did not use herbs/botanicals. Further studies are warranted to confirm the findings and to focus on types of herbal/botanic supplements.

The effect of thickness of cesium lead halide perovskite CsPbBr3 nanoplatelets (NPLs) on their electronic structure and optical properties are investigated using an effective-mass envelope function theory based on the 8-band k·p model with the consideration of exciton binding energy. We first reported the CsPbBr3 nanoplatelets’ band structure and optical gain with exciton effect. As the thickness of NPLs decreases, their bandgap increases and the band mixing is more obvious which influences the transition matrix element (TME). The optical gain of CsPbBr3 nanoplatelets is calculated by taking into account of TME, Fermi factor, injected carrier density and thickness. A blue shift of peak position in optical gain can be observed as the thickness of NPLs decreases. As the injected carrier density arises, the maximum optical gain of thicker NPLs reach saturation much faster than the thinner ones. To obtain high differential gain, NPLs with less thickness are better choices. Experimental work is carried out and the results agree with our theoretical results very well.

The body color of the Pleuronectiformes is bilaterally asymmetric between right and left halves, with a dark ocular-side and a white blind-side. This body color asymmetry develops by restricted differentiation of melanophores and xanthophores on the ocular-side during metamorphosis, accompanied by migration of one eye to the future ocular-side. In this study, we elucidated the developmental regulatory system of this lateralized pigmentation. We found that in flounder, Sox10-positive chromatophore progenitors appear bilaterally both in the ocular- and blind-side skin of metamorphosing larvae, and that those arriving at the ocular-side skin differentiate into gch2-positive chromatoblasts and then chromatophores. Transient exposure of metamorphosing larvae to retinoic acid (RA)-induced progenitors on the blind-side to differentiate into gch2-positive chromatoblasts. On the contrary, exposure to an RA receptor antagonist, BMS493, suppressed the differentiation of gch2-positive chromatoblasts on the ocular-side. Thus, we demonstrated that RA is essential for flounder chromatophore progenitors to differentiate into chromatoblasts. At the time of chromatoblast differentiation on the ocular-side, cyp26b1, which inactivates RA, was upregulated on the blind-side skin compared with the ocular-side. Therefore, we surmise that ocular-side-specific pigmentation is regulated by the inhibition of RA-signaling by cyp26b1 on the blind-side.

In marine aquaculture fish, excessive supplement of vitamin A (VA) to zooplanktons for larval culture and experimental exposure of larvae to retinoic acid (RA: active form of VA) have been known to cause vertebral deformity. However, the tissues in the developing vertebral column that are affected by RA and the progression of vertebral deformity remain undetermined. To examine these questions, we histologically traced the progress of vertebral deformity induced by RA in Japanese flounder (Paralichthys olivaceus). Larvae were exposed to RA for 3 days at mid-metamorphosis (G-stage), a critical stage for vertebral deformity. Intervertebral ligament, which is known to form intervertebral joints in cooperation with the notochord, was severely degenerated by RA, leading to fusion of centra. During further development to adult, growth of centra was severely suppressed in an anterior-posterior direction in RA-treated fish and the notochord tissue was lost from fused centra, resulting in complete loss of intervertebral joints and fusion of centra. We conclude that RA initially damages the intervertebral ligaments, and these defects lead to fusion, narrowing of centra, and loss of intervertebral joints in the vertebral column. The cumulative effect of these modifications is a truncated body form.

Semi-conductive MXene Sc2COx is synthesized by using magnetron sputtering. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) is performed to determine the composition of sample. The bandgap of Sc2COx sample is determined by ultraviolet-visible (UV–VIS) range absorption and photoluminescence (PL) spectrum. The Tauc plot indicates that Sc2COx is a direct bandgap material. The high sensitivity of scandium to oxygen makes the sample contain both scandium carbide and scandium oxide. Thermal annealing introduces more oxidation into the sample. Structure of MXene will be broken when the annealing temperature is higher than 600 °C.

MXenes are a large family of two-dimensional material composed of transition metal carbides or nitrides. This article gives theoretical investigation of a type of MXene that behave like semiconductors.

Pleuronectiform fish develop marked external asymmetry in eye location and skin color at metamorphosis. The bamboo sole, Heteromycteris japonica, also exhibits loss of the pectoral fins at metamorphosis. Because of its small body size, short generation time, and long spawning season, we focused on the bamboo sole as an experimental model to investigate metamorphic asymmetry and pectoral fin loss during development. In the present study, we utilized a small-scale culture system to evaluate bamboo sole larvae and larval development, and a microinjection system for fertilized eggs. The culture system described here uses an 18 L culture tank for rotifers (the first diet for larvae) and 5 L plastic beakers for larval culture. Under this system, most larvae completed metamorphosis, including one-eye migration and pigmentation of the ocular side, by 23 days postfertilization (dpf) at 25°C. Larvae at density of 120–150 per liter were grown from hatching to 23 dpf with a survival ratio of 60–75% per beaker. Pectoral fins, including coracoid and disk cartilage, formed but were completely lost in late metamorphosis without formation of proximal radials and fin rays. The microinjection system designed here is adequate for the bamboo sole and allows injection of 100 one-cell-stage embryos per day. We expect that the culture and microinjection systems described here will facilitate the use of the bamboo sole as an experimental model organism in developmental biology.

In marine aquaculture fish, excessive supplement of vitamin A (VA) to zooplanktons for larval culture and experimental exposure of larvae to retinoic acid (RA: active form of VA) have been known to cause vertebral deformity. However, the tissues in the developing vertebral column that are affected by RA and the progression of vertebral deformity remain undetermined. To examine these questions, we histologically traced the progress of vertebral deformity induced by RA in Japanese flounder (Paralichthys olivaceus). Larvae were exposed to RA for 3 days at mid-metamorphosis (G-stage), a critical stage for vertebral deformity. Intervertebral ligament, which is known to form intervertebral joints in cooperation with the notochord, was severely degenerated by RA, leading to fusion of centra. During further development to adult, growth of centra was severely suppressed in an anterior-posterior direction in RA-treated fish and the notochord tissue was lost from fused centra, resulting in complete loss of intervertebral joints and fusion of centra. We conclude that RA initially damages the intervertebral ligaments, and these defects lead to fusion, narrowing of centra, and loss of intervertebral joints in the vertebral column. The cumulative effect of these modifications is a truncated body form.