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As an emerging two-dimensional nanomaterial with promising prospects, mono- or few-layer black phosphorus (BP) is potentially toxic to humans. We investigated the effects of two types of BPs on adult male mice through intratracheal instillation. Using the flow cytometry method, the generation, migration, and recruitment of immune cells in different organs have been characterized on days 1, 7, 14, and 21 post-exposure. Compared with small BP (S-BP, lateral size at ∼188 nm), large BP (L-BP, lateral size at ∼326 nm) induced a stronger stress lymphopoiesis and B cell infiltration into the alveolar sac. More importantly, L-BP dramatically increased peripheral neutrophil (NE) counts up to 1.9-fold on day 21 post-exposure. Decreased expression of the CXCR4 on NEs, an important regulator of NE retention in the bone marrow, explained the increased NE release into the circulation induced by L-BP. Therefore, BP triggers systemic inflammation via the disruption of both the generation and migration of inflammatory immune cells.

This study analyzed the function of different glutathione S-transferase (GST) isoforms and detoxification metabolism responses in Manila clam, Ruditapes philippinarum, exposed to 4 kinds of polycyclic aromatic hydrocarbons (PAHs) single, and their mixtures for 15 days under laboratory conditions. 13 kinds of GSTs in R. philippinarum were classified, and the results of tissue distribution indicated that 12 kinds of GSTs (except GST sigma 3) expressed most in digestive glands. We detected the mRNA expression levels of aryl hydrocarbon receptor signaling pathway, and detoxification system in digestive glands of clams exposed to benzo[a]pyrene (BaP), chrysene (CHR), benzo[a]anthracene (BaA), benzo[b]fluoranthene (BbF), and BaP + CHR + BaA + BbF, respectively. Among these genes, we selected GST-sigma, GST-omega and GST-pi as potential indicators to BaP; GST-sigma, GST-A and GST-rho to CHR; GST-pi, GST-sigma, GST-A, GST-rho and GST-microsomal to BaA; GST-theta and GST-mu to BbF; while GST-pi and GST-mu to the mixture of BaP, CHR, BaA and BbF. Additionally, the bioaccumulation of PAHs in tissues increased remarkably over time, and showed an obvious dose-effect. Under the same concentration, the bioaccumulation in single exposure group was higher than that in mixture group, and the bioaccumulation of PAHs in tissues with different concentrations of stress was irregular. The results revealed the metabolic differences and bioaccumulation rules in clams exposed to four kinds of PAHs, and provided more valuable information for the PAHs risk assessment.

Virus receptors are highly involved in mediating the entrance of infectious viruses into host cells. Here, we found that typical chemical exposure caused the upregulation of virus receptor mRNA levels. Chemicals with the same structural characteristics can affect the transcription of angiotensin-converting enzyme 2 (ACE2), a dominant receptor of SARS-CoV-2. Some chemicals can also regulate the transcription of ACE2 by similar regulatory mechanisms, such as multilayer biological responses and the crucial role of TATA-box binding protein associated factor 6. The abovementioned finding suggested that chemical mixtures may have a joint effect on the ACE2 mRNA level in the real scenario, where humans are exposed to numerous chemicals simultaneously in daily life. Chemically regulated virus receptor transcription was in a tissue-dependent manner, with the highest sensitivity in pulmonary epithelial cells. Therefore, in addition to genetic factors, exogenous chemical exposure can be an emerging nongenetic factor that stimulates the transcription of virus receptor abundance and may elevate the protein expression. These alterations could ultimately give rise to the susceptibility to virus infection and disease severity. This finding highlights new requirements for sufficient epidemiological data about exposomes on pathogen receptors in the host., Pollutant exposure shows the upregulation of virus receptor mRNA levels, which could ultimately affect host susceptibility to virus infection and disease severity.

Approaches to Learning (ATL) is essential for children’s learning and development. Prior research examined the role of school-related factors, but little research focused on the impacts of family-related factors on the ATL of children. This study examines how family socioeconomic status (SES) of preschool children affects their ATL. Data was collected from the parents and teachers of 988 preschool children in China. The results uncover that the positive effect of family SES on the ATL of preschoolers is mediated by positive involvement and negative discipline. Interestingly, preschool children’s gender moderates the mediating effects of positive involvement and negative discipline: for girls, the mediating roles of positive involvement and negative discipline are both supported. However, for boys, only positive involvement mediates the effect of family SES on ATL. By bridging family investment theory with parenting theory, this study opens the black-box covering the relationship between family SES and preschoolers’ ATL. By elucidating the gender-specific mediation process, this study contributes to the literature from a Chinese parenting culture perspective. In practice, these findings suggest that educational government can boost children’s ATL by organizing parenting training instructed by education experts to improve parents’ parenting skills.

The novel human infectious coronaviruses (CoVs) responsible for severe respiratory syndromes have raised concerns owing to the global public health emergencies they have caused repeatedly over the past two decades. However, the ongoing coronavirus disease 2019 (COVID-19) pandemic induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has received unprecedented attention internationally. Monitoring pathogenic CoVs in environmental compartments has been proposed as a promising strategy in preventing the environmental spread and tracing of infectious diseases, but a lack of reliable and efficient detection techniques is still a significant challenge. Moreover, the lack of information regarding the monitoring methodology may pose a barrier to primary researchers. Here, we provide a systematic introduction focused on the detection of CoVs in various environmental matrices, comprehensively involving methods and techniques of sampling, pretreatment, and analysis. Furthermore, the review addresses the challenges and potential improvements in virus detection techniques for environmental surveillance.

Black phosphorus (BP) has extensive applications in various fields. The release of BP into aquatic ecosystems and the potential toxic effects on aquatic organisms are becoming major concerns. Here, we investigated the developmental toxicity of few-layered BP toward the zebrafish. We found that BP could adsorb on the surface of the chorion and could subsequently penetrate within the embryo. After exposure of embryos to 10 mg/L BP, developmental malformations appeared at 96 hpf, especially heart deformities such as pericardial edema and bradycardia, accompanied by severe circulatory system failure. Using transgenic zebrafish larvae, we further characterized cardiovascular defects with cardiac enlargement and impaired cardiac vessels as indicators of damage to the cardiovascular system upon BP exposure. We performed transcriptomic analysis on zebrafish embryos treated with a lower concentration of 2 mg/L. The results showed disruption in genes associated with muscle development, oxygen involved processes, focal adhesion, and VEGF and MAPK signaling pathways. These alterations also indicated that BP carries a risk of developmental perturbation at lower concentrations. This study provides new insights into the effects of BP on aquatic organisms.

Background: Percutaneous coronary intervention (PCI) is a practical and effective method for the treatment of coronary heart disease (CHD).The aim of this study is to assess the clinical value of ApoB/ApoA-Ι in predicting the major cardiovascular events(MACEs) and hospital readmission risk within one year in CHD patients post PCI. Methods: 1938 patients who underwent PCI treatment from January 2010 to December 2018 were included in this retrospective study. Basic information, medications and biochemical indicators were recorded at admission and the one year follow-up. Univariate and multivariate Cox proportional hazards regression model were performed to determine the relationship between ApoB/ApoA-Ι and MACEs, as well as readmission. The Kaplan-Meier curves were plotted to illustrate the cumulative incidence of MACEs and readmission. Predictive nomograms were established to predict prognosis for MACEs and readmission. Results: Cox regression analysis showed that ApoB/ApoA-Ι is an independent risk factor for MACEs in patients after PCI(P=0.031). The incidence of MACEs in the high-level ApoB/ApoA-Ι group (ApoB/ApoA-Ι ratio>0.824) increased within one year and the difference was statistically significant(P=0.037). The incidence of readmission increased within one year was not statistically significant. In addition, the nomogram predicted one year MACEs more accurately(C-index: 0.647).Conclusions: The ratio of ApoB/ApoA-Ι has important predictive value for the risk of MACEs occurrence in one year for CHD patients post PCI.

Gonadotropin-releasing hormone (GnRH) plays a key role in the control of the reproductive axis in vertebrates, however, little is known about its function in reproductive endocrine regulation in molluscs. In the present study, RNA-seq was used to construct transcriptomes of Ruditapes philippinarum testis and ovaries of control and GnRH suppressed individuals using RNA interference. GnRH suppression caused 112 and 169 enriched KEGG pathways in testis and ovary, with 92 pathways in common in both comparisons. The most enriched KEGG pathways occurred in the "Oxidative phosphorylation", "Dorso-ventral axis formation", "Thyroid hormone synthesis" and "Oxytocin signaling pathway" etc. A total of 1838 genes in testis and 358 genes in ovaries were detected differentially expressed in GnRH suppressed clams. Among the differentially expressed genes, a suit of genes related to regulation of steroid hormones synthesis and gonadal development, were found in both ovary and testis with RNAi of GnRH. These results suggest that GnRH may play an important role in reproductive function in bivalves. This study provides a preliminary basis for studying the function and regulatory mechanism of GnRH in bivalves.

One potential way to promote China’s economic growth is to develop a cultural industry and enhance its competitiveness. To confirm this hypothesis, this study first utilizes the five-element diamond model, principal component analysis, and factor analysis to evaluate the competitiveness of the cultural industry in the 31 Chinese provinces during the period 2013–2019. The results reveal that the competitiveness of cultural industry in the eastern region is the strongest, followed in descending order by the central, northeastern, and western regions of China. Then, the panel regression is employed to explore the impact of the cultural industry’s competitiveness index on economic growth. The results indicate that the cultural industry’s competitiveness is positively associated with China’s economic growth. We also conduct another panel regression analysis by examining the impact of cultural industry factors on China’s economic growth to gain insight into the influence of the cultural industry components on growth. In this analysis, our results indicate that cultural industry factors, including fixed asset investment and labor, significantly play an important role in Chinese growth. This study also finds that total patent applications, the total profit of cultural enterprises, and government expenditure positively impact economic growth, but the evidence is weak. Thus, these three variables could be considered potential future driver factors. The empirical findings offer insights into strategies that the national government could implement to strengthen the cultural industry’s competitiveness as China’s new powerful driver of economic development. Compared with previous empirical studies, this research deepens the competitive cultural analysis, increases the number of observations, and lengthens the period studied.

Heat shock proteins (HSPs) are a class of highly conserved proteins which can protect cells against various types of stress. However, little information on the mechanism involved in the organic contaminants stress response of HSPs is available, especially in marine invertebrates. The present study was conducted to evaluate the responses of HSPs in clams (Ruditapes philippinarum) under Benzo[a] pyrene (BaP) exposure. The clams were exposed to BaP (concentrations: 0, 0.1, 1, 10 μg/L) for 15 days. 6 HSPs mRNA were classified, and the results of tissue distribution indicated that 4 HSPs gene expressed most in the digestive glands. The transcription level of 6 HSPs (HSP22-1, HSP22-2, HSP40A, HSP60, HSP70, HSP90) genes and the aryl hydrocarbon receptor signaling pathway-related genes, and detoxification system-related enzymes activities were analyzed at 0, 1, 3, 6, 10 and 15 days. The activities of phase II detoxification metabolic enzymes and signaling pathway related genes in clams were severely affected by BaP stress and presented significant difference. Our result suggested that HSPs were produced in the presence of BaP and participated in the process of detoxification metabolism to a certain extent. Additionally, the transcription of HSP40A gene may be used as a potential biomarker of BaP exposure due to its evident concentration- and time-dependent expression pattern. Overall, the study investigated the classification of HSPs in R. philippinarum, provided information about the expression profiles of various HSPs after BaP exposure and broadened the understanding mechanism of HSPs in detoxification defense system under PAHs stress in mollusks.

Due to potential applications of black phosphorus nanosheets (BPNSs) in many fields in the near future, the toxicological effects of BPNSs on environmental organisms is becoming a major concern. He...

Growing developments in engineered nanomaterials (NMs) and their wide applications inevitably raise environmental and human health concerns. Upon contact with biological fluids, NMs can attract proteins onto their surfaces to form dynamic layers called protein corona. Such new biological identities are what the bio-systems “see” and react with. Formation of protein corona around NMs determines the biological behavior of NMs and the transformation patterns of proteins. Therefore, characterization of the protein corona on NMs' surface is the first step towards understanding the nature of NMs-mediated biological effects. In this review, the roles of protein corona in NMs' bio-application and biosafety were summarized, with an emphasis on methods for characterizing NMs-protein interactions and the dynamic biological identities. Moreover, we extrapolated the discussion to environmentally relevant nanoparticles (e.g. PM 2.5) and macromolecules, and discussed the possible methods and challenges for studying their interactions with proteins.

As typical brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) and its derivative TBBPA-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) are ubiquitous in various environmental compartments. However, the potential health risk posed by these compounds, especially at environmentally relevant levels, remains unclear. In this study, using adult male mice, we investigated the toxicity of orally administered TBBPA and TBBPA-BDBPE at an environmentally relevant dose (57 nmol/kg body weight). After a single exposure and daily exposure, we assessed lipid metabolism homeostasis, the transcriptome, and immune cell components in the liver. We found that the single exposure to TBBPA or TBBPA-BDBPE alone increased the number of hepatic macrophages, induced alterations in the levels of lipids, including triacylglycerol and free fatty acids, and caused transcriptome perturbation. The results from the daily administration groups showed that TBBPA and TBBPA-BDBPE both significantly increased the triacylglycerol content; however, the elevation of hepatic macrophages was observed only in the TBBPA-BDBPE treatment group. This study confirmed that environmentally relevant levels of TBBPA and TBBPA-BDBPE are toxic to the liver. Our findings revealed that dysfunction of the liver is a health concern, following exposure to BFRs, even at very low concentrations. The chronic effects induced by TBBPA and its derivatives should be further investigated.

Coronavirus is named for its crown shape. Encoded by the genetic material inherited from the coronavirus itself, this intrinsic well-known “viral corona” can be considered the “inherited corona”. After contact with mucosa or the entrance into the host, bare coronaviruses could become covered by a group of dissolved biomolecules to form one or multiple layers of biomolecules. Different from this inherited corona, the layers acquired from the surrounding environment could be named as “acquired corona”. We highlight here the possible role of the acquired corona absorbing onto the surface of coronaviruses, which will generate fresh insight into the nature of various coronavirus-host interactions., Graphical abstract

Background: Tetrabromobisphenol A (TBBPA) mono-ether structural analogs, identified as the by-products or transformation products of commercial TBBPA bis-ether derivatives, have been identified as emerging widespread pollutants. However, there is very little information regarding their toxicological effects. Objective: We aimed to explore the potential thyroid hormone (TH) system–disrupting effect of TBBPA mono-ether structural analogs. Methods: The binding potencies of chemicals toward human TH transport proteins [transthyretin (TTR) and thyroxine-binding globulin (TBG)] and receptors [TRα ligand-binding domain (LBD) and TRβ-LBD] were determined by fluorescence competitive binding assays. Molecular docking was used to simulate the binding modes of the chemicals with the proteins. The cellular TR-disrupting potencies of chemicals were assessed by a GH3 cell proliferation assay. The intracellular concentrations of the chemicals were measured by high-performance liquid chromatography and mass spectrometry. Results: TBBPA mono-ether structural analogs bound to TTR with half maximal inhibitory concentrations ranging from 0.1μM to 1.0μM but did not bind to TBG. They also bound to both subtypes of TR-LBDs with 20% maximal inhibitory concentrations ranging from 4.0μM to 50.0μM. The docking results showed that the analogs fit into the ligand-binding pockets of TTR and TR-LBDs with binding modes similar to that of TBBPA. These compounds likely induced GH3 cell proliferation via TR [with the lowest effective concentrations (LOECs) ranging from 0.3μM to 2.5μM] and further enhanced TH-induced GH3 cell proliferation (with LOECs ranging from 0.3μM to 1.2μM). Compared with TBBPA, TBBPA-mono(2,3-dibromopropyl ether) showed a 4.18-fold higher GH3 cell proliferation effect and 105-fold higher cell membrane transportation ability. Conclusion: This study provided a possible mechanism underlying the difference in TTR or TR binding by novel TBBPA structural analogs. These compounds might exert TH system–disrupting effects by disrupting TH transport in circulation and TR activity in TH-responsive cells. https://doi.org/10.1289/EHP6498

The application and consumption of nanoparticles (NPs) inevitably result in the contamination of environmental water. The internalized NPs in unicellular organisms could travel to human bodies along food chains and raise health concerns. Current research failed to determine the characteristics of cellular uptake of NPs by unicellular organisms at extremely low concentration in the real environment. We here developed a label-free high-throughput mass cytometry method to investigate gold NP (AuNP) uptake in a unicellular organism (Tetrahymena thermophila) at the single-cell level. The limit of detection for Au is as low as to 6.67 × 10-18 g/cell, which equals ∼5.3 5 nm AuNPs. We demonstrated that active engulfment pathways were responsible for the cellular accumulation of AuNPs and T. thermophila could also eliminate the cellular AuNPs rapidly. The interaction between AuNPs and T. thermophila is highly dependent on the sizes of nanoparticles; i.e., the population of T. thermophila containing AuNPs decreased with the increment of the diameters of AuNPs when exposed to the same mass concentration. For each type of AuNP, distinct heterogeneous cellular uptake of AuNPs by T. thermophila was observed. Intriguingly, for 5 nm AuNP, even at 0.001 ng/mL, some T. thermophila cells could concentrate AuNPs, indicating a real environmental concern even when water was contaminated by only trace level of NPs. This method represents a promising tool for simultaneous determination of physiological status of cells together with the intracellular level of heavy metal or metallic NPs in study of biological effects.

Vessel segmentation and anatomical labeling are of great significance for vascular disease analysis. Because vessels in 3D images are the tree-like tubular structures with diverse shapes and sizes, and direct use of convolutional neural networks (CNNs, based on spatial convolutional kernels) for vessel segmentation often encounters great challenges. To tackle this problem, we propose a graph convolutional network (GCN)-based point cloud approach to improve vessel segmentation over the conventional CNN-based method and further conduct semantic labeling on 13 major head and neck vessels. The proposed method can not only learn the global shape representation but also precisely adapt to local vascular shapes by utilizing the prior knowledge of tubular structures to explicitly learn anatomical shape. Specifically, starting from rough segmentation using V-Net, our approach further refines the segmentation and performs labeling on the refined segmentations, with two steps. First, a point cloud network is applied to the points formed by initial vessel voxels to refine vessel segmentation. Then, GCN is employed on the point cloud to further label vessels into 13 major segments. To evaluate the performance of our proposed method, CT angiography images (covering heads and necks) of 72 subjects are used in our experiment. Using four-fold cross-validation, an average Dice coefficient of 0.965 can be achieved for vessel segmentation compared to that of 0.885 obtained by the conventional V-Net based segmentation. Also, for vessel labeling, our proposed algorithm achieves an average Dice coefficient of 0.899 for 13 vessel segments compared to that of 0.829 by V-Net. These results show that our proposed method could facilitate head and neck vessel analysis by providing automatic and accurate vessel segmentation and labeling results.