Gender-specific effects of polystyrene nanoplastic exposure on triclosan-induced reproductive toxicity in zebrafish (Danio rerio).

Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 µg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17ß, cyp19a1) and attenuated the TCS-decreased estradiol (E2) in females. Conversely, testosterone levels were suppressed, and E2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3ß, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects.

From cradle to grave: Deciphering sex-specific disruptions of the nervous and reproductive systems through interactions of 4-methylbenzylidene camphor and nanoplastics in adult zebrafish.

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 µg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish.

Genome-Wide Identification and Expression Analysis of DWARF53 Gene in Response to GA and SL Related to Plant Height in Banana.

Dwarfing is one of the common phenotypic variations in asexually reproduced progeny of banana, and dwarfed banana is not only windproof and anti-fallout but also effective in increasing acreage yield. As a key gene in the strigolactone signalling pathway, DWARF53 (D53) plays an important role in the regulation of the height of plants. In order to gain insight into the function of the banana D53 gene, this study conducted genome-wide identification of banana D53 gene based on the M. acuminata, M. balbisiana and M. itinerans genome database. Analysis of MaD53 gene expression under high temperature, low temperature and osmotic stress based on transcriptome data and RT-qPCR was used to analyse MaD53 gene expression in different tissues as well as in different concentrations of GA and SL treatments. In this study, we identified three MaD53, three MbD53 and two MiD53 genes in banana. Phylogenetic tree analysis showed that D53 Musa are equally related to D53 Asparagales and Poales. Both high and low-temperature stresses substantially reduced the expression of the MaD53 gene, but osmotic stress treatments had less effect on the expression of the MaD53 gene. GR24 treatment did not significantly promote the height of the banana, but the expression of the MaD53 gene was significantly reduced in roots and leaves. GA treatment at 100 mg/L significantly promoted the expression of the MaD53 gene in roots, but the expression of this gene was significantly reduced in leaves. In this study, we concluded that MaD53 responds to GA and SL treatments, but "Yinniaijiao" dwarf banana may not be sensitive to GA and SL.

Revealing new insights: Two-center evidence of microplastics in human vitreous humor and their implications for ocular health.

Microplastics (MPs), an emerging environmental contaminant, have raised growing health apprehension due to their detection in various human biospecimens. Despite extensive research into their prevalence in the environment and the human body, the ramifications of their existence within the enclosed confines of the human eye remain largely unexplored. Herein, we assembled a cohort of 49 patients with four ocular diseases (macular hole, macular epiretinal membrane, retinopathy and rhegmatogenous retinal detachment) from two medical centers. After processing the samples with an optimized method, we utilized Laser Direct Infrared (LD-IR) spectroscopy and Pyrolysis Gas Chromatography/Mass Spectrometry (Py-GC/MS) to analyze 49 vitreous samples, evaluating the characteristics of MPs within the internal environment of the human eye. Our results showed that LD-IR scanned a total of 8543 particles in the composite sample from 49 individual vitreous humor samples, identifying 1745 as plastic particles, predominantly below 50 µm. Concurrently, Py-GC/MS analysis of the 49 individual samples corroborated these findings, with nylon 66 exhibiting the highest content, followed by polyvinyl chloride, and detection of polystyrene. Notably, correlations were observed between MP levels and key ocular health parameters, particularly intraocular pressure and the presence of aqueous humor opacities. Intriguingly, individuals afflicted with retinopathy demonstrated heightened ocular health risks associated with MPs. In summary, this research provides significant insights into infiltration of MP pollutants within the human eye, shedding light on their potential implications for ocular health and advocating for further exploration of this emerging health risk.

1,2-Dichloroethane induces testicular pyroptosis by activating piR-mmu-1019957/IRF7 pathway and the protective effects of melatonin.

1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and lactate dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular pyroptosis, and overexpression of piR-mmu-1019957 did not promote pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.

Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish.

BACKGROUND: Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established endocrine-disrupting effects (EDEs) of HMS, the interaction between MNPs and HMS and its impact on HMS-induced EDEs remain unclear. OBJECTIVES: This study aimed to investigate the influence of MNPs on HMS-induced estrogenic effects and elucidate the underlying mechanisms in vitro and in vivo. METHODS: We assessed the impact of polystyrene nanospheres (PNSs; 50 nm, 1.0mg/L) on HMS-induced MCF-7 cell proliferation (HMS: 0.01-1µM, equivalent to 2.62-262µg/L) using the E-SCREEN assay and explored potential mechanisms through transcriptomics. Adult zebrafish were exposed to HMS (0.0262-262µg/L) with or without PNSs (50 nm, 1.0mg/L) for 21 d. EDEs were evaluated through gonadal histopathology, fertility tests, steroid hormone synthesis, and gene expression changes in the hypothalamus-pituitary-gonad-liver (HPGL) axis. RESULTS: Coexposure of HMS and PNSs resulted in higher expression of estrogen receptor α (ESR1) and the mRNAs of target genes (pS2, AREG, and PGR), a greater estrogen-responsive element transactivation activity, and synergistic stimulation on MCF-7 cell proliferation. Knockdown of serum and glucocorticoid-regulated kinase 1 (SGK1) rescued the MCF-7 cell proliferation induced by PNSs alone or in combination with HMS. In zebrafish, coexposure showed higher expression of SGK1 and promoted ovary development but inhibited spermatogenesis. In addition, coexposure led to lower egg hatchability, higher embryonic mortality, and greater larval malformation. Coexposure also modulated steroid hormone synthesis genes (cyp17a2, hsd17[Formula: see text]1, esr2b, vtg1, and vtg2), and resulted in higher 17ß-estradiol (E2) release in females. Conversely, males showed lower testosterone, E2, and gene expressions of cyp11a1, cyp11a2, cyp17a1, cyp17a2, and hsd17[Formula: see text]1. DISCUSSION: PNS exposure exacerbated HMS-induced estrogenic effects via SGK1 up-regulation in MCF-7 cells and disrupting the HPGL axis in zebrafish, with gender-specific patterns. This offers new mechanistic insights and health implications of MNP and contaminant coexposure. https://doi.org/10.1289/EHP13696.

[Identification of banana ADA1 gene family members and their expression profiles under biotic and abiotic stresses].

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.

Behind the Indolent Facade: Uncovering the Molecular Features and Malignancy Potential in Lung Minimally Invasive Adenocarcinoma by Single-Cell Transcriptomics.

The increased use of low-dose computed tomography screening has led to more frequent detection of early stage lung tumors, including minimally invasive adenocarcinoma (MIA). To unravel the intricacies of tumor cells and the immune microenvironment in MIA, this study performs a comprehensive single-cell transcriptomic analysis and profiles the transcriptomes of 156,447 cells from fresh paired MIA and invasive adenocarcinoma (IA) tumor samples, peripheral blood mononuclear cells, and adjacent normal tissue samples from three patients with synchronous multiple primary lung adenocarcinoma. This study highlights a connection and heterogeneity between the tumor ecosystem of MIA and IA. MIA tumor cells exhibited high expression of aquaporin-1 and angiotensin II receptor type 2 and a basal-like molecular character. Furthermore, it identifies that cathepsin B+ tumor-associated macrophages may over-activate CD8+ T cells in MIA, leading to an enrichment of granzyme K+ senescent CD8+ T cells, indicating the possibility of malignant progression behind the indolent appearance of MIA. These findings are further validated in 34 MIA and 35 IA samples by multiplexed immunofluorescence. These findings provide valuable insights into the mechanisms that maintain the indolent nature and prompt tumor progression of MIA and can be used to develop more effective therapeutic targets and strategies for MIA patients.

Polystyrene nanoplastic exposure induces excessive mitophagy by activating AMPK/ULK1 pathway in differentiated SH-SY5Y cells and dopaminergic neurons in vivo.

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging environmental contaminants detected in human samples, and have raised concerns regarding their potential risks to human health, particularly neurotoxicity. This study aimed to investigate the deleterious effects of polystyrene nanoplastics (PS-NPs, 50 nm) and understand their mechanisms in inducing Parkinson's disease (PD)-like neurodegeneration, along with exploring preventive strategies. METHODS: Following exposure to PS-NPs (0.5-500 µg/mL), we assessed cytotoxicity, mitochondrial integrity, ATP levels, and mitochondrial respiration in dopaminergic-differentiated SH-SY5Y cells. Molecular docking and dynamic simulations explored PS-NPs' interactions with mitochondrial complexes. We further probed mitophagy's pivotal role in PS-NP-induced mitochondrial damage and examined melatonin's ameliorative potential in vitro. We validated melatonin's intervention (intraperitoneal, 10 mg/kg/d) in C57BL/6 J mice exposed to 250 mg/kg/d of PS-NPs for 28 days. RESULTS: In our in vitro experiments, we observed PS-NP accumulation in cells, including mitochondria, leading to cell toxicity and reduced viability. Notably, antioxidant treatment failed to fully rescue viability, suggesting reactive oxygen species (ROS)-independent cytotoxicity. PS-NPs caused significant mitochondrial damage, characterized by altered morphology, reduced mitochondrial membrane potential, and decreased ATP production. Subsequent investigations pointed to PS-NP-induced disruption of mitochondrial respiration, potentially through interference with complex I (CI), a concept supported by molecular docking studies highlighting the influence of PS-NPs on CI. Rescue experiments using an AMPK pathway inhibitor (compound C) and an autophagy inhibitor (3-methyladenine) revealed that excessive mitophagy was induced through AMPK/ULK1 pathway activation, worsening mitochondrial damage and subsequent cell death in differentiated SH-SY5Y cells. Notably, we identified melatonin as a potential protective agent, capable of alleviating PS-NP-induced mitochondrial dysfunction. Lastly, our in vivo experiments demonstrated that melatonin could mitigate dopaminergic neuron loss and motor impairments by restoring mitophagy regulation in mice. CONCLUSIONS: Our study demonstrated that PS-NPs disrupt mitochondrial function by affecting CI, leading to excessive mitophagy through the AMPK/ULK1 pathway, causing dopaminergic neuron death. Melatonin can counteract PS-NP-induced mitochondrial dysfunction and motor impairments by regulating mitochondrial autophagy. These findings offer novel insights into the MNP-induced PD-like neurodegenerative mechanisms, and highlight melatonin's protective potential in mitigating the MNP's environmental risk.

Transcriptome profiling and ceRNA network of small extracellular vesicles from resting and degranulated mast cells.

Aim: This study aimed to investigate the transcriptomic characteristics and interactions between competitive endogenous RNAs (ceRNAs) within small extracellular vesicles (sEVs) derived from mast cells (MCs). Methods: Transcriptome sequencing analyzed lncRNA, circRNA and mRNA expression in resting and degranulated MC-derived sEVs. Constructed ceRNA regulatory network through correlation analysis and target gene prediction. Results: Differentially expressed 1673 mRNAs, 173 lncRNAs and 531 circRNAs were observed between resting and degranulated MCs-derived sEVs. Enrichment analysis revealed involvement of neurodegeneration, infection and tumor pathways. CeRNA networks included interactions between lncRNA-miRNA, circRNA-miRNA and miRNA-mRNA, targeting genes in the hippo and wnt signaling pathways linked to tumor immune regulation. Conclusion: This study provides valuable insights into MC-sEV molecular mechanisms, offering significant data resources for further investigations.

Mast cells (MCs) are important for various health conditions, including allergies, infections, tumors and brain disorders. MCs release tiny structures called small extracellular vesicles (sEVs) that carry different molecules, such as genetic material, to communicate with other cells in the body's immune system. However, we still do not know much about how these sEVs work. In this study, we examined the sEVs from MCs and found specific genetic molecules that change when MCs become activated. We discovered that these molecules are involved in important processes related to diseases like neurodegeneration and infection. We also identified networks of molecules that interact with each other, influencing immune regulation of tumor. By studying this, we gain new knowledge about how MCs use sEVs to communicate with other cells in our body during immune responses.

LncRNA-Anrel promotes the proliferation and migration of synovial fibroblasts through regulating miR-146a-mediated annexin A1 expression.

OBJECTIVE: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) are closely related to multiple human autoimmune diseases, and their dysregulation is tightly linked to inflammation and disease progression. Nonetheless, little is known about the consequences of aberrant expression of lncRNAs during rheumatoid arthritis (RA) development. In this study, we screened for the expressions of lncRNAs in RA synovial fibroblasts (RA-SF) and investigated their functions in RA-SF proliferation and migration, and the relevant underlying mechanisms. METHODS: The lncRNAs expression profiles were interrogated with microarrays. The expressions of key lncRNAs were confirmed in synovial fibroblasts from RA patients and MH7A cells using qRT-PCR. Proliferations and migrations of MH7A and HFL-1 cells were evaluated using CCK-8 assay and cell migration assay kits, respectively. The expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and cell migration related proteins (MMP-1 and MMP-3) were evaluated using qRT-PCR and western blotting. Collagen type II-induced arthritis (CIA) in mice was used as an animal model of RA. RESULTS: Nine lncRNAs were significantly altered in RA-SF, of which lncRNA-000239 showing the most significant upregulation. Overexpression of lncRNA-000239 significantly enhanced the proliferation and migration of human RS-SF cells (MH7A), while the opposite effect was observed with lncRNA-000239 silencing. Importantly, lncRNA-000239 enhanced annexin A1 expression by upregulating the expression of miR-146a. Moreover, locally enhanced expression of lncRNA-000239 promoted the onset of arthritis in CIA. CONCLUSION: These data indicate that lncRNA-000239 upregulates annexin A1 expression via miR-146a and thus, promotes the proliferation and migration of RA-SF. This highlights a potential role of lncRNA-000239 as an inflammatory factor of RA.

Genome-wide identification and expression analysis of the GRAS family under low-temperature stress in bananas.

Introduction: GRAS, named after GAI, RGA, and SCR, is a class of plant-specific transcription factors family that plays a crucial role in growth and development, signal transduction, and various stress responses. Methods: To understand the biological functions of the banana GRAS gene family, a genome-wide identification and bioinformatics analysis of the banana GRAS gene family was performed based on information from the M. acuminata, M. balbisiana, and M. itinerans genomic databases. Result: In the present study, we identified 73 MaGRAS, 59 MbGRAS, and 58 MiGRAS genes in bananas at the whole-genome scale, and 56 homologous genes were identified in the three banana genomes. Banana GRASs can be classified into 10 subfamilies, and their gene structures revealed that most banana GRAS gDNAs lack introns. The promoter sequences of GRASs had a large number of cis-acting elements related to plant growth and development, phytohormone, and adversity stress responsiveness. The expression pattern of seven key members of MaGRAS response to low-temperature stress and different tissues was also examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microRNAs-MaGRASs target prediction showed perfect complementarity of seven GRAS genes with the five mac-miRNAs. The expression of all seven genes was lowest in roots, and the expression of five genes was highest in leaves during low-temperature stress. The expression of MaSCL27-2, MaSCL27-3, and MaSCL6-1 was significantly lower under low-temperature stress compared to the control, except for MaSCL27-2, which was slightly higher than the 28°C control at 4 h. The expression of MaSCL27-2, MaSCL27-3, and MaSCL6-1 dropped to the lowest levels at 24 h, 12 h, and 4 h, respectively. The MaSCL27-4 and MaSCL6-2 expression was intermittently upregulated, rising to the highest expression at 24h, while the expression of MaSCL22 was less variable, remaining at the control level with small changes. Discussion: In summary, it is tentatively hypothesized that the GRAS family has an important function in low-temperature stress in bananas. This study provides a theoretical basis for further analyzing the function of the banana GRAS gene and the resistance of bananas to cold temperatures.

Impact of food matrices on the characteristics and cellular toxicities of ingested nanoplastics in a simulated digestive tract.

Microplastic and nanoplastic (MNP) pollution has become a major global food safety concern. MNPs can interact with food matrices, and their passage through the gastrointestinal tract can modify their properties. To explore whether and how food matrices influence MNP toxicity, we investigated the interactions between polystyrene nanoplastics (PS-NPs) and food matrices, using an in vitro gastrointestinal digestion model. Then, we tested cell viability, particle uptake and cellular toxicities induced by PS-NPs with food matrices in Caco-2 cells. The results showed that PS-NPs were aggregated, both with and without food matrices, after in vitro gastrointestinal digestion. Glyceryl trioleate exerted greater ability to stabilize digestas and to disperse PS-NPs than starch and bovine serum albumin. The protein corona's protein composition on PS-NPs varied when it interacted with different food matrices. Moreover, when combined with food matrices, the PS-NPs' uptake was enhanced, thus aggravating cellular inflammation, stress, and apoptosis levels. Finally, through co-exposure to a mixture of food matrices, we found a combined negative effect of PS-NPs and cadmium on cellular inflammation, stress, and apoptosis levels. This is the first study to compare the impact of various food matrices on the characteristics and cellular toxicities of ingested NPs in a simulated digestive tract.

ELK4 exerts opposite roles in cytokine/chemokine production and degranulation in activated mast cells.

The proliferative potential of mast cells after activation for 3-4h was found to be decreased, which suggests that mast cell degranulation and cell proliferation are differentially regulated. ELK4, a member of the ternary complex factor (TCF) subfamily of Ets transcription factors, is one of the downstream effectors of MAPK signaling that is critical for cell proliferation. And Elk4 has been identified to be vital for macrophage activation in response to zymosan and the transcriptional response to 12-O-tetrade canoyl phorbol-13-acetate (TPA) stimulation in fibroblast. However, the effect of ELK4 on the mast cell transcriptional response to FcϵRI and GPCR mediated activation and its potential functional significance in mast cells remain unclear. Here, we showed that ELK4 expression is downregulated in activated mast cells. Elk4 knockout suppresses cell proliferation and impedes the cell cycle in bone marrow-derived mast cells (BMMCs), which is associated with decreased transcription of cell cycle genes. Additionally, the transcriptional activation of cytokines and chemokines is diminished while mast cell degranulation is enhanced in Elk4 knockout BMMCs. Mechanistically, ELK4 might positively modulate Hdc, Ccl3 and Ccl4 transcription by interacting with MITF and negatively regulate the transcription of degranulation-related genes by complexing with SIRT6. Overall, our study identifies a new physiological role of the transcription factor ELK4 in mast cell proliferation and activation.

Genome-Wide Identification of the MPK Gene Family and Expression Analysis under Low-Temperature Stress in the Banana.

Mitogen-activated protein kinases (MAPKs and MPKs) are important in the process of resisting plant stress. In this study, 21, 12, 18, 16, and 10 MPKs were identified from Musa acuminata, Musa balbisiana, Musa itinerans, Musa schizocarpa, and Musa textilis, respectively. These MPKs were divided into Group A, B, C, and D. Phylogenetic analysis revealed that this difference in number was due to the gene shrinkage of the Group B subfamily of Musa balbisiana and Musa textilis. KEGG annotations revealed that K14512, which is involved in plant hormone signal transduction and the plant-pathogen interaction, was the most conserved pathway of the MPKs. The results of promoter cis-acting element prediction and focTR4 (Fusarium oxysporum f. sp. cubense tropical race 4) transcriptome expression analysis preliminarily confirmed that MPKs were relevant to plant hormone and biotic stress, respectively. The expression of MPKs in Group A was significantly upregulated at 4 °C, and dramatically, the MPKs in the root were affected by low temperature. miR172, miR319, miR395, miR398, and miR399 may be the miRNAs that regulate MPKs during low-temperature stress, with miR172 being the most critical. miRNA prediction and qRT-PCR results indicated that miR172 may negatively regulate MPKs. Therefore, we deduced that MPKs might coordinate with miR172 to participate in the process of the resistance to low-temperature stress in the roots of the banana. This study will provide a theoretical basis for further analysis of the mechanism of MPKs under low-temperature stress of bananas, and this study could be applied to molecular breeding of bananas in the future.

[Genome-wide identification of the banana GLR gene family and its expression analysis in response to low temperature and abscisic acid/methyl jasmonate].

Glutamate receptor-like (GLR) is an important class of Ca2+ channel proteins, playing important roles in plant growth and development as well as in response to biotic and abiotic stresses. In this paper, we performed genome-wide identification of banana GLR gene family based on banana genomic data. Moreover, we analyzed the basic physicochemical properties, gene structure, conserved motifs, promoter cis-acting elements, evolutionary relationships, and used real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) to verify the expression patterns of some GLR family members under low temperature of 4 ℃ and different hormone treatments. The results showed that there were 19 MaGLR family members in Musa acuminata, 16 MbGLR family members in Musa balbisiana and 14 MiGLR family members in Musa itinerans. Most of the members were stable proteins and had signal peptides, all of them had 3-6 transmembrane structures. Prediction of subcellular localization indicated that all of them were localized on the plasma membrane and irregularly distributed on the chromosome. Phylogenetic analysis revealed that banana GLRs could be divided into 3 subclades. The results of promoter cis-acting elements and transcription factor binding site prediction showed that there were multiple hormone- and stress-related response elements and 18 TFBS in banana GLR. RT-qPCR analysis showed that MaGLR1.1 and MaGLR3.5 responded positively to low temperature stress and were significantly expressed in abscisic acid/methyl jasmonate treatments. In conclusion, the results of this study suggest that GLR, a highly conserved family of ion channels, may play an important role in the growth and development process and stress resistance of banana.

Targeting Lewis X oligosaccharide-modified liposomes encapsulated with house dust mite allergen Der f 2 to dendritic cells inhibits Th2 immune response.

Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic diseases. However, the long desensitization phase and potentially dangerous allergic side effects limit its broad application. Therefore, safer and more effective vaccines are required. Targeting dendritic cells (DCs) with novel allergen conjugates is a promising strategy for AIT. In this study, a novel vaccine with a DC-targeting effect for AIT was constructed. Liposomes were used as vehicles, and a targeted nanovaccine (Lex-lip-Der f 2) was constructed by loading the recombinant group 2 allergen of Dermatophagoides farinae (Der f 2) and conjugating with the DC-SIGN ligand Lewis X. The effect of the vaccine on DCs and T cell responses and the safety of the vaccine were investigated in vitro. The results showed that the Lex-lip-Der f 2 vaccine was spherical, with size of approximately 128 nm. The protein-loading capacity of the vaccine was 0.106 ± 0.001 mg per mg liposome and protein was gradually released from the liposomes during the first 12 h. Lex-lip-Der f 2 was taken up more efficiently by DCs than non-targeted liposomes or free Der f 2. Besides, Lex-lip-Der f 2 significantly inhibited the release of IL-4, IL-6, and TNF-a from DCs. Accordingly, Der f 2-lip loaded DCs significantly decreased IL-4 levels in autologous naïve CD4+T cells. Moreover, Lex-lip-Der f 2-treated basophils showed lower activation levels. These results suggest that DC-SIGN targeting mediated by Lewis X could inhibit the Th2 cell response and improve vaccine safety, and may be a novel vaccination strategy.

Long-Chain Acyl Carnitines Aggravate Polystyrene Nanoplastics-Induced Atherosclerosis by Upregulating MARCO.

Exposure to micro- and nanoplastics (MNPs) is common because of their omnipresence in environment. Recent studies have revealed that MNPs may cause atherosclerosis, but the underlying mechanism remains unclear. To address this bottleneck, ApoE-/- mice are exposed to 2.5-250 mg kg-1 polystyrene nanoplastics (PS-NPs, 50 nm) by oral gavage with a high-fat diet for 19 weeks. It is found that PS-NPs in blood and aorta of mouse exacerbate the artery stiffness and promote atherosclerotic plaque formation. PS-NPs activate phagocytosis of M1-macrophage in the aorta, manifesting as upregulation of macrophage receptor with collagenous structure (MARCO). Moreover, PS-NPs disrupt lipid metabolism and increase long-chain acyl carnitines (LCACs). LCAC accumulation is attributed to the PS-NP-inhibited hepatic carnitine palmitoyltransferase 2. PS-NPs, as well as LCACs alone, aggravate lipid accumulation via upregulating MARCO in the oxidized low-density lipoprotein-activated foam cells. Finally, synergistic effects of PS-NPs and LCACs on increasing total cholesterol in foam cells are found. Overall, this study indicates that LCACs aggravate PS-NP-induced atherosclerosis by upregulating MARCO. This study offers new insight into the mechanisms underlying MNP-induced cardiovascular toxicity, and highlights the combined effects of MNPs with endogenous metabolites on the cardiovascular system, which warrant further study.

Investigation of Microplastics (≥10 µm) in Meconium by Fourier Transform Infrared Microspectroscopy.

Microplastics are prevalent emerging pollutants with widespread distribution in air, land and water. They have been detected in human stool, blood, lungs, and placentas. However, human fetal microplastic exposure remains largely under-studied. To assess fetal microplastic exposure, we investigated microplastics using 16 meconium samples. We used hydrogen peroxide (H2O2), nitric acid (HNO3) and a combination of Fenton's reagent and HNO3 pretreatment methods respectively to digest the meconium sample. We analyzed 16 pretreated meconium samples with an ultra-depth three-dimensional microscope and Fourier transform infrared microspectroscopy. The result showed that H2O2, HNO3 and Fenton's reagent combined with HNO3 pretreatment methods could not digest our meconium samples completely. Alternatively, we developed a novel approach with high digestion efficiency using petroleum ether and alcohol (4:1, v/v), HNO3 and H2O2. This pretreatment method had good recovery and non-destructive advantages. We found no microplastics (≥10 µm) in our meconium samples, indicating that microplastic pollution levels in the fetal living environment are miniscule. Different results between previous studies' and ours underscore that comprehensive and strict quality control are necessary for further studies on microplastic exposure using human bio-samples.

CircBCL11B acts as a ceRNA to facilitate 1,2-dichloroethane-induced astrocyte swelling via miR-29b-3p/AQP4 axis in SVG p12 cells.

1,2-Dichloroethane (1,2-DCE) is a pervasive environmental pollutant found in ambient and residential air, as well as ground and drinking water. Brain edema is the primary pathological consequence of 1,2-DCE overexposure. We found that microRNA (miRNA)-29b dysregulation after 1,2-DCE exposure can aggravate brain edema by suppressing aquaporin 4 (AQP4). Moreover, circular RNAs (circRNAs) can regulate the expression of downstream target genes through miRNA, and affect protein function. However, circRNAs' role in 1,2-DCE-induced brain edema via miR-29b-3p/AQP4 axis remains unclear. To address the mechanism's bottleneck, we explored the circRNA-miRNA-mRNA network underlying 1,2-DCE-driven astrocyte swelling in SVG p12 cells by circRNA sequencing, electron microscopy and isotope 3H labeling combined with the 3-O-methylglucose uptake method. The results showed that 25 and 50 mM 1,2-DCE motivated astrocyte swelling, characterized by increased water content, enlarged cell vacuoles, and mitochondrial swelling. This was accompanied by miR-29b-3p downregulation and AQP4 upregulation. We verified that AQP4 were negatively regulated by miR-29b-3p in 1,2-DCE-induced astrocyte swelling. Also, circRNA sequencing highlighted that circBCL11B was upregulated by 1,2-DCE. This was manifested as circBCL11B overexpression playing an endogenous competitive role via upregulating AQP4 by binding to miR-29b-3p, thus leading to astrocyte swelling. Conversely, circBCL11B knockdown reversed the 1,2-DCE-motivated AQP4 upregulation and alleviated the cell swelling. Finally, we demonstrated that the circBCL11B was targeted to miR-29b-3p by fluorescence in situ hybridization and dual-luciferase reporter assay. In conclusion, our findings indicate that circBCL11B acts as a competing endogenous RNA to facilitate 1,2-DCE-caused astrocyte swelling via miR-29b-3p/AQP4 axis. These observations provide new insight into the epigenetic mechanisms underlying 1,2-DCE-induced brain edema.