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Novel brominated flame retardants are widely used in electronics, textiles, furniture, and other products; they can enter the human body through ingestion and respiration and cause harm to the human body, and have been proven to have potential biological toxicity and accumulation effects. 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) is a widely used novel brominated flame retardant; however, there is a lack of research on its mechanism of toxicity, particularly that of intestinal toxicity. Currently, studies on the functionality of iroquois homeobox 3 (IRX3) are extremely limited. In our study, BTBPE was administered to Sprague-Dawley (SD) rats and rat small intestinal crypt epithelial cells (IEC6 cells) in vivo and in vitro, respectively, and hematoxylin and eosin (HE), immunohistochemical, Alcian blue-periodic acid-Schiff (AB-PAS), CCK8, acridine orange/ethidium bromide (AO/EB), fluorescent probes, qPCR, western blotting, and immunofluorescence analyses were performed. To explore the damage mechanism of BTBPE, we used siRNA to silence IRX3 and iNOs-IN-1 (yeast extract-peptone-wheat; YPW) to inhibit nitric oxide synthase 2 (NOS2). The results showed that BTBPE exposure caused inflammation and necroptosis in the jejunum and ileum, as well as destruction of the tight junctions and mucus layer. Moreover, BTBPE activated the IRX3/NOS2 axis both in vivo and in vitro. Silencing IRX3 or inhibiting NOS2 inhibits necroptosis and restores tight junctions in IEC6 cells. In conclusion, our study found that in the jejunum, ileum, and IEC6 cells, BTBPE exposure caused necroptosis and tight junction destruction by activating the IRX3/NOS2 axis. Blocking the IRX3/NOS2 axis can effectively inhibit necroptosis and restore tight junction. In addition, BTBPE exposure caused inflammation and loss of the mucous layer in the jejunum and ileum. Our study is the first to explore the mechanism of intestinal damage caused by BTBPE exposure and to discover new biological functions regulated by the IRX3/NOS2 axis, providing new research directions for necroptosis and tight junctions. [Display omitted] • The mechanism of BTBPE intestinal toxicity has been explored for the first time. • BTBPE caused inflammation, necroptosis, and destruction of tight junction and mucus layer in rat small intestine. • Activation of the IRX3/NOS2 axis leading to necroptosis was first discovered. • It was first found that the activation of IRX3/NOS2 axis would destroy the tight junction. • NOS2 is a key downstream gene that IRX3 plays roles in inducing necroptosis and destroying tight junction. [ABSTRACT FROM AUTHOR]

Bis (2-ethylhexyl) tetrabromophthalate (TBPH) is a new type of brominated flame retardant. Some studies suggest that TBPH exposure may be associated with thyroid damage. However, there is a paucity of research on the authentic exposure-related effects and molecular mechanisms in animals or cells. In this study, we used male Sprague-Dawley (SD) rats and the Nthy ori3–1 cell line (the human thyroid follicular epithelial cell) to explore the potential effects of TBPH (5, 50, 500 mg/kg and 1, 10, 100 nM) on the thyroid. The genes and their proteins of cytokines and thyroid-specific proteins, thyroglobulin (TG), thyroid peroxidase (TPO), and sodium iodide cotransporter (NIS) were examined to investigate the possible mechanisms. At the end of the experiment, it was found that 50 and 500 mg/kg TBPH could increase the levels of total thyroxine (TT4) and free thyroxine (FT4) significantly. The messenger RNAs (mRNAs) of Tg , Tpo , Interleukin-6 (Il6) , and Interleukin-10 (Il10) in the thyroid tissues from the rats treated with 500 mg/kg were enhanced clearly. Meanwhile, the mRNAs of TG , TPO , IL6 , and IL10 were elevated in Nthy ori3–1 cells treated with 100 nM TBPH as well. The mRNAs of TG and TPO were elevated after the knockdown of IL6. To our surprise, after the knockdown of IL10 or the treatment of anti-IL-10-receptor (anti-IL-10-R) antibody, the mRNAs of TG and TPO were significantly reduced, and the effects of TBPH were diminished. In conclusion, our results suggested that the IL-10-IL-10R-TG/TPO-T4 axis is one important target of TBPH in the thyroid. [Display omitted] • Bis (2-ethylhexyl) tetrabromophthalate (TBPH) increased the level of T4 in male rats. • TBPH changed the expressions of thyroglobulin (TG) and thyroid peroxidase (TPO). • IL-10 might contribute to TG and TPO upregulation. [ABSTRACT FROM AUTHOR]

Light pollution is now associated with an increased incidence of mental disorders in humans, and the unfixed light pattern (ULP) is a common light pollution that occurs in such as rotating shift work. However, how much contribution the ULP has to depression and its potential mechanism are yet unknown. Our study aimed to investigate the effect of the ULP on depressive-like behaviors in mice and to explore the links to the circadian-orexinergic system. Male C57BL/6 J mice were exposed to the ULP by subjecting them to an alternating light pattern every 6 days for 54 days. The tail suspension test (TST) and forced swimming test (FST) were conducted to assess depressive-like behaviors. The rhythm of locomotor activity and the circadian expression of cFOS in the suprachiasmatic nucleus (SCN), clock genes in the liver, and corticosterone (CORT) in serum were detected to observe changes in the circadian system. The circadian expression of orexin-A (OX-A) in the lateral hypothalamus area (LHA) and dorsal raphe nucleus (DRN) and serotonin (5-HT) in the DRN were measured to determine alterations in the orexinergic system. The results showed that mice exposed to the ULP exhibited increased immobility time in the TST and FST. The ULP significantly disrupted the circadian rhythm of locomotor activity, clock genes in the liver, and CORT in the serum. Importantly, when exposed to the ULP, cFOS expression in the SCN showed decreased amplitude. Its projection area, the LHA, had a lower mesor of OX-A expression. OX-A projection to the DRN and 5-HT expression in the DRN were reduced in mesor. Our research suggests that the ULP contributes to depressive-like behaviors in mice, which might be related to the reduced amplitude of circadian oscillation in the SCN and hypoactivity of the orexinergic system. These findings may provide novel insights into rotating shift work-related depression. [Display omitted] • The unfixed light pattern in shift work lead to depressive-like behaviors in mice. • Reduced amplitude in SCN is linked to depression caused by the unfixed light pattern. • Reduced levels of OX-A are linked to depression caused by the unfixed light pattern. • Reduced levels of 5-HT are linked to depression caused by the unfixed light pattern. [ABSTRACT FROM AUTHOR]

As an alternative to octabromodiphenyl ether (octa-BDE), 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) has been widely used in a variety of combustible materials, such as plastics, textiles and furniture. Previous studies have demonstrated the thyroid toxicity of traditional brominated flame retardants for example octa-BDE clearly. Nevertheless, little is known about the thyroid toxicity of alternative novel brominated flame retardants BTBPE. In this study, it was demonstrated that BTBPE in vivo exposure induced FT4 reduction in 2.5, 25 and 250 mg/kg bw treated group and TT4 reduction in 25 mg/kg bw treated group. TG, TPO and NIS are key proteins of thyroid hormone synthesis. The results of Western blot and RT-PCR from thyroid tissue showed decreased protein levels and gene expression levels of TG, TPO and NIS as well as regulatory proteins PAX8 and TTF2. To investigate whether the effect also occurred in humans, anthropogenic Nthy-ori 3–1 cells were selected. Similar results were seen in vitro condition. 2.5 mg/L BTBPE reduced the protein levels of PAX8, TTF1 and TTF2, which in turn inhibited the protein levels of TG and NIS. The results in vitro experiment were consistent with that in vivo , suggesting possible thyrotoxic effects of BTBPE on humans. It was indicated that BTBPE had the potential interference of T4 generation and the study provided more evidence of the effects on endocrine disorders. [Display omitted] [ABSTRACT FROM AUTHOR]

PM2.5 still poses a threat to public health even at very low levels. Black carbon (BC) is a key component of PM2.5. Macrophage extracellular traps (METs) are a means by which macrophages capture and destroy invading pathogens. Necroptosis is an inflammatory programmed cell death. However, there is no research on the crosstalk mechanism between necroptosis and METs after BC exposure. In our study, fluorescence labeling, fluorescent probes, qPCR, and immunofluorescence were applied. Our research found that under normal physiological conditions, when macrophages receive external stimuli (in our experiment, phorbol 12-myristate 13-acetate (PMA)), they will form METs, thus exhibiting innate immune function. However, exposure to BC can cause necroptosis in macrophages accompanied by increased levels of ROS and cytosolic calcium ions as well as altered expression of inflammatory factors and chemokines that prevent the formation of METs, and weakening innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibits the formation of METs. Our experiment will enrich the understanding of the mechanism of macrophage injury caused by BC exposure, provide a new direction for studying harmful atmospheric particle toxicity, and propose new therapeutic insights for diseases caused by atmospheric particulate matter. This study is the first to explore the crosstalk mechanism between necroptosis and METs after BC exposure. [Display omitted] • Black carbon (BC) can cause necroptosis in macrophages. • BC can prevent the formation of macrophage extracellular traps (METs). • BC induced necroptosis inhibits the formation of METs. • Necroptosis and METs could interconvert. • This study is the first to investigate the crosstalk mechanism between necroptosis and METs after BC exposure. [ABSTRACT FROM AUTHOR]

2-Acetyl-4-tetrahydroxybutylimidazole (THI), a by-product of Class Ⅲ caramel color, is generally recognized to cause lymphopenia in mammals. However, it remains unknown whether THI exposure during gestation and lactation causes damage to the immune system of offspring. In this study, pregnant Balb/c mice were gavaged with 0, 0.5, 2.5 and 12.5 mg/kg THI from gestation day (GD) 6 to postanal day (PND) 21, after which we treated another batch of dams from GD6 to PND21 and the offspring for 3 weeks after weaning with 0, 2, 10, 50 mg/L THI in drinking water respectively, and investigated the immunological anomalies of dams and offspring. The results showed that lymphopenia was observed in dams but not in weaning pups on PND21, which were exposed to THI during gestation and lactation. 2 mg/L THI and 2.5 mg/kg THI began to cause a remarkable reduction of the numbers of white blood cells and lymphocytes in dams. Besides both the cellular and the humoral immune response was not affected in weaning pups, which were measured by plaque-forming cell (PFC) assay and delayed-type hypersensitivity (DTH) assay respectively. Furthermore, THI could be detected in the plasma of dams with a dose-dependent manner, but not in that of both female and male weaning pups. In both male and female offspring being treated with 10 and 50 mg/L THI for another 3 weeks after weaning, lymphocytopenia was observed and T lymphocytes including CD4+ and CD8+ cells were significantly reduced in their spleens except lymph nodes. 10 and 50 mg/L THI treatment increased CD4+ and CD8+ single positive cells in thymus of female and male weaning mice. Mitogen-induced proliferation ability of T cells in the spleen and lymph nodes was impaired in female weaning mice exposed 50 mg/L THI, while male weaning mice treated with 10 and 50 mg/L THI showed impairment in the spleen but not lymph nodes. Based on the results in this study, no observed adverse effect level (NOAEL) for 3-week THI treatment in weaning mice was considered to be 2 mg/L (0.30 mg/kg bw for female mice and 0.34 mg/kg bw for male mice). And NOAEL for THI treatment in dams might be set to 0.5 mg/kg bw/day. Collectively from the perspective of NOAEL, offspring are not more sensitive than dams or adult mice. [ABSTRACT FROM AUTHOR]

The exponential growth of the demand for broadband services has imposed great challenges on the design of spectrum-efficient optical transmission system in Passive Optical Network (PON). Recently, an innovative Orthogonal Frequency Division Multiplexing (OFDM) scheme, called Polar-OFDM (P-OFDM), has emerged as a promising solution to boost the spectral efficiency of optical transmission in PON. However, the traditional P-OFDM does not yet perform best in spectral efficiency as it only uses half of the total subcarriers. In this paper, we verify a promising complementation between Polarization Multiplexing (POLMUX) and P-OFDM aiming at higher spectral efficiency. We then propose the full-subcarriers P-OFDM by loading data on the even-indexed subcarriers of X polarization and the odd-indexed subcarriers of Y polarization, respectively. Thus, all of the subcarriers will be utilized for effective data transmission, which can double the spectral efficiency. More importantly, because the subcarriers are interlaced on different polarizations, the cross-polarization interference can be significantly mitigated, which enables the independent channel estimation and equalization at the receiver to recover the data carried on each polarization. Our evaluation results demonstrate that the proposed system realizes the double spectral efficiency of the traditional P-OFDM with reasonable Bit Error Rate (BER) performance loss. [ABSTRACT FROM AUTHOR]

Objectives: Ambient light has a vital impact on mood and cognitive functions. Blue light has been previously reported to play a salient role in the antidepressant effect via melanopsin. Whether blue light filtered white light (BFW) affects mood and cognitive functions remains unclear. The present study aimed to investigate whether BFW led to depression-like symptoms and cognitive deficits including spatial learning and memory abilities in rats, and whether they were associated with the light-responsive function in retinal explants. Methods: Male Sprague-Dawley albino rats were randomly divided into 2 groups (n = 10) and treated with a white light-emitting diode (LED) light source and BFW light source, respectively, under a standard 12 : 12 h L/D condition over 30 days. The sucrose consumption test, forced swim test (FST) and the level of plasma corticosterone (CORT) were employed to evaluate depression-like symptoms in rats. Cognitive functions were assessed by the Morris water maze (MWM) test. A multi-electrode array (MEA) system was utilized to measure electro-retinogram (ERG) responses induced by white or BFW flashes. Results: The effect of BFW over 30 days on depression-like responses in rats was indicated by decreased sucrose consumption in the sucrose consumption test, an increased immobility time in the FST and an elevated level of plasma CORT. BFW led to temporary spatial learning deficits in rats, which was evidenced by prolonged escape latency and swimming distances in the spatial navigation test. However, no changes were observed in the short memory ability of rats treated with BFW. The micro-ERG results showed a delayed implicit time and reduced amplitudes evoked by BFW flashes compared to the white flash group. Conclusions: BFW induces depression-like symptoms and temporary spatial learning deficits in rats, which might be closely related to the impairment of light-evoked output signals in the retina. [ABSTRACT FROM AUTHOR]

[Display omitted] • The mode of DNA damage action was dependent on the exposed modes. • DNA damage caused by high-level short-term PM 2.5 can be alleviated by natural repair. • RAD51 hypermethylation caused by PM 2.5 might be the epigenetic mechanism for DSBs. • MiRNAs could regulate the expression level of repair genes in lungs. Ambient air pollution was classified as carcinogenic to humans (Group 1) for lung cancer. DNA damage was an important first step in the process of carcinogenesis, and could also be induced by air pollution. In this study, intratracheal instillation and real-time air exposure system were combined to establish SHP (short-term high-level PM 2.5) and LLPO (long-term low-level PM 2.5 and O 3) exposure patterns, respectively. Hierarchical levels of genetic biomarkers were analyzed to explore DNA damage effects in rats. Representative DNA repair genes from different repair pathways were selected to explore the relative expression levels. The methylation level of differentially expressed repair genes were also determined. Besides, miRNA sequencing and non-targeted metabolomic analysis were performed in rat lungs. KEGG and multi-omics analysis were used to explore the potential mechanism of genetic damage under different air pollution patterns. We found that LLPO exposure induced DSBs and chromosome damage. SHP exposure could induce DSBs and DNA oxidative damage, and the effects of genetic damage under this pollution pattern could be repaired by natural repair. Repair genes involved in two pattern were different. SHP exposure could induce higher methylation levels of RAD51, which might be a potential epigenetic mechanism for high-level PM 2.5 induced down-regulated expression of RAD51 and DSBs. Besides, 29 overlapped alterations in metabolic pathways were identified by metabolomic and miRNA sequencing, including purine metabolism and pyrimidine metabolism after LLPO exposure. Differential miRNAs expression in lung tissue were associated with apoptosis, DNA damage and damage repair. We concluded that under different air pollution patterns, DNA damage biomarkers and activated targets of DNA damage repair network were both different. The genetic damage effects caused by high-level short-term PM 2.5 can be alleviated by natural repair. We provided possible mechanisms by multi-omics which could explain the increased carcinogenic risk caused by air pollution. [ABSTRACT FROM AUTHOR]

As the main composition of combustion, black carbon (BC) is becoming more and more noticeable at home and abroad. Ozone-oxidized black carbon (oBC) was produced through aging of ozone, one of the near-surface pollutants, to black carbon. And oBC was found to be more oxidation and cell toxicity when compared with BC. Besides, as a key cell of immunity, whether CD4 + T cell would involve in lung inflammation induced by particular matter is still unclear. This study aims to observe the effect of oBC on lung damage in mice and discuss how the functional MAP4K4 defect CD4 + T cells (conditional knockout of MAP4K4) presents its role in this process. In our study, MAP4K4 deletion in CD4 + T cells (MAP4K4 cKO) could increase cell number of macrophages, lymphocytes and neutrophils in bronchoalveolar lavage fluid (BALF) exposed to oBC. MAP4K4 deletion in CD4 + T cell also affected CD4 + T cell differentiation in mediastinal lymph nodes after oBC stimulation. The number of CD4 + IL17 + T cell increased obviously. The levels of IL-6 mRNA of lung in MAP4K4 cKO mice was higher than that in wild type mice after exposed to oBC, while the level of IL-6 in BALF had the same trend. Histological examination showed that MAP4K4 deletion in CD4 + T cells affected lung inflammation induced by oBC. Results indicated that MAP4K4 cKO in CD4 + T cells upgraded the level of inflammation in lung when exposed to oBC, which may be connected to the CD4 + T cell differentiation and JNK, ERK and P38 pathways. [ABSTRACT FROM AUTHOR]

Highlights: [•] MAP4K4 is required for the proliferation and activation of CD4+ T cells. [•] MAP4K4 deletion in CD4+ T cells suppresses the IL-2 and IFN-γ production. [•] MAP4K4 is essential for promoting the development of CD25+ CD4+ Tregs. [•] MAP4K4 deficiency prevents the phosphorylation of Erk, Jnk, p38 and PKC-θ. [ABSTRACT FROM AUTHOR]

Highlights: [•] Bisphenol A and genistein were classified as weakly and strongly embryotoxic respectively in embryonic stem cell test. [•] The combined exposure effects of BPA and GEN were evaluated using a 4×4 full factorial design. [•] BPA and GEN have a synergistic effect on embryonic stem cells differentiation at lower dosages. [ABSTRACT FROM AUTHOR]

Abstract: Contact hypersensitivity (CHS) is a delayed-type hypersensitivity reaction which is mediated by hapten-specific T cells. Strong haptens, such as 2, 4-dinitrofluorobenzene (DNFB) can induce it. Grape seed proanthocyanidins extract (GSPs), which is an antioxidant derived from grape seeds, has been reported to possess a variety of potent properties. However, few reports demonstrated the effects of GSPs on contact hypersensitivity. Therefore, the present study was devised to describe the role of GSPs on a mouse model of experimental CHS induced by DNFB and try to explore the possible underlying mechanisms. We observed that, GSPs when orally administrated into the CHS mice, inhibited the aggravation of inflammation. After administration of GSPs, there was obvious fewer inflammatory cell infiltration in the inflamed ears. Ear swelling after challenge was significantly reduced. In addition, we investigated the effects of GSPs on T cells in vitro, which play critical role during the progress of CHS. It was found that GSPs inhibited proliferative activity of T cells by blocking the activation of mitogen-activated protein kinases (MAPK) and NF-кB signaling pathways. Collectively, these results showed that GSPs has protective effect on CHS induced by DNFB and it also could inhibit the proliferation ability of T cells in vitro, suggesting the potential of GSPs as new and effective compound for the treatment of T-cell mediated inflammatory diseases. [Copyright &y& Elsevier]

Previous studies have demonstrated that Galactooligosaccharides (GOS), known as "bifidus factor", has anti-inflammatory effects. Colitis, a kind of colonic inflammatory damage could be induced by different chemicals. The pathogenesis and mechanism of colitis remains unclear, and may be related to intestinal microflora, genetic susceptibility or immune factors. The aim is to explore the effects of GOS on intestinal flora and its anti-inflammatory effects in Dextran Sulfate Sodium (DSS) induced murine colitis and extrapolate the underlying mechanism. Initially, 5% DSS was used to induced colitis by free access to drinking water for 5–7 days. Then the mice were treated with GOS 1 day after DSS treatment. Colon samples were evaluated grossly using a microscope. The percentage of Treg and Th17 cells was analyzed by flow cytometry. The levels of cytokines secretion and mRNA expression were detected by ELISA and real-time PCR. The level of protein was detected by western blot. GOS attenuated DSS induced body weight loss and also reduced the increase in disease index caused by DSS. GOS ameliorated DSS induced colonic histological damage. The protective effect of GOS on DSS induced colitis may be partly attributed to intestinal flora regulation and Th17/Treg imbalance. Furthermore, GOS markedly decreased cytokines (IL-6, IL-18, IL-13 and IL-33) secretion and mRNA expression in colon tissues, through inhibiting activation of NF-κB pathways. GOS could prevent the DSS induced colitis through intestinal flora regulation and reduce the secretion of inflammation related cytokines relying on the NF-κB signaling pathway. Unlabelled Image • GOS ameliorated DSS induced colitis. • GOS could regulate intestinal flora and balance Th17/Treg cells. • GOS inhibited NF-κB activation, reduce secretion of inflammatory cytokines. • GOS might act as a protective candidate for acute colitis induced by DSS. [ABSTRACT FROM AUTHOR]

This study explored the effects of 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) and bis (2-ethylhexyl) tetrabromophthalate (TBPH) on serum metabolites and lipids in male Sprague-Dawley (SD) rats. Rats were orally gavaged 250 mg/kg bw of BTBPE and 500 mg/kg bw of TBPH for 28 consecutive days. Serum samples were collected for metabolomics and lipidomics analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to explore changes in rat metabolic patterns. Least absolute shrinkage and selection operator (LASSO) regression models were established using serum levels of total thyroxine (TT4), free thyroxine (FT4), and rats' grouping information as variables to screen for robust differential substances. SuperPred was the database to obtain potential targets. The metabolomics and lipidomics results showed that BTBPE and TBPH had an impact on rat metabolic patterns, affecting pathways such as vitamin B6 synthesis. For BTBPE treatment, pyridoxal and ceramide (Cer) 24:0;4O were selected as differential substances related to thyroid hormones. For TBPH treatment, dehydroascorbic acid, acylcarnitine (CAR) 19:0, and diglyceride (DG) 38:4 were selected as differential substances related to thyroid hormones. Serotonin 2c receptor and cyclooxygenase-2 were chosen as potential targets of BTBPE and TBPH, respectively. In conclusion, this study found that BTBPE and TBPH impacted the metabolism of rats, and this effect may be related to changes in thyroid function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The brominated flame retardant 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) widely used in manufacturing is inevitably released into the environment, resulting in the exposure of organisms to BTBPE. Therefore, it is particularly important to explore its toxic mechanism. The liver is one of the main accumulating organs of BTBPE, but the mechanism underlying BTBPE hepatotoxicity has not been thoroughly investigated. In our study, BTBPE was administered to Sprague-Dawley (SD) rats and rat hepatocytes (BRL cells) in vivo and in vitro, respectively, and HE staining, AO/EB staining, fluorescent probes, qPCR, immunofluorescence, and dual-luciferase reporter assays were performed. We investigated the mechanism of action of growth arrest-specific 5 (GAS5), miR-743a-5p, and NUAK family kinase 1 (NUAK1) in BTBPE-induced necroptosis from the perspective of competing endogenous RNAs (ceRNAs) using NUAK1 inhibitors, siRNAs, mimics, and overexpression plasmids. Our study showed that exposure to BTBPE caused necroptosis in the liver and BRL cells, accompanied by an oxidation-reduction imbalance and an inflammatory response. It is worth noting that NUAK1 is a newly discovered upstream regulatory target for necroptosis. In addition, miR-743a-5p was shown to inhibit necroptosis by targeting NUAK1 and down-regulating NUAK1. GAS5 upregulates NUAK1 expression by competitively binding to miR-743a-5p, thereby inducing necroptosis. This study demonstrated, for the first time, that the GAS5-miR-743a-5p-NUAK1 axis is involved in the regulation of necroptosis via ceRNAs. Thus, GAS5 and NUAK1 induce necroptosis by competitively binding to miR-743a-5p., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Caramel color is a widely used food pigment, and 2-Acetyl-4-tetrahydroxybutylimidazole (THI) is a by-products of Class III caramel color. Some studies have shown that THI can reduce the number of peripheral blood lymphocytes. However, the comprehensive mechanism of THI immunotoxicity requires further study. In this study, the effects of THI on lymphocyte count, humoral immunity, cellular immunity and nonspecific immunity were determined and the effect of the nutritional status of VB6 on THI immunotoxicity was evaluated. Female BALB/c mice were divided into 3 groups and fed chow containing different doses of VB6: VB6-normal (6 mg/kg VB6), VB6-deprived (0.5 mg/kg VB6) or VB6-enhanced (12 mg/kg VB6) feed. Each group was further divided into 4 subgroups and treated with THI (0.5, 2.5 or 12.5 mg/kg bw) or the solvent control by gavage for 30 days. The thymic cortical thickness was measured with ViewPoint; the proportions of major immune cells and T cells in peripheral blood and tissues were detected via flow cytometry; the transformation and proliferation abilities of T and B cells were detected via T and B lymphocyte proliferation assays; NK cell activity was assessed via lactate dehydrogenase assays; humoral immune function was assessed via plaque-forming cell assays; and the immune function of T lymphocytes was assessed via delayed type hypersensitivity assays. The results showed that compared with those in the corresponding control group, the white blood cell count and lymphocyte count decreased significantly in all the VB6-deprived groups, in the 2.5 and 12.5 mg/kg VB6 groups, and in the 12.5 mg/kg VB6-enhanced group. With increasing THI dose, the thymic cortical layer became thinner. In the thymus, THI increased the proportions of CD3+ T cells and mature CD8+ T cells and decreased the proportions of immature double-positive, double-negative T cells and CD69-expressing lymphocytes. The proportions of naïve T cells and Tcm (central memory T) cells related to homing decreased. The proportion of mature T cells in the spleen decreased significantly. The proliferation of T cells stimulated by ConA decreased after THI exposure. VB6-deficient mice were more sensitive to THI immunotoxicity, and supplementation with VB6 had a certain protective effect on these mice. The results of the PFC and NK cell activity assays indicated that THI exposure might not affect humoral immune or innate immune function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo, pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality. This effect worsened after cessation of CCC exposure for the next 30 days. RNA-seq and western blot analysis revealed that CCC induced aryl hydrocarbon receptor (AhR) signaling, endoplasmic reticulum stress (ERS) and ferritinophagy. Increased iron content and lipid peroxidation levels were also observed in CCC-treated testes. In vitro, it was identified that iron overload mediated by enhanced ferritinophagy occurred in CCC-treated GC-1 cells, which might be attributed to the PERK pathway in ERS. Further, for the first time, our study elucidated the involvement of AhR in CCC-induced iron overload, which aggravated testicular oxidative damage via lipid peroxidation. Considering the adverse impact of CCC exposure on rodents, supportive evidence from GC-1 cells, and the critical importance of spermatogenesis on male development, the effects of CCC on the male reproduction warrant increased attention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lanthanum (La) is widely used in modern industry and agriculture because of its unique physicochemical properties and is broadly exposed in the population. Some studies have shown that La may have some effects on adipogenesis, but there is a lack of related in vivo evidence. In this study, the effects of La(NO 3 ) 3 on adipogenesis and its associated mechanism were studied using C57BL/6J mouse model. The results showed that La(NO 3 ) 3 exposure caused a decrease in body weight and the percentage of fat content in mice. In addition, the adipose marker molecules and specific adipogenic transcription factors decreased in both white adipose tissue (WAT) and brown adipose tissue (BAT). Detection of signaling pathway-related molecules revealed that canonical wnt/β-catenin pathway-related molecules were upregulated in both adipose tissues. In summary, in vivo exposure to La(NO 3 ) 3 might inhibited adipogenesis in mice, possibly through upregulation of the canonical Wnt/β-catenin signaling pathway., (© 2023 John Wiley & Sons, Ltd.)

Sn-2 palmitate is widely used in infant formula. However, little is known about its effects on metabolism and body composition in middle-aged and elderly adults. In a double-blinded, randomized controlled trial, we enrolled Chinese adults aged 45-75 years with self-reported constipation. Individuals were randomly assigned in a 1:1 ratio to a 1,3-dioleoyl-2-palmitoyl-glycerol (OPO)-enriched oil (66% palmitic acid in the sn-2 position) or a control vegetable oil (24% palmitic acid in the sn-2 position) daily for 24 weeks. Skim milk powder was used as the carrier for both fats. Interviews and body composition were performed at baseline, week 4, week 12 and week 24. A fasting blood draw was taken except at week 4. This study was a secondary analysis and considered exploratory. A total of 111 adults (83 women and 28 men, mean age 64.2 ± 7.0 years) were enrolled, of whom 53 were assigned to the OPO group and 57 to the control group. During the intervention, blood glucose, triglyceride, the triglyceride-glucose index, total cholesterol, low-density lipoprotein cholesterol and remnant cholesterol remained stable, while high-density lipoprotein cholesterol decreased in both groups ( p = 0.003). No differences in change were observed between the groups (all p > 0.05). From baseline to week 24, the level of visceral fat increased slightly ( p = 0.017), while body weight, total body water, protein, soft lean mass, fat-free mass, skeletal muscle and skeletal muscle mass index (SMI) decreased in two groups ( p < 0.01). At weeks 4, 12 and 24, the SMI decreased less in the OPO group than in the control group, with a trend towards significance ( p = 0.090). A 24-week daily intake of sn-2-palmitate-enriched oil had no adverse impact on fasting blood glucose, lipids and body composition compared with the control vegetable oil in Chinese adults (funded by Chinese Nutrition Society National Nutrition Science Research Grant, National Key Research and Development Program of China and Wilmar (Shanghai) Biotechnology Research & Development Center Co., Ltd.; ChiCTR1900026480).

Yttrium is a typical heavy rare earth element with widespread use in numerous sectors. Only one previous study has indicated that yttrium has the potential to cause developmental immunotoxicity (DIT). Therefore, there remains a paucity of evidence on the DIT of yttrium. This study aimed to explore the DIT of yttrium nitrate (YN) and the self-recovery of YN-induced DIT. Dams were treated with 0, 0.2, 2, and 20 mg/kg bw/day YN by gavage during gestation and lactation. No significant changes were found in innate immunity between the control and YN-treated groups in offspring. In female offspring at postnatal day 21 (PND21), YN markedly inhibited humoral and cellular immune responses, the proliferative capacity of splenic T lymphocytes, and the expression of costimulatory molecules in splenic lymphocytes. Moreover, the inhibitory effect on cellular immunity in female offspring persisted to PND42. Unlike females, YN exposure did not change the adaptive immune responses in male offspring. Overall, maternal exposure to YN showed a strong DIT to offspring, with the lowest effective dose of 0.2 mg/kg in the current study. The toxicity of cellular immunity could persist throughout development into adulthood. There were sex-specific differences in YN-induced DIT, with females being more vulnerable., (© 2023 Wiley Periodicals LLC.)

The impacts of environmental PM 2.5 on public health have become a major concern all over the world. Many studies have shown that PM 2.5 still poses a threat to public health even at very low levels. Physical or chemical reactions occur between primary particles and other components in the environment, which changes the properties of primary particles. Such newly formed particles with changed properties are called secondary particles. Ozone-oxidized black carbon (oBC) is a key part of PM 2.5 and a representative secondary particle. Macrophages extracellular traps (METs) is a means for macrophages to capture and destroy invading pathogens, thereby exercising innate immunity. Necroptosis is a kind of programmed cell death, which is accompanied by the destruction of membrane integrity, thus inducing inflammatory reaction. However, there is no research on the crosstalk mechanism between necroptosis and MET after oBC exposure. In our study, AO/EB staining, SYTOX Green staining, fluorescent probe, qPCR, Western blot, and immunofluorescence were applied. This experiment found that under normal physiological conditions, when macrophages receive external stimuli (such as pathogens; in our experiment: phorbol 12-myristate 13-acetate (PMA)), they will form METs, capture and kill pathogens, thus exerting innate immune function. However, exposure to oBC can cause necroptosis in macrophages, accompanied by increased levels of reactive oxygen species (ROS) and cytosolic calcium ions, as well as the expression disorder of inflammatory factors and chemokines, and prevent the formation of METs, lose the function of capturing and killing pathogens, and weaken the innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibited the formation of METs. This study was the first to explore the crosstalk mechanism between necroptosis and METs after oBC exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Visible-light-based transmission application plays an important role in various types of sensor services for the Internet of Things (IoTs). However, in big data scenarios, current visible-light-based systems cannot achieve concurrent high-speed communication, low-speed communication, and positioning. Therefore, in this article, we propose a smart visible-light-based fusion applications system, named Fasys, to solve the above problem for the big data traffic with heterogeneity. Specifically, for low-speed data services, we propose a novel linear block coding and bit interleaving mechanism, which enhances the LED positioning accuracy and recovers the lost data bits in the interframe gap (IFG). For high-speed data services with traffic possessing burstiness, an elegant statistical reliability analysis framework in regard to latency is proposed based on martingale theory. The backlog martingale process is constructed. Leveraging stopping time theory, a tight upper bound of unreliability is obtained. An arrival abstraction and traffic allocation scheme is designed, which contributes to decouple the reliability requirement as the maximum supportable arrival load. Finally, we implement our Fasys system, and extensive experimental results show that our system can achieve consistent high-precision positioning and low-BER data communication for low-speed data services. And the proposed martingale-based traffic allocation scheme can achieve the provisioning of reliability in regard to the latency for high-speed data services.

1,4-Naphthoquinone-coated BC (1,4 NQ-BC) is an important component of PM 2.5 and a representative secondary particle. However, there is no research on the crosstalk mechanism between necroptosis and macrophage extracellular traps (METs) after 1,4 NQ-BC exposure. In this study, we treated RAW264.7 cells with 50, 100, and 200 mg/L 1,4 NQ-BC for 24 h, with 10 μM necrostatin-1 for 24 h, and with 2.5 μM phorbol 12-myristate 13-acetate (PMA) for 3 h. Our experiment revealed that under normal physiological conditions, when macrophages receive external stimuli (such as pathogens; in this experiment, PMA), they will form METs and capture and kill pathogens, thus exerting innate immune function. However, exposure to 1,4 NQ-BC can cause necroptosis in macrophages, accompanied by increased levels of reactive oxygen species (ROS) and cytosolic calcium ions, as well as the expression disorder of inflammatory factors and chemokines, prevent the formation of METs, lead to loss of the function of capturing and killing pathogens, and weaken the innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibited the formation of METs. Our study was the first to explore the crosstalk mechanism between necroptosis and METs. This experiment will enrich the mechanism of macrophage injury caused by 1,4 NQ-BC exposure.

Lanthanum (La) as a rare earth element is widely used in agriculture, industry, and medicine. It has been suggested in several studies that La might influence glycolipid metabolism in vivo. In this study, we used 3T3-L1 preadipocytes as in vitro cell model to elucidate the effects of La(NO 3 ) 3 on adipogenesis and the underlying mechanisms. The results showed that La(NO 3 ) 3 could inhibit the adipogenic differentiation of 3T3-L1 preadipocytes, which showed a decrease in lipid accumulation and the downregulation of specific adipogenic transcription factors. La(NO 3 ) 3 exerted its inhibitory effect mainly at the early differentiation stage. Furthermore, La(NO 3 ) 3 influenced the S-phase entry and cell cycle process during the mitotic clonal expansion and regulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expressions of the proteins in phosphatidylinositol 3-kinase (PI3K)/Akt pathway at the early stage of differentiation. Besides, La(NO 3 ) 3 upregulated the expressions of wnt10b mRNA and β-catenin protein and promoted the nucleus translocation of β-catenin. Additionally, we found that La(NO 3 ) 3 could promote the growth of 3T3-L1 preadipocytes both with and without MDI (3-isobutyl-1-methylxanthine [IBMX], dexamethasone [Dex], and insulin) stimulation. Collectively, these results indicated that La(NO 3 ) 3 could inhibit adipogenesis in 3T3-L1 preadipocytes and influence cell proliferation., (© 2022 John Wiley & Sons Ltd.)

With the increasing application of cerium and rare-earth elements (REEs), cerium exposure is becoming more widespread. However, there remains a paucity of evidence on developmental immunotoxicity of cerium. This study was designed to examine the developmental immunotoxicity of gestational and postnatal exposure to cerium nitrate (CN) in BALB/C mouse offspring. Dams were given CN by oral gavage at 0, 0.002, 0.02 and 0.2 mg/kg from gestation day 5 (GD5) to postnatal day 21 (PND 21). On PND 21, the highest dose of CN significantly suppressed the NK cell cytotoxicity, and reduced the proportions of NK cells in peripheral blood and spleen of both female and male pups, however, the proportions of monocytes in peripheral blood and macrophages in spleen only increased in female pups. For adaptive immunity, on PND 21, the suppression of T/B lymphocyte proliferation, humoral and cellular immune responses (number of splenic plaque-forming cells, PFC, and delayed-type hypersensitivity, DTH) were observed in both female and male pup mice exposed to 0.2 mg/kg CN. However, the fall of proportions of T/B lymphocytes in peripheral blood (PB), spleen and mesenteric lymph node (MLN) only found in female pups at 0.2 mg/kg on PND 21. Most indications recovered to normal after 3-week cessation of CN exposure, except the reduction of DTH and PFC. From the findings in this study, the lowest-observed-adverse-effect level (LOAEL) of CN for developmental immunotoxicity was estimated to be 0.2 mg/kg bw per day., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Black carbon (BC) is an important component of atmospheric PM 2.5 and the second largest contributor to global warming. 1,4-naphthoquinone-coated BC (1,4 NQ-BC) is a secondary particle with great research value, so we chose 1,4 NQ-BC as the research object. In our study, mitochondria and lysosomes were selected as targets to confirm whether they were impaired by 1,4 NQ-BC, label free proteomics technology, fluorescent probes, qRT-PCR and western blots were used to investigate the mechanism of 1,4 NQ-BC toxicity. We found 494 differentially expressed proteins (DEPs) in mitochondria and 86 DEPs in lysosomes using a proteomics analysis of THP1 cells after 1,4 NQ-BC exposure for 24 h. Through proteomics analysis and related experiments, we found that 1,4 NQ-BC can damage THP-1-M cells by obstructing autophagy, increasing lysosomal membrane permeability, disturbing the balance of ROS, and reducing the mitochondrial membrane potential. It is worth noting that 1,4 NQ-BC prevented the removal of FTL by inhibiting autophagy, and increased IL-33 level by POR/FTL/IL-33 axis. We first applied proteomics to study the damage mechanism of 1,4 NQ-BC on THP1 cells. Our research will enrich knowledge of the mechanism by which 1,4 NQ-BC damages human macrophages and identify important therapeutic targets and adverse outcome pathways for 1,4 NQ-BC-induced damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The effect of nonacylated and acylated anthocyanins on urinary metabolites in diabetic rats was investigated. Nonacylated anthocyanins extract from bilberries (NAAB) or acylated anthocyanins extract from purple potatoes (AAPP) was given to Zucker diabetic fatty (ZDF) rats for 8 weeks at daily doses of 25 and 50 mg/kg body weight. 1 H NMR metabolomics was applied to study alterations in urinary metabolites from three time points (weeks 1, 4, and 8). Both types of anthocyanins modulated the metabolites associated with the tricarboxylic acid cycle, gut microbiota metabolism, and renal function at weeks 1 and 4, such as 2-oxoglutarate, fumarate, alanine, trigonelline, and hippurate. In addition, only a high dose of AAPP decreased monosaccharides, formate, lactate, and glucose levels at week 4, suggesting improvement in energy production in mitochondria, glucose homeostasis, and oxidative stress. This study suggested different impacts of AAPP and NAAB on the metabolic profile of urine in diabetes.

Black carbon (BC) correlates with the occurrence and progression of atherosclerosis and other cardiovascular diseases. Increasing evidence has demonstrated that BC could impair vascular endothelial cells, but the underlying mechanisms remain obscure. It is known that IL-33 exerts a significant biological role in cardiovascular disease, but little is known about the molecular regulation of IL-33 expression at present. We first found that BC significantly increased IL-33 mRNA in EA.hy926 cells in a concentration and time-dependent manner, and we conducted this study to explore its underlying mechanism. We identified that BC induced mitochondrial damage and suppressed autophagy function in EA.hy926 cells, as evidenced by elevation of the aspartate aminotransferase (GOT2), reactive oxygen species (ROS) and p62, and the reduction of mitochondrial membrane potential (ΔΨm). However, ROS cannot induce IL-33 mRNA-production in BC-exposed EA.hy926 cells. Further, experiments revealed that BC could promote IL-33 mRNA production through the PI3K/Akt/AP-1 and p38/AP-1 signaling pathways. It is concluded that BC could induce oxidative stress and suppress autophagy function in endothelial cells. This study also provided evidence that the pro-cardiovascular-diseases properties of BC may be due to its ability to stimulate the PI3K/AKT/AP-1 and p38/AP-1 pathway, further activate IL-33 and ultimately result in a local vascular inflammation., (© 2022 Wiley Periodicals LLC.)

Lanthanum, a major rare earth element, can exert detrimental effects on the adult immune system, but its developmental immunotoxicity (DIT) remains obscure. This study was designed to evaluate the DIT of lanthanum nitrate (LN) and the self-recovery of LN-induced DIT 21 days following cessation of exposure. BALB/c pregnant dams were exposed to 0, 0.1, 1, and 10 mg/kg body weight/day LN by gavage during gestation and lactation. Results showed that in male offspring, LN markedly inhibited the adaptive immunity at postanal day 21 (PND21) and the inhibitory effect on cellular immunity continued to PND42 (after three weeks of self-recovery). In female offspring, LN suppressed cellular immunity at both PND21 and PND42. Moreover, decreased relative organ weight of thymus, humoral immunity and proportion of double-positive T cells in thymus were also observed at PND42. Bcl-xl protein level decreased in thymus of female at PND42, while the level of β-catenin increased. These changes might contribute to accelerating the degeneration and weight loss of thymus. Overall, in-utero and postanal exposure to LN could induce impairments of immunity in offspring, especially the female, and adaptive immunosuppression would persist throughout development into adulthood. The LOAEL of LN for DIT should be 1 mg/kg., (Copyright © 2022. Published by Elsevier B.V.)

Outdoor air pollution has been classified as carcinogenic to humans (Group 1) for lung cancer, but the underlying mechanism and key toxic components remain incompletely understood. Since DNA damage and metabolite alterations are associated with cancer progression, exploring potential mechanisms linking air pollution and cancer might be meaningful. In this study, a real-time ambient air exposure system was established to simulate the real-world environment of adult male SD rats in Beijing from June 13th, 2018, to October 8th, 2018. 8-OHdG in the urine, γ-H2AX in the lungs and mtDNA copy number in the peripheral blood were analyzed to explore DNA damage at different levels. Serum non-targeted metabolomics analysis was performed. Pair-wise spearman was used to explore the correlation between DNA damage biomarkers and serum differential metabolites. Carcinogenic risks of heavy metals and PAHs via inhalation were assessed according to US EPA guidelines. Results showed that PM 2.5 and O 3 were the major air pollutants in the exposure group and not detected in the control group. Compared with control group, higher levels of 8-OHdG, mtDNA copy number, γ-H2AX and PCNA-positive nuclei cells were observed in the exposure group. Histopathological evaluation suggested ambient air induced alveolar wall thickening and inflammatory cell infiltration in lungs. Perturbed metabolic pathways identified included glycolysis/gluconeogenesis metabolism, purine and pyrimidine metabolism, etc. γ-H2AX was positively correlated with serum ADP, 3-phospho-D-glyceroyl phosphate and N-acetyl-D-glucosamine. The BaPeq was 0.120 ng/m 3 . Risks of Cr(VI), As, V, BaP, BaA and BbF were above 1 × 10 -6 . We concluded that low-level air pollution was associated with DNA damage and serum metabolomic alterations in rats. Cr(VI) and BaP were identified as key carcinogenic components in PM 2.5 . Our results provided experimental evidence for hazard identification and risk assessment of low-level air pollution., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Environmental pollution is a risk factor for adverse birth outcomes, especially preterm birth (PTB) and early-term birth (ETB). It has been revealed that exposure to fine particulate matter (PM 2.5 ) during pregnancy increase the prevalence of PTB. However, the relationship between PM 2.5 exposure and ETB has not been elucidated. In high-risk pregnancies, whether PM 2.5 exposure will bring higher risk of PTB and ETB than in normal pregnancies is still unclear, and the susceptible exposure window is obscure. Therefore, it is worthy of assessing the risk on PTB and ETB and identifying the susceptible exposure windows of PM 2.5 exposure in high-risk pregnant women., Results: This paper collected the clinical data of 7974 singletons, high-risk pregnant women in Peking University First Hospital from 2014 to 2018, and analyzed them using logistic regression and stratified analysis. We observed that exposure to high-level (≥ 75 µg/m 3 ) of PM 2.5 during the third trimester of pregnancy increases the risk of PTB and ETB (PTB: odds ratio[OR] = 1.43, 95% confidence interval [CI]:1.05-1.93. ETB: OR = 1.29, 95%CI: 1.09-1.54). Furthermore, the effects of each 10ug/m 3 increase in PM 2.5 on PTB and ETB were significant during the third trimester (PTB: OR = 1.35, 95%CI:1.16-1.58. ETB: OR = 1.12, 95%CI:1.02-1.22) and the entire pregnancy (PTB: OR = 6.12, 95%CI:4.27-8.89. ETB: OR = 1.96, 95%CI:1.59-2.43) in the high-level exposure group., Conclusions: These results suggest that high-level PM 2.5 exposure during pregnancy is associated with high risk of PTB and ETB in high-risk pregnancies. The third trimester of pregnancy is speculated to be the susceptible exposure window., (© 2022. The Author(s).)

Anthocyanins have been shown to have prebiotic properties. This study investigated the impact of nonacylated anthocyanins and acylated anthocyanins on fecal and cecal metabolites and colonic gut microbiota in diabetic state using 1 H nuclear magnetic resonance (NMR) metabolomics and metagenomic sequencing. Zucker diabetic fatty rats fed with high-fat diet were gavaged with nonacylated anthocyanins extracted from bilberries (NAAB) or acylated anthocyanins extracted from purple potatoes (AAPP) at daily doses of 25 and 50 mg/kg body weight for 8 weeks. Lean Zucker rats fed with normal diet (ND) and high-fat diet (Con) were used as healthy controls groups. Binned NMR spectra and sequenced gene abundance were used for data analysis. Dysbiosis of colonic microbiota and gut metabolites in the diabetic rats were observed compared to the lean Zucker rats. Both anthocyanin extracts increased cecal sugar levels and the abundance of Peptostreptococcaceae sp. and decreased the abundance of Parabacteroides spp. in colon. In addition to the increased fecal short-chain fatty acids, AAPP decreased colonic Ruminococcus torques and Lachnospiraceae bacterium 4&#95;1&#95;37FAA abundances and increased oxidative phosphorylation. The anthocyanin extracts modulated the gut metabolism and microbiota in diabetes, with AAPP showing more regulatory and beneficial effects on diabetes., (Copyright © 2022. Published by Elsevier Ltd.)

Anthocyanins have been reported to possess antidiabetic effects. Recent studies indicate acylated anthocyanins have better stability and antioxidative activity compared to their nonacylated counterparts. This study compared the effects of nonacylated and acylated anthocyanins on hepatic gene expression and metabolic profile in diabetic rats, using full-length transcriptomics and 1 H NMR metabolomics. Zucker diabetic fatty (ZDF) rats were fed with nonacylated anthocyanin extract from bilberries (NAAB) or acylated anthocyanin extract from purple potatoes (AAPP) at daily doses of 25 and 50 mg/kg body weight for 8 weeks. Both anthocyanin extracts restored the levels of multiple metabolites (glucose, lactate, alanine, and pyruvate) and expression of genes ( G6pac , Pck1 , Pklr , and Gck ) involved in glycolysis and gluconeogenesis. AAPP decreased the hepatic glutamine level. NAAB regulated the expression of Mgat4a , Gstm6 , and Lpl , whereas AAPP modified the expression of Mgat4a , Jun , Fos , and Egr1 . This study indicated different effects of AAPP and NAAB on the hepatic transcriptomic and metabolic profiles of diabetic rats.

Background: Air pollution increases the morbidity and mortality of cardiovascular disease (CVD). Atherosclerosis (AS) is the pathological basis of most CVD, and the progression of atherosclerosis and the increase of fragile plaque rupture are the mechanism basis of the relationship between atmospheric particulate pollution and CVD. The aim of the present study was to investigate the effects of coal-fired fine particulate matter (PM 2.5 ) on the expression levels of atherosclerosis-related proteins (von Willebrand factor (vWF), Endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin, and to explore the role and mechanism of the progression of atherosclerosis induced by coal-fired PM 2.5 via the mitogen-activated protein kinase (MAPK) signaling pathways., Methods: Different concentrations of PM 2.5 were given to apolipoprotein-E knockout (ApoE -/- ) mice via intratracheal instillation for 8 weeks. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of vWF, ET-1 in serum of mice. Immunohistochemistry was used to observe the expression and distribution of ICAM-1 and E-selectin in the aorta of mice. Western blot was used to investigate the phosphoylation of proteins relevant to MAPK signaling pathways., Results: Coal-fired PM 2.5 exacerbated atherosclerosis induced by a high-fat diet. Fibrous cap formation, foam cells accumulation, and atherosclerotic lesions were observed in the aortas of PM 2.5 -treated mice. Coal-fired PM 2.5 increased the protein levels of ET-1, ICAM-1, and E-selectin, but there was no significant difference in the vWF levels between the PM 2.5 -treatment mice and the HFD control mice. Coal-fired PM 2.5 promoted the phosphorylation of p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) in aortic tissues of mice., Conclusion: Coal-derived PM 2.5 exacerbated the formation of atherosclerosis in mice, increased the expression levels of atherosclerosis-related proteins in mice serum, and promoted the phosphorylation of proteins relevant to MAPK signaling pathway. Thus, MAPK signaling pathway may play a role in the atherosclerosis pathogenesis induced by Coal-derived PM 2.5 .

In fracture treatment, biological bone union generally depends on the bone's natural fracture healing capacity, even in surgically treated cases. Hydroxyapatite/collagen composite (HAp/Col) has high osteoconductivity and stimulates osteogenic progenitors. Furthermore, it has the potent capacity to adsorb bone morphogenetic proteins (BMPs). In this study, we prepared an injectable HAp/Col paste and evaluated its augmentation of bone union. Furthermore, the effect of HAp/Col paste combined with BMP-2 was also evaluated. We used a rat femur osteotomy model with a defect size of 1 mm. Male Wistar rats were assigned to one of the following four groups; a control group without any implant, a HAp/Col implant group, a group that received an absorbable collagen sponge (ACS) implant impregnated with BMP-2 (1 μg), and a group that received a HAp/Col implant impregnated with BMP-2 implant. Micro-CT analysis, three-point bending tests, and histological evaluation were performed. Bone union was achieved in two of eight cases in the HAp/Col group, five of eight cases in the ACS + BMP-2 group, and all cases in the HAp/Col + BMP-2 group at 8 weeks post-surgery. The control group did not achieve bone union. In addition, in the HAp/Col + BMP-2 group, the biomechanical strength of the fused femurs was comparable to that of the contralateral intact femur; the ratio of the mechanical load at the breaking point of the osteotomy side relative to that of the contralateral side was 1.00 ± 0.151 (SD). These results indicate that HAp/Col paste with or without BMP-2 augments bone union. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:129-137, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Dendritic cells (DCs) are important in the initiation of primary T-cell responses, while transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is a critical regulator of DC survival and homeostasis. This study evaluated the T-cell dependent antibody response (TDAR) to sheep red blood cells (SRBC) on a DC-specific TAK1-deficient mice model. The results showed that TAK1 deficiency in DCs significantly suppressed the humoral and cellular immune response in mice. DC-specific TAK1 deletion impaired splenic T-cell population and conventional DCs, abolished the cytokine production of splenic T cells and down-regulated some functional gene expression in the spleen. Collectively, this study suggests that TAK1 plays an essential role in the development of the humoral immune response.

Objective: To study the changes of immune function in mice offspring whose mothers were exposed to Rare Earth (RE)(NO(3))(3)., Methods: RE(NO(3))(3) was administered to mother mice after giving birth by gavage at dosages of 2, 20 and 200 mg/kg bw during breast-feeding period. The weights of spleen and thymus, the spleen plaque forming cells (PFC), the delayed type hypersensitivity (DTH) and the charcoal clearance of the offspring were determined., Results: The results obtained from the offspring after weaning showed that the body weight of offspring treated with 200 mg/kg RE(NO(3))(3) was 18.8% lower than that of the control group; at the dosage of 2 mg/kg, the number of IgM-PFC was increased by 82.7%; and at the dosage of 20 mg/kg the rate of clearance and clearance index were significantly higher than that of the control group. No difference in DTH was found in any treated group as compared to the control group. The results of offspring at three weeks after weaning showed that the number of IgM-PFC of the 20 and 200 mg/kg bw dose groups were 47.0% and 44.7% lower than that of control group respectively; the rate of clearance and clearance index of the 200 mg/kg group were significantly lower than that of the control group. No significant changes in DTH were observed in each exposed group., Conclusion: RE(NO(3))(3) treatment affected the immune function of mice offspring which may caused by breast milk.

Objective: To study the immunotoxicity induced by 9,10-dimethyl-1,2-benzathrancene (DMBA) in metallothionein gene-knocked-out mice [MT(-/-)] as compared with that in wild-type mice [(MT(+/+)]., Methods: Female mice were treated with 25 mg/kg and 50 mg/kg of DMBA i.p., respectively and immunized with sheep red blood cells (SRBC) i.v. on the following day and rechallenged by injection of SRBC via footpad s.c. on the fourth day post-immunization. Humoral and cell-mediated immune function was assessed by the number of spleen IgM antibody plaque formation cells (PFC) to SRBC and cell-mediated delayed-type hypersensitivity (DTH) measured by footpad swelling thickness., Results: After treatment with 25 mg/kg DMBA, a decrease in weight of their spleen and thymus and PFC/spleen were observed in MT(-/-) mice, while only decrease in thymus weight of MT(+/+) mice. The humoral function was suppressed by 72% in MT(-/-) mice. No obvious change in cell-mediated immune function was observed both in MT(-/-) and MT(+/+) mice. Both humoral and cell-mediated immune function were suppressed more severe (91%) in MT(-/-) mice treated with 50 mg/kg DMBA than those treated with 25 mg/kg DMBA (72%). DTH was not altered by DMBA in MT(+/+) mice. The weight of their spleen and thymus decreased and humoral immune function suppressed in MT(+/+) mice, but these changes were significantly less severe. No obvious suppression of cell-mediated immune function was observed in MT(+/+) mice., Conclusion: Their humoral and cell-mediated immune function was more susceptible to being suppressed by DMBA in MT(-/-) mice, indicating that MT could protect their immune function from damage caused by DMBA.