Effects of trichlorobisphenol A on the expression of proteins and genes associated with puberty initiation in GT1-7 cells and the relevant molecular mechanism.

This study evaluated the effects of Cl3BPA on kisspeptin-G-protein coupled receptor 54 (GPR54)/gonadotropin-releasing hormone (GnRH) (KGG) signals and analyzed the roles of estrogen receptor alpha (ERɑ) and G-protein coupled estrogen receptor 1 (GPER1) in regulating KGG signals. The results showed that Cl3BPA at 50 µM increased the levels of intracellular reactive oxygen species (ROS) and GnRH, upregulated the protein levels of kisspeptin and the expression of fshr, lhr and gnrh1 genes related to KGG in GT1-7 cells. In addition, 50 µM Cl3BPA significantly upregulated the phosphorylation of extracellular regulated protein kinases 1/2 (Erk1/2), the protein levels of GPER1 and the expression of the gper1 as well as the most target genes associated with mitogen-activated protein kinase (MAPK)/Erk1/2 pathways. Specific signal inhibitor experiments found that Cl3BPA activated KGG signals by activating the GPER1-mediated MAPK/Erk1/2 signaling pathway at the mRNA level. A docking test further confirmed the interactions between Cl3BPA and GPER1. The findings suggest that Cl3BPA might induce precocious puberty by increasing GnRH secretion together with KGG signaling upregulation, which is driven by GPER1-mediated signaling pathway. By comparison, ClxBPAs with fewer chlorine atoms had more obvious effects on the expression of proteins and partial genes related to KGG signals in GT1-7 cells.

Anisotropic structure deformation of ß-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine under high pressure: vibration spectra calculation and resolution based on AIMD simulation.

The phase transition of the ß-HMX crystal has been widely studied under high pressure, but the microscopic transition mechanism is not sufficiently understood. In this article, we perform a series of ab initio molecular dynamics simulations focusing on structure deformation and the corresponding vibration spectra resolution of ß-HMX at 0-40 GPa. Several typical pressure-induced phase transition processes are confirmed by analyzing the chemical bond, dihedral angle, charge transfer, and IR and Raman spectra. The corresponding relationship between molecular structure and spectral signal is constructed through the partial spectra calculations of special functional groups within the HMX molecule. The anisotropic effects of different groups on the initial structural phase transition are uncovered. The equatorial C-N and axial N-N bonds have the largest compression ratio as pressure increases, which is the intrinsic factor for the initiation of structure transformation. The C-N molecular ring plays an important role in the entire phase transition process. In addition, the phase transition of ß â†’ ζ is also closely related to the deformation of NO2, while that of ζ → ε is induced by the axial N-NO2 group. Regarding the higher-pressure phase transition, the synergetic effect of N-NO2, CH2 groups, and molecular rings becomes more considerable.

Recombinant Porcine Interferon-α Decreases Pseudorabies Virus Infection.

Interferon (IFN) is a cell-secreted cytokine possessing biological activities including antiviral functioning, immune regulation, and others. Interferon-alpha (IFN-α) mainly derives from plasmacytoid dendritic cells, which activate natural killer cells and regulate immune responses. IFN-α responds to the primary antiviral mechanism in the innate immune system, which can effectively cure acute infectious diseases. Pseudorabies (PR) is an acute infectious disease caused by pseudorabies virus (PRV). The clinical symptoms of PRV are as follows: reproductive dysfunction among pregnant sows and high mortality rates among piglets. These pose a severe threat to the swine industry. Related studies show that IFN-α has broad applications in preventing and treating viral diseases. Therefore, a PRV mouse model using artificial infection was established in this study to explore the pathogenic effect of IFN-α on PRV. We designed a sequence with IFN-α4 (M28623, Genbank) and cloned it on the lentiviral vector. CHO-K1 cells were infected and identified using WB and RT-PCR; a CHO-K1 cell line with a stable expression of the recombinant protein PoIFN-α was successfully constructed. H&E staining and virus titer detection were used to investigate the recombinant protein PoIFN-α's effect on PR in BALB/c mice. The results show that the PoIFN-α has a preventive and therapeutic impact on PR. In conclusion, the recombinant protein can alleviate symptoms and reduce the replication of PRV in vivo.

The Structure Properties of Carbon Materials Formed in 2,4,6-Triamino-1,3,5-Trinitrobenzene Detonation: A Theoretical Insight for Nucleation of Diamond-like Carbon.

The structure and properties of nano-carbon materials formed in explosives detonation are always a challenge, not only for the designing and manufacturing of these materials but also for clearly understanding the detonation performance of explosives. Herein, we study the dynamic evolution process of condensed-phase carbon involved in 2,4,6-Triamino-1,3,5-trinitrobenzene (TATB) detonation using the quantum-based molecular dynamics method. Various carbon structures such as, graphene-like, diamond-like, and "diaphite", are obtained under different pressures. The transition from a C sp2- to a sp3-hybrid, driven by the conversion of a hexatomic to a non-hexatomic ring, is detected under high pressure. A tightly bound nucleation mechanism for diamond-like carbon dominated by a graphene-like carbon layer is uncovered. The graphene-like layer is readily constructed at the early stage, which would connect with surrounding carbon atoms or fragments to form the tetrahedral structure, with a high fraction of sp3-hybridized carbon. After that, the deformed carbon layers further coalesce with each other by bonding between carbon atoms within the five-member ring, to form the diamond-like nucleus. The complex "diaphite" configuration is detected during the diamond-like carbon nucleation, which illustrates that the nucleation and growth of detonation nano-diamond would accompany the intergrowth of graphene-like layers.

ETNPPL modulates hyperinsulinemia-induced insulin resistance through the SIK1/ROS-mediated inactivation of the PI3K/AKT signaling pathway in hepatocytes.

Hyperinsulinemia is a critical risk factor for the pathogenesis of insulin resistance (IR) in metabolic tissues, including the liver. Ethanolamine phosphate phospholyase (ETNPPL), a newly discovered metabolic enzyme that converts phosphoethanolamine (PEA) to ammonia, inorganic phosphate, and acetaldehyde, is abundantly expressed in liver tissue. Whether it plays a role in the regulation of hyperinsulinemia-induced IR in hepatocytes remains elusive. Here, we established an in vitro hyperinsulinemia-induced IR model in the HepG2 human liver cancer cell line and primary mouse hepatocyte via a high dose of insulin treatment. Next, we overexpressed ETNPPL by using lentivirus-mediated ectopic to investigate the effects of ETNPPL per se on IR without insulin stimulation. To explore the underlying mechanism of ETNPPL mediating hyperinsulinemia-induced IR in HepG2, we performed genome-wide transcriptional analysis using RNA sequencing (RNA-seq) to identify the downstream target gene of ETNPPL. The results showed that ETNPPL expression levels in both mRNA and protein were significantly upregulated in hyperinsulinemia-induced IR in HepG2 and primary mouse hepatocytes. Upon silencing ETNPPL, hyperinsulinemia-induced IR was ameliorated. Under normal conditions without IR in hepatocytes, overexpressing ETNPPL promotes IR, reactive oxygen species (ROS) generation, and AKT inactivation. Transcriptome analysis revealed that salt-inducible kinase 1 (SIK1) is markedly downregulated in the ETNPPL knockdown HepG2 cells. Moreover, disrupting SIK1 prevents ETNPPL-induced ROS accumulation, damage to the PI3K/AKT pathway and IR. Our study reveals that ETNPPL mediates hyperinsulinemia-induced IR through the SIK1/ROS-mediated inactivation of the PI3K/AKT signaling pathway in hepatocyte cells. Targeting ETNPPL may present a potential strategy for hyperinsulinemia-associated metabolic disorders such as type 2 diabetes.

Development and validation of machine learning models for postoperative venous thromboembolism prediction in colorectal cancer inpatients: a retrospective study.

Background: Colorectal cancer (CRC) is a heterogeneous group of malignancies distinguished by distinct clinical features. The association of these features with venous thromboembolism (VTE) is yet to be clarified. Machine learning (ML) models are well suited to improve VTE prediction in CRC due to their ability to receive the characteristics of a large number of features and understand the dataset to obtain implicit correlations. Methods: Data were extracted from 4,914 patients with colorectal cancer between August 2019 and August 2022, and 1,191 patients who underwent surgery on the primary tumor site with curative intent were included. The variables analyzed included patient-level factors, cancer-level factors, and laboratory test results. Model training was conducted on 30% of the dataset using a ten-fold cross-validation method and model validation was performed using the total dataset. The primary outcome was VTE occurrence in postoperative 30 days. Six ML algorithms, including logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), weighted support vector machine (SVM), a multilayer perception (MLP) network, and a long short-term memory (LSTM) network, were applied for model fitting. The model evaluation was based on six indicators, including receiver operating characteristic curve-area under the curve (ROC-AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Brier score. Two previous VTE models (Caprini and Khorana) were used as the benchmarks. Results: The incidence of postoperative VTE was 10.8%. The top ten significant predictors included lymph node metastasis, C-reactive protein, tumor grade, anemia, primary tumor location, sex, age, D-dimer level, thrombin time, and tumor stage. In our results, the XGBoost model showed the best performance, with a ROC-AUC of 0.990, a SEN of 96.9%, a SPE of 96.1% in training dataset and a ROC-AUC of 0.908, a SEN of 77.5%, a SPE of 93.7% in validation dataset. All ML models outperformed the previously developed models (Caprini and Khorana). Conclusions: This study developed postoperative VTE predictive models using six ML algorithms. The XGBoost VTE model might supply a complementary tool for clinical VTE prophylaxis decision-making and the proposed risk factors could shed some light on VTE risk stratification in CRC patients.

Viability of mitochondria-labeled retinal ganglion cells in organotypic retinal explant cultures by two methods.

Retinal explant cultures provide a valuable system to study retinal function in vitro. This study established a new retinal explant culture method to prolong the survival of retinal ganglion cells (RGCs). Explants were prepared in two different ways: with or without optic nerve. Retinas from newborn mice that had received an injection of MitoTracker Red into the contralateral superior colliculus to label axonal mitochondria were cultured as organotypic culture for 7 days in vitro. At several time points during the culture, viability of RGCs was assessed by multi-electrode array recording, and morphology by immunohistochemical methods. During the culture, the thickness of the retinal tissue in both groups gradually decreased, however, the structure of the layers of the retina could be identified. Massive apoptosis in the retinal ganglion cell layer (GCL) appeared on the first day of culture, thereafter the number of apoptotic cells decreased. Glial activation was observed throughout the culture, and there was no difference in morphology between the two groups. RGCs loss was exacerbated on 3rdday of culture, and RGCs loss in retinal explants with preserved optic nerve was significantly lower than in retinas that did not preserve the optic nerve. More and longer-lasting mitochondrial signals were observed in the injured area of the optic nerve-preserving explants. Retinal explants provide an invaluable tool for studying retinal function and developing treatments for ocular diseases. The optic nerve-preserving culture helps preserve the integrity of RGCs. The higher number of mitochondria in the nerve-preserving cultures may help maintain viability of RGCs.

Arginase: Biological and Therapeutic Implications in Diabetes Mellitus and Its Complications.

Arginase is a ubiquitous enzyme in the urea cycle (UC) that hydrolyzes L-arginine to urea and L-ornithine. Two mammalian arginase isoforms, arginase1 (ARG1) and arginase2 (ARG2), play a vital role in the regulation of ß-cell functions, insulin resistance (IR), and vascular complications via modulating L-arginine metabolism, nitric oxide (NO) production, and inflammatory responses as well as oxidative stress. Basic and clinical studies reveal that abnormal alterations of arginase expression and activity are strongly associated with the onset and development of diabetes mellitus (DM) and its complications. As a result, targeting arginase may be a novel and promising approach for DM treatment. An increasing number of arginase inhibitors, including chemical and natural inhibitors, have been developed and shown to protect against the development of DM and its complications. In this review, we discuss the fundamental features of arginase. Next, the regulatory roles and underlying mechanisms of arginase in the pathogenesis and progression of DM and its complications are explored. Furthermore, we review the development and discuss the challenges of arginase inhibitors in treating DM and its related pathologies.

Arginase: shedding light on the mechanisms and opportunities in cardiovascular diseases.

Arginase, a binuclear manganese metalloenzyme in the urea, catalyzes the hydrolysis of L-arginine to urea and L-ornithine. Both isoforms, arginase 1 and arginase 2 perform significant roles in the regulation of cellular functions in cardiovascular system, such as senescence, apoptosis, proliferation, inflammation, and autophagy, via a variety of mechanisms, including regulating L-arginine metabolism and activating multiple signal pathways. Furthermore, abnormal arginase activity contributes to the initiation and progression of a variety of CVDs. Therefore, targeting arginase may be a novel and promising approach for CVDs treatment. In this review, we give a comprehensive overview of the physiological and biological roles of arginase in a variety of CVDs, revealing the underlying mechanisms of arginase mediating vascular and cardiac function, as well as shedding light on the novel and promising therapeutic approaches for CVDs therapy in individuals.

Enhanced Effect of an External Electric Field on NH3BH3 Dehydrogenation: an AIMD Study for Thermolysis.

How to improve the dehydrogenation properties of ammonia borane (AB, NH3BH3) is always a challenge for its practical application in hydrogen storage. In this study, we reveal the enhanced effect of an external electric field (E ext) on AB dehydrogenation by means of the ab initio molecular dynamics method. The molecular rotation induced by an electrostatic force can facilitate the formation of the H-N···B-H framework, which would aggregate into poly-BN species and further suppress the generation of the volatile byproducts. Meanwhile, the dihydrogen bond (N-Hδ+···Î´-H-B) is favorably formed under E ext, and the interaction between relevant H atoms is enhanced, leading to a faster H2 liberation. Correspondingly, the apparent activation energy for AB dissociation is greatly reduced from 18.42 to around 15 kcal·mol-1 with the application of an electric field, while that for H2 formation decreases from 20.4 to about 16 kcal·mol-1. In the whole process, the cleavage of the B-H bond is more favorable than that of the N-H bond, no matter whether the application of E ext. Our results give a deep insight into a positive effect of an electric field on AB dehydrogenation, which would provide an important inspiration for hydrogen storage in industry applications.

Anisotropic Reaction Properties for Different HMX/HTPB Composites: A Theoretical Study of Shock Decomposition.

Plastic-bonded explosives (PBXs) consisting of explosive grains and a polymer binder are commonly synthesized to improve mechanical properties and reduce sensitivity, but their intrinsic chemical behaviors while subjected to stress are not sufficiently understood yet. Here, we construct three composites of ß-HMX bonded with the HTPB binder to investigate the reaction characteristics under shock loading using the quantum-based molecular dynamics method. Six typical interactions between HMX and HTPB molecules are detected when the system is subjected to pressure. Although the initial electron structure is modified by the impurity states from HTPB, the metallization process for HMX does not significantly change. The shock decompositions of HMX/HTPB along the (100) and (010) surface are initiated by molecular ring dissociation and hydrogen transfer. The initial oxidations of C and H within HTPB possess advantages. As for the (001) surface, the dissociation is started with alkyl dehydrogenation oxidation, and a stronger hydrogen transfer from HTPB to HMX is detected during the following process. Furthermore, considerable fragment aggregation is observed, which mainly derives from the formation of new C-C and C-N bonds under high pressure. The effect of cluster evolution on the progression of the following reaction is further studied by analyzing the bonded structure and displacement rate.

Chlorobisphenol A activated kisspeptin/GPR54-GnRH neuroendocrine signals through ERα and GPER pathway in neuronal GT1-7 cells.

Chlorobisphenol A (ClxBPA) is a kind of novel estrogenic compounds. The present study aims to investigate the effects of three ClxBPA compounds on the kisspeptin/G protein-coupled receptor 54 (GPR54, also named KissR1)-gonadotropin-releasing hormone (GnRH) (KGG) system in neuronal GT1-7 cells with mechanistic insights by estrogen receptor signaling pathways. The study demonstrated that low-concentration ClxBPA induced the cell proliferation, promoted GnRH secretion, upregulated the expression of KGG neuroendocrine signal-related proteins (KissR1, GnRH1 and kisspeptin) and genes including Kiss1, GnRH1, KissR1, luteinizing hormone receptor (Lhr) and follicle-stimulating hormone receptor (Fshr) in GT1-7 cells. Additionally, ClxBPA activated nuclear estrogen receptor alpha (ERα) and member estrogen receptor G protein-coupled estrogen receptor (GPER)-regulated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (Erk1/2) signaling pathways. Pretreatment of GT1-7 cells with GPER inhibitor G15 and ERα inhibitor ICI reduced the expression of KissR1, GnRH1 and kisspeptin proteins, attenuated mRNA levels of Kiss1, GnRH1, KissR1, Fshr and Lhr genes, and decreased ClxBPA-induced GT1-7 cell proliferation. The results suggested that ClxBPA activated the KGG neuroendocrine signals and induced the proliferation of GT1-7 cells via ERα and GPER signaling pathways. This study provides a new perspective to explore the neuroendocrine toxicity mechanism of ClxBPA. CAPSULE: ClxBPA activated KGG neuroendocrine signaling pathway via ERα and GPER and induced the proliferation of GT1-7 cells.

An ethylene-responsive transcription factor and a flowering locus KH domain homologue jointly modulate photoperiodic flowering in chrysanthemum.

The timely transition from vegetative to reproductive development is coordinated through the quantitative regulation of floral pathway genes in response to physiological and environmental cues. The function of ethylene-responsive element-binding protein (ERF) transcription factors in the regulation of flowering in chrysanthemum (Chrysanthemum morifolium Ramat.) is not well understood. Here, chrysanthemum overexpressing CmERF110 flowered earlier than the wild-type plants, while those in which CmERF110 was suppressed flowered later. RNA-seq results revealed that several genes involved in the circadian rhythm were transcribed differently in CmERF110 transgenic plants from that of the wild-type plants. The rhythm peak of the circadian clock genes in transgenic plants was delayed. Yeast two-hybrid screening of CmERF110 interactors identified a chrysanthemum FLOWERING LOCUS KH DOMAIN (FLK) homologue CmFLK, which was further confirmed with both in vitro and in vivo assays. KEGG pathway enrichment also revealed that CmFLK is involved in the regulation of circadian rhythm-related genes. CmFLK transgenic plants showed a change in flowering time and delayed rhythm peak of the circadian rhythm genes. Taken together, the present data not only suggest that CmERF110 interacts with CmFLK to promote floral transition by tuning the circadian clock, but also provides evidence for the evolutionary conservation of the components in the autonomous pathway in chrysanthemum.

Enhanced selective adsorption of lead(II) from complex wastewater by DTPA functionalized chitosan-coated magnetic silica nanoparticles based on anion-synergism.

Simultaneously removing heavy metal and dye from complex wastewater is of great significance to industrial wastewater treatment. Herein, a novel magnetic adsorbent, DTPA-modified chitosan-coated magnetic silica nanoparticle (FFO@Sil@Chi-DTPA), was successfully prepared and used to enhance the Pb(II) selective adsorption from multi-metal wastewater based on anion-synergism. In the competitive experiment conducted in a multi-ion solution, the type of selective adsorption of metals was changed by the adsorbents before and after amidation, in which FFO@Sil@Chi-DTPA exhibited an excellent selectively for capturing Pb(II), while FFO@Sil@Chi demonstrated highly selective adsorption of silver. More importantly, the selective adsorption of Pb(II)S by FFO@Sil@Chi-DTPA was enhanced from 111.71 to 268.01 mg g-1 when the coexisting MB concentrations ranged from 0 to 100 mg L-1 at pH 6.0. In the Pb(II)-MB binary system, Pb(II) and MB exhibited a synergistic effect, in which the presence of MB strengthened the adsorption effect of Pb(II) due to the sulfonic acid groups in MB molecules that create new specific sites for Pb(II) adsorption, while MB adsorption was also enhanced by the presence of Pb(II). This work provides a new strategy for exploring novel adsorbents that can enhance the selective removal of heavy metal in complex wastewater based on anion-synergism.

The Difference in Expression of Autophagy-Related Proteins in Lesional and Perilesional Skin in Adult Patients with Active and Stable Generalized Vitiligo-A Cross-Sectional Pilot Study.

BACKGROUND: Autophagy plays an important role in maintaining intracellular homeostasis and is essential for cell survival and cell death. Dysfunction of autophagy has been described in many autoimmune diseases but data on vitiligo are scarce. AIMS: The aim of this pilot study was to investigate the expression of autophagy-related proteins in patients with vitiligo. METHODS: Western blotting was used to analyze the expression of microtubule-associated protein light chain 3 (LC3II/I), autophagy-related gene 5 (Agt5), mammalian target of rapamycin (mTOR) and p62 in lesional and perilesional vitiligo skin from seven patients with active generalized vitiligo and nine patients with stable generalized vitiligo compared to control skin from six healthy subjects. RESULTS: Our data showed increased expression of the autophagy marker LC3II/I and decreased p62 protein expression in lesional skin of active and stable vitiligo compared to control skin (P < 0.01). No significant difference in the expression of LC3II/I and p62 was found in perilesional skin of active vitiligo patients (P > 0.05) compared to control skin. Expression of LC3II/I in stable vitiligo lesional skin was higher and p62 expression was lower compared to active vitiligo lesional skin (P < 0.01). Decreased p62 expression was shown in perilesional skin of stable vitiligo patients (P < 0.05). Agt5 protein in lesional and perilesional skin of both active and stable vitiligo patients were increased (P < 0.01 and P< 0.05) compared to control skin. The expression of mTOR protein in lesional and perilesional skin of active and stable vitiligo patients was significantly lower than in control skin (P < 0.01). CONCLUSIONS: The present study indicates increased autophagy in lesional skin in vitiligo patients. Stable vitiligo lesional skin showed increased autophagy compared to active vitiligo lesional skin. Missing activation of autophagy in active vitiligo perilesional skin suggests disturbed autophagy to be associated with vitiligo.

Comprehensive analysis of the prognostic value of the chemokine-like factor-like MARVEL transmembrane domain-containing family in gastric cancer.

BACKGROUND: The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family refers to a family of transcriptional repressor genes. CMTMs are closely associated with the epigenetic regulatory mechanisms and development of multiple malignancies, including gastric cancer. However, their specific biological functions and prognostic values in gastric cancer have yet to be elucidated. METHODS: Tumor sample datasets were retrieved and analyzed using databases including Oncomine, STRING, GEPIA2, cBioportal, and Kaplan-Meier plotter. To investigate the prognostic role of CMTMs in gastric cancer, we applied unsupervised hierarchical clustering analysis of CMTM gene expression patterns. RESULTS: While the mRNA levels of CMTM1/3/6/7/8 were upregulated in gastric cancer, CMTM2/4/5 showed no statistically significant difference at the mRNA level in patients with gastric cancer. Moreover, the mRNA expressions of different CMTMs exhibited strong correlations with various clinical parameters of patients with gastric cancer, including tumor stage, metastatic lymph node status, H. pylori status, and tumor grade. Also, the results suggested that elevated levels of CMTM3/5 mRNA had a significant association (P<0.05) with poor overall survival, progression-free survival, and post-progression survival. Conversely, elevated expression of CMTM2/4/6 mRNA had a significant association with better overall survival, progression-free survival, and post-progression survival. Unsupervised hierarchical clustering analysis successfully identified 2 major clusters of patients as follows: signature #1: CMTM4/6/8 and signature #2: CMTM1/2/3/5/7. Signature #2 was closely correlated with poorer overall survival, which indicated that the expression pattern of the CMTM family could be a novel prognostic factor for patients with gastric cancer. CONCLUSIONS: These results suggest that the expression levels of CMTM genes possibly have prognostic value as a biomarker of gastric cancer.

Molecular mechanism study of BPAF-induced proliferation of ERα-negative SKBR-3 human breast cancer cells in vitro/in vivo.

Bisphenol AF (BPAF) is a known estrogen disruptor of the ERα pathway. The aim of the present study was to characterize the proliferation effects of BPAF on ERα-negative SKBR-3 breast cancer cells with mechanistic insights. BPAF at low concentrations (0.001-0.1 µM) significantly induced the proliferation of SKBR-3 cells. In a SKBR-3 tumor model in BALB/c nude mice, BPAF at 100 mg/kg body weight/day also significantly promoted the growth of SKBR-3 tumors. Low concentrations of BPAF markedly increased the expression of G protein-coupled estrogen receptor (GPER1), c-Myc, CyclinD1 and c-Fos proteins, and enhanced phosphorylation of extracellular signal-regulated kinase (Erk) and protein kinase B (Akt) in SKBR-3 cells. Further, BPAF significantly upregulated mRNA levels of related target genes in SKBR-3 cells and SKBR-3 tumor tissues in nude mice. The GPER1 inhibitor G15 and phosphatidylinositide 3-kinase (PI3K) inhibitor wortmannin (WM) inhibited phosphorylation of Erk and Akt. The specific signal inhibitors also markedly decreased the expression of target genes and weakened the cell proliferation induced by low-concentration BPAF. The findings showed that GPER1 could independently regulate BPAF-induced proliferation of SKBR-3 cells without requiring ERα. These results provide mechanistic insights into the effects of BPAF regarding ERα-negative human breast cancer development.

Insight into the mechanism of tetrachlorobisphenol A (TCBPA)-induced proliferation of breast cancer cells by GPER-mediated signaling pathways.

Tetrachlorobisphenol A (TCBPA), a chlorinated derivative of bisphenol A, is an endocrine disruptor based on interaction with nuclear estrogen receptor alpha (ERα). However, there is only limited data on the mechanisms through which TCBPA-associated estrogenic activity is related to the membrane G protein-coupled estrogen receptor (GPER) pathway. In this study, three human breast cancer cell lines-MCF-7, SKBR3, and MDA-MB-231 cells were used to evaluate whether, as well as how, TCBPA at concentration range of 0.001-50 µM affect cell proliferation. The role of GPER signaling in TCBPA-induced cell proliferation was studied by analyzing the protein expression and mRNA levels of relevant signal targets. The results showed that low concentrations of TCBPA significantly induced the proliferation of MCF-7, SKBR3, and MDA-MB-231 cells, with MCF-7 cells being the most sensitive to TCBPA exposure. Low-concentration TCBPA also upregulated the expression of GPER, CyclinD1, c-Myc, and c-Fos proteins, as well as increased the phosphorylation of extracellular signal-regulated-kinase 1/2 (Erk1/2) and protein kinase B (Akt). Additionally, the mRNA levels of genes associated with estrogen signaling pathways also increased upon exposure to TCBPA. However, the phosphorylation of Erk1/2 and Akt decreased when the cells were treated with GPER inhibitor G15 and phosphatidylinositide 3-kinase (PI3K) inhibitor wortmannin (WM) prior to TCBPA exposure. Besides, the increased proliferation of breast cancer cells induced by TCBPA were also inhibited. In ERα-positive MCF-7 cells, TCBPA also upregulated ERα expression, and ERα was found to interact with GPER-mediated signaling. The results indicate that GPER activates the PI3K/Akt and Erk1/2 signal cascades to drive the cell proliferation observed for low concentrations of TCBPA. The presented results suggest a new mechanism by which TCBPA exerts estrogenic action in breast cancer cells, namely, GPER signaling in an ERα-independent manner, and also highlights the potential risks to human health of the usage of TCBPA.

Magnetic phosphorylated chitosan composite as a novel adsorbent for highly effective and selective capture of lead from aqueous solution.

Separating and recovering lead from heavy metal contaminated wastewater is crucial for the environment remediation and reutilization of lead resources. Herein, a novel adsorbent, the phosphorylated chitosan-coated magnetic silica nanoparticles (Fe3O4@SiO2@CS-P), was successfully fabricated and applied to highly selective adsorption of lead. Competitive experiments were conducted in a multi-ion solution (7 metal ions coexist) at pH 6.0, Fe3O4@SiO2@CS-P exhibited an excellent selectively for capturing lead with the distribution coefficient (0.75 L g-1) more ten times than other metal, while Fe3O4@SiO2@CS demonstrated a highly selective adsorption of silver. These implied that phosphorylation of adsorbent not only improves the sorption performance of lead, but also changes the selective adsorption of metal types. Acidity experiments can draw conclusions that Fe3O4@SiO2@CS-P exhibited better acid resistance (with barely any iron leaching) than silica-uncoated adsorbent (Fe3O4@CS-P) at pH 1.0. Furthermore, the FTIR and XPS spectra after adsorption suggested that the high adsorption performance and selective capture lead were predominantly controlled by the coordination of the phosphate groups on the surface of the adsorbent. This work shows a broad prospect of developing a series of novel, acid-resistant, good reusable and rapidly separable magnetic materials that can be used to efficiently and selectively capture lead from aqueous solutions.