The Combination of circEPSTI1 and MIF Offers Diagnostic Value for Endometrial Cancer.

Background: Circular RNAs (circRNAs) exhibit unique patterns of expression and high levels of stability in patient plasma samples such that they represent ideal non-invasive biomarkers that can be leveraged to detect a wide array of diseases including endometrial cancer (EC). This study was designed to identify circRNAs with potential diagnostic utility in serum samples from EC patients while also evaluating the utility of macrophage migration inhibitory factor (MIF) as a biomarker when screening for this form of cancer in the clinic. Methods: Levels of circEPSTI1 and MIF were assessed in the plasma of EC patients and healthy subjects (n=186 each) through qPCR and ELISAs. The diagnostic utility of these biomarkers was assessed with receiver operating characteristic curve (ROC) analyses. Results: Relative to healthy subjects, EC patient serum contained significantly elevated circEPSTI1 and MIF. An association was noted between circEPSTI1 expression in stages, histologic grade, and residual tumor. ROC curves confirmed that serum circEPSTI1 levels distinguished between controls and patients with EC with an Area of 0.835 and serum MIF levels distinguished between controls and patients with EC with an Area of 0.6646. When instead diagnosing patients based on the combination of MIF and circEPSTI1, the Area further rose to 0.8604. Conclusion: Assessing the combination of circEPSTI1 and MIF may be a viable approach to reliably diagnosing EC.

Transcriptome Analysis Reveals Anti-Cancer Effects of Isorhapontigenin (ISO) on Highly Invasive Human T24 Bladder Cancer Cells.

Bladder cancer, the most common malignancy of the urinary tract, has a poor overall survival rate when the tumor becomes muscle invasive. The discovery and evaluation of new alternative medications targeting high-grade muscle invasive bladder cancer (MIBC) are of tremendous importance in reducing bladder cancer mortality. Isorhapontigenin (ISO), a stilbene derivative from the Chinese herb Gnetum cleistostachyum, exhibits a strong anti-cancer effect on MIBCs. Here, we report the whole transcriptome profiling of ISO-treated human bladder cancer T24 cells. A total of 1047 differentially expressed genes (DEGs) were identified, including 596 downregulated and 451 upregulated genes. Functional annotation and pathway analysis revealed that ISO treatment induced massive changes in gene expression associated with cell movement, migration, invasion, metabolism, proliferation, and angiogenesis. Additionally, ISO treatment-activated genes involved in the inflammatory response but repressed genes involved in hypoxia signaling, glycolysis, the actin cytoskeleton, and the tumor microenvironment. In summary, our whole transcriptome analysis demonstrated a shift in metabolism and altered actin cytoskeleton in ISO-treated T24 cells, which subsequently contribute to tumor microenvironment remodeling that suppresses tumor growth and progression.

The effect of varicella-zoster virus reactivation on the long-term outcomes of patients undergoing allogeneic hematopoietic stem cell transplantation.

BACKGROUND: A virus infection may lead the body to produce more immune cells of particular types or stimulate the production of new ones, both of which may have anti-leukemic effects. There has been no research on whether immune cells stimulated by varicella-zoster virus (VZV) infection have anti-leukemic effects. The objective of this investigation is to assess the impact of VZV infection on patients' long-term survival following allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: This retrospective study investigated the association between varicella-zoster virus (VZV) reactivation and outcomes in 219 individuals who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the Sun Yat-sen University's First Affiliated Hospital. According to being diagnosed with VZV infection or not, these patients were grouped into two groups. The comparison of cumulative incidence of relapse, non-recurrent mortality, and overall survival (OS) was conducted between the two groups. RESULTS: Analyzing multivariate data, VZV reactivation was linked to lower relapse incidence in the group containing all individuals (hazard ratio [HR] = 0.27; 95% confidence interval [CI], 0.12-0.64), patients suffering from acute myeloid leukaemia (HR = 0.10; 95% CI, 0.01-0.83), and patients suffering from acute lymphoblastic leukaemia (HR = 0.25; 95% CI, 0.08-0.77). Moreover, VZV reactivation was linked with decreased non-relapse mortality in all individuals (HR = 0.20; 95% CI, 0.05-0.79), but no statistical significance was found for any disease subgroup. Further, VZV reactivation was an independent predictor for improved OS in the group containing all individuals (HR = 0.10; 95% CI, 0.03-0.29), patients suffering from acute myeloid leukaemia (HR = 0.09; 95% CI, 0.01-0.66), and patients suffering from acute lymphoblastic leukaemia (HR = 0.16; 95% CI, 0.04-0.68). CONCLUSION: This is the first study to show that VZV reactivation following allo-HSCT is an independent predictor for lower relapse rates and improved OS, providing novel therapeutic approaches to improve patients' long-term survival following allo-HSCT.

Isorhapontigenin (ISO) inhibits malignant cell transformation, migration, and invasion through MEG3/NEDD9 signaling in Cr(VI)-transformed cells.

Cr(VI) compounds are confirmed human carcinogens. Maternally expression 3 (MEG3) is the first long non-coding RNA to be identified as a tumor suppressor. MEG3 is frequently downregulated or lost in various primary human tumor tissues and cancer cell lines. Downregulation of MEG3 is associated with cancer initiation, progression, and metastasis. Our previous study has revealed that MEG3 was lost and NEDD9 was upregulated in Cr(VI)-transformed cells compared to those in passage-matched normal BEAS-2B cells. Overexpression of MEG3 reduced NEDD9. ß-Catenin was activated in Cr(VI)-transformed cells, overexpression of MEG3 or knockdown of NEDD9 inhibited the activation of ß-Catenin. The results from the present study showed that isorhapontigenin (ISO) treatment is able to suppress cell proliferation, migration, and invasion of Cr(VI)-transformed cells. Further study showed that ISO treatment in Cr(VI)-transformed cells decreases the levels of Ki67, a biomarker for cell proliferation, and of cyclin D1, a regulator for the cell cycle. ISO elevated the MEG3 expression level in Cr(VI)-transformed cells. The DNA methylation transferases DNMT3a, DNMT3b, and DNMT1 levels were reduced upon ISO treatment. ISO treatment decreased both mRNA and protein levels of NEDD9. In addition, ISO treatment reduced the activation of ß-catenin. Slug was upregulated and E-Cadherin was downregulated in Cr(VI)-transformed cells, treatment with ISO decreased Slug and increased E-Cadherin. This study demonstrated that ISO is a potent therapeutical agent against lung cancer induced by Cr(VI).

Loss of MEG3 contributes to the enhanced migration and invasion in arsenic-induced carcinogenesis through NQO1/FSCN1 pathway.

Arsenic ranks at the top among all toxic metals and poses a serious threat to human health. Inorganic arsenite and arsenate compounds have been classified as human carcinogens in various types of cancers. Maternally expressed gene 3 (MEG3), a tumor suppressor that is commonly lost in cancer, was investigated in this study for its role in the migration and invasion of arsenic-transformed cells. Our results showed that MEG3 was downregulated in both arsenic-transformed cells (As-T) and cells treated with low doses of arsenic for three months (As-treated). The analysis using TCGA dataset revealed that MEG3 expression was significantly reduced in the tumor tissues from human lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) compared to normal lung tissues. The results from the methylation-specific PCR (MSP) assay demonstrated enhanced methylation in the MEG3 promoters in both As-T and As-treated cells, indicating that increased methylation of the MEG3 promoter caused MEG3 downregulation in these cells. Moreover, As-T cells displayed increased migration and invasion and higher levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and fascin actin-bundling protein 1 (FSCN1). Consistently, the results from immunohistochemistry staining showed that both NQO1 and FSCN1 are highly expressed in human lung squamous cell carcinoma tissues compared to those in normal lungs. Knockdown of MEG3 in normal BEAS-2B cells also led to increased migration and invasion, along with elevated levels of NQO1 and FSCN1. The negative regulation of MEG3 on FSCN1 was restored by NQO1 overexpression in both As-T and BEAS-2B cells. The results from immunoprecipitation assays confirmed the direct binding of NQO1 to FSCN1. Overexpression of NQO1 increased migration and invasion abilities in BEAS-2B cells, while knockdown of NQO1 by its shRNA reduced these two hallmarks of cancer. Interestingly, the reduced migration and invasion by NQO1 knockdown were restored by FSCN1. Collectively, the loss of MEG3 upregulated NQO1, which in turn stabilized FSCN1 protein through its direct binding, resulting in elevated migration and invasion in arsenic-transformed cells.

GPR Clutter Removal Based on Weighted Nuclear Norm Minimization for Nonparallel Cases.

Ground-penetrating radar (GPR) is an effective geophysical electromagnetic method for underground target detection. However, the target response is usually overwhelmed by strong clutter, thus damaging the detection performance. To account for the nonparallel case of the antennas and the ground surface, a novel GPR clutter-removal method based on weighted nuclear norm minimization (WNNM) is proposed, which decomposes the B-scan image into a low-rank clutter matrix and a sparse target matrix by using a non-convex weighted nuclear norm and assigning different weights to different singular values. The WNNM method's performance is evaluated using both numerical simulations and experiments with real GPR systems. Comparative analysis with the commonly used state-of-the-art clutter removal methods is also conducted in terms of the peak signal-to-noise ratio (PSNR) and the improvement factor (IF). The visualization and quantitative results demonstrate that the proposed method outperforms the others in the nonparallel case. Moreover, it is about five times faster than the RPCA, which is beneficial for practical applications.

IGFBP­rP1 affects the proliferation, apoptosis and macrophage polarization of endometrial cancer cells by regulating the PI3K/AKT pathway.

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a potential tumor suppressor gene in a variety of cancers including colorectal cancer and breast cancer. However, its role and the potential mechanism in endometrial carcinoma (EC) are still unclear. The purpose of this study was to explore the effect of IGFBP-rP1 on EC cell proliferation and apoptosis and its underlying mechanism. Western blot analysis and reverse transcription-quantitative PCR were used to assess protein and gene expression levels of IGFBP-rP1 in EC cells. Overexpression of IGFBP-rP1 and/or AKT serine/threonine kinase was used to analyze their effects on cell proliferation and apoptosis of the EC cells. Co-immunoprecipitation and glutathione S transferase pull-down assays were used to analyze the interaction between IGFBP-rP1 and AKT. The expression of IGFBP-rP1 in EC cells was downregulated. Overexpression of IGFBP-rP1 inhibited the proliferation and induced apoptosis of EC cells, which were abolished by the overexpression of AKT. In addition, IGFBP-rP1 directly interacted with AKT to inhibit PI3K/AKT signaling. Additionally, M0 macrophages were induced by EC cells to differentiate into M2 macrophages, which was reversed by IGFBP-rP1. Overexpression of AKT in EC cells abolished the inhibitory effect of IGFBP-rP1 on M2 polarization. IGFBP-rP1 as an oncogenic factor inhibits M2 polarization of TAMs through PI3K/AKT signaling pathway and may be a potentially valuable target for EC therapy.

Effects of escitalopram oxalate plus low-dose trazodone on psychological state and quality of life in patients with treatment-refractory depression.

OBJECTIVE: To analyze the effect of escitalopram oxalate (ESC) plus low-dose (LD) trazodone (TRA) on the psychological state and quality of life (QOL) of patients with treatment-refractory depression (TRD). METHODS: In this retrospective study, we selected 111 TRD patients treated in the People's Hospital of Oedos Dongsheng District between February 2019 and February 2021; 54 patients who were treated with ESC were assigned to the control group (the Con) and the remaining 57 patients treated with ESC + LD-TRA were placed into the research group (the Res). The scores of Hamilton Anxiety/Depression Scale (HAMA, HAMD), Generic Quality of Life Inventory (GQOLI), Pittsburgh Sleep Quality Index Scale (PSQI), and Treatment Emergent Signs and Symptoms (TESS), as well as the levels of brain-derived neurotrophic factor (BDNF), S-100B protein (S-100B), and neuron-specific enolase (NSE) were determined before and after intervention. Besides, the curative effect and incidence of adverse reactions were compared. Furthermore, the risk factors affecting treatment ineffectiveness in TRD patients were analyzed by the multivariate Logistic model. RESULTS: Evident reductions were observed in the Res in terms of HAMA, HAMD and PSQI scores and S-100B and NSE levels after intervention. Eight weeks after intervention, the TESS score was significantly reduced in the Res but not significantly different from the Con; while the scores of various dimensions of the GQOIL and the BDNF level were elevated markedly in the Res that were higher than those of the Con. Moreover, the Res presented with an evidently higher overall response rate than the Con. The two groups had no statistical significance in the overall incidence of adverse reactions (fever, irritability, insomnia, nausea, etc.). Based on the multivariate Logistic model analysis, HAMA, HAMD, PSQI, TESS, BDNF, S-100B, NSE, and treatment modality were not independent risk factors for treatment ineffectiveness in TRD patients. CONCLUSIONS: ESC + LD-TRA can significantly improve the psychological status, QOL, sleep quality and neurological function of patients with TRD while improving efficacy and ensuring patient safety.

Correction: Zhu et al. A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-like Properties and Invasion in Human Bladder Cancer. Cancers 2019, 11, 349.

In the original article [...].

Long Non-Coding RNA MEG3 in Metal Carcinogenesis.

Most transcripts from human genomes are non-coding RNAs (ncRNAs) that are not translated into proteins. ncRNAs are divided into long (lncRNAs) and small non-coding RNAs (sncRNAs). LncRNAs regulate their target genes both transcriptionally and post-transcriptionally through interactions with proteins, RNAs, and DNAs. Maternally expressed gene 3 (MEG3), a lncRNA, functions as a tumor suppressor. MEG3 regulates cell proliferation, cell cycle, apoptosis, hypoxia, autophagy, and many other processes involved in tumor development. MEG3 is downregulated in various cancer cell lines and primary human cancers. Heavy metals, such as hexavalent chromium (Cr(VI)), arsenic, nickel, and cadmium, are confirmed human carcinogens. The exposure of cells to these metals causes a variety of cancers. Among them, lung cancer is the one that can be induced by exposure to all of these metals. In vitro studies have demonstrated that the chronic exposure of normal human bronchial epithelial cells (BEAS-2B) to these metals can cause malignant cell transformation. Metal-transformed cells have the capability to cause an increase in cell proliferation, resistance to apoptosis, elevated migration and invasion, and properties of cancer stem-like cells. Studies have revealed that MEG is downregulated in Cr(VI)-transformed cells, nickel-transformed cells, and cadmium (Cd)-transformed cells. The forced expression of MEG3 reduces the migration and invasion of Cr(VI)-transformed cells through the downregulation of the neuronal precursor of developmentally downregulated protein 9 (NEDD9). MEG3 suppresses the malignant cell transformation of nickel-transformed cells. The overexpression of MEG3 decreases Bcl-xL, causing reduced apoptosis resistance in Cd-transformed cells. This paper reviews the current knowledge of lncRNA MEG3 in metal carcinogenesis.

Advances in Sorptive Removal of Hexavalent Chromium (Cr(VI)) in Aqueous Solutions Using Polymeric Materials.

Sorptive removal of hexavalent chromium (Cr(VI)) bears the advantages of simple operation and easy construction. Customized polymeric materials are the attracting adsorbents due to their selectivity, chemical and mechanical stabilities. The mostly investigated polymeric materials for removing Cr(VI) were reviewed in this work. Assembling of robust functional groups, reduction of self-aggregation, and enhancement of stability and mechanical strength, were the general strategies to improve the performance of polymeric adsorbents. The maximum adsorption capacities of these polymers toward Cr(VI) fitted by Langmuir isotherm model ranged from 3.2 to 1185 mg/g. Mechanisms of complexation, chelation, reduction, electrostatic attraction, anion exchange, and hydrogen bonding were involved in the Cr(VI) removal. Influence factors on Cr(VI) removal were itemized. Polymeric adsorbents performed much better in the strong acidic pH range (e.g., pH 2.0) and at higher initial Cr(VI) concentrations. The adsorption of Cr(VI) was an endothermic reaction, and higher reaction temperature favored more robust adsorption. Anions inhibited the removal of Cr(VI) through competitive adsorption, while that was barely affected by cations. Factors that affected the regeneration of these adsorbents were summarized. To realize the goal of industrial application and environmental protection, removal of the Cr(VI) accompanied by its detoxication through reduction is highly encouraged. Moreover, development of adsorbents with strong regeneration ability and low cost, which are robust for removing Cr(VI) at trace levels and a wider pH range, should also be an eternally immutable subject in the future. Work done will be helpful for developing more robust polymeric adsorbents and for promoting the treatment of Cr(VI)-containing wastewater.

DNMT3A/miR-129-2-5p/Rac1 Is an Effector Pathway for SNHG1 to Drive Stem-Cell-like and Invasive Behaviors of Advanced Bladder Cancer Cells.

The stem-cell-like behavior of cancer cells plays a central role in tumor heterogeneity and invasion and correlates closely with drug resistance and unfavorable clinical outcomes. However, the molecular underpinnings of cancer cell stemness remain incompletely defined. Here, we show that SNHG1, a long non-coding RNA that is over-expressed in ~95% of human muscle-invasive bladder cancers (MIBCs), induces stem-cell-like sphere formation and the invasion of cultured bladder cancer cells by upregulating Rho GTPase, Rac1. We further show that SNHG1 binds to DNA methylation transferase 3A protein (DNMT3A), and tethers DNMT3A to the promoter of miR-129-2, thus hyper-methylating and repressing miR-129-2-5p transcription. The reduced binding of miR-129-2 to the 3'-UTR of Rac1 mRNA leads to the stabilization of Rac1 mRNA and increased levels of Rac1 protein, which then stimulates MIBC cell sphere formation and invasion. Analysis of the Human Protein Atlas shows that a high expression of Rac1 is strongly associated with poor survival in patients with MIBC. Our data strongly suggest that the SNHG1/DNMT3A/miR-129-2-5p/Rac1 effector pathway drives stem-cell-like and invasive behaviors in MIBC, a deadly form of bladder cancer. Targeting this pathway, alone or in combination with platinum-based therapy, may reduce chemoresistance and improve longer-term outcomes in MIBC patients.

Loss of MEG3 and upregulation of miR-145 play an important role in the invasion and migration of Cr(VI)-transformed cells.

Chronic exposure of human bronchial epithelial BEAS-2B cells to hexavalent chromium (Cr(VI)) causes malignant cell transformation. These transformed cells exhibit increases in migration and invasion. Neuronal precursor of developmentally downregulated protein 9 (NEDD9) is upregulated in Cr(VI)-transformed cells compared to that of passage-matched normal BEAS-2B cells. Knockdown of NEDD9 by its shRNA reduced invasion and migration of Cr(VI)-transformed cells. Maternally expressed gene 3 (MEG3), a long noncoding RNA, was lost and microRNA 145 (miR-145) was upregulated in Cr(VI)-transformed cells. MEG3 was bound to miR-145 and this binding reduced its activity. Overexpression of MEG3 or inhibition of miR-145 decreased invasion and migration of Cr(VI)-transformed cells. Overexpression of MEG3 was able to decrease miR-145 level and NEDD9 protein level in Cr(VI)-transformed cells. Ectopic expression of MEG3 was also shown to reduce ß-catenin activation. Inhibition of miR-145 in Cr(VI)-transformed cells decreased Slug, an important transcription factor that regulates epithelial-to-mesenchymal transition (EMT). Inhibition of miR-145 was found to increase MEG3 in Cr(VI)-transformed cells. Further studies showed that mutation of MEG3 at the binding site for miR-145 did not change NEDD9 and failed to decrease invasion and migration. The present study demonstrated that loss of MEG3 and upregulation of miR-145 elevated NEDD9, resulting in activation of ß-catenin and further upregulation of EMT, leading to increased invasion and migration of Cr(VI)-transformed cells.

Identification of Ubiquitin-Related Gene-Pair Signatures for Predicting Tumor Microenvironment Infiltration and Drug Sensitivity of Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer worldwide, and new biomarkers are urgently required to guide more effective individualized therapy for patients. Ubiquitin-related genes (UbRGs) partially participate in the initiation and progression of lung cancer. In this study, we used ubiquitin-related gene pairs (UbRGPs) in tumor tissues to access the function of UbRGs in overall survival, immunocyte infiltration, and tumor mutation burden (TMB) of patients with LUAD from The Cancer Genome Atlas (TCGA) database. In addition, we constructed a prognostic signature based on six UbRGPs and evaluated its performance in an internal (TCGA testing set) and an external validation set (GSE13213). The prognostic signature revealed that risk scores were negatively correlated with the overall survival, immunocyte infiltration, and expression of immune checkpoint inhibitor-related genes and positively correlated with the TMB. Patients in the high-risk group showed higher sensitivity to partially targeted and chemotherapeutic drugs than those in the low-risk group. This study contributes to the understanding of the characteristics of UbRGPs in LUAD and provides guidance for effective immuno-, chemo-, and targeted therapy.

Emotion Expression in Modern Literary Appreciation: An Emotion-Based Analysis.

Background: Modern literary appreciation seems to be reading literary works phenomenally. In fact, appreciation is not a general reading, which has an important difference from general reading. It is the identification and appreciation of literary works and a complex spiritual activity for people to feel, understand, and imagine literary and artistic works. At the same time, literary appreciation is also a cognitive activity, an aesthetic activity, and a re-creation activity. Method: In this paper, the machine learning algorithm was creatively used to classify the emotions of figures in modern literary works, to analyze the emotions of the figures that the writer wanted to depict in modern literary works. Results: Experimental results verify the accuracy of the emotion classification method through experiments, which is helpful for us to better understand the emotion expression in modern literary works.

A Combined Sensing System for Intrusion Detection Using Anti-Jamming Random Code Signals.

In order to prevent illegal intrusion, theft, and destruction, important places require stable and reliable human intrusion detection technology to maintain security. In this paper, a combined sensing system using anti-jamming random code signals is proposed and demonstrated experimentally to detect the human intruder in the protected area. This sensing system combines the leaky coaxial cable (LCX) sensor and the single-transmitter-double-receivers (STDR) radar sensor. They transmit the orthogonal physical random code signals generated by Boolean chaos as the detection signals. The LCX sensor realizes the early intrusion alarm at the protected area boundary by comparing the correlation traces before and after intrusion. Meanwhile, the STDR radar sensor is used to track the intruder's moving path inside the protected area by correlation ranging and ellipse positioning, as well as recognizing intruder's activities by time-frequency analysis, feature extraction, and support vector machine. The experimental results demonstrate that this combined sensing system not only realizes the early alarm and path tracking for the intruder with the 13 cm positioning accuracy, but also recognizes the intruder's eight activities including squatting, picking up, jumping, waving, walking forward, running forward, walking backward, and running backward with 98.75% average accuracy. Benefiting from the natural randomness and auto-correlation of random code signal, the proposed sensing system is also proved to have a large anti-jamming tolerance of 27.6 dB, which can be used in the complex electromagnetic environment.

Analysis of Serum Levels of IFN-γ, IL-4, and TNF-α in Patients with Cervicitis Complicated by HPV Infection and Their Clinical Significance.

In order to investigate the expression levels of serum IFN-γ, IL-4, and tumor necrosis TNF-α in patients with cervicitis complicated with human papillomavirus (HPV) infection and clinical significance, a retrospective study was conducted on 90 patients with chronic cervicitis complicated by HP V infection who visited our hospital from June 2020 to June 2021, and they are included in the research group. According to the degree of HPV infection, the patients are divided into low-risk HPV type group (n = 65 cases) and high-risk HPV type group (n = 25 cases); 50 patients with cervicitis (without HPV infection) who received treatment in our hospital are selected as control group 1. Fifty healthy women who underwent physical examination are selected as the control group 2. The general data of the two groups of patients during hospitalization are collected, and HPV-DNA, IFN-γ, IL-4, and TNF-α are detected in all patients. For patients with cervicitis complicated by HPV infection, the IFN-indexes in the body are significantly decreased, IL-4 and TNF-αare significantly increased, and with the degree of HPV infection, IFN-γ, IL-4, and TNF-α have high diagnostic performance with HPV infection, and there is a significant correlation between the three, which can be used in cervicitis complicated with HPV infection. It is widely used in the early diagnosis and screening of infected patients.

Donor plasmacytoid dendritic cells limit graft-versus-host disease through vasoactive intestinal polypeptide expression.

Vasoactive intestinal polypeptide (VIP), an anti-inflammatory neuropeptide with pleiotropic cardiovascular effects, induces differentiation of hematopoietic stem cells into regulatory dendritic cells that limit graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We have previously shown that donor plasmacytoid dendritic cells (pDCs) in bone marrow (BM) donor grafts limit the pathogenesis of GVHD. In this current study we show that murine and human pDCs express VIP, and that VIP-expressing pDCs limit T-cell activation and expansion using both in vivo and in vitro model systems. Using T cells or pDCs from transgenic luciferase+ donors in murine bone marrow transplantation (BMT), we show similar homing patterns of donor pDCs and T cells to the major sites for alloactivation of donor T cells: spleen and gut. Cotransplanting VIP-knockout (KO) pDCs with hematopoietic stem cells and T cells in major histocompatibility complex mismatched allogeneic BMT led to lower survival, higher GVHD scores, and more colon crypt cell apoptosis than transplanting wild-type pDCs. BMT recipients of VIP-KO pDCs had more T helper 1 polarized T cells, and higher plasma levels of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α than recipients of wild-type pDCs. T cells from VIP-KO pDC recipients had increasing levels of bhlhe40 transcripts during the first 2 weeks posttransplant, and higher levels of CyclophilinA/Ppia transcripts at day 15 compared with T cells from recipients of wild-type pDCs. Collectively, these data indicate paracrine VIP synthesis by donor pDCs limits pathogenic T-cell inflammation, supporting a novel mechanism by which donor immune cells regulate T-cell activation and GVHD in allogeneic BMT.

Phenylarsonics in concentrated animal feeding operations: Fate, associated risk, and treatment approaches.

Phenylarsonics are present as additives in animal feed in some countries. As only a small fraction of these additives is metabolized in animals, they mostly end up in the environment. A comprehensive investigation of the fate of these additives is crucial for evaluating their risks. This review aims to provide a clear understanding of the transformation mechanism of phenylarsonics in vivo and in vitro and to evaluate their fate and associated risks. Degradation of phenylarsonics releases toxic As species (mainly as inorganic arsenic (iAs)). Trivalent phenylarsonics are the metabolites or biotic degradation intermediates of phenylarsonics. The cleavage of As groups from trivalent phenylarsonics catalyzed by C-As lyase or other unknown pathways generates arsenite (As(III)). As(III) can be further oxidized to arsenate (As(V)) and methylated to methyl-arsenic species. The half-lives associated with abiotic degradation of phenylarsonics ranged from a few minutes to tens of hours, while those associated with biotic degradation ranged from several days to hundreds of days. Abiotic degradation resulted in a higher yield of iAs than biotic degradation. The use of phenylarsonics led to elevated total As and iAs levels in animal products and environmental matrices, resulting in As exposure risk to humans. The oxidation of phenylarsonics to As(V) facilitated the sorptive removal of As, which provides a general approach for treating these compounds. This review provides solid evidence that the use of phenylarsonics has adverse effects on both human health and environmental safety, and therefore, supports their withdrawal from the global market.

Concentrations of bisphenols, benzophenone-type ultraviolet filters, triclosan, and triclocarban in the paired urine and blood samples from young adults: Partitioning between urine and blood.

Bisphenols (BPs), benzophenone-type UV filters (BP-type UV filters), triclosan (TCS), and triclocarban (TCC) are endocrine-disrupting chemicals (EDCs) and commonly used in consumer and personal care products. In the present study, seven BPs, eight BP-type UV filters, TCS, and TCC were quantified in 196 paired urine and blood samples collected from young adults in South China. Benzophenone-7 and benzophenone-9 were not detected in all samples, while other target compounds were widely detected in 39%-96% of the urine and 14%-96% of the blood samples, and the median concentrations ranged from <0.02 (specific gravity adjusted: < 0.02) to 2.33 (2.05) ng/mL and <0.01-2.66 ng/mL in the urine and blood samples, respectively. Females had higher levels of most target analytes, and gender-related differences (p < 0.05) were found in the blood levels of benzophenone-2 (females vs. males: 0.84 vs. <0.01 ng/mL), ΣBP (sum of BP-type UV filters; 1.61 vs. 0.98 ng/mL), TCS (3.89 vs. 1.69 ng/mL), and ΣTC (sum of TCS and TCC; 5.77 vs. 3.02 ng/mL). We calculated the portioning of the target compounds between blood and urine (B/U ratios). The B/U ratios of bisphenol F, benzophenone-2, benzophenone-6, 4-hydroxy benzophenone, TCS, and TCC were higher than 1, showing that these analytes have higher enrichment capacities in human blood. To the best of our knowledge, this is the first study to simultaneously analyze the concentrations of BPs, BP-type UV filters, TCS, and TCC in the paired urine and blood samples of young adults in South China.