The Essential Role of PGF2α/PTGFR in Molding Endometrial Breakdown and Vascular Dynamics, Regulated by HIF-1α in a Mouse Menstrual-like Model.

In women of childbearing age, extensive decidualization, shedding and remodeling of the endometrium during the menstrual cycle are fundamental for successful pregnancy. The role of prostaglandins (PGs) in menstruation has long been proposed in humans, and the rate-limiting enzyme cyclooxygenase was shown to play a key role in endometrial breakdown and shedding in a mouse menstrual-like model in our previous study. However, the specific types of PGs involved and their respective roles remain unclear. Therefore, our objective was to investigate the mechanism through which PGs regulate endometrial disintegration. In this study, the microscopy was observed by HE; the protein levels of prostaglandins E1 (PGE1), prostaglandins E2 (PGE2), prostaglandin F2α (PGF2α) and Prostaglandin I2 (PGI2) were detected by ELISA; the mRNA level of Pfgfr2, Vascular Endothelial Growth Factor(Vegf), Angiostatin and Hypoxia inducible factor-1α (Hif1α) were examined by real-time PCR; PTGFR Receptor (PTGFR), VEGF, Angiostatin and HIF-1α protein levels were investigated by western blotting; the locations of protein were observed by Immunohistochemistry; HIF-1α binding PTGFR promoter was detected by Chromatin Immunoprecipitation (ChIP) and real-time PCR. We found that the concentrations of PGE1, PGE2, and PGF2α all increased significantly during this process. Furthermore, Ptgfr mRNA increased soon after Progesterone (P4) withdrawal, and PTGFR protein levels increased significantly during abundant endometrial breakdown and shedding processes. PTGFR inhibitors AL8810 significantly suppressed endometrial breakdown and shedding, promoted Angiostatin expression, and reduced VEGF-A expressions and vascular permeability. And HIF-1α and PTGFR were mainly located in the luminal/gland epithelium, vascular endothelium, and pre-decidual zone. Interestingly, HIF-1α directly bound to Ptgfr promoter. Moreover, a HIF-1α inhibitor 2-methoxyestradiol (2ME) significantly reduced PTGFR expression and suppressed endometrial breakdown which was in accord with PTGFR inhibitor's effect. Similar changes occurred in human stromal cells relevant to menstruation in vitro. Our study provides evidence that PGF2α/PTGFR plays a vital role in endometrial breakdown via vascular changes that are regulated by HIF-1α during menstruation.

Electrical impedance tomography-guided positive end-expiratory pressure titration in ARDS: a systematic review and meta-analysis.

PURPOSE: Assessing efficacy of electrical impedance tomography (EIT) in optimizing positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) patients to enhance respiratory system mechanics and prevent ventilator-induced lung injury (VILI), compared to traditional methods. METHODS: We carried out a systematic review and meta-analysis, spanning literature from January 2012 to May 2023, sourced from Scopus, PubMed, MEDLINE (Ovid), Cochrane, and LILACS, evaluated EIT-guided PEEP strategies in ARDS versus conventional methods. Thirteen studies (3 randomized, 10 non-randomized) involving 623 ARDS patients were analyzed using random-effects models for primary outcomes (respiratory mechanics and mechanical power) and secondary outcomes (PaO2/FiO2 ratio, mortality, stays in intensive care unit (ICU), ventilator-free days). RESULTS: EIT-guided PEEP significantly improved lung compliance (n = 941 cases, mean difference (MD) = 4.33, 95% confidence interval (CI) [2.94, 5.71]), reduced mechanical power (n = 148, MD = - 1.99, 95% CI [- 3.51, - 0.47]), and lowered driving pressure (n = 903, MD = - 1.20, 95% CI [- 2.33, - 0.07]) compared to traditional methods. Sensitivity analysis showed consistent positive effect of EIT-guided PEEP on lung compliance in randomized clinical trials vs. non-randomized studies pooled (MD) = 2.43 (95% CI - 0.39 to 5.26), indicating a trend towards improvement. A reduction in mortality rate (259 patients, relative risk (RR) = 0.64, 95% CI [0.45, 0.91]) was associated with modest improvements in compliance and driving pressure in three studies. CONCLUSIONS: EIT facilitates real-time, individualized PEEP adjustments, improving respiratory system mechanics. Integration of EIT as a guiding tool in mechanical ventilation holds potential benefits in preventing ventilator-induced lung injury. Larger-scale studies are essential to validate and optimize EIT's clinical utility in ARDS management.

Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer.

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 µM) significantly enhanced the anti-tumor efficacy of osimertinib (1 µM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.

Neuroprotective effects of dendrobium endophytes metabolites in SH-SY5Y cells via the Nrf2/Keap1 pathway.

Recent studies have revealed that endophytes in plants can produce metabolites with activity that is comparable to or identical to the host. Dendrobine has attracted much attention in the field of neurodegenerative diseases by exhibiting anti-oxidative stress and neuroprotective effects. This study aimed to investigate the protective effects and mechanisms of metabolites of dendrobium endophytes Pseudomonas protegens CM-YJ44 and Priestia megaterium D-HT207 against H2O2-induced oxidative stress injury in SH-SY5Y cells. Results showed that there were 50 neuroprotective compounds in CM-YJ44 and 72 neuroprotective compounds in D-HT207. Those both increased significantly cell viability, decreased contents of ROS in H2O2-induced SH-SY5Y cells. It was confirmed that metabolites of CM-YJ44 and D-HT207 inhibited the H2O2-induced oxidative stress injury in SH-SY5Y cells, which mechanism is related to inhibition of ROS production, alteration of MMP, and inhibition of apoptosis and inflammatory factors expression via the Nrf2/Keap1 pathway.

Structural Characterization and Antidepressant-like Effects of Polygonum sibiricum Polysaccharides on Regulating Microglial Polarization in Chronic Unpredictable Mild Stress-Induced Zebrafish.

Polysaccharides are one of the main active ingredients of Polygonum sibiricum (PS), which is a food and medicine homolog used throughout Chinese history. The antidepressant-like effects of PSP and its underlying mechanisms remain elusive, especially the regulation of microglial polarization. The current study determined the chemical composition and structural characteristics of PSP. Then, the chronic unpredictable mild stress (CUMS) procedure was carried out on the zebrafish for 5 weeks, and PSP was immersed for 9 days (1 h/d). The body weight of zebrafish was monitored, and behavioral tests, including the novel tank test and light and dark tank test, were performed to evaluate the antidepressant-like effects of PSP. Then, the function of the hypothalamic-pituitary-interrenal (HPI) axis, the levels of peripheral inflammation, neuronal and blood-brain barrier damage in the mesencephalon and telencephalon, and the mRNA expression of M1/M2 phenotype genes in the brain were examined. PSP samples had the typical structural characteristics of polysaccharides, consisting of glucose, mannose, and galactose, with an average Mw of 20.48 kDa, which presented porous and agglomerated morphologies. Compared with untreated zebrafish, the depression-like behaviors of CUMS-induced zebrafish were significantly attenuated. PSP significantly decreased the levels of cortisol and pro-inflammatory cytokines and increased the levels of the anti-inflammatory cytokines in the body of CUMS-induced depressive zebrafish. Furthermore, PSP remarkably reversed the neuronal and blood-brain barrier damage in the mesencephalon and telencephalon and the mRNA expression of M1/M2 phenotype genes in the brain. These findings indicated that the antidepressant-like effects of PSP were related to altering the HPI axis hyperactivation, suppressing peripheral inflammation, inhibiting neuroinflammation induced by microglia hyperactivation, and modulating microglial M1/M2 polarization. The current study provides the foundations for future examinations of PSP in the functional foods of emotional regulation.

Investigating the Antidepressant Mechanisms of Polygonum sibiricum Polysaccharides via Microglial Polarization.

Polygonum sibiricum, with its medicinal and edibility dual properties, has been widely recognized and utilized throughout Chinese history. As a kind of its effective component, Polygonum sibiricum polysaccharides (PSP) have been reported to be a promising novel antidepressant agent. Meanwhile, the precise mechanisms underlying its action remain elusive. The polarization state transition of microglia is intricately linked to neuroinflammation, indicating its crucial involvement in the pathophysiology of depression. Researchers are vigorously pursuing the exploration of this potential treatment strategy, aiming to comprehend its underlying mechanisms. Hence, the current study was designed to investigate the antidepressant mechanisms of PSP via Microglial M1/M2 Polarization, based on the lipopolysaccharide (LPS)-induced BV2 cell activation model. The results indicate that PSP significantly inhibited NO and LDH release and reduced ROS levels in LPS-induced BV2 cells. PSP could significantly reduce the protein expression level of Iba-1, decreased the mRNA levels of TNF-α, IL-1ß, and IL-6, and increased the mRNA level of IL-10. PSP also significantly reduced the protein expression level of CD16/32 and increased that of CD206, reduced the mRNA level and fluorescence intensity of iNOS, and increased those of Arg-1. However, PSP pretreatment reversed the alterations of the BDNF/TrkB/CREB and Notch/Hes1 pathways in LPS-induced BV2 cells. These results suggested that PSP exerted the anti-inflammatory effects by inhibiting M1 phenotype polarization and promoting microglia polarization toward the M2 phenotype, and its regulation of microglia M1/M2 polarization may be associated with modulating the BDNF/TrkB/CREB and Notch/Hes1 pathways.

Age of hypertension onset and cognitive function in the elderly: an observational study from the NHANES 2011-2014.

PURPOSE: This study aims to evaluate the association between age of hypertension onset and cognitive function in a representative sample of US older adults. METHODS: We assessed 2334 elderly adults (including 1655 hypertensive patients) who participated in the National Health and Nutrition Examination Survey 2011-2014. We used the age when the participants were first informed by the doctor that they had hypertension or were first clinically diagnosed with hypertension as the age of onset of hypertension. The Digit Symbol Substitution test (DSST), the Animal Fluency test, the Consortium to Establish a Registry for Alzheimer's disease (CERAD), and a composite-z score calculated by summing z-scores from these three individual tests, were used to assess cognitive function. RESULTS: Participants with hypertension onset age < 35 years (early onset hypertension) had the worst performance in almost all cognitive tests, followed by those with onset age ≥ 65 years. Compared with those without hypertension, early onset hypertension was associated with - 4.15 (95% CI - 6.63, - 1.68), - 1.10 (95% CI - 2.08, - 0.12), - 0.75 (95% CI - 1.91, 0.42), and - 0.56 (95% CI - 0.94, - 0.19) scores for DSST, animal fluency test, CERAD, and composite z-score. Participants with early onset hypertension (onset age < 35 years) had higher odds for cognitive decline defined by DSST (OR: 3.28, 95% CI 1.94, 5.54) and composite z-score (OR: 1.77, 95% CI 1.07, 2.92). CONCLUSIONS: Early onset hypertension was associated with the worst performance in cognitive function and an increased odds of cognitive decline in the elderly.

A rare complication: hydrophilic coating of puncture guide wire found floating in the pulmonary artery.

A 62-year-old woman with atrial fibrillation was admitted to Sichuan Provincial People's Hospital, and radiofrequency ablation therapy was planned.

Comparison of the Metabolomics of Different Dendrobium Species by UPLC-QTOF-MS.

Dendrobium Sw. (family Orchidaceae) is a renowned edible and medicinal plant in China. Although widely cultivated and used, less research has been conducted on differential Dendrobium species. In this study, stems from seven distinct Dendrobium species were subjected to UPLC-QTOF-MS/MS analysis. A total of 242 metabolites were annotated, and multivariate statistical analysis was employed to explore the variance in the extracted metabolites across the various groups. The analysis demonstrated that D. nobile displays conspicuous differences from other species of Dendrobium. Specifically, D. nobile stands out from the remaining six taxa of Dendrobium based on 170 distinct metabolites, mainly terpene and flavonoid components, associated with cysteine and methionine metabolism, flavonoid biosynthesis, and galactose metabolism. It is believed that the variations between D. nobile and other Dendrobium species are mainly attributed to three metabolite synthesis pathways. By comparing the chemical composition of seven species of Dendrobium, this study identified the qualitative components of each species. D. nobile was found to differ significantly from other species, with higher levels of terpenoids, flavonoids, and other compounds that are for the cardiovascular field. By comparing the chemical composition of seven species of Dendrobium, these qualitative components have relevance for establishing quality standards for Dendrobium.

Plant-Wide Target Metabolomics Provides a Novel Interpretation of the Changes in Chemical Components during Dendrobium officinale Traditional Processing.

The traditional processing of Dendrobium officinale (DO) is performed in five necessary processing steps: processing fresh strips, drying at 85 °C, curling, molding, and drying at 35 °C (Fengdou). The antioxidant activity of DO is increased after it is processed into Fengdou. To comprehensively analyze the changes in the functional components, a plant-wide target metabolomics approach was employed. In total, 739 differential chemical components were identified in five processing treatments, mainly highlighting differences in the levels of phenolic acids, flavonoids, lipids, and amino acids and their derivatives, and the glycosylation of aglycone resulted in the upregulation of flavonoid glycoside levels. Temperature is a key factor in DO processing during production. In addition, the enrichment of specific differential chemical components was found mainly in five different metabolic pathways: glucosinolate biosynthesis, linoleic acid metabolism, flavonoid biosynthesis, phenylpropanoid biosynthesis, and ubiquinone and other terpene quinone biosynthesis. A correlation analysis clarified that total phenols and flavonoids show a significant positive correlation with antioxidant capacity. This study provides new insights into the influence of the processing processes on DO quality, which may provide guidance for the high-quality production of DO.

Research Progress on the Relationship between Vitamins and Diabetes: Systematic Review.

Diabetes is a serious chronic metabolic disease that causes complications over time, bringing serious public health challenges that affect different countries across the world. The current clinical drugs for diabetes may lead to adverse effects such as hypoglycemia and liver and abdominal distension and pain, which prompt people to explore new treatments for diabetes without side effects. The research objective of this review article is to systematically review studies on vitamins and diabetes and to explain their possible mechanism of action, as well as to assess the role of vitamins as drugs for the prevention and treatment of diabetes. To achieve our objective, we searched scientific databases in PubMed Central, Medline databases and Web of Science for articles, using "vitamin" and "diabetes" as key words. The results of numerous scientific investigations revealed that vitamin levels were decreased in humans and animals with diabetes, and vitamins show promise for the prevention and/or control of diabetes through anti-inflammation, antioxidation and the regulation of lipid metabolism. However, a few studies showed that vitamins had no positive effect on the development of diabetes. Currently, studies on vitamins in the treatment of diabetes are still very limited, and there are no clinical data to clarify the dose-effect relationship between vitamins and diabetes; therefore, vitamins are not recommended as routine drugs for the treatment of diabetes. However, we still emphasize the great potential of vitamins in the prevention and treatment of diabetes, and higher quality studies are needed in the future to reveal the role of vitamins in the development of diabetes.

Inhibition of EphA2 protects against atherosclerosis by synergizing with statins to mitigate macrophage inflammation.

Statins are highly prevalent in patients with coronary artery disease. Statins exert their anti-inflammatory effects on the vascular wall and circulating levels of pro-inflammatory cytokines. However, increasing attention revealed the exacerbation of macrophage inflammation induced by statins, and a clear mechanistic explanation of whether the detrimental effects of statins on macrophage inflammatory phenotypes outweigh the beneficial effects is has not yet been established. Here, RNA-sequencing and RT-qPCR analyses demonstrated that statins significantly upregulated EphA2, Nlrp3, IL-1ß and TNF-α expression in macrophages. Mechanistically, we found that atorvastatin reduced KLF4 binding to the EphA2 promoter using KLF4-chromatin immunoprecipitation, suppressed HDAC11-mediated deacetylation and subsequently led to enhanced EphA2 transcription. The 4D-label-free proteomics analysis further confirmed the upregulated EphA2 and inflammatory signals. Furthermore, the proinflammatory effect of atorvastatin was neutralized by an addition of recombinant Fc-ephrinA1, a selective Eph receptor tyrosine kinase inhibitor (ALW-II-41-27) or EphA2-silencing adenovirus (siEphA2). In vivo, EphA2 was identified a proatherogenic factor and apoE-/- mice placed on a high-fat diet following gastric gavage with atorvastatin exhibited a consistent elevation in EphA2 expression. We further observed that the transfection with siEphA2 in atorvastatin-treated mice significantly attenuated atherosclerotic plaque formation and abrogated statin-orchestrated macrophages proinflammatory genes expression as compared to that in atorvastatin alone. Increased plaque stability index was also observed following the addition of siEphA2, as evidenced by increased collagen and smooth muscle content and diminished lipid accumulation and macrophage infiltration. The data suggest that blockage of EphA2 provides an additional therapeutic benefit for further improving the anti-atherogenic effects of statins.

Estimation of transpulmonary driving pressure during synchronized mechanical ventilation using a single lower assist maneuver (LAM) in rabbits: a comparison to measurements made with an esophageal balloon.

BACKGROUND: Mechanical ventilation is applied to unload the respiratory muscles, but knowledge about transpulmonary driving pressure (ΔPL) is important to minimize lung injury. We propose a method to estimate ΔPL during neurally synchronized assisted ventilation, with a simple intervention of lowering the assist for one breath ("lower assist maneuver", LAM). METHODS: In 24 rabbits breathing spontaneously with imposed loads, titrations of increasing assist were performed, with two neurally synchronized modes: neurally adjusted ventilatory assist (NAVA) and neurally triggered pressure support (NPS). Two single LAM breaths (not sequentially, but independently) were performed at each level of assist by acutely setting the assist to zero cm H2O (NPS) or NAVA level 0 cm H2O/uV (NAVA) for one breath. NPS and NAVA titrations were followed by titrations in controlled-modes (volume control, VC and pressure control, PC), under neuro-muscular blockade. Breaths from the NAVA/NPS titrations were matched (for flow and volume) to VC or PC. Throughout all runs, we measured diaphragm electrical activity (Edi) and esophageal pressure (PES). We measured ΔPL during the spontaneous modes (PL_PES) and controlled mechanical ventilation (CMV) modes (PL_CMV) with the esophageal balloon. From the LAMs, we derived an estimation of ΔPL ("PL_LAM") using a correction factor (ratio of volume during the LAM and volume during assist) and compared it to measured ΔPL during passive (VC or PC) and spontaneous breathing (NAVA or NPS). A requirement for the LAM was similar Edi to the assisted breath. RESULTS: All animals successfully underwent titrations and LAMs for NPS/NAVA. One thousand seven-hundred ninety-two (1792) breaths were matched to passive ventilation titrations (matched Vt, r = 0.99). PL_LAM demonstrated strong correlation with PL_CMV (r = 0.83), and PL_PES (r = 0.77). Bland-Altman analysis revealed little difference between the predicted PL_LAM and measured PL_CMV (Bias = 0.49 cm H2O and 1.96SD = 3.09 cm H2O). For PL_PES, the bias was 2.2 cm H2O and 1.96SD was 3.4 cm H2O. Analysis of Edi and PES at peak Edi showed progressively increasing uncoupling with increasing assist. CONCLUSION: During synchronized mechanical ventilation, a LAM breath allows for estimations of transpulmonary driving pressure, without measuring PES, and follows a mathematical transfer function to describe respiratory muscle unloading during synchronized assist.

Inhalation of ACE2 as a therapeutic target on sex-bias differences in SARS-CoV-2 infection and variant of concern.

Despite similar infection rates, COVID-19 has resulted in more deaths in men than women. To understand the underlying mechanisms behind this sex-biased difference in disease severity, we infected K18-human angiotensin converting enzyme 2 (ACE2) mice of both sexes with SARS-CoV-2. Our study revealed a unique protein expression profile in the lung microenvironment of female mice. As a result, they were less vulnerable to severe infection, with higher ACE2 expression and a higher estrogen receptor α (ERα)/androgen receptor (AR) ratio that led to increased antiviral factor levels. In male mice, inhaling recombinant ACE2 neutralized the virus and maintained the ERα/AR ratio, thereby protecting the lungs. Our findings suggest that inhaling recombinant ACE2 could serve as a decoy receptor against SARS-CoV-2 and protect male mice by offsetting ERα-associated protective mechanisms. Additionally, our study supports the potential effectiveness of recombinant ACE2 therapy in human lung organoids infected with the Delta variant.

CXCR4, regulated by HIF1A, promotes endometrial breakdown via CD45+ leukocyte recruitment in a mouse model of menstruation.

Menstruation is a specific physiological phenomenon in female humans that is regulated by complex molecular mechanisms. However, the molecular network involved in menstruation remains incompletely understood. Previous studies have suggested that C-X-C chemokine receptor 4 (CXCR4) is involved; however, how CXCR4 participates in endometrial breakdown remains unclear, as do its regulatory mechanisms. This study aimed to clarify the role of CXCR4 in endometrial breakdown and its regulation by hypoxia-inducible factor-1 alpha (HIF1A). We first confirmed that CXCR4 and HIF1A protein levels were significantly increased during the menstrual phase compared with the late secretory phase using immunohistochemistry. In our mouse model of menstruation, real-time PCR, western blotting, and immunohistochemistry showed that CXCR4 mRNA and protein expression levels gradually increased from 0 to 24 h after progesterone withdrawal during endometrial breakdown. HIF1A mRNA and HIF1A nuclear protein levels significantly increased and peaked at 12 h after progesterone withdrawal. Endometrial breakdown was significantly suppressed by the CXCR4 inhibitor AMD3100 and the HIF1A inhibitor 2-methoxyestradiol in our mouse model, and HIF1A inhibition also suppressed CXCR4 mRNA and protein expression. In vitro studies using human decidual stromal cells showed that CXCR4 and HIF1A mRNA expression levels were increased by progesterone withdrawal and that HIF1A knockdown significantly suppressed the elevation in CXCR4 mRNA expression. CD45+ leukocyte recruitment during endometrial breakdown was suppressed by both AMD3100 and 2-methoxyestradiol in our mouse model. Taken together, our preliminary findings suggest that endometrial CXCR4 expression is regulated by HIF1A during menstruation and may promote endometrial breakdown, potentially via leukocyte recruitment.

DPHL v.2: An updated and comprehensive DIA pan-human assay library for quantifying more than 14,000 proteins.

A comprehensive pan-human spectral library is critical for biomarker discovery using mass spectrometry (MS)-based proteomics. DPHL v.1, a previous pan-human library built from 1,096 data-dependent acquisition (DDA) MS data of 16 human tissue types, allows quantifying of 10,943 proteins. Here, we generated DPHL v.2 from 1,608 DDA-MS data. The data included 586 DDA-MS data acquired from 18 tissue types, while 1,022 files were derived from DPHL v.1. DPHL v.2 thus comprises data from 24 sample types, including several cancer types (lung, breast, kidney, and prostate cancer, among others). We generated four variants of DPHL v.2 to include semi-tryptic peptides and protein isoforms. DPHL v.2 was then applied to two colorectal cancer cohorts. The numbers of identified and significantly dysregulated proteins increased by at least 21.7% and 14.2%, respectively, compared with DPHL v.1. Our findings show that the increased human proteome coverage of DPHL v.2 provides larger pools of potential protein biomarkers.

Contamination characteristics and potential health risk of brominated flame retardants in paddy soils and rice plants around a typical e-waste recycling site in south China.

Brominated flame retardants (BFRs) are widely used in various productions. As typical BFRs, polybrominated diphenyl ethers (PBDEs) are prohibited because of their toxicity and persistence. Some of the alternatives to PBDEs, new brominated flame retardants (NBFRs), have also been found in the environment and some have assigned hazardous properties and were categorized as persistent. In this study, a typical e-waste dismantling area was chosen as the study area, and the soil and rice samples were collected from the paddy fields around the circular economy park in Guiyu, China. The contaminations of PBDEs and NBFRs in soils and rice plants were detected, and the health risks associated with consumption and exposure to the environment were calculated as well. The concentrations of ∑PBDEs and ∑NBFRs in soil ranged from 283 to 928 µg/kg and 54.7-437 µg/kg, respectively. In rice plants, the majority of BFRs were concentrated in the following order: root > leaf > stem > grain. Additionally, only the PBT exhibited a stronger bioaccumulation ability in rice with the bioconcentration factors more than 1.00. The results of the health quotient calculation shown that BDE-47 might have an impact on people's health that only the HQ of BDE-47 in the soil was higher than 1.00, while there had no significant health risk in grain of BFRs. We believe that our work could assist researchers in investigating and revealing the human health effects of BFRs in soil and rice.

Biochar supported nanoscale zero-valent iron for the kinetics removal and mechanism of decabromodiphenyl ethane in the sediment.

The extensive applications of decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, have induced its accumulation in sediment, which may have a great negative impact on the ecological environment. In this work, the biochar/nano-zero-valent iron materials (BC/nZVI) were synthesized to remove DBDPE in the sediment. Batch experiments were carried out to investigate the influencing factors of the removal efficiency, and kinetic model simulation and thermodynamic parameter calculation were performed. The degradation products and mechanisms were probed. The results indicated that the addition of 0.10 g·g-1 BC/nZVI to the sediment with an initial concentration of 10 mg·kg-1 DBDPE could remove 43.73% of DBDPE during 24 h. The water content of the sediment was a critical factor in the removal of DBDPE, which was optimal at 1:2 of sediment to water. The removal efficiency and reaction rate were enhanced by increasing dosage, water content, and reaction temperature or decreasing initial concentration of DBDPE based on the fitting results of the quasi-first-order kinetic model. Additionally, the calculated thermodynamic parameters suggested that the removal process was a spontaneously and reversibly endothermic reaction. The degradation products were further determined by GC-MS, and the mechanisms were presumed that DBDPE was debrominated to produce octabromodiphenyl ethane (octa-BDPE). This study provides a potential remediation method for highly DBDPE-contaminated sediment by using BC/nZVI.

Indoxyl sulfate in atherosclerosis.

Atherosclerosis (AS), a chronic vascular inflammatory disease, has become a main focus of attention worldwide for its chronic progressing disease course and serious complications in the later period. Nevertheless, explanations for the exact molecular mechanisms of AS initiation and development remain to be an unsolved problem. The classic pathogenesis theories, such as lipid percolation and deposition, endothelium injury, inflammation and immune damage, provide the foundation for discovering the new key molecules or signaling mechanisms. Recently, indoxyl sulfate (IS), one of non-free uremia toxins, has been noticeable for its multiple atherogenic effects. IS exists at high concentration in plasma for its great albumin binding rate. Patients with uremia have markedly elevated serum levels of IS due both to the deterioration of renal function and to the high binding affinity of IS to albumin. Nowadays, elevated incidence of circulatory disease among patients with renal dysfunction indicates correlation of uremic toxins with cardiovascular damage. In this review, the atherogenic effects of IS and the underlying mechanisms are summarized with emphasis on several key pathological events associated with AS developments, such as vascular endothelium dysfunction, arterial medial lesions, vascular oxidative stress, excessive inflammatory responses, calcification, thrombosis and foam cell formation. Although recent studies have proved the great correlation between IS and AS, deciphering cellular and pathophysiological signaling by confirming key factors involved in IS-mediated atherosclerosis development may enable identification of novel therapeutic targets.