Association between elevated preoperative red cell distribution width and mortality after brain tumor craniotomy.

BACKGROUND: Red cell distribution width (RDW) has been recognized as a potential inflammatory biomarker, with elevated levels associated with adverse outcomes in various diseases. However, its role in predicting outcomes after brain tumor craniotomy remains unclear. We aimed to assess whether preoperative RDW influences mortality and postoperative complications in patients undergoing brain tumor craniotomy. METHODS: This retrospective cohort study analyzed serum RDW levels in patients undergoing brain tumor craniotomy at West China Hospital. RDW was evaluated in two forms: RDW-CV and RDW-SD, and was categorized into four quartiles for analysis by using logistic regression and multivariate analysis to adjust for confounding. RESULTS: The study encompassed 10,978 patients undergoing brain tumor craniotomy. our analysis revealed no significant difference in 30-day mortality across various RDW-CV levels. However, we observed a dose-response relationship with preoperative RDW-CV levels in assessing long-term mortality risks. Specifically, patients with RDW-CV levels of 12.6-13.2% (HR 1.04, 95% CI 1.01-1.18), 13.2-13.9% (HR 1.12, 95% CI 1.04-1.26), and > 13.9% (HR 1.34, 95% CI 1.18-1.51) exhibited a significantly higher hazard of long-term mortality compared to those with RDW-CV < 12.6%. When preoperative RDW-CV was analyzed as a continuous variable, for each 10% increase in RDW-CV, the adjusted OR of long-term mortality was 1.09 (95% CI 1.05-1.13). we also observed significant associations between preoperative higher RDW-CV levels and certain postoperative complications including acute kidney injury (OR 1.46, 95% CI: 1.10-1.94), pneumonia infection (OR 1.19 95% CI: 1.05-1.36), myocardial infarction (OR 1.32, 95% CI: 1.05-1.66), readmission (OR 1.15, 95% CI: 1.01-1.30), and a prolonged length of hospital stay (OR 1.11, 95% CI: 1.02-1.21). For RDW-SD levels, there was no significant correlation for short-term mortality, long-term mortality, and postoperative complications. CONCLUSIONS: Our study showed elevated preoperative RDW-CV is significantly associated with increased long-term mortality and multiple postoperative complications, but no such association is observed with RDW-SD. These findings show the prognostic importance of RDW-CV, reinforcing its potential as a valuable tool for risk stratification in the preoperative evaluation of brain tumor craniotomy patients.

Association between postoperative changes in natremia and outcomes in patients undergoing elective craniotomy.

Postoperative dysnatremias, characterized by imbalances in serum sodium levels, have been linked to increased resource utilization and mortality in surgical and intensive care patients. The management of dysnatremias may involve medical interventions based on changes in sodium levels. In this study, we aimed to investigate the impact of postoperative changes in natremia on outcomes specifically in patients undergoing craniotomy.We conducted a retrospective analysis of patient records from the Department of Neurosurgery at West China Hospital, Sichuan University, covering the period from January 2011 to March 2021. We compared the highest and lowest sodium values in the first 14 postoperative days with the baseline values to define four categories for analysis: no change < 5 mmol/L; decrease > 5 mmol/L; increase > 5 mmol/L; both increase and decrease > 5 mmol/L. The primary outcome measure was 30-day mortality.A total of 12,713 patients were included in the study, and the overall postoperative mortality rate at 30 days was 2.1% (264 patients). The increase in sodium levels carried a particularly high risk, with a tenfold increase (OR 10.21; 95% CI 7.25-14.39) compared to patients with minimal or no change. Decreases in sodium levels were associated with an increase in mortality (OR 1.60; 95% CI 1.11-2.23).Moreover, the study revealed that postoperative sodium decrease was correlated with various complications, such as deep venous thrombosis, pneumonia, intracranial infection, urinary infection, seizures, myocardial infarction, and prolonged hospital length of stay. On the other hand, postoperative sodium increases were associated with acute kidney injury, deep venous thrombosis, pneumonia, intracranial infection, urinary infection, surgical site infection, seizures, myocardial infarction, and prolonged hospital length of stay.Changes in postoperative sodium levels were associated with increased complications, prolonged length of hospital stay, and 30-day mortality. Moreover, the severity of sodium change values correlated with higher mortality rates.

Glimepiride, a novel soluble epoxide hydrolase inhibitor, protects against heart failure via increasing epoxyeicosatrienoic acids.

BACKGROUND: Epoxyeicosatrienoic acids (EETs), which exert multiple endogenous protective effects, are hydrolyzed into less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). However, commercial drugs related to EETs or sEH are not yet in clinical use. METHODS: Firstly, the plasma concentration of EETs and DHETs of 316 patients with heart failure (HF) were detected and quantitated by liquid chromatography-tandem mass spectrometry. Then, transverse aortic constriction (TAC)-induced HF was introduced in cardiomyocyte-specific Ephx2-/- mice. Moreover, Western blot, real-time PCR, luciferase reporter, ChIP assays were employed to explore the underlying mechanism. Finally, multiple sEH inhibitors were designed, synthesized, and validated in vitro and in vivo. RESULTS: The ratios of DHETs/EETs were increased in the plasma from patients with HF. Meanwhile, the expression of sEH was upregulated in the heart of patients and mice with HF, especially in cardiomyocytes. Cardiomyocyte-specific Ephx2-/- mice ameliorated cardiac dysfunction induced by TAC. Consistently, Ephx2 knockdown protected Angiotensin II (AngII)-treated cardiomyocytes via increasing EETs in vitro. Mechanistically, AngII could enhance the expression of transcript factor Krüppel-like factor 15 (KLF15), which in turn upregulated sEH. Importantly, glimepiride was identified as a novel sEH inhibitor, which benefited from the elevated EETs during HF. CONCLUSIONS: Glimepiride attenuates HF in mice in part by increasing EETs. CLINICAL TRIAL IDENTIFIER: NCT03461107 (https://clinicaltrials.gov).

Increased circulating phenylacetylglutamine concentration elevates the predictive value of cardiovascular event risk in heart failure patients.

BACKGROUND: Phenylacetylglutamine (PAGln)-a newly discovered microbial metabolite produced by phenylalanine metabolism-is reportedly associated with cardiovascular events via adrenergic receptors. Nonetheless, its association with cardiovascular outcomes in heart failure (HF) patients remains unknown. OBJECTIVES: This study aimed to prospectively investigate the prognostic value of PAGln for HF. METHODS: Plasma PAGln levels were quantified by liquid chromatography-tandem mass spectrometry. We first assessed the association between plasma PAGln levels and the incidence of adverse cardiovascular events in 3152 HF patients (including HF with preserved and reduced ejection fraction) over a median follow-up period of 2 years. The primary endpoint was the composite of cardiovascular death or heart transplantation. We then assessed the prognostic role of PAGln in addition to the classic biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP). The correlation between PAGln levels and ß-blocker use was also investigated. RESULTS: In total, 520 cardiovascular deaths or heart transplantations occurred in the HF cohort. Elevated PAGln levels were independently associated with a higher risk of the primary endpoint in a dose-response manner, regardless of HF subtype. Concurrent assessment of PAGln and NT-proBNP levels enhanced risk stratification among HF patients. PAGln further showed prognostic value at low NT-proBNP levels. Additionally, the interaction effects between PAGln and ß-blocker use were not significant. CONCLUSIONS: Plasma PAGln levels are an independent predictor of an increased risk of adverse cardiovascular events in HF. Our work could provide joint and complementary prognostic value to NT-proBNP levels in HF patients.

Macrophage MST1/2 Disruption Impairs Post-Infarction Cardiac Repair via LTB4.

[Figure: see text].

Lower versus higher oxygen targets for out-of-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen is commonly administered to patients after out-of-hospital cardiac arrest. However, the findings from studies on oxygen targeting for out-of-hospital cardiac arrest are inconclusive. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of lower oxygen target compared with higher oxygen target on patients after out-of-hospital cardiac arrest. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, from inception to February 6, 2023, for randomized controlled trials comparing lower and higher oxygen target in adults (aged ≥ 18 years) after out-of-hospital cardiac arrest. We screened studies and extracted data independently. The primary outcome was mortality at 90 days after cardiac arrest. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study was registered with PROSPERO, number CRD42023409368. RESULTS: The analysis included 7 randomized controlled trials with a total of 1451 participants. Compared with lower oxygen target, the use of a higher oxygen target was not associated with a higher mortality rate (relative risk 0.97, 95% confidence intervals 0.82 to 1.14; I2 = 25%). Findings were robust to trial sequential, subgroup, and sensitivity analysis. CONCLUSION: Lower oxygen target did not reduce the mortality compared with higher oxygen target in patients after out-of-hospital cardiac arrest.

White Blood Cell Count Predicts Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between white blood cell (WBC) counts and mortality in patients with intracerebral hemorrhage (ICH) has not been established. The aim of this study is to determine whether higher WBC is associated with mortality at 90 days. METHODS: A retrospective observational study was conducted at two medical hospitals in China. Baseline WBC count on admission served as the primary predictor variable. Longitudinal WBC counts within the first week after admission were collected to assess the effects of WBC trajectory and the median and maximum WBC counts on outcomes following ICH. Associations of WBC count with outcomes were evaluated in multivariable regression analyses. RESULTS: We identified 3613 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, patients with increased WBC count had a significantly higher risk of 90-day mortality (p < 0.001 for trend). In the receiver operating characteristic analyses, the capacity for all-cause mortality prediction by WBC count on admission (area under the ROC curve (AUC) = 0.65) was superior to other important inflammatory markers, including neutrophil (AUC = 0.64) , lymphocyte (AUC = 0.57), albumin (AUC = 0.57), and platelet count (AUC = 0.53), p < 0.001 for WBC vs. neutrophil, and the median WBC count (AUC = 0.66) within the first week after admission was a better marker than admission WBC count (p = 0.02). CONCLUSIONS: In patients with ICH, WBC count on admission was associated with all-cause mortality at 90 days. Additionally, the median and maximum WBC counts within the first week after admission showed better predictive ability for the 90-day mortality compared with the WBC count on admission.

Association Between Red Blood Cell Distribution width and Long-Term Mortality in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between the red cell distribution width (RDW) and long-term mortality in patients with intracerebral hemorrhage (ICH) has not been clearly established. METHODS: We conducted a retrospective cohort study of patients with ICH admitted to two tertiary hospitals. The primary outcome was long-term mortality, and the effect of elevated RDW (RDW coefficient of variation [RDW-CV]; RDW standard deviation [RDW-SD]) on outcomes was assessed by using logistic regression analysis. Serum RDW levels was divided into four levels by quartiles (the lowest quartile [Q1]; the highest quartile [Q4]). RESULTS: This study included 4223 patients with ICH. After adjustment for potential confounders, admission RDW-CV (Quartile 4 [Q4] vs. Quartile 1 [Q1], adjusted hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.34-1.92) and median RDW-CV within the first month after admission (Q4 vs. Q1, adjusted HR 1.69, 95% CI 1.40-2.04) were both associated with 1-year mortality following ICH. Parallel results were found for RDW-SD. In the receiver operating characteristic analyses, both RDW-CV and RDW-SD outperformed some inflammatory biomarkers, such as albumin, hemoglobin, total cholesterol, platelet count, lymphocyte, and fibrinogen, in predicting long-term mortality following ICH. Additionally, compared with admission RDW, median RDW-CV and RDW-SD (areas under the curve [AUC] 0.668 and 0.652, respectively) was superior to predict long-term mortality, (P < 0.001). Furthermore, median RDW-CV level was a better predictor than RDW-SD (P = 0.03). CONCLUSIONS: In patients with ICH, RDW independently predicted long-term mortality. Median RDW levels within the first month after admission were better predictors of long-term mortality compared with RDW levels on admission. Additionally, median RDW-CV showed superior predictive capacity than median RDW-SD for long-term mortality following ICH.

Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/ß-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA.

BACKGROUND: Hypoxia, a typical hallmark of solid tumors, exhibits an essential role in the progression of colorectal cancer (CRC), in which the dysregulation of long non-coding RNAs (lncRNAs) is frequently observed. However, the underlying mechanisms are not clearly defined. METHODS: The TCGA database was analyzed to identify differential lncRNA expression involved in hypoxia-induced CRC progression. qRT-PCR was conducted to validate the upregulation of lncRNA STEAP3-AS1 in CRC cell lines and tumor-bearing mouse and zebrafish models under hypoxia. ChIP-qRT-PCR was used to detect the transcriptional activation of STEAP3-AS1 mediated by HIF-1α. RNA-seq, fluorescent in situ hybridization, RNA pulldown, RNA immunoprecipitation, co-immunoprecipitation, immunofluorescence and immunoblot experiments were used to ascertain the involved mechanisms. Functional assays were performed in both in vitro and in vivo models to investigate the regulatory role of STEAP3-AS1/STEAP3/Wnt/ß-catenin axis in CRC proliferation and metastasis. RESULTS: Here, we identified a hypoxia-induced antisense lncRNA STEAP3-AS1 that was highly expressed in clinical CRC tissues and positively correlated with poor prognosis of CRC patients. Upregulation of lncRNA STEAP3-AS1, which was induced by HIF-1α-mediated transcriptional activation, facilitated the proliferation and metastasis of CRC cells both in vitro and in vivo. Mechanistically, STEAP3-AS1 interacted competitively with the YTH domain-containing family protein 2 (YTHDF2), a N6-methyladenosine (m6A) reader, leading to the disassociation of YTHDF2 with STEAP3 mRNA. This effect protected STEAP3 mRNA from m6A-mediated degradation, enabling the high expression of STEAP3 protein and subsequent production of cellular ferrous iron (Fe2+). Increased Fe2+ levels elevated Ser 9 phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) and inhibited its kinase activity, thus releasing ß-catenin for nuclear translocation and subsequent activation of Wnt signaling to support CRC progression. CONCLUSIONS: Taken together, our study highlights the mechanisms of lncRNA STEAP3-AS1 in facilitating CRC progression involving the STEAP3-AS1/STEAP3/Wnt/ß-catenin axis, which may provide novel diagnostic biomarkers or therapeutic targets to benefit CRC treatment. Hypoxia-induced HIF-1α transcriptionally upregulates the expression of lncRNA STEAP3-AS1, which interacts competitively with YTHDF2, thus upregulating mRNA stability of STEAP3 and consequent STEAP3 protein expression. The enhanced STEAP3 expression results in production of cellular ferrous iron (Fe2+), which induces the Ser 9 phosphorylation and inactivation of GSK3ß, releasing ß-catenin for nuclear translocation and contributing to subsequent activation of Wnt signaling to promote CRC progression.

Target identification of anti-diabetic and anti-obesity flavonoid derivative (Fla-CN).

Fla-CN is a flavonoid derivative with anti-diabetic and anti-obesity effects; however, its biological targets are still unknown. In this study, we developed bifunctional affinity-based probes to identify the direct targets of Fla-CN. When using probe 3, we observed the co-location of probe 3 and mitochondria in both HepG2 and 3T3-L1 cells. The putative target proteomes were obtained using activity-based protein profiling (ABPP) and photo-affinity labelling. Pyruvate carboxylase, mitochondrial malate dehydrogenase, mitochondrial complex I, and F1FO-ATPase were validated as the direct targets of Fla-CN by surface plasmon resonance (SPR) and biochemical assays. It was elucidated that the Tyr651, Gln870 and Lys912 were the key amino acid residues near the binding site of pyruvate carboxylase with Fla-CN. The direct interaction of Fla-CN and the above four targets allowed elucidation of its complicated molecular mechanism, including the activation of adenosine 5-monophosphate (AMP)-activated protein kinase (AMPK), and the inhibition of gluconeogenesis. Further investigation for activation of AMPK in normal and insulin resistance (IR) HepG2 cells, indicated that Fla-CN could target insulin resistance tissues.

Association Between Serum Albumin and Hospital-Acquired Infections After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Low serum albumin levels have been identified as a predictor of infectious complications in critically ill patients. However, the association in patients with aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. We aimed to evaluate the prognostic value of hypoalbuminemia using blood samples at admission in patients with aSAH. METHODS: In a multicenter observational study of patients with aSAH, serum albumin counts were collected on admission. Hypoalbuminemia was defined as a total albumin level < 35 g/L. Multivariable logistic regression analyses and propensity score matching were performed to obtain the adjusted odds ratios (ORs) with 95% confidence intervals (CI) for the primary outcome of hospital-acquired infections. RESULTS: A total of 5448 patients were included in the observational cohort study. The odds of hospital-acquired infections were significantly higher in patients with albumin levels 30-34.9 g/L (OR 1.62, 95% CI 1.38-1.90), 25-29.9 g/L (OR 1.97, 95% CI 1.54-2.51), and < 24.9 g/L (OR 2.43, 95% CI 1.53-3.86) compared with patients with albumin level ≥ 35 g/L. The odds of hospital-acquired infections with a change in albumin levels from admission to 48-72 h later of lower than - 10 g/L and - 10 to - 5 g/L were 1.67 (95% CI 1.41-1.86) and 1.24 (95% CI 1.05-1.46), respectively, compared with a change in albumin levels of - 5 to 5 g/L. CONCLUSIONS: In this large study of matched patients with aSAH, hypoalbuminemia at admission was associated with hospital-acquired infections. A decrease in serum albumin levels within 72 h of admission was associated with higher hospital-acquired infections.

Widespread myocardial dysfunction in COVID-19 patients detected by myocardial strain imaging using 2-D speckle-tracking echocardiography.

COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (<-21.0%) in about 83% of the patients. GLS reduction was more common in critically sick patients (98% vs. 78.3%, P < 0.001), and the mean GLS was significantly lower in the critically sick patients than those noncritical (-13.7% ± 3.4% vs. -17.4% ± 3.2%, P < 0.001). The alteration of GLS was more prominent in the subepicardium than in the subendocardium (P < 0.001). GLS was correlated to mean serum pulse oxygen saturation (SpO2, RR = 0.42, P < 0.0001), high-sensitive C-reactive protein (hsCRP, R = -0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = -0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.

Increased lipoxygenase and decreased cytochrome P450s metabolites correlated with the incidence of diabetic nephropathy: Potential role of eicosanoids from metabolomics in type 2 diabetic patients.

Diabetic nephropathy (DN) is the major cause of chronic kidney disease and end-stage renal disease. Previous studies have demonstrated that long-chain omega-3 polyunsaturated fatty acids (PUFAs) might have therapeutic potential in reducing proteinuria in DN. However, the local level of eicosanoids derived from PUFAs in the plasma of DN patients remains unclear. This work aims to study the eicosanoid profile difference in plasma of DN patients and type 2 diabetes (T2D) without DN. A total of 27 T2D patients with similar diabetic duration were recruited and divided into T2D+DN group and T2D+NDN (non-DN) group based on urinary albumin excretion (UAE) detection. Using LC-MS/MS-based metabolomics, DN patients showed increased level of lipoxygenase (LOX) metabolites (5-HETE and LTB4) and decreased levels of eicosanoids derived according to the cytochrome P450s (CYP450) metabolic pathway (5,6-DHET; 14,15-DHET and 9,10-diHOME). Receiver operating characteristics and logistic regression analysis revealed increased level LOX metabolites and decreased level of CYP450 metabolites were significantly correlated with the incidence of DN in T2D patients. LOX and CYP450 metabolites correlated with DN incidence in T2D patients, which might be treatment targets for DN in T2D patients.

[A Review of Progress of the Relation Between Stress Response and Diabetes Mellitus].

Stress response is an adaptive process of the organism to confront environmental perturbation. Moderate stress response induces the organism to establish effective adaptive strategies for survival, while excessive stress response results in stress injury, which is a major cause of a variety of physical or psychological diseases, including diabetes mellitus. Diabetes mellitus is a typical stress-related disease, with numerous evidence indicating that the development and progression of diabetes mellitus are closely related to stress response, such as metabolic stress, oxidative stress and endoplasmic reticulum stress. However, the detailed mechanisms of stress response mediated regulation of diabetes mellitus and how to prevent or treat diabetes mellitus via modification of stress response remain to be further investigated. Here, we will introduce the definition and regulatory mechanisms of stress response, as well as discuss the biological functions and mechanisms of various stress responses during the pathogenesis of diabetes mellitus. This review highlights recent advances of stress medicine associated with diabetes mellitus, in order to provide theoretical basis and reference for prevention and treatment of diabetes mellitus. Future studies should focus on elucidating the clinical application potential of the key factors of stress response that mediate the pathogenesis of diabetes mellitus, as well as boosting the related translational medicine studies.

Calycosin inhibits viability, induces apoptosis, and suppresses invasion of cervical cancer cells by upregulating tumor suppressor miR-375.

Calycosin, a functional phytoestrogen isoflavone isolated from Radix astragali, has been shown to possess multiple pharmacological properties including anti-cancer activity. However, up to now, the anti-cancer effect and the related mechanism of calycosin on cervical cancer (CC) cells have not been explored. It has been demonstrated that tumor suppressor miR-375 was downregulated in CC and calycosin upregulated miR-375 expression in cerebral ischemia/reperfusion. Thus we supposed that calycosin exerted anti-cancer effect by upregulating miR-375 expression in CC cells. Effects of calycosin or combined with miR-375 on cell viability and lactate dehydrogenase (LDH) release were detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetra zoliumromide (MTT) and LDH release assay. Apoptosis, caspase-3 activity, and cell invasion were determined by flow cytometry, caspase-3 activity assay, and Transwell assay, respectively. miR-375 expression was detected by quantitative real-time PCR (qRT-PCR). Our results showed that Calycosin dose-dependently inhibited cell viability and increased LDH release in CC cells, suggesting the cytotoxic effect of calycosin on CC cells. Calycosin enhanced the apoptotic rate and caspase-3 activity and decreased the number of invaded cells in CC cells. In addition, we found that miR-375 expression was decreased in CC cells but was upregulated in response to calycosin. Mechanistically, knockdown of miR-375 significantly reversed the anti-cancer effect of calycosin on CC cells. In conclusion, calycosin inhibited viability, induced apoptosis, and suppressed invasion of CC cells by upregulating tumor suppressor miR-375.

In vitro lung and gastrointestinal bioaccessibility of potentially toxic metals in Pb-contaminated alkaline urban soil: The role of particle size fractions.

Potentially toxic metals (PTMs), associated with different size particles in soil, may play an important role in adverse health effect and risk for human. The objective is to evaluate the lung and gastrointestinal bioaccessibility and risk of PTMs in Pb-contaminated alkaline urban soil depending on the particle size fractions. The size fractions of 50-250 µm, 5-50 µm, 1-5 µm, <1 µm in Pb-contaminated alkaline urban soil from Baoji Heavy Industrial Base City, NW China, were screened by Sequential Wet Sieving Separation Procedure (SWSSP) based on Stokes' Law. The concentrations of 9 potentially toxic metals (As, Ba, Co, Cr, Cu, Mn, Ni, Pb and Zn) in each particle size fractions were characterized by ICP-OES and ICP-MS, and the in vitro bioaccessibility dependent of size fractions were evaluated by the simulation fluids of Artificial Lysosomal Fluid (ALF) and Gamble for lung, PBET, SBET, IVG, SBRC, UBM for gastric and intestinal, respectively. Health risks were assessed considering simulated external exposure using intestinal and lung bioaccessibility. The lung and gastrointestinal bioaccessibility and exposure risks of PTMs in fine particle size (i.e. <1 µm) was higher than larger particle size fractions (i.e. 50-250 µm, 5-50 µm, 1-5 µm), however, some different variations of bioaccessibility observed the simulation fluids and time dependent. In case of single PTMs, the lung bioaccessibilities of PTMs in ALF were higher than those in Gamble fluids, most prominent in Co, Cu, Mn and Zn, while the gastrointestinal [G + I] bioaccessibility of PTMs was less than those in gastric [G], like Cu, Mn, Pb and Zn mostly. The non-carcinogenic risks of these PTMs to children via inhalation were acceptable and higher than those of adults, but reverse for carcinogenic risk. Comparatively, the non-carcinogenic and carcinogenic risks of PTMs via ingestion pathway were both higher than those for adults. Although the risks from ingestion were in acceptable range, the total carcinogenic risks for children were more than 10-4, which would bring carcinogenic risks and should be paid attention to. It was noted that the toxic metal, Co in all size fractions was the most important contributor for noncarcinogenic risks and Cr mostly for carcinogenic risks via inhalation pathway for adults and children in local areas. However, Pb was the most important contributor for noncarcinogenic risk both for adults and children via ingestion pathway relative to Co and Cr for carcinogenic risks through hand-to-mouth ingestion. Those observations demonstrated the important role that the smaller particle fractionations in Pb-contaminated alkaline soil played in both bioaccessibility and the refinement of human health-risk assessments for the inhalation and ingestion pathway.

Metabolomics revealed decreased level of omega-3 PUFA-derived protective eicosanoids in pregnant women with pre-eclampsia.

Pre-eclampsia (PE) is considered a leading cause of mortality and morbidity in pregnant women worldwide. Eicosanoids derived from polyunsaturated fatty acids (PUFAs) might play an important role in the occurrence and development of PE. Omega-3 PUFAs are nutrients that are popular supplements for pregnant women and can reduce blood pressure. However, the levels of eicosanoids derived from omega-3 PUFAs in women with PE is not clear. The purpose of this study was to investigate the eicosanoid metabolic signature of PE. We performed a case-control study using data for pregnant women (n = 10) with PE and normotensive pregnant women (n = 10). We investigated the difference in eicosanoid profile between the groups by LC-MS/MS-based metabolomics. The plasma levels of arachidonic acid metabolites and some of the lipoxygenase metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) showed an increasing trend, and those of the cytochrome P450 metabolites of EPA and DHA were decreased in women with PE. Levels of leukotriene B4, 14,15-dihydroxy-eicosatetraenoate, 16-hydroxydocosahexaenoic acid and 8,9-epoxy eicosatetraenoic acid were significantly correlated with PE occurrence. These eicosanoids might take part in the progression of PE in pregnant women.

Plasma metabolic profile reveals PGF2α protecting against non-proliferative diabetic retinopathy in patients with type 2 diabetes.

Diabetic retinopathy (DR) is the most frequent microvascular complications of diabetes and the leading cause of blindness in adults worldwide. Non-proliferative DR (NPDR) is the first stage of DR but currently has few recommended intervention. Eicosanoids play important roles in maintaining vessel homeostasis. However, the functions of eicosanoids in NPDR are still unknown. In this study, we investigated the eicosanoids profile difference in plasma between type 2 diabetes with NPDR or not. A total of 50 patients with type 2 diabetes were recruited and divided into non-DR (NDR) group and NPDR group based on fundus photographs. The eicosanoids profiles in plasma were determined by LC-MS/MS. Adhesion and transwell assay were used to detect the adhesion and migration effects of metabolites on primary bovine retinal pericyte cells (BRPC), respectively. Streptomycin (STZ)-induced diabetic mouse model was used to test the protective effects of selected metabolites according to retinal immunofluorescence staining and fluorescence confocal microscopy. Prostaglandin 2α (PGF2α) was decreased significantly in NPDR group compared to NDR group and negatively correlated with NPDR. In vitro, PGF2α was found to accelerate adhesion and migration by activating prostaglandin F receptor (FP receptor) and subsequent increasing RhoA activity in primary bovine retinal pericyte. Administration of PGF2α analogue diminished the damage on retinal capillary in an STZ-induced diabetic mouse model. Our results suggested that PGF2α may be a protective factor in the progression of NPDR in T2D patients. The protective mechanism of PGF2α was to increase pericyte mobility through FP receptor/RhoA pathway.

Anomalous electroluminescent blue-shift behavior induced by well widths variance and localization effect in InGaN/GaN multi-quantum wells.

Twelve InGaN MQW LED samples with varying well thickness grown via metal-organic chemical vaper deposition (MOCVD) are investigated. It is observed from electroluminescence (EL) measurement that at low current densities, the peak energy shifts to blue with increasing current, and when the current change by fixed increment, the peak energy shifts to blue end to different extent among samples. This blue shift was expected to be stronger when the well thickness increases, however, for well widths above 5 nm we observe a decrease in emission energy. Since no relaxation was detected from reciprocal space mapping (RSM), the deteriorated homogeneity is found to be responsible for this phenomenon. Temperature dependent photoluminescence (TDPL) results analyzed by band-tail model fitting show that the localization effect gets more prominent with increasing well thickness. It is found that elevating the growth temperature of active region from 710°C to 750°C significantly improves the homogeneity of InGaN layer.