A homogeneous electrochemiluminescence immunoassay platform based on carbon quantum dots and magnetic beads enrichment for detection of thyroglobulin in serum.

Considering the high probability of recurrence or metastasis after thyroidectomy, it is meaningful to develop a rapid, sensitive and specific method for monitoring thyrophyma-related biomarkers. In this study, a homogeneous electrochemiluminescence immunoassay (HO-ECLIA) coupled with magnetic beads (MBs)-based enrichment tactic was established for the determination of thyrophyma-related thyroglobulin (Tg). Importantly, owing to the abundant surface groups and good biocompatibility of carbon quantum dots (CQDs), the incorporation of CQDs onto the Tg antigen surface was achieved, resulting in the formation of Tg-encapsulated CQDs (CQDs-Tg), which served not only as an ECL probe but as a biorecognition element. Under optimal experimental conditions, the proposed platform demonstrated a wide linear range from 0.01 to 100 ng·mL-1 with a detection limit of 6.9 pg·mL-1 (S/N = 3), and performed well in real serum sample analysis against interference. Collectively, the proposed platform exhibited the rapid response, satisfactory sensitivity and specificity toward Tg in complex serum milieu, and held a considerable potential for clinical prognosis monitoring of thyrophyma.

Flubendazole suppresses VEGF-induced angiogenesis in HUVECs and exerts antitumor effects in PC-3 cells.

Flubendazole, an FDA-approved anthelmintic, has been predicted to show strong VEGFR2 inhibitory activity in silico screening combined with in vitro experimental validation, and it has shown anti-cancer effects on some human cancer cell lines, but little is known about the anti-angiogenesis effects and anti-prostate cancer effects. In this study, we analyzed the binding modes and kinetic analysis of flubendazole with VEGFR2 and first demonstrated that flubendazole suppressed VEGF-stimulated cell proliferation, wound-healing migration, cell invasion and tube formation of HUVEC cells, and decreased the phosphorylation of extracellular signal-regulated kinase and serine/threonine kinase Akt, which are the downstream proteins of VEGFR2 that are important for cell growth. What's more, our results showed that flubendazole decreased PC-3 cell viability and proliferation ability, and suppressed PC-3 cell wound healing migration and invasion across a Matrigel-coated Transwell membrane in a concentration-dependent manner. The antiproliferative effects of flubendazole were due to induction of G2-M phase cell cycle arrest in PC-3 cells with decreasing expression of the Cyclin D1 and induction of cell apoptosis with the number of apoptotic cells increased after flubendazole treatment. These results indicated that flubendazole could exert anti-angiogenic and anticancer effects by inhibiting cell cycle and inducing cell apoptosis.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

The prognostic value of dynamic changes in SII for the patients with STEMI undergoing PPCI.

BACKGROUND: Predicting the prognosis of primary percutaneous coronary intervention(PPCI) in ST-segment elevation myocardial infarction (STEMI) patients in the perioperative period is of great clinical significance. The inflammatory response during the perioperative period is also an important factor. This study aimed to investigate the dynamic changes in the systemic immune inflammatory index (SII) during the perioperative period of PPCI and evaluate its predictive value for in-hospital and out-of-hospital outcomes in patients with STEMI. METHODS: This retrospective study included 324 consecutive patients with STEMI who were admitted to the cardiac care unit. Blood samples were collected before PPCI, 12 h (T1), 24 h, 48 h after PPCI, the last time before hospital discharge (T2), and 1 month after hospital discharge. The SII was calculated as (neutrophils×platelets)/lymphocytes. Based on whether the primary endpoint occurred, we divided the patients into event and non-event groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors that might influence the occurrence of the primary endpoint. Dynamic curves of SII were plotted, and receiver operating characteristic (ROC) curves were drawn for each node to calculate the optimal critical value, sensitivity, and specificity to assess their predictive ability for in-hospital and out-of-hospital courses. Kaplan-Meier curves were used to analyze the differences in survival rates at different SII inflammation levels. RESULTS: High levels of SII were individually related to the occurrence of the in-hospital period and long-term outcomes during the post-operative follow-up of STEMI patients (in-hospital SII: T1:OR 1.001,95%CI 1.001-1.001, P < 0.001; SII following hospital discharge: T1M: OR 1.008,95%CI 1.006-1.010, P < 0.001). Patients with high SII levels had lower survival rates than those with low SII levels. The analysis showed that the SII 12 h after (T1) and SII 1 month (T1M) had excellent predictive values for the occurrence of in-hospital and out-of-hospital outcomes, respectively (AUC:0.896, P < 0.001; AUC:0.892, P < 0.001). CONCLUSION: There is a significant relationship between the dynamic status of SII and prognosis in patients with STEMI. This study found that the 12 h and SII 1 month affected in-hospital and out-of-hospital outcomes, respectively. Consequently, we focused on the dynamic changes in the SII.

Drinking water quality evaluation in supply systems in Wuhan, China: application of entropy weight water quality index and multivariate statistical analysis.

In this study, source water, finished water, and tap water were sampled monthly from two large drinking water treatment plants in Wuhan city, China for 12 months where physicochemical and microbiological parameters were measured, and the complex monitoring data was analyzed using single-factor assessment method, entropy weight water quality index (EWQI), and multivariate statistical techniques (i.e., cluster analysis (CA), discriminant analysis, and correlation analysis). The results of the single-factor assessment method showed that the total nitrogen pollution was the main problem in the source water quality, and the finished and tap water met the required quality standards. The EWQI values indicated that the overall quality of the source, finished, and tap water samples was "Excellent." In addition, strengthening monitoring of parameters with high entropy weights, including Pb, Hg, sulfide, Cr in surface water and Hg, aerobic bateria count, and As in drinking water, were suggested, as they were prone to drastic changes. Spatial CA grouped the finished and tap water samples from the same plant into a cluster. Temporal CA grouped 12 sampling times of source water into Cluster 1 (June), Cluster 2 (April-May, and July-November), and Cluster 3 (December-March). Concerning finished and tap water, except the October was regrouped, the result of temporal CA was consistent to that of the source water. Based on similar characteristics of water samples, monitoring sites and frequency can be optimized. Moreover, stepwise discriminant analysis indicated that the spatiotemporal variations in water quality among CA-groups were enough to be explained by four or five parameters, which provided a basis for the selection of monitoring parameters. The results of correlation analysis showed that few pairwise correlations were both significant (P < 0.05) and stable across sampling sites, suggesting that the number of monitoring parameters was difficult to reduce through substitution. In summary, this study illustrates the usefulness of EWQI and the multivariate statistical techniques in the water quality assessment and monitoring strategy optimization.

In Vivo Characterization of Cerebellar Peduncles in Chronic Ankle Instability: A Single and Multishell Diffusion-Weighted Imaging Study.

BACKGROUND: Ankle sprain causes proprioceptor injuries and prolonged joint deafferentation, which might lead to maladaptive neuroplasticity in patients with chronic ankle instability (CAI), especially in the cerebellum. Previous studies have indicated the impairment of superior cerebellar peduncle (SCP), but the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) have not been fully analyzed. HYPOTHESIS: The cerebellar peduncles of participants with CAI would have altered fractional anisotropy (FA) and orientation dispersion index (ODI) in comparison with healthy controls without ankle injury history. In addition, FA and ODI would be correlated with the duration or severity of the sensorimotor deficits in CAI. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A group of 27 participants with CAI and 26 healthy controls underwent diffusion-weighted imaging scanning, with the cerebellar peduncles as the regions of interest. The measures obtained by single-shell diffusion tensor imaging and the multishell neurite orientation dispersion and density imaging were used. Correlation analyses were performed to examine the potential relationship between the FA/ODI and both the normalized Y-balance scores and the durations of ankle instability. RESULTS: The ipsilateral ICP of the injured ankle in participants with CAI showed significantly lower FA (Cohen d 95% CI, -1.33 to -0.21; P = 0.04) and marginally significant higher ODI (Cohen d 95% CI, 0.10 to 1.20, P = 0.08) when compared with the same measures in the control group, with the ODI being positively correlated with the duration of ankle instability (r = 0.42, P = 0.03). CONCLUSION: The ICP in participants with CAI exhibited impaired integrity and a trend of abnormally organized neurites in comparison with a healthy control group. CLINICAL RELEVANCE: The impairments of ICP might be an ongoing part of the pathological process of CAI, having the potential to become a target for the diagnostic evaluation of this clinical entity.

B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC.

BACKGROUND: The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). RESULTS: In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. CONCLUSION: This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.

An electrochemiluminescence resonance energy transfer biosensor based on CDs/PAMAM/rGO nanocomposites and Au@Ag2S nanoparticles for PML/RARα fusion gene detection.

In recent years, electrochemiluminescence resonance energy transfer (ECL-RET) with low background signal and high specificity has attracted much attention among researchers. Herein, we established a novel ECL-RET biosensor for PML/RARα fusion gene detection. In this ECL-RET system, carbon dots (CDs) with low toxicity and prominent electrochemical activity were used as donor and Au@Ag2S core-shell nanoparticles (Au@Ag2S NPs) were employed as ECL acceptor. The Au@Ag2S NPs possessed a wide ultraviolet-visible (UV-vis) absorption spectrum between 500 nm and 700 nm, which completely overlapped with the ECL spectrum of CDs. Furthermore, the CDs-decorated poly-amidoamine/reduced graphene oxide (CDs/PAMAM/rGO) nanocomposites were prepared to improve the ECL signals and served as a substrate to stably load capture probe deoxyribonucleic acid (DNA). Based on the ECL-RET biosensing strategy, the Au@Ag2S NPs-labeled assistant probes and target DNA could pair with capture probes to form the sandwich-type DNA structure and the distance between donor and accepter was closed, leading to quenching of the ECL signal of CDs. The ECL-RET biosensor represented eminent analytical performance for PML/RARα fusion gene detection with a wide linear relationship from 5 fM to 500 pM and a low detection limit of 0.72 fM, which provided a novel technical means and theoretical basis for detection and diagnosis of acute promyelocytic leukemia.

Pterostilbene alleviated cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction via inhibiting early endothelial cytoskeleton reorganization and late basement membrane degradation.

Pterostilbene, an important analogue of the star molecule resveratrol and a novel compound naturally occurring in blueberries and grapes, exerts a significant neuroprotective effect on cerebral ischemia/reperfusion (I/R), but its mechanism is still unclear. This study aimed to follow the molecular mechanisms behind the potential protective effect of pterostilbene against I/R induced injury. For fulfilment of our aim, we investigated the protective effects of pterostilbene on I/R injury caused by middle cerebral artery occlusion (MCAO) in vivo and oxygen-glucose deprivation (OGD) in vitro. Machine learning models and molecular docking were used for target exploration and validated by western blotting. Pterostilbene significantly reduced the cerebral infarction volume, improved neurological deficits, increased cerebral microcirculation and improved blood-brain barrier (BBB) leakage. Machine learning models confirmed that the stroke target MMP-9 bound to pterostilbene, and molecular docking demonstrated the strong binding activity. We further found that pterostilbene could depolymerize stress fibers and maintain the cytoskeleton by effectively increasing the expression of the non-phosphorylated actin depolymerizing factor (ADF) in the early stage of I/R. In the late stage of I/R, pterostilbene could activate the Wnt pathway and inhibit the expression of MMP-9 to decrease the degradation of the extracellular basement membrane (BM) and increase the expression of junction proteins. In this study, we explored the protective mechanisms of pterostilbene in terms of both endothelial cytoskeleton and extracellular matrix. The early and late protective effects jointly maintain BBB stability and attenuate I/R injury, showing its potential to be a promising drug candidate for the treatment of ischemic stroke.

A Y-shape-structured electrochemiluminescence biosensor based on carbon quantum dots and locked nucleic acid probe for microRNA determination with single-base resolution.

Since microRNAs (miRNAs) are predictors of tumorigenesis, accurate identification and quantification of miRNAs with highly similar sequences are expected to reflect tumor diagnosis and treatment. In this study, a highly selective and sensitive electrochemiluminescence (ECL) biosensor was constructed for miRNAs determination based on Y-shaped junction structure equipped with locked nucleic acids (LNA), graphene oxide-based nanocomposite to enrich luminophores, and conductive matrix. Specifically, two LNA-modified probes were designed for specific miRNA recognition, that is, a dual-amine functionalized hairpin capture probe and a signal probe. A Y-shaped DNA junction structure was generated on the electrode surface upon miRNA hybridizing across the two branches, so as to enhance the selectivity. Carbon quantum dots-polyethylene imine-graphene oxide (CQDs-PEI-GO) nanocomposites were developed to enrich luminophores CQDs, and thus enhancing the ECL intensity. For indirect signal amplification, an electrochemically activated poly(2-aminoterephthalic acid) (ATA) film decorated with gold nanoparticles was prepared on electrode as an effective matrix to accelerate the electron transfer. The fabricated ECL biosensor achieved sensitive determination of miRNA-222 with a limit-of-detection (LOD) as low as 1.95 fM (S/N = 3). Notably, Y-shaped junction structures equipped with LNA probes endowed ECL biosensor with salient single-base discrimination ability and anti-interference capacity. Overall, the proposed Y-shaped ECL biosensor has considerable promise for clinical biomarker determination.

Development and Validation of a Nomogram for Predicting All-Cause Mortality in Patients with Hemodialysis Having Pulmonary Hypertension.

INTRODUCTION: Patients with end-stage renal disease receiving hemodialysis (HD) have a high morbidity and mortality rate associated with pulmonary hypertension (PH). A nomogram was developed to predict all-cause mortality in HD patients with PH. In this study, we aimed to validate the usefulness of this nomogram. METHODS: A total of 274 HD patients with PH were hospitalized at the Affiliated Hospital of Xuzhou Medical University between January 2014 and June 2019 and followed up for 3 years. Echocardiography detected PH when the peak tricuspid regurgitation velocity (TRV) was more than 2.8 m/s. To evaluate the all-cause mortality for long-term HD patients with PH, Cox regression analysis was performed to determine the factors of mortality that were included in the prediction model. Next, the area under the receiver-operating characteristic curve (AUC-ROC) was used to assess the predictive power of the model. Calibration plots and decision curve analysis (DCA) were used to assess the accuracy of the prediction results and the clinical utility of the model. RESULTS: The all-cause mortality rate was 29.20% throughout the follow-up period. The nomogram comprised six commonly available predictors: age, diabetes mellitus, cardiovascular disease, hemoglobin, left ventricular ejection fraction, and TRV. The 1-year, 2-year, and 3-year AUC-ROC values were 0.842, 0.800, and 0.781, respectively. The calibration curves revealed excellent agreement with the nomogram, while the DCA demonstrated favorable clinical practicability. CONCLUSION: The first developed nomogram for predicting all-cause mortality in HD patients with PH could guide clinical decision-making and intervention planning.

Artificial Post-Cycled Structure Modulation Towards Highly Stable Li-Rich Layered Cathode.

High-capacity Li-rich layered oxides (LLOs) suffer from severe structure degradation due to the utilization of hybrid anion- and cation-redox activity. The native post-cycled structure, composed of progressively densified defective spinel layer (DSL) and intrinsic cations mixing, is deemed as the hindrance of the rapid and reversible de/intercalation of Li+ . Herein, the artificial post-cycled structure consisting of artificial DSL and inner cations mixing is in situ constructed, which would act as a shield against the irreversible oxygen emission and undesirable transition metal migration by suppressing anion redox activity and modulating cation mixing. Eventually, the modified DSL-2% Li-rich cathode demonstrates remarkable electrochemical properties with a high discharge capacity of 187 mAh g-1 after 500 cycles at 2 C, and improved voltage stability. Even under harsh operating conditions of 50 °C, DSL-2% can provide a high discharge capacity of 168 mAh g-1 after 250 cycles at 2 C, which is much higher than that of pristine LLO (92 mAh g-1 ). Furthermore, the artificial post-cycled structure provides a novel perspective on the role of native post-cycled structure in sustaining the lattice structure of the lithium-depleted region and also provides an insightful universal design principle for highly stable intercalated materials with anionic redox activity.

Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) pandemic is still rage worldwide, there are still very limited treatments for human coronaviruses (HCoVs) infections. Xiaochahu decoction (XCHD), which is one of the traditional Chinese medicine (TCM) prescriptions in Qingfeipaidu decoction (QFPDD), is widely used for COVID-19 treatment in China and able to relieve the symptoms of fever, fatigue, anorexia, and sore throat. To explore the role and mechanisms of XCHD against HCoVs, we presented an integrated systems pharmacology framework in this study. METHODS: We constructed a global herb-compound-target (H-C-T) network of XCHD against HCoVs. Multi-level systems pharmacology analyses were conducted to highlight the key XCHD-regulated proteins, and reveal multiple HCoVs relevant biological functions affected by XCHD. We further utilized network-based prediction, drug-likeness analysis, combining with literature investigations to uncover the key ani-HCoV constituents in XCHD, whose effects on anit-HCoV-229E virus were validated using cytopathic effect (CPE) assay. Finally, we proposed potential molecular mechanisms of these compounds against HCoVs via subnetwork analysis. RESULTS: Based on the systems pharmacology framework, we identified 161 XCHD-derived compounds interacting with 37 HCoV-associated proteins. An integrated pathway analysis revealed that the mechanism of XCHD against HCoVs is related to TLR signaling pathway, RIG-I-like receptor signaling pathway, cytoplasmic DNA sensing pathway, and IL-6/STAT3 pro-inflammatory signaling pathway. Five compounds from XCHD, including betulinic acid, chrysin, isoliquiritigenin, schisandrin B, and (20R)-Ginsenoside Rh1 exerted inhibitory activity against HCoV-229E virus in Huh7 cells using in vitro CPE assay. CONCLUSION: Our work presented a comprehensive systems pharmacology approach to identify the effective molecules and explore the molecular mechanism of XCHD against HCoVs.

A dual-readout sensing platform for the evaluation of cell viability integrating with optical and digital signals based on a closed bipolar electrode.

Cell viability is essential for predicting drug toxicity and assessing drug effects in drug screening. However, the over/underestimation of cell viability measured by traditional tetrazolium colorimetric assays is inevitable in cell-based experiments. Hydrogen peroxide (H2O2) secreted by living cells may provide more comprehensive information about the cell state. Hence, it is significant to develop a simple and rapid approach for evaluating cell viability by measuring the excreted H2O2. In this work, we developed a dual-readout sensing platform based on optical and digital signals by integrating a light emitting diode (LED) and a light dependent resistor (LDR) into a closed split bipolar electrode (BPE), denoted as BP-LED-E-LDR, for evaluating cell viability by measuring the H2O2 secreted from living cells in drug screening. Additionally, the customized three-dimensional (3D) printed components were designed to adjust the distance and angle between the LED and LDR, achieving stable, reliable and highly efficient signal transformation. It only took 2 min to obtain response results. For measuring the exocytosis H2O2 from living cells, we observed a good linear relationship between the visual/digital signal and logarithmic function of MCF-7 cell counts. Furthermore, the fitted half inhibitory concentration curve of MCF-7 to doxorubicin hydrochloride obtained by the BP-LED-E-LDR device revealed a nearly identical tendency with the cell counting kit-8 assay, providing an attainable, reusable, and robust analytical strategy for evaluating cell viability in drug toxicology research.

The efficacy and mechanism of salmeterol against influenza A virus in vitro and in vivo.

Influenza A virus (IAV) is the most harmful pathogen to human beings among the various subtypes of influenza virus, which can lead to immune response, cause serious inflammation and damage to the lung. Salmeterol is a candidate compound with anti-IAV activity screened by virtual network proximity predication. In this paper, we further evaluated the pharmacodynamics of salmeterol against IAV in vivo and in vitro. The results showed that salmeterol could inhibit the activity of three IAV strains (H1N1, H3N2 and H1N1 strain resistant to oseltamivir and amantadine) in the MDCK cells. In vivo, salmeterol could improve the survival state of infected mice, and further mechanism studies shown that salmeterol could improve the pathological characteristics of the lungs, reduce the loads of virus and the expression of M2 and IFITM3 proteins in the lungs of mice. In addition, salmeterol could inhibit the formation of NLRP3 inflammasome, thus reducing the production of the TNF-α, IL-6 and MCP-1 and alleviating inflammatory symptoms. Further results showed that salmeterol can protect A549 cells from cytopathic effect caused by IAV and reduce the production of inflammasome by decreasing the expression of RIG-1 in A549 cells. Finally, salmeterol could improve the spleen morphology and significantly increase the ratio of lymphocyte CD4+/CD8+ to improve immune function of infected mice. In our study, it is confirmed that salmeterol has certain anti-IAV activity through pharmacodynamic study in vivo and in vitro, which lays an important research foundation for the new indication of salmeterol and discovery of new drug against IAV.

Using Pgst-4::GFP-transformed Caenorhabditis elegans for drinking water quality monitoring.

Biological effect-based monitoring is essential for predicting or alerting to a possible deterioration in drinking water quality. In the present study, a reporter gene assay based on oxidative stress-mediated Pgst-4::GFP induction in the Caenorhabditis elegans strain VP596 (VP596 assay) was assessed for its applicability in evaluating drinking water safety and quality. This assay was used to measure the oxidative stress response in VP596 worms exposed to six ubiquitous components (As3+, Al3+, F-, NO3--N, CHCl3, and residual chlorine) in drinking water, eight mixtures of these six components designed through orthogonal design, ninety-six unconcentrated water samples from source to tap water in two supply systems, and organic extracts (OEs) of twenty-five selected water samples. Pgst-4::GFP fluorescence was not induced by Al3+, F-, NO3--N, and CHCl3, and was significantly enhanced by As3+ and residual chlorine only at concentrations higher than their respective drinking water guideline levels. Pgst-4::GFP induction was not detected in any of the six-component mixtures. Induction of Pgst-4::GFP was observed in 9.4% (3/32) of the source water samples but not in the drinking water samples. However, a notable induction effect was revealed in the three OEs of drinking water, with a relative enrichment factor of 200. These results suggest that the VP596 assay has limited utility for screening drinking water safety by testing unconcentrated water samples; however, it offers a supplemental in vivo tool for prioritizing water samples for an enhanced quality assessment, monitoring pollutant removal performance by drinking water treatment plants, and evaluating water quality in water supplies.

Toxicological characteristics of drinking water in two large-scale municipal water supply systems of a metropolitan city in Central China.

Drinking water safety is threatened by numerous toxic organic pollutants difficult to chemically monitor. This study aimed to determine the toxicological profiles of organic extracts (OEs) of water samples from source to tap in two drinking water supply systems in a metropolitan city, Central China, during different hydrological periods. Mortality, DNA damage, growth, and development of Caenorhabditis elegans were evaluated following exposure to OEs. The median lethal doses of OEs of drinking water samples (n = 48) ranged from 266 REF (relative enrichment factor) to > 1563 REF. When tested at a dose of 100 REF, 56.25% (27/48) of OEs induced genotoxicity, 4.17% (2/48) inhibited the growth, and 45.83% (22/48) decreased the offspring number in C. elegans. No clear temporal-spatial variation patterns of the OEs toxicity indicators were observed. The correlations among the toxicity indicators were generally poor. The observed toxicities were not closely related to the level of dissolved organic carbon in drinking water. These findings support using multiple endpoint bioassays, such as C. elegans-based approaches, as complementary tools to conventional chemical analysis for drinking water quality monitoring.

Sleeve gastrectomy improved microvascular phenotypes from obesity cohort, detected with optical coherence tomography angiography.

AIMS: To examine how metabolic status is associated with microvascular phenotype and to identify variables associated with vascular remodeling after bariatric surgery, using noninvasive optical coherence tomography angiography (OCTA). METHODS: The study included 136 obese subjects scheduled for bariatric surgery and 52 normal-weight controls. Patients with obesity were divided into metabolically healthy obesity (MHO) and metabolic syndrome (MetS) groups according to the diagnosis criteria of the Chinese Diabetes Society. Retinal microvascular parameters were measured by OCTA, including superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities. Follow-ups were performed at the baseline and 6 months after bariatric surgery. RESULTS: Fovea SCP, average DCP, fovea DCP, parafovea DCP, and perifovea DCP vessel densities were significantly lower in the MetS group, compared to controls (19.91% vs. 22.49%, 51.60% vs. 54.20%, 36.64% vs. 39.14%, 56.24% vs. 57.65% and 52.59% vs. 55.58%, respectively, all p < .05). Parafovea SCP, average DCP, parafovea DCP, and perifovea DCP vessel densities significantly improved in patients with obesity 6 months after surgery, compared to baseline (54.21% vs. 52.97%, 54.43% vs. 50.95%, 58.29% vs. 55.54% and 55.76% vs. 51.82%, respectively, all p < .05). Multivariable analyses showed that baseline blood pressure and insulin were independent predictors of vessel density changes 6 months after surgery. CONCLUSIONS: Retinal microvascular impairment occurred mainly in MetS rather than MHO patients. Retinal microvascular phenotype improved 6 months after bariatric surgery and baseline blood pressure and insulin status may be key determinants. OCTA may be a reliable method to evaluate the microvascular complications associated with obesity.