SUMOylation modification of FTO facilitates oxidative damage response of arsenic by IGF2BP3 in an m6A-dependent manner.

N6-methyladenosine (m6A) is the most common form of internal post-transcriptional methylation observed in eukaryotic mRNAs. The abnormally increased level of m6A within the cells can be catalyzed by specific demethylase fat mass and obesity-associated protein (FTO) and stay in a dynamic and reversible state. However, whether and how FTO regulates oxidative damage via m6A modification remain largely unclear. Herein, by using both in vitro and in vivo models of oxidative damage induced by arsenic, we demonstrated for the first time that exposure to arsenic caused a significant increase in SUMOylation of FTO protein, and FTO SUMOylation at lysine (K)- 216 site promoted the down-regulation of FTO expression in arsenic target organ lung, and therefore, remarkably elevating the oxidative damage via an m6A-dependent pathway by its specific m6A reader insulin-like growth factor-2 mRNA-binding protein-3 (IGF2BP3). Consequently, these findings not only reveal a novel mechanism underlying FTO-mediated oxidative damage from the perspective of m6A, but also imply that regulation of FTO SUMOylation may serve as potential approach for treatment of oxidative damage.

Utilization of CRISPR-Cas genome editing technology in filamentous fungi: function and advancement potentiality.

Filamentous fungi play a crucial role in environmental pollution control, protein secretion, and the production of active secondary metabolites. The evolution of gene editing technology has significantly improved the study of filamentous fungi, which in the past was laborious and time-consuming. But recently, CRISPR-Cas systems, which utilize small guide RNA (sgRNA) to mediate clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas), have demonstrated considerable promise in research and application for filamentous fungi. The principle, function, and classification of CRISPR-Cas, along with its application strategies and research progress in filamentous fungi, will all be covered in the review. Additionally, we will go over general matters to take into account when editing a genome with the CRISPR-Cas system, including the creation of vectors, different transformation methodologies, multiple editing approaches, CRISPR-mediated transcriptional activation (CRISPRa) or interference (CRISPRi), base editors (BEs), and Prime editors (PEs).

The Profiles of Venous Thromboembolism at Different High Altitudes.

Xiong, Shiqiang, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, and Haifeng Pei. The profiles of venous thromboembolism at different high altitudes High Alt Med Biol. 00:000-000, 2024.-This study investigated the incidence of venous thromboembolism (VTE) in high altitude (HA) and very HA areas. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) diagnosed between 2004 and 2022 in Yecheng, China, were retrospectively analyzed. The results showed that patients with PE at very HA had a higher risk of lower extremity DVT (OR 16.3 [95% CI 1.2-223.2], p = 0.036), than those at HA, especially in the early stages of very HA entry, and the harsh environment of very HA further exacerbated the risk of VTE. These findings emphasize the higher risk of PE development in very HA and the need for enhanced prevention and treatment in this area.

Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report.

BACKGROUND: Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention. CASE SUMMARY: A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC. CONCLUSION: BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.

Comparison of bleb morphologies between phacoemulsification combined with Ex-PRESS mini shunt implantation, phacotrabeculectomy and trabeculectomy alone: a two-year retrospective in vivo confocal microscopy study.

BACKGROUND: To compare the bleb morphologies of phacoemulsification combined with Ex-PRESS implantation (Phaco-ExPRESS), phaco trabeculectomy (Phaco-Trab), and trabeculectomy (Trab) in postoperative two years. METHODS: Patients with primary open-angle glaucoma (POAG) with or without cataracts were included in this study. All patients underwent surgeries of either Phaco-ExPRESS, Phaco-Trab, or Trab. The morphologic structures of the filtering bleb, including microcysts area, hyperreflective dot density, and stromal connective tissue under in vivo confocal microscope (IVCM), were compared between the three groups. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months. RESULTS: Eighty-nine eyes from 89 patients were enrolled, including 32 in the Phaco-ExPRESS group, 25 in the Phaco-Trab group, and 32 in the Trab group. In a 24-month follow-up, bleb morphologies in Phaco-ExPRESS were similar to the Trab group. The area of epithelial microcysts was significantly increased in Phaco-ExPRESS and Trab groups while significantly decreased in Phaco-Trab. At postoperative 24 months, the complete success rate was 65.1% in Phaco-ExPRESS, 32.0% in Phaco-Trab, and 59.4% in the Trab group (P = 0.03). The phaco-Trab group had more postoperative anti-glaucoma medications than the other two groups (P < 0.05). CONCLUSIONS: Phaco-ExPRESS group and Trab group had similar blebs morphologies in IVCM, with larger microcyst area, looser connective tissue, and less inflammation than Phaco-Trab, indicating that the function of blebs in the Phaco-ExPRESS and Trab group, was more potent than that of Phaco-Trab. All these surgical methods provided adequate IOP control, but Phaco-Trab required more anti-glaucoma medications.

Sexually dimorphic control of affective state processing and empathic behaviors.

Recognizing the affective states of social counterparts and responding appropriately fosters successful social interactions. However, little is known about how the affective states are expressed and perceived and how they influence social decisions. Here, we show that male and female mice emit distinct olfactory cues after experiencing distress. These cues activate distinct neural circuits in the piriform cortex (PiC) and evoke sexually dimorphic empathic behaviors in observers. Specifically, the PiC → PrL pathway is activated in female observers, inducing a social preference for the distressed counterpart. Conversely, the PiC → MeA pathway is activated in male observers, evoking excessive self-grooming behaviors. These pathways originate from non-overlapping PiC neuron populations with distinct gene expression signatures regulated by transcription factors and sex hormones. Our study unveils how internal states of social counterparts are processed through sexually dimorphic mechanisms at the molecular, cellular, and circuit levels and offers insights into the neural mechanisms underpinning sex differences in higher brain functions.

Double-Branch Multi-Scale Contextual Network: A Model for Multi-Scale Street Tree Segmentation in High-Resolution Remote Sensing Images.

Street trees are of great importance to urban green spaces. Quick and accurate segmentation of street trees from high-resolution remote sensing images is of great significance in urban green space management. However, traditional segmentation methods can easily miss some targets because of the different sizes of street trees. To solve this problem, we propose the Double-Branch Multi-Scale Contextual Network (DB-MSC Net), which has two branches and a Multi-Scale Contextual (MSC) block in the encoder. The MSC block combines parallel dilated convolutional layers and transformer blocks to enhance the network's multi-scale feature extraction ability. A channel attention mechanism (CAM) is added to the decoder to assign weights to features from RGB images and the normalized difference vegetation index (NDVI). We proposed a benchmark dataset to test the improvement of our network. Experimental research showed that the DB-MSC Net demonstrated good performance compared with typical methods like Unet, HRnet, SETR and recent methods. The overall accuracy (OA) was improved by at least 0.16% and the mean intersection over union was improved by at least 1.13%. The model's segmentation accuracy meets the requirements of urban green space management.

Difference of central foveal thickness measurement in patients with macular edema using optical coherence tomography in different display modes.

Purpose: To assess the differences in the measurement of central foveal thickness (CFT) in patients with macular edema (ME) between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT). Design: This is a retrospective, cross-sectional study. Methods: Group A consisted of participants with well-horizontal OCT B-scan images and group B consisted of participants with tilted OCT B-scan. We manually measured the CFT under the two display modes, and the values were compared statistically using the paired t-test. Spearman's test was used to assess the correlations between the OCT image tilting angle (OCT ITA) and the differences in CFT measurement. The area under the curve (AUC) was calculated to define the OCT ITA cutoff for a defined CFT difference. Results: In group A, the mean CFT in the 1:1 pixel display mode was 420.21 ± 130.61 µm, similar to the mean CFT of 415.27 ± 129.85 µm in the 1:1 micron display mode. In group B, the median CFT in the 1:1 pixel display mode is 409.00 µm (IQR: 171.75 µm) and 368.00 µm (IQR: 149.00 µm) in the 1:1 micron display mode. There were significant differences between the two display modes with the median (IQR) absolute difference and median (IQR) relative difference of 38.00 µm (75.00 µm) and 10.19% (21.91%) (all p = 0.01). The differences in CFT measurement between the two display modes were correlated with the OCT ITA (absolute differences, r = 0.88, p < 0.01; relative differences, r = 0.87, p < 0.01). The AUC for a predefined CFT difference was 0.878 (10 µm), 0.933 (20 µm), 0.938 (30 µm), 0.961 (40 µm), 0.962 (50 µm), and 0.970 (60 µm). Conclusion: In patients with DM, when the OCT B-scan images were well-horizontal, manual CFT measurements under the two display modes were similar, but when the B-scan images were tilted, the CFT measurements were different under the two display modes, and the differences were correlated to the OCT ITA.

The impact of lymphadenectomy on ovarian clear cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) shares treatment strategies with epithelial ovarian cancer (EOC). Due to OCCC's rarity, there's a lack of prospective studies on its surgery, resulting in heterogeneous and limited existing data. This study aims to clarify the prognostic significance of lymphadenectomy in OCCC patients. METHODS: We systematically searched Web of Science, Scopus, PubMed, and Google Scholar until July 2023 for studies investigating lymphadenectomy's effects on OCCC patients. We calculated pooled hazard ratios (HR) with 95% confidence intervals (CI). This study is registered in PROSPERO (CRD42021270460). RESULTS: Among 444 screened articles, seven studies (2883 women) met inclusion criteria. Our analysis revealed that lymphadenectomy significantly improved disease-specific survival (DSS) (HR = 0.76, 95%CI = 0.60-0.95, P = 0.02) and disease-free survival (DFS) (HR = 0.58, 95%CI = 0.34-0.99, P = 0.05). However, it did not significantly affect overall survival (OS) (HR = 0.80, 95%CI = 0.60-1.06, P = 0.12) or progression-free survival (PFS) (HR = 0.95, 95%CI = 0.64-1.42, P = 0.79). Notably, some earlier studies reported no survival benefit, warranting cautious interpretation. CONCLUSION: Lymphadenectomy does not significantly enhance OS and PFS for OCCC but does improve DFS and DSS. Tailoring treatment to individual patient profiles is imperative for optimal outcomes. Precise preoperative or intraoperative lymph node metastasis detection is essential for identifying candidates benefiting from lymphadenectomy. Collaborative international efforts and an OCCC database are pivotal for refining future treatment strategies.

Targeted exome sequencing strategy (NeoEXOME) for Chinese newborns using a pilot study with 3423 neonates.

BACKGROUND: Newborn screening (NBS) aims to detect congenital anomalies, and next-generation sequencing (NGS) has shown promise in this aspect. However, the NBS strategy for monogenic inherited diseases in China remains insufficient. METHODS: We developed a NeoEXOME panel comprising 601 genes that are relevant to the Chinese population found through extensive research on available databases. An interpretation system to grade the results into positive (high-risk, moderate-risk, and low-risk genotypes), negative, and carrier according to the American College of Medical Genetics (ACMG) guidelines was also developed. We validated the panel to evaluate its efficacy by using data from the "1000 Genomes Project" and conducted a pilot multicenter study involving 3423 neonates. RESULTS: The NGS positive rate in the 1000 Genomes Project was 7.6% (23/301), whereas the rate was 12.0% in the multicenter study, including 3249 recruited neonates. Notably, in 200 neonates, positive per conventional NBS, 58.5% (69/118) showed results consistent with NGS. In the remaining 3049 neonates showing negative results in conventional NBS, 271 (8.9%) were positive per NGS, and nine of them were clinically diagnosed with diseases in the follow-up. CONCLUSION: We successfully designed a NeoEXOME panel for targeted sequencing of monogenic inherited diseases in NBS. The panel demonstrated high performance in the Chinese population, particularly for the early detection of diseases with no biochemical markers.

Determination of trace fluoroquinolones in honey and milk based on cyclodextrin modified magnetic metal-organic frameworks solid phase extraction coupled with ultra-high performance liquid chromatography.

Long-term intake of animal-derived foods with excessive fluoroquinolones (FQs) will cause damage to human health, so it is critical to establish a feasible approach for sensitive and rapid monitoring of FQs residues. In this study, a new cyclodextrin modified magnetic metal-organic frameworks (Fe3O4@UiO-66-CD) was successfully synthesized by amidation reaction and applied to magnetic solid phase extraction (MSPE) for FQs analysis. The adsorption behavior of Fe3O4@UiO-66-CD was consistent with the pseudo-second-order kinetics and Freundlich isothermal adsorption model, which indicated that the designed material had various interactions on FQs, such as host-guest interaction and π-π interaction. The parameters of MSPE were optimized and the determination method of norfloxacin, enrofloxacin, lomefloxacin and gatifloxacin was established by using MSPE combined with ultra-high performance liquid chromatography (UHPLC) and fluorescence detector (FLD). The method validation results displayed that the detection limits were 0.02-0.09 ng/mL, and the RSDs of intra-day and inter-day precision were less than 4.1 and 6.4 %, respectively. In the target FQs analysis of real honey and milk samples, the recoveries at different fortified concentrations were in the ranges of 88.4 % to 108.6 % with RSD ≤ 5.7 %. The results showed that the proposed method was sensitive, accurate and reliable for the determination of trace FQs in animal-derived foods.

Molecular Simulation of H2/CH4 Mixture Storage and Adsorption in Kaolinite Nanopores for Underground Hydrogen Storage.

Hydrogen has been regarded as an important type of renewable energy; however, the usage of pure hydrogen remains a challenge due to the difficulty of transportation and storage. To facilitate the hydrogen usage, it has been proposed to add hydrogen into the existing natural gas pipeline and storage systems, and therefore, the blended hydrogen is injected into the underground gas reservoirs, which is often used for the seasonal storage of natural gas. However, the mechanism of the H2/CH4 mixture storage in the porous formations of underground reservoirs still remains unclear. In this work, we have used molecular simulations to study the storage of the H2/CH4 mixture in dry and wet kaolinite pores of gibbsite and siloxane structures aiming at the clays in the underground porous reservoirs. The results showed that the hydrogen storage density increases as the injected H2 fraction increases in the dry pores but is nearly not affected by the pore size in the range of 5-200 nm. For the H2 fraction below 20%, the percentage of the H2 stored in the pores from the injected gas mixture is higher than that of CH4, and the larger pores are more preferential for H2 storage, but the H2 molecule distribution is more diffused than that of CH4 across the pore. The CH4 molecules adopt the tripod and inclined configurations with an angle of 110° or 70° toward the surface, while the H2 molecules are perpendicular to the surface. But both the molecular structures of H2 and CH4 are not affected by the gibbsite/siloxane structure or water content. However, the siloxane pores have a better selective storage capacity for H2 from the H2/CH4 mixture. The existence of water in the formation weakens both the H2 and CH4 storage densities. For gibbsite pores, the water molecules form a film on the surface, driving the H2 and CH4 molecules to the middle of the pore. But for siloxane pores, the water molecules form water cluster across the pore, leaving less pore volumes for H2 and CH4 storage, which causes a weaker H2 storage capacity than that of the gibbsite pores.

Ocular Characteristics of Pseudophakic Eyes with Malignant Glaucoma.

INTRODUCTION: The aim of the study was to investigate the clinical characteristics and treatment outcomes of the pseudophakic eyes with malignant glaucoma (MG). METHODS: This retrospective case-control study enrolled 53 eyes of 47 patients with primary angle-closure glaucoma having cataract surgery history, including 19 patients (25 eyes) diagnosed with MG and 28 patients (28 eyes) without MG as the match. Among patients diagnosed with MG, 14 patients (18 eyes) underwent zonulo-hyaloido-vitrectomy (ZHV) and the other 5 patients (7 eyes) received conservative treatments. The visual acuity, refraction status, intraocular pressure (IOP), extent of peripheral anterior synechia, classes of anti-glaucoma medications, and ultrasound biomicroscopy (UBM) examination were recorded before cataract surgery, at the diagnosis of MG, and 3 months after ZHV or atropine application, respectively. RESULTS: In the pseudophakic eyes with MG, the IOP cannot be well controlled compared to the matched eyes (27.24 ± 8.72 mm Hg vs. 14.30 ± 2.63 mm Hg, p < 0.001). In addition, there was a difference in the average spherical equivalent refractive error between 2 groups of patients (-2.23 ± 0.84 D in MG vs. -0.12 ± 0.64 D in the matched eyes, p < 0.001). By UBM analysis, the anterior chamber depth (ACD) was shallower in MG than that in the matched eyes (2.34 ± 0.20 mm vs. 3.47 ± 0.29 mm, p < 0.001). The difference between the anterior vault distance of the pseudophakic eyes with MG and that of the matched eyes was also significant (p < 0.001). After treated with ZHV, the IOP was greatly decreased from 27.84 ± 10.14 mm Hg to 15.85 ± 4.41 mm Hg (p < 0.001). The refractive error also changed from -2.11 ± 0.91 D to +0.42 ± 0.99 D (p < 0.001). At the same time, the central ACD was significantly deepened from 2.30 ± 0.39 mm to 3.30 ± 0.31 mm (p < 0.001). CONCLUSION: Uncontrolled IOP and shallow anterior chamber both centrally and peripherally are the primary clinical characteristics for the pseudophakic eyes with MG. An unexpected refractive error or myopic shift for the eyes with PACG after cataract surgery can be an important hint for diagnosis of MG. The typical UBM image is an anterior displacement of the lens-iris diaphragm and a bow-shaped change of the intraocular lens. It is an effective way to treat pseudophakic MG with the ZHV through a peripheral iridectomy.

Down Regulation of EGF and AZGP1 Were Associated with Clinical Characteristics in Chronic Rhinosinusitis with Nasal Polyps: An Observation Study.

Objective: The mechanisms underlying the chronic rhinosinusitis with nasal polyps (CRSwNP) remained unclear. This study aimed to identify differentially expressed genes (DEGs) in nasal polyps from CRSwNP patients compared to healthy controls and explore key genes and pathways associated with CRSwNP pathophysiology and prognosis. Methods: Three datasets were obtained from the Gene Expression Omnibus database and the intersecting DEGs were identified in CRSwNP patients. Gene Ontology (GO) and protein-protein interaction (PPI) network analysis were applied to investigate the function of DEGs. Nasal specimens from 90 CRSwNP and 45 controls were further collected and qRT-PCR was applied to verify the mRNA expression of hub genes, and moreover, their association with tissue eosinophilia and clinical characteristics in CRSwNP were analyzed. Results: Sixty-eight co-DEGs including 8 upregulated and 60 downregulated genes were identified and GO analyses identified the terms including positive regulation of ERK1 and ERK2 cascade, transforming growth factor beta receptor signaling pathway. PPI networks identified hub genes including EGF, ERBB4, AZGP1, CRISP3 and PIP which were validated to be significantly down-regulated in CRSwNP and showed well diagnostic prediction quality. In addition, lower mRNA expressions level of EGF and AZGP1 in eosinophilic CRSwNP compared with non-eosinophilic CRSwNP were found. Aberrant low expressions of EGF and AZGP1 protein in CRSwNP were identified, and there was good consistency between their mRNA expression level and protein relative expression level. Furthermore, the expressions of EGF and AZGP1 mRNA were significantly correlated with clinical severity parameters. Conclusion: Integrated analysis revealed 68 co-DEGs between nasal polyps and controls and identified hub genes, of which EGF and AZGP1 expression was significantly downregulated in eosinophilic CRSwNP and correlated with disease severity. Downregulation of EGF and AZGP1 may contribute to epithelial barrier dysfunction and type 2 inflammation in CRSwNP, suggesting them as potential diagnostic biomarkers and therapeutic targets.

Research on the hemostasis and coagulation effects of Callicarpa nudiflora based on the spectrum-effect relationship.

Callicarpa nudiflora (C. nudiflora) is widely used in the treatment of bleeding related diseases. However, its main material basis has not been fully defined which limits the in-depth study of screening out the material basis of hemostasis and coagulation from C. nudiflor. In this study, the method of spectrum-effect relationship was used to quickly screen the material basis of hemostasis and coagulation. The five compounds related to hemostasis and coagulation were screened as Alyssonoside (P24), Luteolin (P25), Quercetin (P26), Apigenin (P28), Isorhamnetin (P29). And the contribution of these five peaks to hemostasis and coagulation efficacy was P24 > P25 > P28 > P26 > P29.

Benzamidine Conjugation Converts Expelled Potential Active Agents into Antifungals against Drug-Resistant Fungi.

Fungal infections present a growing global public health concern, necessitating the development of novel antifungal drugs. However, many potential antifungals, particularly the expelled potential active agents (EPAAs), are often underestimated owing to their limitations in cellular entry or expulsion by efflux pumps. Herein, we identified 68 EPAAs out of 2322 candidates with activity against a Candida albicans efflux pump-deficient strain and no inhibitory activity against the wild-type strain. Using a novel conjugation strategy involving benzamidine (BM) as a mitochondrion-targeting warhead, we successfully converted EPAAs into potent antifungals against various urgent-threat azole-resistantCandida strains. Among the obtained EPAA-BM conjugates, IS-2-BM (11) exhibited excellent antifungal activities and induced negligible drug resistance. Furthermore, IS-2-BM prevented biofilm formation, eradicated mature biofilms, and exhibited excellent therapeutic effects in a murine model of systemic candidiasis. These findings provide a promising strategy for increasing the possibilities of discovering more antifungals.

Exploring the ECG "6+2" Phenomenon in Coronary Artery Disease and Coronary Artery Spasm: A Case Report Analysis and Treatment Implications.

BACKGROUND Although coronary artery disease and coronary artery spasm (CAS) can lead to acute myocardial infarction, there are clear differences in treatment between coronary heart disease and CAS, and the therapeutic schedule should not be confused. Furthermore, electrocardiogram (ECG) "6+2" phenomenon is recommend as a specific ECG indicator for lesions in the left main coronary artery or multiple vessels. Currently, no reports of this phenomenon in CAS exist. CASE REPORT A 72-year-old man had history of recurrent chest pain for over 6 years, with episodes lasting about 10 min and resolving with rest. He experienced symptom recurrence and exacerbation due to substance abuse. He was admitted to our Emergency Department for chest pain at rest. His emergency ECG revealed a 6+2 phenomenon, accompanied by troponin levels exceeding 18 times the reference value. Promptly, we conducted coronary angiography, with unexpected normal findings. Following thorough assessment, we postulated the patient could have CAS. Subsequent to medical team intervention, the patient's ECG normalized, leading to his discharge upon condition stabilization. CONCLUSIONS We report a case of CAS in a patient with ECG 6+2 phenomenon, without significant coronary artery stenosis. This differs from transient ST-segment elevation on ECG, a well-recognized hallmark of CAS; however, such a presentation has not been documented before. Additionally, treatment strategies for myocardial ischemic conditions stemming from coronary atherosclerosis diverge from those employed for CAS. Therefore, clinicians should advocate for coronary angiography whenever feasible. This approach serves to elucidate the underlying disease etiology and facilitates the administration of precision-targeted interventions for patients.

A magnetic solid phase extraction microfluidic chip coupled with gas chromatography-mass spectrometry for the determination of polycyclic aromatic hydrocarbons in aqueous samples.

In this paper, we designed and manufactured a reliable magnetic solid phase extraction (MSPE) microfluidic chip for determination of polycyclic aromatic hydrocarbons (PAHs) in water combined with gas chromatography-mass spectrometry. Sample loading, washing and elution are implemented with microinjection pump and integrated on a single chip, which reduced manual operation. Magnets were used to fix octadecyl/phenyl bifunctional Fe3O4@SiO2 extractant to avoid the design of weir structure in extraction chamber. The whole microfluidic chip was simple and low cost. Based on the microfluidic chip extraction platform, the on-chip MSPE method for the determination of PAHs was optimized and established. The results showed that this method required only 2 mL of sample, 2 mg of extractant, and 50 µL of elution organic solvent for whole on-chip MSPE process, which was environmentally friendly and consistent with green chemistry. Method verification results were displayed which the linear range of five PAHs was between 1-100 ng/mL with good linearity (R2≥ 0.9985), and the detection limits (S/N = 3) were 0.08-0.26 ng/mL. The RSDs of intra-day precision (n=6) and inter-day precision (n=9) for PAHs were less than 6.1 % and 7.2 %, respectively. Enrichment factors were determined to be 31.3-37.7. The recoveries of river water, tap water, bottle water, waste water and urine at three spiked levels were in the range of 89.9% to 113.7% and the matrix effect values were between 83.8% to 109.6%. The extraction platform has the advantages of accurate analysis, simple design and cost-effective, which is conducive to the widespread use of microfluidic chips.

Cerebral Hemodynamic and Metabolic Abnormalities in Neonatal Hypocalcemia: Findings from Advanced MRI.

BACKGROUND AND PURPOSE: Neonatal hypocalcemia is the most common metabolic disorder, and whether asymptomatic disease should be treated with calcium supplements remains controversial. We aimed to quantify neonatal hypocalcemia's global CBF and cerebral metabolic rate of oxygen (CMRO2) using physiologic MR imaging and elucidate the pathophysiologic vulnerabilities of neonatal hypocalcemia. MATERIALS AND METHODS: A total of 37 consecutive patients with neonatal hypocalcemia were enrolled. They were further divided into subgroups with and without structural MR imaging abnormalities, denoted as neonatal hypocalcemia-a (n = 24) and neonatal hypocalcemia-n (n = 13). Nineteen healthy neonates were enrolled as a control group. Brain physiologic parameters determined using phase-contrast MR imaging, T2-relaxation-under-spin-tagging MR imaging, and brain volume were compared between patients with neonatal hypocalcemia (their subgroups) and controls. Predictors for neonatal hypocalcemia-related brain injuries were identified using multivariate logistic regression analysis and expressed as ORs with 95% CIs. RESULTS: Patients with neonatal hypocalcemia showed significantly lower CBF and CMRO2 compared with controls. Furthermore, the neonatal hypocalcemia-a subset (versus controls or neonatal hypocalcemia-n) had significantly lower CBF and CMRO2. There was no obvious difference in CBF and CMRO2 between the neonatal hypocalcemia-n subset and controls. CBF and CMRO2 were independently associated with neonatal hypocalcemia. The ORs were 0.80 (95% CI, 0.65-0.99) and 0.97 (95% CI, 0.89-1.05) for CBF and CMRO2, respectively. CONCLUSIONS: Neonatal hypocalcemia with structural damage may exhibit lower hemodynamics and cerebral metabolism. CBF may be useful in assessing the need for calcium supplementation in asymptomatic neonatal hypocalcemia to prevent brain injury.

A liquid chromatography-tandem mass spectrometry method for comprehensive determination of metabolites in the purine pathway of rat plasma and its application in anti-gout effects of Lycium ruthenicum Murr.

It has been proved that purine metabolites are implicated in various biological syndromes and disorders. Therefore, the realization of panoramic detection of purine metabolites will be of great significance to the pathogenesis of purine metabolic disorders. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry method was developed for the comprehensive quantification of purine metabolites in rat plasma. The 17 purine metabolites were separated and quantified in the short running time of 15 min. The proposed method was strictly validated by applying SeraSub solution as a matrix and proved to be linear (R2 ≥ 0.9944), accurate (the recoveries of all analytes ranged from 85.3% to 103.0%, with relative standard deviation values ≤ 9.3%), and precise (the intra- and inter-day precisions were less than 10.8% and 12.4%, respectively). The method was then successfully applied to the qualification of the endogenous purine metabolites in acute gouty arthritis rats, as well as colchicine and anthocyanin-intervened rats. Results showed that uric acid, xanthine, hypoxanthine, and xanthine were considered the key factors of acute gouty arthritis. The established method and measurement of purines in rat plasma might help the investigation of the action mechanisms between purine disorders and related diseases.