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Purpose: The fibroblast activation protein inhibitor-04 (FAPI-04) specifically binds to the FAP of activated myocardial fibroblasts, which makes 68 Ga-labelled FAPI-04 ( 68 Ga-FAPI-04) positron emission tomography (PET)/magnetic resonance (MR) a new potential imaging technique for the evaluation of myocardial fibrosis. This study aimed to evaluate the potential value of 68 Ga-FAPI-04 PET/MR in assessing and predicting changes in renal function in patients with acute ST-elevation myocardial infarction (STEMI)., Methods: Thirty-three patients with STEMI were included in this study. 68 Ga-FAPI-04 PET/MR and cardiac magnetic resonance were performed before discharge in all patients. Worsening renal function(WRF) was defined as ≥20% decrease in estimated glomerular filtration rate(eGFR) from baseline to 12 months., Results: The WRF group demonstrated higher 68 Ga-FAPI-04 uptake volume (UV) at baseline than the non-WRF group(P = 0.009). 68 Ga-FAPI-04 UV at baseline was correlated with follow-up eGFR (r = -0.493, P = 0.004). 68 Ga-FAPI-04 UV at baseline was a significant predictor of WRF (OR = 1.014, P = 0.029) at 12 months after STEMI., Conclusions: As an effective tool to non-invasively quantify myocardial fibroblast activation, 68 Ga-FAPI-04 PET/MR has potential value for assessing and predicting worsening renal function in patients with STEMI., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Heavy metals (HMs) present in the natural aquatic environment can form a ternary aggregate of "EPS-DOM-HMs" with the prevalent microalgae extracellular polymers substances (EPS) and macromolecular dissolved organic matters (DOMs), which show special molecular structure and biological interaction. This study reveals the formation of "EPS-TA-HMs" and the mechanism of their physiological and metabolic effects on Raphidocelis subcapitata. Results indicate that TA-Cr(III) can bind to EPS to form ternary aggregates with substances coexisting large and small hydrodynamic diameters and that the interactions are dominated by hydrophobic interactions of the protein binding to the pyrrole ring of the polyphenol and hydrogen bonding interactions formed by OC-(N R O). The protein structure of EPS has the largest proportion of proline, glycine, aspartic acid, and tryptophan. These interactions promoted the secretion of EPS components and reduced the growth inhibition of Raphidocelis subcapitata by 45.9 % compared with Cr(III) exposure. TEM analysis combined with EDS analysis indicated that Cr(III) was taken intracellularly and TA-Cr(III) was not. In addition, metabolomics analyses revealed that microalgae initiate adaptive mechanisms via the activation of a two-component system (i.e., maintenance of high metabolic activity). This study underscored the morphology of HMs in real aquatic environments and the mechanisms of metabolic effects on aquatic organisms., Competing Interests: Declaration of Competing Interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydrogel-based tissue clearing technologies have shown significant promise for deep-tissue imaging and subcellular-level optical 3D reconstruction of whole organs. This study proposes a novel approach utilizing a deep eutectic solvent (DES) formulated with glucose and m-xylylene-diamine (MXDA) to create a highly efficient tissue-clearing hydrogel system named the passive hydrogel clearing system (PHCS). PHCS achieved efficient tissue clearing through a single-step tissue gelation process. The resulting hydrogel-tissue complex exhibited thermoreversible properties, transitioning into a sol state upon heating and vice versa upon cooling. Notably, PHCS enabled media embedding, facilitating immunofluorescence histopathology. Additionally, the system demonstrated compatibility with various fluorescent probes, particularly lipophilic dyes. Our study successfully employed PHCS for the reconstruction of vascular structures within the intestine, enabling the generation of a 3D pathology model. These findings suggest that PHCS is a promising novel method for fabricating hydrogels for tissue clearing and holds great potential for application as a mounting medium for morphological imaging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests of personal relationships that could have appeared to influence in the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Bladder cancer (BCa) is a highly aggressive malignancy of the urinary system. Timely detection is imperative for enhancing BCa patient prognosis., Materials and Methods: This study introduces a novel approach for detecting long non-coding RNA (lncRNA) Mitochondrial RNA Processing Endoribonuclease (RMRP) in urine exosomes from BCa patients using the reverse transcription recombinase-aided amplification (RT-RAA) and clustered regularly interspaced short palindromic repeats and associated Cas12a proteins (CRISPR/Cas12a) technique. Various statistical methods were used to evaluate its diagnostic value for BCa., Results: The specificity of urine exosomal RMRP detection for BCa diagnosis was enhanced by using RT-RAA combined with CRISPR/Cas12a. The testing process duration was reduced to 30 min, which supports rapid detection. Moreover, this approach allows the identification of target signals in real-time using blue light, facilitating immediate detection. In clinical sample analysis, this methodology exhibited a high level of diagnostic efficacy. This was evidenced by larger area under the curve values with receiver operating characteristic curve analysis compared with using traditional RT-qPCR methods, indicating superior diagnostic accuracy and sensitivity. Furthermore, the combined analysis of RMRP expression in urine exosomes detected by RT-RAA-CRISPR/Cas12a and NMP-22 expression may further enhance diagnostic accuracy., Conclusions: The RT-RAA-CRISPR/Cas12a technology is a swift, sensitive, and uncomplicated method for nucleic acid detection. Because of its convenient and non-invasive sampling approach, user-friendly operation, and reproducibility, this technology is very promising for automated detection and holds favorable application possibilities within clinical environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to improve the eating quality of yellow-feathered broiler chicks by feeding them corn-soybean meal diets supplemented with 250, 500, and 1,000 mg/kg quercetin. we examined the impact of varying doses of dietary quercetin on the sensory quality of chicken breast meat as well as on the antioxidant enzymes, antioxidant-related signaling molecules, structure and thermal stability of myofibrillar protein (MPs), and microstructure of myogenic fibers in the meat during 24 h of postslaughter aging. Additionally, we investigated the potential correlations among antioxidant capacity, MP structure, and meat quality parameters. The results indicated that dietary supplementations with 500 and 1,000 mg/kg quercetin improved the physicochemical properties and eating quality of yellow-feathered broiler chicken breast meat during 12 to 24 h postslaughter. Additionally, quercetin improved the postslaughter oxidative stress status and reduced protein and lipid oxidation levels. It also increased hydrogen bonding interactions and α-helix content during 6 to 12 h postslaughter and decreased β-sheet content during 12 to 24 h postslaughter in chicken breast MP. This resulted in improved postslaughter MP structure and thermal stability. The correlation results indicated that the enhancement of antioxidant capacity and MP structure enhanced the physicochemical and edible qualities of yellow-feathered broiler chicken breast meat. In conclusion, the current findings suggest that dietary supplementation with quercetin is an ideal approach for improving the eating quality of chicken meat, thereby broadening our understanding of theoretical and technological applications for improving the quality of chicken., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Auditory verbal hallucinations (AVH) are a core positive symptom of schizophrenia and are regarded as a consequence of the functional breakdown in the related sensory process. Yet, the potential mechanism of AVH is still lacking. In the present study, we explored the difference between AVHs (n = 23) and non-AVHs (n = 19) in schizophrenia and healthy controls (n = 29) by using multidimensional electroencephalograms data during an auditory oddball task. Compared to healthy controls, both AVH and non-AVH groups showed reduced P300 amplitudes. Additionally, the results from brain networks analysis revealed that AVH patients showed reduced left frontal to posterior parietal/temporal connectivity compared to non-AVH patients. Moreover, using the fused network properties of both delta and theta bands as features for in-depth learning made it possible to identify the AVH from non-AVH patients at an accuracy of 80.95%. The left frontal-parietal/temporal networks seen in the auditory oddball paradigm might be underlying biomarkers of AVH in schizophrenia. This study demonstrated for the first time the functional breakdown of the auditory processing pathway in the AVH patients, leading to a better understanding of the atypical brain network of the AVH patients., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ammonia (NH 3 ) measurements were performed with a mobile platform deploying a cavity ring-down spectroscopy NH 3 analyzer in Beijing. The transect and loop sampling strategy revealed that the Beijing urban area is more strongly affected by NH 3 emissions than surrounding areas. Although average enhancements of on-road NH 3 were small compared to background levels, traffic emissions clearly dominated city enhancements of NH 3 , carbon dioxide (CO 2 ), acetaldehyde and acetone. Increments of on-road NH 3 ranged between 5.1 ppb and 11.4 ppb in urban areas, representing an enhancement of 20.6 % to 47.9 % over the urban background. The vehicle NH 3 :CO 2 emission ratio was 0.26 ppb/ppm, about a factor of 1.5 higher than the value derived from the available emission inventory. The obtained NH 3 emission factor was approximately 306.9 mg/kg. If the annual gasoline consumption in Beijing is accurate, annual NH 3 emissions from vehicles are estimated at 1.5 Gg. The influx and outflux of NH 3 in Beijing during monitoring periods fluctuated due to variations of wind direction (WD), wind speed (WS), and planetary boundary layer height (PBLH). Net fluxes at the 4 th Ring Road were larger than zero, suggesting that local emissions were important in urban Beijing. Negative net fluxes at the 6 th Ring Road reveal a large amount of NH 3 transported from agricultural regions south of Beijing lost during transport across the city, for example by deposition or particle formation in the city. Our analyses have important implications for regional NH 3 emission estimates and for improving vehicular NH 3 emission inventory allocations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Studies have demonstrated that the viscosity and SO 2 in mitochondria are involved in various physiological processes, which are both important for maintaining the normal function of mitochondria. In this research, we rationally designed and synthesized a novel mitochondria-targetable fluorescent probe Mito-MG with near-infrared absorption and emission for dual-response of viscosity and SO 2 . Based on the TICT mechanism and Michael addition reaction, the probe Mito-MG responds to viscosity and SO 2 with different near-infrared fluorescence signals. Importantly, Mito-MG presented outstanding mitochondrial targeting ability (Pearson's colocalization coefficient is 0.8602) and has been successfully applied to imaging of the cells, zebrafish and mice. We believe that Mito-MG could be applied as a powerful tool for a deep understanding of the connection of viscosity and SO 2 in biological systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Social determinants of health (SDOH) are non-medical factors that can profoundly impact patient health outcomes. However, SDOH are rarely available in structured electronic health record (EHR) data such as diagnosis codes, and more commonly found in unstructured narrative clinical notes. Hence, identifying social context from unstructured EHR data has become increasingly important. Yet, previous work on using natural language processing to automate extraction of SDOH from text (a) usually focuses on an ad hoc selection of SDOH, and (b) does not use the latest advances in deep learning. Our objective was to advance automatic extraction of SDOH from clinical text by (a) systematically creating a set of SDOH based on standard biomedical and psychiatric ontologies, and (b) training state-of-the-art deep neural networks to extract mentions of these SDOH from clinical notes., Design: A retrospective cohort study., Setting and Participants: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC-III) database. The corpus comprised 3,504 social related sentences from 2,670 clinical notes., Methods: We developed a framework for automated classification of multiple SDOH categories. Our dataset comprised narrative clinical notes under the "Social Work" category in the MIMIC-III Clinical Database. Using standard terminologies, SNOMED-CT and DSM-IV, we systematically curated a set of 13 SDOH categories and created annotation guidelines for these. After manually annotating the 3,504 sentences, we developed and tested three deep neural network (DNN) architectures - convolutional neural network (CNN), long short-term memory (LSTM) network, and the Bidirectional Encoder Representations from Transformers (BERT) - for automated detection of eight SDOH categories. We also compared these DNNs to three baselines models: (1) cTAKES, as well as (2) L2-regularized logistic regression and (3) random forests on bags-of-words. Model evaluation metrics included micro- and macro- F1, and area under the receiver operating characteristic curve (AUC)., Results: All three DNN models accurately classified all SDOH categories (minimum micro-F1 = 0.632, minimum macro-AUC = 0.854). Compared to the CNN and LSTM, BERT performed best in most key metrics (micro-F1 = 0.690, macro-AUC = 0.907). The BERT model most effectively identified the "occupational" category (F1 = 0.774, AUC = 0.965) and least effectively identified the "non-SDOH" category (F = 0.491, AUC = 0.788). BERT outperformed cTAKES in distinguishing social vs non-social sentences (BERT F1 = 0.87 vs. cTAKES F1 = 0.06), and outperformed logistic regression (micro-F1 = 0.649, macro-AUC = 0.696) and random forest (micro-F1 = 0.502, macro-AUC = 0.523) trained on bag-of-words., Conclusions: Our study framework with DNN models demonstrated improved performance for efficiently identifying a systematic range of SDOH categories from clinical notes in the EHR. Improved identification of patient SDOH may further improve healthcare outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

18β-Glycyrrhetinic acid (GA) is often topically applied in clinical treatment of inflammatory skin diseases. However, GA has poor solubility in water, which results in poor skin permeability and low bioavailability. Nanocrystallization of drugs can enhance their permeability and improve bioavailability. We prepared GA nanocrystals (Nano GA) by high-pressure homogenization. These nanocrystals were characterized by photon correlation spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray diffractometry. The ability of Nano GA to improve dermal permeability was investigated ex vivo using Franz diffusion vertical cells and mouse skin. The topical anti-inflammatory activity of Nano GA was assessed in vivo by a 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced model in mouse ears. The average particle size of a GA nanocrystalline suspension was 288.6 ± 7.3 nm, with a narrow particle-size distribution (polydispersity index ∼0.13 ± 0.10), and the particle size of the lyophilized powder increased (552.0 ± 9.8 nm). After nanocrystallization, the thermal stability and crystallinity decreased but solubility increased significantly. Nano GA showed higher dermal permeability than Coarse GA. Macroscopic and staining-based observations of mouse ears and the levels of proinflammatory factors and myeloperoxidase revealed that the Nano GA hydrogel exhibited better anti-edema ability and more strongly inhibited inflammation development than the Coarse GA hydrogel and indomethacin hydrogel (positive drug). These results suggest that Nano GA could be an efficacious topical therapeutic agent for skin inflammation., (Copyright © 2021. Published by Elsevier B.V.)

An increasing number of epidemiological studies suggest that adherence to Western dietary patterns (WDPs) is associated with risk of gestational diabetes mellitus (GDM), but results remain inconsistent. Therefore, we conducted a systematic review and meta-analysis of the effect of WDPs and typical Western dietary foods on GDM. A literature search was performed in PubMed, Embase, Web of Knowledge, and the Cochrane Library up to December 2019. Cohort studies investigating the combined associations of WDPs with incidence of GDM were included. Reviewers were paired, and they independently reviewed and assessed studies, extracted data, and evaluated study quality. Pooled HRs were calculated using random-effects models. Heterogeneity and publication bias tests were also conducted. Twenty-one prospective cohort studies with 191,589 participants, including 12,331 women with GDM, were included in our analysis. The pooled risk ratio (RR) of WDPs was 1.52 (95% CI: 1.21, 1.91), indicating a significant association with GDM risk in Western countries. Potatoes (pooled RR: 1.12; 95% CI: 0.93, 1.35) showed a nonsignificant (P > 0.05) relation to GDM risk. However, consumption of animal meat (pooled RR: 1.35; 95% CI: 1.16, 1.57) and fast food (pooled RR: 1.75; 95% CI: 1.41, 2.19) showed a positive association with the risk of developing GDM. Subgroup analysis demonstrated that the consumption of red meat and processed red meat increased the risk of GDM more than either poultry or fish intake. Our study provides further evidence for understanding the relation between dietary factors and increased GDM risk and contributes to reducing the incidence of GDM through healthy diets., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The impact of NaCl and tripolyphosphate (TPP)/pyrophosphate (PP) on protein oxidation and Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) formation in roasted beef patties was investigated. The content of CML and CEL in patties treated with salts was approximately 1.1-1.7 and 1.2-3.2 times higher than that of the control samples, respectively. An increase in salt content caused higher oxidation of tryptophan and protein carbonylation with a decrease in Schiff bases (P < 0.05) and a slight decrease in lipid oxidation (P < 0.05). Significant correlations (P < 0.05) between CML, CEL, and protein oxidation measurements was found. The higher salts content, causing less cooking loss and higher moisture content, significantly correlated (P < 0.05) with CML, CEL content, and protein oxidation of the patties. The increase in CML and CEL content and protein oxidation in roasted patties with salts might be related to the pro-oxidation of salts, and also partly due to the temperature changes caused by the water-holding capacity of salts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chitosan-based thermosensitive hydrogels have been widely used in drug delivery and tissue engineering, but their poor bioactivity has limited their further applications. Integral active oyster peptide microspheres (OPM) with an average particle diameter of 3.9 μm were prepared with high encapsulation efficiency (72.8%) and loading capacity (11.9%), exhibiting desirable sustained release effects. Using catechol functionalized chitosan (CS-C) as the polymeric matrix, OPM as the filler, and β-sodium glycerophosphate (β-GP) as a thermal sensitizer, the thermosensitive hydrogel CS-C/OPM/β-GP was prepared. Besides, the application of the hydrogel on wound healing was studied, and its biosafety was evaluated. The results of cell migration in vitro showed that the cell migration rate of CS-C/OPM/β-GP reached 97.47 ± 5.41% within 48 h, indicating that the hydrogel accelerated the migration of L929 cells. As demonstrated in the mouse skin wound experiment, CS-C/OPM/β-GP hydrogel not only inhibited the aggregation of diversified inflammatory cells and accelerated the generation of collagen fibers and new blood vessels of the wound, but also enhanced the synthesis of total protein (TP) in granulation tissue, and up-regulated the expression of Ki-67 and VEGF in the injury, thereby achieving fast wound healing. Safety evaluation results showed that CS-C/OPM/β-GP hydrogel was not cytotoxic to L929 cells, and the hemolysis ratio was less than 5% within 1 mg/mL. In conclusion, CS-C/OPM/β-GP hydrogel is expected as a promising medical dressing for wound healing., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Nitrogen (N) deposition-induced N input in alpine meadow soils may affect the soil exchange of methane (CH 4 ) with the atmosphere. The quantities and spatiotemporal variation in CH 4 uptake remain largely unknown for this ecosystem on a global scale. Previous studies regarding CH 4 flux have mainly focused on the growing season in alpine meadows. Thus, the impact of N deposition on the non-growing season uptake of CH 4 is unknown. In this study, we investigated the effects of N deposition on CH 4 uptake during both the growing and non-growing seasons in an alpine meadow on the central Qinghai-Tibet Plateau (QTP). The CH 4 fluxes were measured using static chambers and gas chromatography in four N deposition treatment areas (Control; N7, 7 kg N ha -1  yr -1 ; N20, 20 kg N ha -1  yr -1 ; N40, 40 kg N ha -1  yr -1 ) from May 2015 to August 2018. Our results showed that alpine meadow soils acted as CH 4 sinks throughout the year. N deposition significantly decreased CH 4 uptake fluxes (P < 0.05) and the annual mean CH 4 uptake fluxes declined at N deposition levels of 7, 20, and 40 kg N ha -1  yr -1 by 12.3%, 14.4%, and 20.5%, respectively, compared with that of the control. Annual CH 4 uptake was significantly correlated with total annual precipitation, mean annual air temperature, and N deposition rate. Annual cumulative CH 4 uptake in the four treatments across 3 years was 75.1 mg C m -2 , where approximately 40% of the total annual CH 4 uptake occurred during the non-growing season. Our results showed that CH 4 uptake in the non-growing season cannot be ignored when estimating annual uptake of CH 4 because of the large CH 4 uptake during the non-growing season in the alpine meadow on the QTP under N deposition conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Traditional methods for the quantification of OSA severity may not encapsulate potential relationships between hypoxemia in OSA and cardiovascular risk., Research Question: Do novel nocturnal oxygen saturation (Spo 2 ) metrics have prognostic value in patients with OSA and high cardiovascular event risk?, Study Design and Methods: We conducted post hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. In 2687 individuals, Cox proportional hazards models that were stratified for treatment allocation were used to determine the associations between clinical characteristics, pulse oximetry-derived metrics that were designed to quantify sustained and episodic features of hypoxemia, and cardiovascular outcomes. Metrics included oxygen desaturation index, time <90% Spo 2 , average Spo 2 for the entire recording (mean Spo 2 ), average Spo 2 during desaturation events (desaturation Spo 2 ), average baseline Spo 2 interpolated across episodic desaturation events (baseline Spo 2 ), episodic desaturation event duration and desaturation/resaturation-time ratio, and mean and SD of pulse rate., Results: Neither apnea-hypopnea index, oxygen desaturation index, nor any of the novel Spo 2 metrics were associated with the primary SAVE composite cardiovascular outcome. Mean and baseline Spo 2 were associated with heart failure (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .009; and HR, 0.78; 95% CI, 0.67-0.90; P = .001, respectively) and myocardial infarction (HR, 0.86; 95% CI, 0.77-0.95; P = .003; and HR, 0.81; 95% CI, 0.73-0.90; P < .001, respectively). Desaturation duration and desaturation/resaturation time ratio, with established risk factors, predicted future heart failure (area under the curve, 0.86; 95% CI, 0.79-0.93)., Interpretation: Apnea-hypopnea index and oxygen desaturation index were not associated with cardiovascular outcomes. In contrast, the pattern of oxygen desaturation was associated with heart failure and myocardial infarction. However, concomitant risk factors remained the predominant determinants for secondary cardiovascular events and thus deserve the most intensive management., (Copyright © 2020. Published by Elsevier Inc.)

Background: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown., Patients and Methods: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City., Results: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49)., Conclusion: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis., Clinical Trial Number: NCT00941538., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fluoroquinolones (FQs) have attracted wide concerns due to their pseudo-persistent and universal presence in natural water. Here we exposed zebrafish separately to two FQs (enrofloxacin (ENR) and ofloxacin (OFL)) in different copper (Cu) concentrations for 20 days (d) in a flow-through system, followed by a 11 d depuration period in clean water to investigate compound specific bioaccumulation and tissue distribution. Two FQs could accumulate in zebrafish, and the high concentration was observed in liver. Moreover, the levels of FQs in different treatment groups were higher than the corresponding control fish group. The uptake rates (k 1 ), elimination rates (k 2 ), BCF value, and half-lives (t 1/2 ) of FQs ranged from 0.02 to 3.28 d -1 , 0.01 to 0.97 d -1 , 0.33 to 109.33, 9.90 to 69.31 d, respectively. With Cu exposure concentration's increasing, k 1 values in three tissues (liver, skin and gill) obviously decreased. The exposure concentration affected the BCF value significantly, but didn't change their relative compositions in liver, gill, skin, and muscle after long time exposure. BCF values of ENR were always a little bit higher than those of OFL in almost all the tissues (liver, skin and gill) in the low Cu concentration treatments, whereas, in the high Cu concentration treatments the bioconcentration factors (BCF) values of ENR were lower than the values of OFL. The exposure of Cu played an important role in the FQs bioconcentration and BCF. These results are meaningful for improved understanding and prediction of the behavior and fate of metallic and antibiotics in aqueous environments., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Red blood cell distribution width (RDW) is a parameter of standard full blood count tests that reflects the size variability of erythrocytes In recent studies, RDW levels have been associated with ischemic heart disease, acute and chronic heart failure, hypertension, and inflammatory bowel disease. However, it is unclear whether RDW is associated with colorectal cancer., Methods: Eighty-five patients were diagnosed with colorectal cancer. Fifty-four other patients each diagnosed with colon polyps during the same period served as the control group. The patients were classified according to the seventh edition of the AJCC Cancer Staging Manual of 2009 into groups of different cancer stages, and simultaneously divided into groups with or without metastasis. The multigroup metering data was tested by a non-parametric Kruskal-Wallis H test, and the two subsets of patients formed above were compared using a Mann-Whitney U test. The association between continuous variables was assessed by Spearman correlation analysis while the association between RDW and colorectal cancer metastasis was estimated by receiver operating characteristic (ROC) curve analysis., Results: Increased RDW was observed in patients with colorectal cancer. The RDW was significantly different for each subgroup of colorectal cancer as follows: stage III + IV > stage III, T3 + T4 > T1 + T2, N1 + N2 > N0, and M1 > M0 (P < 0.05). The area under the receiver-operating characteristic curve of the RDW in the diagnosis of colorectal cancer metastasis was 0.721 (95% confidence interval of 0.612-0.831)., Conclusions: The value of RDW is closely related to colorectal cancer metastasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

It has been reported in alphabetic languages that individuals with schizophrenia showed language-related cognitive impairments including phonological deficits, which were in turn associated with clinical symptoms such as auditory hallucinations and thought disorders. To date, however, the phonological deficits involved in schizophrenia in Chinese and its neural basis have not been well established. In order to establish such a relationship we conducted a behavioral study using lexical tone judgment and digit span tasks as well as an event-related potential (ERP) study with an auditory oddball paradigm, in particular, for P300 effects, the event-related brain potential (ERP) index of discrimination. Chinese patients with schizophrenia and Chinese healthy controls in China participated in the current study. Compared to the healthy controls, the patients with schizophrenia showed significant impairments in phonological processing skills, which in turn significantly correlated with smaller P300 effects. Thus these behavioral and electrophysiological findings in Chinese patients with schizophrenia were critically evaluated in terms of their phonological processing abilities., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Understanding the trend of chemical composition of precipitation is of great importance for air pollution control strategies in Northern China. A comprehensive study on the long-term chemical compositions of precipitation was carried out from 2003 to 2014 at the Shangdianzi (SDZ) regional background station in northern China. All samples were analyzed for pH, electrical conductivity and major ions (F - , Cl - , NO 3 - , SO 4 2- , NH 4 + , Mg 2+ , Ca 2+ , K + and Na + ). The average pH during this period was 4.53±0.35, which is considerably lower than those reported in other background stations in China (Linan, Waliguan and Longfengshan). NH 4 + , SO 4 2- , Ca 2+ and NO 3 - were the dominant ions in precipitation, with concentrations (volume-weighted mean) of 212.99μeqL -1 , 200.20μeqL -1 , 116.88μeqL -1 and 98.56μeqL -1 , respectively. The ion concentrations at SDZ were much higher than those of other background stations and megacities in China. A significantly increasing trend was observed for NO 3 - (7.26%year -1 ), and a decreasing trend was observed for SO 4 2- /NO 3 - , suggesting that the precipitation of SDZ evolved from a sulfuric acid type to a mixed type dominated by both sulfuric and nitric acid. The source identification indicated that SO 4 2- , NO 3 - , NH 4 + and F - were dominated by secondary sources, Mg 2+ , Ca 2+ and Na + mostly originated from natural sources, and K + and Cl - probably associated with anthropogenic sources. Long-range transport of air masses could influence the acidity, electrical conductivity and ion concentrations of precipitation at SDZ. The higher acidity and ion concentrations mainly occurred in the southerly and westerly trajectory pathways and partially in northwest pathways. Anthropogenic pollutants and crustal sources along these pathways were significant contributors to the chemical composition of precipitation in SDZ., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background and Objectives: Laryngeal morphologic changes are important in risk assessment of upper airway obstruction (UAO) after inhalation injury. This retrospective study evaluates the clinical application of laryngeal burn classification system., Materials and Methods: Clinical data from January 1999 to June 2013 were analyzed retrospectively. The following data collected: age, gender, total burned surface area (TBSA), third-degree burn surface area, co-morbid injuries and complications, proportion of patients with tracheotomy, interval between tracheotomy and injury, incidence and mortality of UAO, and reasons for death., Results: Four hundred and forty-three patients were included; 405 patients underwent multiple fibro-laryngoscopic observation, of which I, II and III types of laryngeal burns were present in 49.9, 38.0, and 12.1% patients, respectively. Laryngeal burn severity was related to TBSA and third-degree burn surface area. Overall tracheotomy rate (n=443) was 37.02%. The mean interval between tracheotomy and injury was 10.0±12.17h. Over 75% patients underwent tracheotomy within 12h. Compared with moderate inhalation burn group, the severe inhalation burn group showed a significantly higher tracheotomy rate within 12h and a significantly shorter interval between tracheotomy and injury. Patient mortality was significantly related to the severity of inhalation injury., Conclusion: The classification system of the morphologic laryngeal changes in laryngeal burn patients could effectively evaluate the UAO risk, enable earlier prophylactic tracheotomy after UAO onset, reduce surgical difficulties and risks, decrease clinical pressure of doctors, and prevent UAO. Laryngeal burn severity was related to TBSA and mortality and may be an important severity and prognosis indicator of inhalation injury., (Copyright © 2015. Published by Elsevier Ltd.)

Background and Purpose: It is well known that inflammation influence chronic subdural hematoma (CSDH) formation to a large extent. Atorvastatin has pleiotropic effects on restraining inflammation and promoting angiogenesis besides its cholesterol-lowering function. Hence, atorvastatin may induce anti-inflammation effects and facilitate therapeutic effects for subdural hematoma (SDH)., Methods: Adult male Wistar rats were subjected to SDH and successful establishment of SDH was confirmed by magnetic resonance imaging (MRI). The treatment was initiated 6 hours after SDH induction. For the treatment, rats suffering SDH were randomly divided into saline group (the control group, rats were treated by saline, n=29) and atorvastatin group (rats were treated by atorvastatin, 3mg/kg/day, n=30). The volume of lesion before treatment as well as on day 2 and day 7 after initial treatment was measured by MRI, respectively. The behaviors before SDH induction and on the days 1, 3, 5 and 7 after the initial treatment were dynamically evaluated. Gene expression, cytokine secretion and the number of neutrophilic granulocyte and vascular density were measured in both neomembrane and SDH lesion on the day 2 and day 7 after the initial treatment., Results: It was found that the SDH rats treated by atorvastatin had a better behavior recovery compared to the ones treated by saline (p<0.05). By virtue of MRI scanning, it was revealed that SDH volumes were eliminated at a high speed by administration of atorvastatin than that of saline. With the help of the microscopic examination in the neomembrane, it was detected that the density of CD31+ neovasculars in the atorvastatin group was significantly higher than that in the saline group and the number of neutrophilic granulocyte in the atorvastatin group is less than that in the saline group. In comparison with saline treatment, the atorvastatin treatment did not change IL-10 expression and secretion, but it significantly decreased TNF-α and IL-6 level as well as VEGF gene expression., Conclusions: Atorvastatin treatment may eliminate SDH and improve the neural function of the rats through its anti-inflammatory effects. Hence, it indicated that statin induced inflammatory modulation might play a significant role in rats' SDH elimination and the functional recovery., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Chronic subdural hematoma (CSDH) is common and more prevalent in the aged population. Surgical intervention is the treatment of choice, but its outcomes may not be satisfactory because of recurrence and physical infirmity associated with aging. Aberrant angiogenesis and localized inflammation contribute to the formation of CSDH. Atorvastatin is active in promoting angiogenesis and modulating inflammation. We hypothesize that atorvastatin is effective in reducing CSDH and have tested the hypothesis in a preliminary prospective study of small cohort of patients., Methods: Twenty-three patients with CT- or MRI-confirmed CSDH were recruited from three regional medical centers and evaluated using Markwalder's Grading Scale (MGS) and the Glasgow Coma Scale (GCS). These patients received oral atorvastatin 20 mg/day for 1-6 months (3.02±1.77 months) and were followed for 3 to 36 months (18.62±13.13) after the therapy. Hematoma volume, neurological functions and daily activities (measured using the Activities of Daily Life-the Barthel Index scale, ADL-BI) were compared before and after treatment with Linear Trend Chi-Square test., Results: Twenty-two of the 23 patients experienced improvements in symptoms, and the reduction in hematoma volume from 48.70±20.38 ml to 16.64±14.28 ml (paired-sample t-test, p<0.01) within the first month of the treatment. Hematoma was completely resolved in 17 patients (77.3%) and shrank by more than 73.99%±11.17% in 5 patients (22.7%) 3 months after the treatment was initiated. One patient experienced an initial relief of symptoms, but his condition deteriorated with an enlarged hematoma during the 4th week of treatment and underwent surgery. At 6 months, 18 patients presented no hematoma by CT or MRI and four patients, whose hematoma was completely resolved at 3 months, were not followed. None of these 22 patients relapsed during the entire follow-up period of 3-36 months. All have improved MGS, GCS, and ADL-BI. No atorvastatin-related side effects were documented., Conclusion: Results of this preliminary prospective study show that the oral administration of atorvastatin is safe and effective in treating CSDH, offering a cost-effective alternative to surgery. A prospective randomized clinical trial is required to validate the effect of atorvastatin., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Correlation of heavy metals in the tissues of typical organisms (i.e., fishes and crabs) and those in their living environments (i.e., surface water, bottom water, and sediment) in Yangtze River Estuary has been qualitatively and quantitatively analyzed. Metal levels followed the trend: sediments > Eriocheir sinensis > Eriocheir leptognathus > benthic fish > pelagic fish > bottom water > surface water. Tissues in fishes and crabs of different species and sizes had diverse metal bioaccumulation characteristics, which was significantly affected by environment factors and their living habits. Metal levels in legs of crabs, and heads and skins of fishes showed significant correlations with those in their living environments. Collichthys lucidus is an effective bioindicator for assessing metal levels in water. No significant health risk was identified by the estimated daily intake and target hazard quotients analyses., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The mechanism of FFA-induced insulin resistance is not fully understood. We have searched for effector molecules(s) in FFA-induced insulin resistance. Palmitic acid (PA) but not oleic acid (OA) induced insulin resistance in L6 myotubes through C-Jun N-terminal kinase (JNK) and insulin receptor substrate 1 (IRS-1) Ser307 phosphorylation. Inhibitors of ceramide synthesis did not block insulin resistance by PA. However, inhibition of the conversion of PA to lysophosphatidylcholine (LPC) by calcium-independent phospholipase A₂ (iPLA₂) inhibitors, such as bromoenol lactone (BEL) or palmitoyl trifluoromethyl ketone (PACOCF₃), prevented insulin resistance by PA. iPLA₂ inhibitors or iPLA₂ small interfering RNA (siRNA) attenuated JNK or IRS-1 Ser307 phosphorylation by PA. PA treatment increased LPC content, which was reversed by iPLA₂ inhibitors or iPLA₂ siRNA. The intracellular DAG level was increased by iPLA₂ inhibitors, despite ameliorated insulin resistance. Pertussis toxin (PTX), which inhibits LPC action through the G-protein coupled receptor (GPCR)/Gα(i), reversed insulin resistance by PA. BEL administration ameliorated insulin resistance and diabetes in db/db mice. JNK and IRS-1Ser307 phosphorylation in the liver and muscle of db/db mice was attenuated by BEL. LPC content was increased in the liver and muscle of db/db mice, which was suppressed by BEL. These findings implicate LPC as an important lipid intermediate that links saturated fatty acids to insulin resistance.

Chitosan composite rods (CS-Fe(3+)) were prepared via an in situ precipitation method. The relationships among the preparation, structures, and properties of the CS-Fe(3+) composite rods have been investigated. The results of Fourier-transform infrared spectroscopy (FTIR) and core electron X-ray photoelectron spectroscopy (XPS) indicate that the CS and Fe(3+) are coordinated via a chelation mechanism. The content of Fe(3+) in the complex was determined by atomic absorption spectrometry (AAS) and elemental analysis (EA), the results of which suggested that the content of Fe(3+) in the complex can be controlled by the concentration of the ferric salts during coordination. The changes in thermal stability and crystallization properties were measured by thermogravimetric analysis (TGA) and X-ray diffraction (XRD) patterns, respectively. Scanning electron microscopy (SEM) was used to observe the morphological change of the CS-Fe(3+) complex rod. After coordination with Fe(3+), the CS rod had a denser, layered structure. However, the layered structure cannot remain intact when the ratios of -NH(2)/Fe(3+) are 100/15 and 100/20. Moreover, its thermal stability decreased, and its bending strength was improved significantly (from 86 MPa to more than 210 MPa), despite the remarkable decrease in the degree of crystallinity., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

ERK activation by dopamine D(2) receptor (D(2)R) has been extensively characterized in various cell types including brain tissues. However, the involvement of beta-arrestin in the D(2)R-mediated ERK activation is not clear yet. Three different strategies were employed in this study to determine the roles of G protein or beta-arrestin in D(2)R-mediated ERK activation. The cellular level of beta-arrestins was reduced by RNA interference and pertussis toxin-insensitive Gi proteins were used to identify the G protein involved. Finally point mutations of D(2)R in which coupling with G protein was abolished but the interaction with beta-arrestin was increased, were employed to determine whether the affinity between D(2)R and beta-arrestin is a critical factor for beta-arrestin-mediated ERK activation. Our results show that G(i2) protein is involved in D(2)R-mediated ERK activation but beta-arrestins are either not involved or play minor role.

We examined the variation in aboveground biomass accumulation and tissue concentrations of nitrogen (N), phosphorus (P), copper (Cu), zinc (Zn) and lead (Pb) in Phragmites australis (common reed), Spartina alterniflora (salt cordgrass), and Scirpus mariqueter throughout the growing season (April-October 2005), in order to determine the differences in net element accumulation and distribution between the three salt marsh macrophytes in the Yangtze River estuary, China. The aboveground biomass was significantly greater in the plots of S. alterniflora than in the plots of P. australis and S. mariqueter throughout the growing season (P<0.05). In August, the peak aboveground biomass was 1246+/-89 gDW/m(2), 2759+/-250 gDW/m(2) and 548+/-54 gDW/m(2) for P. australis, S. alterniflora and S. mariqueter, respectively. The concentrations of nutrients and heavy metals in plant tissues showed similar seasonal patterns. There was a steady decline in element concentrations of the aboveground tissues from April to October. Relative element concentrations in aboveground tissues were at a peak during the spring sampling intervals with minimum levels during the fall. But the concentrations of total nitrogen and total phosphorus in the belowground tissues were relatively constant throughout growing season. Generally, trace metal concentrations in the aboveground tissues of S. mariqueter was the highest throughout the growing season, and the metal concentrations of S. alterniflora tissues (aboveground and belowground) were greater than those of P. australis. Furthermore, the aboveground pools of nutrients and metals were consistently greater for S. alterniflora than for P. australis and S. mariqueter, which suggested that the rapid replacement of native P. australis and S. mariqueter with invasive S. alterniflora would significantly improve the magnitude of nutrient cycling and bioavailability of trace metals in the salt marsh and maybe transport more toxic metals into the water column and the detrital food web in the estuary.

Dopaminergic drugs increase the expression of the proto-oncogene, c-fos, in the brain, which is involved in the coordination of neurobiological changes caused by repeated cocaine or amphetamine use. This study examined the roles of five dopamine receptor subtypes on the c-fos promoter activity. D(1)R or D(5)R significantly increased the expression of c-fos promoter by activating protein kinase A. However, D(2)R, D(3)R, or D(4)R did not show any noticeable effects. The co-expression of D(1)R/D(3)R or D(1)R/D(2)R synergistically activated the basal and agonist-induced expression of the c-fos promoter, respectively. The Ral guanine-nucleotide-dissociation-stimulator-like, which was found to interact with the 3rd cytoplasmic loop of D(3)R, mediated the inhibitory activity of D(3)R in c-fos expression. In summary, the expression of the c-fos promoter was increased by the D1-like receptors and enhanced synergistically by the D2-like receptors via the modulation of cellular cAMP. D(3)R inhibited the expression of the c-fos promoter through an interaction with RGL.

Objective: presenilin-2 is one of the causative genes for familial Alzheimer's disease, and the apolipoprotein E epsilon4 allele is a major genetic risk factor for late-onset and sporadic early-onset Alzheimer's disease. Polymorphism of the regulatory region of presenilin-2 has recently been reported to be associated with sporadic Alzheimer's disease in a Russian population. The purpose of this study was to determine whether Alzheimer's disease is associated with the presenilin-2 gene polymorphism and the apolipoprotein E genotype in an extended case-control study., Methods: We examined 230 patients with Alzheimer's disease, along with an equal number of age- and sex-matched controls from the same community, in a Japanese population by using a Chi-square test for homogeneity and a logistic regression analysis., Results: The presenilin-2 polymorphism frequencies were similar in early-onset Alzheimer's disease patients (0.17) and younger controls (0.15), and in late-onset Alzheimer's disease (0.20) and elderly controls (0.20). We found no evidence for an association between the presenilin-2 polymorphism and the apolipoprotein E epsilon4 allele., Conclusions: Our results fail to support an association of presenilin-2 gene polymorphism with Alzheimer's disease. The discrepancy between our results and the results of the Russian study appear to be due to racial differences.

The earthworm-derived chemoattractant ES20 interacts with its G-protein-coupled receptors on the plasma membrane of vomeronasal (VN) sensory neurons of garter snakes, resulting in an increase in inositol trisphosphate [J. Biol. Chem. 269 (1994) 16867] and a rapid phosphorylation of the membrane-bound proteins, p42/44 [Biochim. Biophys. Acta 1450 (1999) 320]. The phosphorylation of p42/44 proteins are countervailingly regulated by a protein kinase and an okadaic acid-insensitive but fluoride-sensitive protein phosphatase (PPase) [J. Liu et al. (loc. cit.)]. The phosphorylation of p42/44 induced by ES20 appears to play a role in the regulation of signal transduction pathways by modulating the GTPase activity [J. Liu et al. (loc. cit.)]. A 564-bp fragment of cDNA was obtained from VN RNA of garter snakes by reverse transcription polymerase chain reaction with degenerate primers. The 564-bp fragment was amplified, cloned, and sequenced. Northern blot analysis revealed that both the VN organ (VNO) and brain contained the gene of PPase 2C. A full-length complementary 4119-bp DNA containing an open reading frame of 1146bp that encodes a protein of 382 amino acids with a molecular mass of 49,123Da was obtained from the VN cDNA library of garter snakes. The deduced amino acid sequence showed 88% amino acid identity to bovine protein phosphatase 2C alpha and 87% identity to human and rat PP2C alpha and to Mg(2+)-dependent protein phosphatase 1A of rat and rabbit. In situ hybridization revealed that the mRNA of VN protein phosphatase 2C is expressed in the vomeronasal sensory epithelium. This is the first report of the identification of a type 2C serine/threonine protein phosphatase in the VN system.

The concentration of 1-hydroxypyrene in human urine was determined in six volunteers who lived under the same conditions. Samples were collected four times per day for three consecutive days; the maximum concentration of 1-hydroxypyrene was found in the samples collected late in the evening (21:00-23:00 h) which is the time recommended as suitable for determination of urinary 1-hydroxypyrene for the purpose of evaluating human exposure to polycyclic aromatic hydrocarbons (PAHs). Statistical tests show that the influence of sex, age, and smoking on urinary 1-hydroxypyrene is statistically insignificant.

Urinary 1-hydroxypyrene of residents of Beijing, Shenyang and Taiyuan, and workers at two coke plants, a steel plant and control groups was determined using high pressure liquid chromatography. Polycyclic aromatic hydrocarbons (PAHs) of airborne particulates from these cities and coke plants were analyzed using GC-MS; chromatogram profiles, from which 15 chemical compounds were quantified, were similar. The percentage of pyrene and benzo[a]pyrene in PAHs was fairly constant. Statistical analysis showed significant correlation of urinary 1-hydroxypyrene with the concentration of pyrene and benzo[a]pyrene in the ambient PAHs; the correlation coefficient was 0.978 and 0.959, respectively. It is suggested that urinary 1-hydroxypyrene can be used as a biological monitoring index for human exposure to genotoxic PAHs from the burning of coal.