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Insufficient research has focused on the effects of metal mixtures on children's neurodevelopment and TSH's potential mediating effect. Plasma concentrations of ten metals were measured among 2887 pregnant women in a persistent Chinese birth cohort. At age two, children's neurodevelopment was assessed using mental development indexes (MDIs) and psychomotor development indexes (PDIs), defining neurodevelopmental delay as MDI≤ 79 (cognitive delay) or PDI≤ 79 (motor delay). The associations between single and mixed metals with neurodevelopment delay risk were examined using generalized linear regression complemented by weighted quantile sum (WQS) regression. To investigate the mediated effects of infant Thyroid-Stimulating Hormone (TSH) on metal-associated neurodevelopment delay risk, mediation analyses were conducted. According to the single-metal model, V, Mn, and Pb levels are positively associated with neurodevelopment delay. The WQS model found consistent associations (Odds Ratio [OR] 1.55, 95% Confidence Interval [CI] 1.23 to 1.95), highlighting V, Mn, and Pb as the main causes of cognitive delay. Further mediation analysis revealed that the association between metals (mainly V, Mn, and Pb) and neurodevelopment delay risk is mediated by TSH, with proportions ranging from 3.18 to 10.14% (all P < 0.05). Our findings highlighted prenatal exposure to metals was associated with higher risks of neurodevelopmental delay, with TSH possibly mediating this effect., 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 Ltd. All rights reserved.)

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 μg/L (1973-1983) to 51.99 μg/L (1984-2004) and to 21.90 μg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10 -5 and 7.63 × 10 -2 , respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018., 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.)

Pentachlorophenol (PCP), a persistent organic pollutant, has been banned in many countries, but it is still used in China as a wood preservative, molluscicide, or reagent for fish-pond cleaning, which may pose risks to the ecosystem and humans. However, data on the occurrence of PCP in the environment are scarce in the recent decade. The Yangtze River was regarded as a priority area of PCP pollution according to previous documents. This study aimed to examine the spatial distribution of PCP in the Yangtze River water, the differences in dry and wet seasons, the ecological risk for aquatic organisms, and its removal efficiency in tap water treatment plants. The river water samples (n = 144) were collected from the upper, middle, and lower reaches across ten provinces (or municipalities) in December 2020 and June 2021, respectively. PCP was detected in 88.9% of all the samples, ranging from Max: 0.02) to aquatic organisms posed by PCP in the river. In addition, 100% removal of PCP in tap water treatment plants was observed, while the transformation products of PCP need further studies. The risk of human exposure to PCP through water ingestion only was negligible. However, human exposure risks of PCP in highly contaminated areas still require attention, considering its bioaccumulation and biomagnification in the environment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D), a widely used hormonal herbicide, may disrupt steroid hormone homeostasis. However, evidence from population-based studies is limited, especially for one-month-old infants whose steroid hormones are in a state of adjustment to extrauterine life and can be important indicators of endocrine development. This study aimed to explore the associations between maternal 2,4-D exposure during early pregnancy and infant steroid hormone levels., Methods: The 885 mother-infant pairs were from a birth cohort in Wuhan, China. Maternal exposure to 2,4-D was determined in urine samples from early pregnancy, and nine steroid hormones were determined in infant urine. The associations of maternal 2,4-D exposure with infant steroid hormones and their product-to-precursor ratios were estimated based on generalized linear models, and bioinformatic analysis was conducted with public databases to explore the potential mechanisms involved., Results: The detection frequency of 2,4-D was 99.32 %, and the detection frequency of steroid hormones ranged from 98.42 % to 100.00 %. After adjusting for covariates, an interquartile range increase in 2,4-D concentrations was associated with a 7.84 % decrease in 11-deoxycortisol (95 % confidence interval, CI: -14.12 %, -1.10 %), an 8.09 % decrease in corticosterone (95 % CI: -14.56 %, -1.14 %), an 8.67 % decrease in cortisol (95 % CI: -14.43 %, -2.52 %), a 13.00 % decrease in cortisone (95 % CI: -20.64 %, -4.62 %), and an 11.17 % decrease in aldosterone (95 % CI: -19.62 %, -1.83 %). Maternal 2,4-D was also associated with lower infant cortisol/17α-OH-progesterone, cortisol/pregnenolone, and aldosterone/pregnenolone ratios. In bioinformatic analysis, pathways/biological processes related to steroid hormone synthesis and secretion were enriched from target genes of 2,4-D exposure., Conclusions: Maternal urinary 2,4-D during early pregnancy was associated with lower infant urinary 11-deoxycortisol, corticosterone, cortisol, cortisone, and aldosterone, reflecting that 2,4-D exposure may interfere with infant steroid hormone homeostasis. Further efforts are still needed to study the relevant health effects of exposure to 2,4-D, particularly for vulnerable populations., 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 © 2023 Elsevier B.V. All rights reserved.)

While prosocial exclusion has been proposed as a mechanism to maintain cooperation in one-shot social dilemma games, the evolution of prosocial peer exclusion in response to the threat of antisocial peer exclusion, particularly in structured populations, remains insufficiently understood. In this study, we employ an extended spatial public goods game to investigate the evolution of prosocial peer exclusion and its impact on cooperation in the presence of both prosocial and antisocial peer exclusion. Our model encompasses four primary strategies: traditional cooperation and defection, prosocial peer exclusion targeting defectors, and antisocial peer exclusion targeting cooperators. Our findings illuminate that the presence of antisocial peer exclusion significantly disrupts network reciprocity and suppresses cooperation. However, when coexisting with prosocial peer exclusion, it does not undermine the latter's efficacy in upholding cooperation, except in scenarios with low exclusion costs Unlike the cooperation-sustaining cyclic dominance pattern observed in the exclusive presence of prosocial peer exclusion, the co-presence of prosocial and antisocial peer exclusion gives rise to more intricate pathways for maintaining cooperation. These pathways include cyclic dominance involving traditional cooperation, prosocial peer exclusion, and antisocial peer exclusion, or a similar pattern involving traditional defection and the two exclusion strategies, or even cyclic dominance among all four strategies. In essence, our study enhances the theoretical framework concerning the effectiveness of the prosocial exclusion strategy, contributing to a more comprehensive understanding of its dynamics., 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 © 2023 Elsevier Ltd. All rights reserved.)

A comprehensive contamination profile of organophosphate esters (OPEs) in the Yangtze River in China has not yet been characterized. In this study, we investigated the occurrence, spatial variation, and seasonal difference of 18 selected OPEs in surface water samples of the Yangtze River mainstream. To characterize the contamination profile of the OPEs, we collected 144 Yangtze River water samples from 72 sampling sites in December 2020 and June 2021. Four alkyl-OPEs [trimethyl phosphate, triethyl phosphate (TEP), tributyl phosphate, and tris(2-butoxyethyl) phosphate (TBOEP)] and three halogenated OPEs [tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), and tris(1,3-dichloro-2-propyl) phosphate] were the most frequently detected target compounds (>95%). TCIPP (median: 34.6 ng/L), TEP (median: 26.2 ng/L), and TCEP (median: 17.9 ng/L) were the most abundant compounds, while the median values of the others were below 10 ng/L. Additionally, the concentrations of most OPEs gradually/dramatically increased from upstream to downstream Yangtze River. Notably, the median concentration of summed OPEs in Shanghai (415 ng/L; downstream) was approximately ten times higher than that in Qinghai (45.7 ng/L; upstream). Urban sampling sites had significantly or slightly higher concentrations of most OPEs than rural sampling sites. Moreover, the OPE concentrations in the river water differed between the winter and summer. The concentrations of summed OPEs (median: 117 vs. 106 ng/L), summed alkyl-OPEs (67.0 vs. 45.8 ng/L; p < 0.05), and summed aryl-OPEs (0.48 vs. 0.17 ng/L; p < 0.05) were slightly or significantly higher in December than those in June; nevertheless, summed halogenated OPEs were slightly higher in June (62.2 vs. 50.2 ng/L) than that in December. Compared with previously reported data for OPEs in other major rivers worldwide, the Yangtze River water had relatively lower concentrations of the OPEs than those in the rivers of developed countries and regions. Ecological risk assessment suggested that tris(2-ethylhexyl) phosphate and TCEP posed relatively high risks (RQ: 1.01 and 0.98, respectively) at the maximum concentration, and TBOEP posed a moderate risk (RQ: 0.25). This is the first study to comprehensively characterize the contamination profile of the Yangtze River by the OPEs., 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.)

Chemodynamic therapy (CDT) is a cancer treatment that converts endogenous H 2 O 2 into hydroxyl radicals (˙OH) through Fenton reaction to destroy cancer cells. However, there are still some challenges in accelerating the Fenton reaction of CDT and improving the biodegradability of nanocatalysts. Herein, a multifunctional biomimetic BPQDs-Cu@GOD (BCG) Fenton nanocatalyst for boosting synergistically enhanced H 2 O 2 -guided and photothermal CDT of cancer is reported. Cu 2+ in BCG can be reduced to Cu + by black phosphorus quantum dots (BPQDs), triggering a Cu + -mediated Fenton-like reaction to degrade H 2 O 2 and generate abundant ˙OH for cancer CDT. The loaded glucose oxidase (GOD) can consume the glucose in the tumor to produce abundant H 2 O 2 for Fenton-like reaction. In addition, Cu 2+ in BCG can react with GSH in tumor cells to alleviate the antioxidant capacity of tumor tissues, further improving the CDT efficacy. Furthermore, the photothermal performance of BPQDs can be enhanced by capturing Cu 2+ , improving the photoacoustic imaging and photothermal therapy (PTT) functions. More importantly, the enhanced photothermal performance can rapidly accelerate the Fenton-like reaction under NIR irradiation. Finally, Cu 2+ can accelerate the degradation of BPQDs, which can reduce the retention of reagents. As a novel multifunctional biocompatible Fenton nanocatalyst, BCG have great potential in cancer therapy.

Rice straw and pig manure pellets (RPP) and sorghum straw and pig manure pellets (SPP) were used to identify their competition as the flexible feedstock of anaerobic digestion with one-year indoor storage. The results indicated the effect of time on their characteristic was tiny during storage period, such as density, calorific value, total solid, volatile solid, ratio of carbon and nitrogen, and lignocellulosic components. Biogas yields of stored RPP and SPP were 8.8% and 26.7% lower than that of fresh pig manure (PM), and 45.4% and 56.1% higher than the sum of corresponding straw and PM digestion alone, respectively. Improvements in biodegradability were observed in co-densified biomass anaerobic digestion. Net biogas yield of RPP was 24.2% higher than that of rice straw, considering volatile matter loss and biogas yield decline during densification and storage stage. Priority of manure and supplement of co-densified biomass were proposed for feedstock supply on demand., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chiral nanomaterials have great potential in improving the clinical therapeutic effect due to the unique chiral selectivity of biosystems. However, such a promising therapeutic strategy has so far received little attention in cancer treatment. Here, we report a first chiral Fenton catalyst, d-/l-penicillamine-modified Cu 2- x Se nanoparticles (d-/l-NPs), for enhanced synergistic cancer chemodynamic therapy (CDT) and photothermal therapy (PTT) under the second near-infrared (NIR-II) light irradiation. The chiral effect study of chiral Cu 2- x Se NPs on cancer cells shows that d-NPs exhibit stronger CDT-induced cytotoxicity than l -NPs due to the stronger internalization ability. Moreover, the hydroxyl radicals ( • OH) produced in d-NP-treated cancer cells via the CDT effect can be further improved by NIR-II light irradiation, thereby increasing the apoptosis of cancer cells. In vivo experiments show that, compared with l-NPs, d-NPs exhibit a stronger photothermal effect on the tumor site under NIR-II light irradiation and could completely eliminate the tumor under the synergistic effect of CDT and PTT. This work shows that the chirality of the surface ligand of the nanomaterials could significantly affect their cancer curative effect, which opens up a new way for the development of anticancer nanomedicine.

Caffeine is considered the most representative pharmaceutical emerging contaminant (PEC) because of its ubiquity, high environmental abundance, uncovered ecological risks, and its indicator property for anthropogenic environmental inputs of PECs. Ecopharmacovigilance (EPV) targeting caffeine has been proposed as an optimized measure for the control of caffeine pollution sources and the related anthropogenic behaviors from the perspective of pharmacy administration. This cross-sectional study was conducted to evaluate the environmental knowledge, behaviors, and attitudes regarding caffeine consumption among university students, one of the groups with high caffeine consumption, from an EPV perspective. Three hundred and seven usable survey instruments were acquired. The mean score for environmental knowledge about caffeine consumption was 3.66 out of a total of 7. The consumption frequency of caffeinated drinks, food, or drugs among student respondents was low. Throwing away in "household garbage" was an important disposal mechanism for unconsumed caffeinated products. Most students showed positive attitudes and strong intentions toward caffeine pollution control from the perspective of targeted EPV. These data suggested high acceptance of EPV program targeting caffeine among university students. However, more should be done to enhance their related knowledge, and some strengthening interventions for the effective removal of residual caffeine in garbage are needed.

From a perspective of drug administration, eco-pharmacovigilance (EPV) has been proposed as a new approach to prevent the environmental risks posed by pharmaceutical emerging contaminants. However, it is impracticable to practice unitary and rigor EPV process for all the pharmaceutical substances with complex and diversified chemical, biological or toxicological properties. We proposed the "targeted EPV" that is the science and activities associated with the targeted detection, evaluation, understanding, and prevention of adverse effects of high-priority hazardous pharmaceuticals in the environment, especially focusing on the control of main anthropogenic sources of pharmaceutical emission among key stakeholders in high-risk areas could be used as an optimized management strategy for pharmaceutical pollution. "Targeted EPV" implementation should focus on the targeted monitoring of the occurrence of high-priority pharmaceuticals in environmental samples, the targeted reporting of over-standard discharge, the targeted management for main emission sources, the targeted legislation and researches on high-priority pharmaceutical pollutants, as well as the targeted educational strategies for specific key populations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Acrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats., Methods: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40 mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the cerebral homogenates were detected using ELISA assay., Results: ACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1β and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group., Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

Owing to the substantial consumption of caffeinated food, beverages, and medicines worldwide, caffeine is considered the most representative pharmaceutically active compound (PhAC) pollutant based on its high abundance in the environment and its suitability as an indicator of the anthropogenic inputs of PhACs in water bodies. This review presents a worldwide analysis of 132 reports of caffeine residues in freshwater environments. The results indicated that more than 70% of the studies reported were from Asia and Europe, which have densely populated and industrially developed areas. However, caffeine pollution was also found to affect areas isolated from human influence, such as Antarctica. In addition, the maximum concentrations of caffeine in raw wastewater, treated wastewater, river, drinking water, groundwater, lake, catchment, reservoir, and rainwater samples were reported to be 3.60 mg/L, 55.5, 19.3, 3.39, 0.683, 174, 44.6, 4.87, and 5.40 μg/L, respectively. The seasonal variation in caffeine residues in the freshwater environment has been demonstrated. In addition, despite the fact that there was a small proportion of wastewater treatment plants in which the elimination rates of caffeine were below 60%, wastewater treatment is generally believed to have a high caffeine removal efficiency. From a pharmacy perspective, we proposed to adopt effective measures to minimize the environmental risks posed by PhACs, represented by caffeine, through a new concept known as ecopharmacovigilance (EPV). Some measures of EPV aimed at caffeine pollution have been advised, as follows: improving knowledge and perceptions about caffeine pollution among the public; listing caffeine as a high-priority PhAC pollutant, which should be targeted in EPV practices; promoting green design and production, rational consumption, and environmentally preferred disposal of caffeinated medicines, foods, and beverages; implementing intensive EPV measures in high-risk areas and during high-risk seasons; and integrating EPV into wastewater treatment programs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Neurosurgical intensive care unit patients are at high risk for delirium. A risk prediction model could help the staff screen for patients at high risk for delirium. On the basis of this risk, preventive measures could be taken to reduce the undesired effects of delirium., Objectives: To establish a delirium prediction model for neurosurgical intensive care unit patients and to verify the sensitivity and specificity of this model., Design: A prospective, observational, single-centre study., Methods: Data were collected from a total of 310 patients admitted to the neurosurgery intensive care unit between January 2017 and February 2018. A risk factor prediction model was then created using multivariate logistic regression. Further data were collected from another 60 patients between March 2018 and June 2018 to validate the model., Results: The model consisted of six predictors, namely, cognitive dysfunction on admission, fever, hypoalbuminaemia, abnormal liver function, sedative use four or more times, and physical restraint. The area under the curve of the model was 0.80, with sensitivity and specificity of 0.68 and 0.83, respectively., Conclusions: This study established a delirium prediction model for neurosurgical intensive care unit patients, which we believe would help focused prevention of delirium in intensive care unit patients., (© 2020 John Wiley & Sons Australia, Ltd.)

Introduction: Eco-directed sustainable prescribing (EDSP) is an effective upstream way to reduce the environmental footprints of active pharmaceutical ingredients (APIs), a kind of emerging contaminants, from the patients' excretion. EDSP is one of the key steps in the programme of ecopharmacovigilance (EPV), a drug administration route on API pollution., Objective: To assess the attitudes of physicians prescribing medicines regarding EDSP from the perspective of EPV., Design: A cross-sectional study conducted from March 2019 to June 2019., Setting: 5 government general hospitals in Hubei province, China., Participants: 405 physicians were randomly selected and 262 valid questionnaires were obtained., Outcome Measures: A self-developed questionnaire, which inquired about the participant characteristics, perceptions and attitudes toward API pollution, EPV and EDSP from an EPV perspective, was emailed to collect data from physicians., Results: Most physicians agreed the existence of APIs in environment, worried about the potential environmental and ecological risks of API residues, supported the effectiveness and necessity of EDSP under an EPV perspective in decreasing environmental exposure of excreted APIs, and showed their willingness to participate in the EDSP practices. Nevertheless, no respondent identified the environmental impacts as the aspects regarding medicines affecting his(her) prescription decision, none was satisfied with knowledge on EDSP and showed confidence toward EDSP. The most important barrier to the effective implementation of EDSP was identified as 'poor awareness of EDSP and EPV'. Most responding physicians (97%) reported that they held the wait-and-see or conservative attitudes towards EDSP practice. The biggest concerns in low-dose prescribing and prescribing of drugs possessing environment-friendly excretion profiles , two EDSP approaches, were the possible negative impact on therapeutic outcomes and too complicated and professional drug evaluation process, respectively., Conclusions: Chinese physicians had positive attitudes towards EDSP from the perspective of EPV. However, their environmental consciousness during prescribing and the related education were insufficient., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the psychometric properties of the short form Community Attitudes toward Mentally Illness (SF-CAMI) scale among medical students and primary healthcare workers in China., Methods: Original English version CAMI was translated following a standard procedure. and then short-form CAMI developed through the multistage procedure. The psychometric properties were tested among two separate samples which contained 1,092 primary healthcare workers and 1,228 medical students. Reliability was assessed by internal consistency reliability and test-retest reliability. Exploratory factor and confirmatory factor analyses were performed to determine the structure and to assess the validity of the scale., Results: The Chinese version of SF-CAMI consists of 20 items and with three subscales: Benevolence, Fear and Exclusion, and Support and Tolerance. The confirmatory factor analysis indicated good fitting models for medical students and primary healthcare workers. The Cronbach α of total scale for both samples was good (0.82 for medical students and 0.85 for primary healthcare workers), and acceptable test-retest reliability was found (intraclass correlation coefficient is 0.62 for medical students and 0.60 for primary healthcare workers)., Conclusion: The Chinese version of SF-CAMI performed good reliability and validity among both primary healthcare workers and medical students, provide more feasible and available tools for assessing the effect of mental health service programs in China., (Copyright © 2020 Tong, Wang, Sun and Li.)

Background: Our previous in vitro study reported that the ethyl acetate fraction (EAF) of Semen sojae germinatum (SSG), the processed sprout of Chinese black soybean, possessed the potent anti-inflammatory and chondroprotective properties. The aim of the present work was to verify the in vivo antiosteoarthritic effect of EAF from SSG on a rat osteoarthritis (OA) model ., Methods: A classical rat OA model was surgically induced by anterior cruciate ligament transaction (ACLT). The OA rats were intra-articularly administered EAF from SSG for 8 weeks. The cartilage and synovial tissues were stained with hematoxylin and eosin (HE) to observe the histopathological changes. Safranin O/fast green staining was used to assess the glycosaminoglycan content in cartilage tissue sections. The expression of type II collagen and matrix metalloproteinase (MMP)-13 in cartilage was measured by immunohistochemistry. The apoptotic chondrocytes in the cartilage sections were detected using TUNEL assay. The concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-ɑ in synovial fluid were determined using ELISA., Results: Intra-articular administration of EAF from SSG well retained the structure and superficial layer of cartilage tissues, ameliorated cartilage lesion and the degradation of cartilage matrix, including proteoglycan and type II collagen, induced by ACLT operation. The ACLT-induced upregulation of MMP-13 expression in the cartilage tissues was resisted by EAF from SSG. Moreover, EAF from SSG inhibited the ACLT-induced chondrocyte apoptosis. Compared to OA model group, the inflammatory status of synovial membrane was improved, the levels of inflammatory cytokines IL-1β and TNF-ɑ in synovial fluid were decreased in rats administrated with EAF from SSG., Conclusion: These data suggested that EAF from SSG displayed in vivo protective effect on OA development via preventing the degeneration of articular cartilage, inhibiting chondrocyte apoptosis and suppressing synovial inflammation.

Due to the huge consumption of caffeinated food, beverages and medicines around the world, caffeine has been considered as a most representative pharmaceutically active compound (PhAC) pollutant based on its high abundance in environment and its indicator property for anthropogenic inputs of PhACs to water bodies. This review analyzed the existing literature about the bioaccumulation and environmental risks of caffeine residues in non-target organisms. There are 6 studies which were published in the last 5 years have reported the distribution of caffeine in tissues of aquatic organisms including fishes, clams, macroalgae and other aquatic plants, suggesting bioaccumulation of caffeine in organisms. The maximum detected levels of caffeine residues in tissues ranged from 1.55 to 344.9 ng/g. Importantly, definitive evidences have been provided that environmentally relevant caffeine concentrations exert adverse impacts on aquatic species and terrestrial insects, which included lethality, decreasing general stress, inducing oxidative stress and lipid peroxidation, affecting energy reserves and metabolic activity, neurotoxic effects, affecting reproduction and development, etc. In view of the severity and potential adverse impacts of caffeine pollution in the environment, we proposed that caffeine should be considered as a high-priority environmentally hazardous PhAC pollutant, and it is necessary to implement an ecopharmacovigilance (EPV) program targeting caffeine to minimize its environmental load from a pharmacy perspective., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pancreatic cancer (PaC) is characterized by a highly inflammatory tumor microenvironment, and inflammatory mediators are implicated in the progression of this cancer. Regenerating gene protein (Reg) 3A is significantly upregulated during pancreatic inflammation, and has been demonstrated to serve an important role during PaC progression, based on its increased expression levels in PaC and potent cell proliferation-promoting activity. The aim of the present study was to investigate the effect of eckol, a phlorotannin compound with a variety of biological activities including anti-inflammatory, anti-tumor and cytoprotective effects, on Reg3A-induced proliferation of human SW1990 PaC cells. SW1990 cells were pre-treated with eckol for 48 h at concentrations of 5, 10 and 20 µg/ml. Subsequently, Reg3A protein was added to the culture media at a final concentration of 50 ng/ml in the presence or absence of eckol for 24 h. The cytotoxicity and proliferative capacity of the SW1990 cells was determined using an MTT and flow cytometry analysis. Cell colony formation was also used to determine the effect of eckol on the anchorage-independent growth and colony-forming capacity of Reg3A-treated PaC cells. The expression levels of cyclin D1, STAT3, JAK2, and NF-κB p65 were measured with reverse transcription-quantitative PCR and western blotting. Eckol reduced Reg3A-promoted cell survival, inhibited Reg3A-induced cell cycle progression and inhibited colony growth of SW1990 cells in soft agar in a concentration-dependent manner. Additionally, the Reg3A-mediated upregulation of expression of JAK2, STAT3, NF-κBp65 and cyclin D1 was reduced when treated with eckol. Reg3A is upregulated during pancreatic inflammation and exhibits a pro-growth function and may thus serve a critical role during inflammation-driven PaC malignancies. Eckol may be a potential protective agent against progression of PaC accompanied by pancreatic inflammation., (Copyright: © Zhang et al.)

Purpose: In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT)., Methods: The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively., Results: Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees., Conclusion: The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.

Background: High resolution ultrasonography (US) is the first choice for diagnosis of thyroid cancer and is based on many sonographic features: composition, echogenicity, margins, calcifications, shape and vascularity. Here, we tried to develop a nomogram to evaluate papillary thyroid carcinoma (PTC) based on sonographic features., Methods: From Aug 2016 to Dec 2017, a primary cohort of 382 patients with suspicious thyroid nodules and accepted US examinations were included in Gansu Provincial Hospital. Sonographic features were used to develop a nomogram with Cox regression analysis. The nomogram was validated using prospective data from 162 patients as the validation group., Results: The primary and validation cohort showed comparable clinical and US features in all aspects. Univariate and multivariate analyses showed solid composition [odds ratio (OR): 3.785; 95% confidence interval (CI): 1.504-9.528, P=0.005], hypoechoic (OR: 15.840; 95% CI: 5.754-43.602, P<0.001) and irregular margins (OR: 15.953; 95% CI: 5.897-43.160, P<0.001), microcalcifications (OR: 21.730; 95% CI: 7.119-66.329, P<0.001), taller than wide shape (OR: 5.153; 95% CI: 1.997-13.311, P=0.001), internal high vascularization (OR: 6.288; 95% CI: 2.175-18.181, P=0.001), and obscure borders (OR: 5.648; 95% CI: 2.118-15.065, P=0.001) as risk factors for PTC. Based on the seven risk factors, nomogram was developed and validated by a prospective group, and discrimination and calibration were measured using the concordance index (C-index)., Conclusions: Our novel nomogram risk score model based on the US features accurately predicted PTC nodule diagnosis., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Due to the expensive cost and uncertain effectiveness of environmental management options in eliminating pharmaceutical residues, recently, decreasing the emission of pharmaceutical pollutants from a drug administration perspective has been considered a hot area of research. As a kind of drug administration for the environment, ecopharmacovigilance (EPV) emphasizes the source control of pharmaceutical pollutants. Disposal of unwanted medicines has been considered as the easiest target for source control of pharmaceutical contamination. Here, we focused on public attitudes and practice regarding disposal of unwanted medicines from the EPV perspective among 365 Chinese university young adults and 206 elderly retirement home residents. The results showed that the majority of respondents had positive attitudes, but exhibited inadequate awareness and poor practice. In addition, the young-adult respondents were found to pay more attention to the environmental problems posed by pharmaceutical residues, and be more supportive of the EPV intervention predominantly performed by pharmaceutical industries and pharmacists. Therefore, it is urgent to establish the standard medicine disposal protocols and educate the general public on the best way for medication disposal under the principle of EPV in China, and efforts on environmentally-preferred drug disposal under EPV should target for the specific demographics.

A simple aqueous approach for synthesizing biocompatible red and near-infrared (NIR) emitting Ag2S quantum dots (QDs) at low temperature without a required oxygen-free process has been developed. The fluorescence of the obtained red emitting Ag2S QDs could be selectively quenched by Cu2+. Based on this, a novel Ag2S QD based fluorescent sensor for highly selective and sensitive detection of Cu2+ was developed. This method showed a low limit of detection (LOD) of 27.6 nM for Cu2+ sensing in a wide linear range concentration of 25 nM-10 μM. The quenching mechanism was discussed by the time-resolved photoluminescence, absorption spectra, TEM and energy-dispersive X-ray (EDX) results. Cation exchange of Ag2S QDs between Cu(ii) and Ag(i), and dynamic quenching due to excited state electron transfer from Ag2S QDs to Cu2+ were considered to be the quenching mechanism. Furthermore, to understand the interaction between Ag2S QDs and Cu2+, the thermodynamic process was investigated by means of isothermal titration calorimetry (ITC). The values of ΔH, ΔS and ΔG were calculated from the ITC results to be -79.43 kJ mol-1, -142.18 J K-1 mol-1 and -37.06 kJ mol-1, respectively. The Ag2S QD based Cu2+ detection had advantages of nontoxicity, fast response, high sensitivity and selectivity, wide linear range and easy preparation.

Several in vitro studies have shown the potential hepatoprotective properties of eckol, a natural phlorotannin derived from the brown alga. However, the in vivo hepatoprotective potential of eckol has not been determined. In this study, we performed an in vivo study to investigate the protective effect of eckol and its possible mechanisms on the carbon tetrachloride (CCl₄)-induced acute liver injury model in mice. Results revealed that eckol pre-treatment at the dose of 0.5 and 1.0 mg/kg/day for 7 days significantly suppressed the CCl₄-induced increases of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum and meliorated morphological liver injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis showed that the number of positive apoptotic hepatocytes in the eckol-treated group was lower than that in the CCl₄ model group. Western blotting analysis also demonstrated the enhanced expression of bcl-2 and suppressed expression of cleaved caspase-3 by eckol. The CCl₄-induced oxidative stress in liver was significantly ameliorated by eckol, which was characterized by reduced malondialdehyde (MDA) formations, and enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content. Moreover, the CCl₄-induced elevations of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were markedly suppressed in the eckol-treated group. However, eckol enhanced the level of IL-10, a potent anti-inflammatory cytokine, and recruited CD11c⁺ dendritic cells into the liver tissues of CCl₄-treated mice. These results indicated that eckol has the protective effect on CCl₄-induced acute liver injury via multiple mechanisms including anti-apoptosis, anti-oxidation, anti-inflammation and immune regulation.

As a well-accepted drug-administration strategy for the minimization of environmental risks posed by pharmaceutical residues, ecopharmacovigilance (EPV) needs to guard against and control the pharmaceutical pollution sources. However, the underlying routes by which pharmaceuticals reach the environment vary significantly under different scenes, so it is necessary to implement different EPV measures in different backgrounds. This study detected the occurrence of antibiotic residues in two ponds within a Chinese rural community; assessed their ecological risks; compared and analyzed the geographic and demographic information, as well as the antibiotic-related anthropogenic behaviors of residents living around ponds, in order to trace the main entrances of antibiotics into the water environment; and then propose the EPV measures according to rural conditions. The results showed that the pollution degree of antibiotic residues was different between two studied ponds, which was manifested by the different antibiotic types and levels in water samples. And the possible main sources of antibiotic pollution in the studied rural water environment might include the application of human excretions and animal manures as fertilizers on the farmland, antibiotic use and inappropriate disposal in the clinic, and the direct disposal of the leftover antibiotics. From the perspective of drug administration, we then identified some suggestions on EPV measures which could be taken under existing rural conditions, including encouraging eco-directed sustainable prescribing of antibiotics in human and animals, improving take-back collection of unused antibiotics, building monitoring mechanism for antibiotic residues in the natural environment, identifying high-priority antibiotic residues, and implementing targeted EPV.

Now, the occurrence of pharmaceuticals in natural environment has been frequently reported around the world. As a kind of biologically active compounds specially designed to be effective even at very low concentration levels, pharmaceuticals in the environment could have adverse impacts to the health of human beings or other non-targeted organisms due to long-term exposures. To minimize the pharmaceutical pollution from the perspective of drug administration, a new concept called as eco-pharmacovigilance (EPV) has been proposed as a kind of pharmacovigilance(PV) for the environment. However, as a new and comprehensive science, EPV has not sophisticated methods in practice and formalized implementation model up to now. Since EPV is a special kind of PV, it could be feasible to draw on the experience of PV as a possible and reasonable starting point for EPV. In this paper, we discussed the common methods and activities used in PV including spontaneous reporting, intensive monitoring, database studies, and their potential applicability to the environment. And we concluded that these common methods in PV could be adapted and applied to EPV. But there is still the need for organizational, technical and financial supports of the EPV system., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims and Objectives: To explore the incidence of delirium in cerebrovascular patients admitted in our Neurosurgery Intensive Care Unit and analyse the risk factors leading to delirium., Background: Delirium is one of the most common mental disorders in general hospitals, but the incidence of different kinds of diseases and studies varies. Cerebrovascular patients in our Neurosurgery Intensive Care Unit are high-risk groups for delirium; identifying risk factors for delirium and taking early interventions are crucial for patient prognosis., Design: A prospective study., Methods: A convenience sampling method was used to collect data from 128 patients in the Neurosurgery Intensive Care Unit of Xuanwu Hospital, Capital Medical University, Beijing, China, between May 2016-January 2017. Researchers used Confusion Assessment Method for the Intensive Care Unit (Chinese version) to assess each patient's delirium statement twice a day at regular times. We also collected other independent data variables and followed up the short-term clinical outcomes daily., Results: On the basis of Confusion Assessment Method for the Intensive Care Unit evaluation, patients were divided into a delirium group and a nondelirium group. The prevalence of delirium among the 128 patients was 42.2%. Multivariate analysis showed that severity of illness, fever, the use of physical restraints and sleep deprivation were independent predictors of delirium in cerebrovascular patients in the Neurosurgery Intensive Care Unit., Conclusions: Cerebrovascular patients in the Neurosurgery Intensive Care Unit with a critical condition, fever or use of physical restraints or experiencing sleep deprivation were more prone to delirium., Relevance to Clinical Practice: Cerebrovascular patients in the Neurosurgery Intensive Care Unit showed a high incidence of delirium. There are many risk factors leading to delirium, some of which are independent predictors of intensive care delirium. Patients with delirium will suffer various adverse effects upon their short-term clinical outcomes. Therefore, nurses should pay close attention to changes in a patient's mental state and learn about the risk factors associated with delirium, in order to be able to take early measures to prevent delirium., (© 2017 John Wiley & Sons Ltd.)

This research was aimed at establishing the pilot-scale purification technology of lipopeptide from marine-derived Bacillus marinus. We studied lipopeptide surfactivity interferences on scale-up unit technologies including acid precipitation, methanol extraction, solvent precipitation, salting out, extraction, silica gel column chromatography and HZ806 macroporous absorption resin column chromatography. Then, the unit technologies were combined in a certain order, to remove the impurities gradually, and to gain purified lipopeptide finally, with high recovery rate throughout the whole process. The novel pilot-scale purification technology could effectively isolate and purify lipopeptide with 87.51% to 100% purity in hectograms from 1 ton of Bacillus marinus B-9987 fermentation broth with more than 81.73% recovery rate. The first practical hectogram production of highly purified lipopeptide derived from Bacillus marinus was achieved. With this new purification method, using complex media became possible in fermentation process to reduce the fermentation cost and scale-up the purification for lipopeptide production. For practicability and economy, foaming problem resulting from massive water evaporation was avoided in this technology.

A novel cultivation strategy called "Sequential Heterotrophy-Dilution-Photoinduction" was successfully applied in the cultivation of Galdieria sulphuraria for efficient production of phycocyanin (PC). Algae cells were firstly cultivated heterotrophically to achieve high cell density. The maximal dry cell weight of 17.8gL(-1) and maximal biomass productivity of 103.1mgL(-1)h(-1) were obtained. Then, a dilution step was applied to obtain a suitable cell concentration and finally these cells were transferred to high light condition for phycocyanin accumulation. During the photoinduction step, cells could accumulate phycocyanin up to 13.88% of dry cell weight in a cultivation period of 8days. By this technology, total PC productivity far surpassed those reported in all literatures of Galdieria sulphuraria, and was 147-fold and 12-fold of those in photoautotrophic and heterotrophic technologies, respectively. Therefore, this strategy provides a promising approach for high-efficient phycocyanin production from Galdieria sulphuraria to meet its mass cultivation and commercialization application., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The complete mitogenome sequence of Eurasian water shrew (Neomys fodiens) was determined using long PCR. The genome was 17,260 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 control region. The overall base composition of the heavy strand is A (33.0%), C (23.2%), T (30.9%) and G (12.9%). The base compositions present clearly the A-T skew, which is most obviously in the control region and protein-coding genes. The extended termination-associated sequence domain, the central conserved domain and the conserved sequence block domain are defined in the mitochondrial genome control region of Eurasian water shrew. Mitochondrial genomes analyses based on MP, ML, NJ and Bayesian analyses yielded identical phylogenetic trees. Neomys elegans, Soriculus fumidus, and N. fodiens formed a monophyletic group with the high bootstrap value (100%) in all examinations. This clade with the Anourosorex squamipes as the sister taxon to Sorex.

Although the relationship between asthma and exposure to fine particulate matter (PM2.5) has been frequently measured, reported conclusions have not been consistent. As emergency department (ED) visits are an effective way to estimate health outcomes for people with asthma and short-term exposure to PM2.5, this review systematically searched five databases without language or geographical restrictions from inception to January 13, 2015 to study the impact of PM2.5 on asthma ED visits. A random-effects model was used to calculate the pooled risk ratio (RR) and 95% confidence intervals (CI). With respect to short-term effects, asthma ED visits increased at higher PM2.5 concentrations (RR 1.5% per 10 μg/m(3); 95% CI 1.2-1.7%), and children were more susceptible (3.6% per 10 μg/m(3); 95% CI 1.8, 5.3%) than adults (1.7, 95% CI 0.7%, 2.8%) to increased PM2.5; the ED visits increased during the warm season by 3.7% (95% CI 0.5, 6.9%) per 10 μg/m(3) increase in PM2.5, which was higher than the corresponding increase during the cold season (2.6, 95% CI 0.7-4.6%). This demonstrates that ambient PM2.5 has an adverse impact on asthma ED visits after short-term exposure and that children are a high-risk population when PM2.5 concentrations are high, particularly in warm seasons, during which measures should be taken to prevent PM2.5.

Objective: To investigate the changes of Wnt7b/β-catenin signaling pathway molecules in the differentiation of fetal rat alveolar epithelial type II cells (fAEC2)., Methods: Fetal rat lung tissues were extracted from pregnant SD rats (19 days), and then fAEC2 were isolated and purified. After fAEC2 were cultured for 48, 72, 96 hours, the morphological changes of fAEC2 and the expression of β-catenin were respectively observed by inverted microscope and immunofluorescence. The mRNA expressions of Wnt7b, cyclin D1, pulmonary surfactant C (SP-C) and aquaporin 5 (AQP5) were detected by real-time quantitative PCR. The protein expressions of cyclin D1, nucleus β-catenin, SP-C and AQP5 were measured by Western blotting., Results: β-catenin was expressed in cell membrane when fAEC2 were cultured for 48 hours; the expression of β-catenin decreased in cell membrane while enhanced in cytoplasm and nucleus at 72 hours; whole-cell β-catenin expression was lowered at 96 hours. The expressions of Wnt7b and cyclin D1 mRNAs were significantly raised at 72 hours and reduced obviously at 96 hours compared with 48 hours. SP-C mRNA expression level went down gradually with the extended culture time, and AQP5 mRNA level went up gradually. The protein expressions of cyclin D1 and nucleus β-catenin were significantly enhanced at 72 hours and weakened at 96 hours compared with 48 hours. SP-C protein expression was down-regulated with the prolonged culture time, and AQP5 protein expression was up-regulated., Conclusion: Wnt7b/β-catenin signaling pathway may play an important role in fAEC2 transdifferentiation.

With its rapid development, the rural area of Southwest China has been puzzled by the waste management problem, especially for increasing solid waste and water pollution from the domestic waste. Therefore, in order to efficiently and effectively manage the domestic waste in the rural area of Southwest China, 22 villages were selected randomly to analyse the characteristics of domestic waste, the influence factors of characteristics and resident's willingness of participation in domestic waste management by questionnaires, field samplings and laboratory tests. The results of the rural area of Southwest China indicated that the generation of domestic waste was 178 g d(-1) per capita and it was mainly composed of kitchen waste, inert waste, plastics and paper with a total proportion of 81.98%. The waste bulk density, moisture, ash, combustible and lower calorific value were 107 kg m(-3), 37.04%, 25.73%, 37.23% and 8008 kJ kg(-1), respectively. These characteristics were influenced by the topography, the distance from towns or cities, the villagers' ethnicities and income sources to some extent. Moreover, the distance of 50-800 m between each collection facility and the disposal fee of around ¥5.00 per household per month could be accepted. The working hours of participation in waste management is suggested as 5 hours per day with the income of ¥1000 per capita per month. Based on the outcome of this survey, a waste management system consisting of classified collection, centralised treatment and decentralised treatment was proposed. It is important to ensure financial viability and practical considerations of this system., (© The Author(s) 2014.)

Adequate cardiopulmonary resuscitation (CPR) skill is essential in improving survival rate of sudden cardiac arrest (SCA). However, the skill deteriorates rapidly following CPR training. We developed a computer game by using 3-Dimensional virtual technology (3-D CPR game) for laypersons in the purpose to improve skill retention. As the testing phase, a randomized control trial, in which we recruited 97 freshman medical students who had no prior CPR training experience, was used to test its effect on 3-month CPR Skill retention. The usability of the game was also tested using a 33 item questionnaire rated with 5-point Likert scale. Three months after the initial CPR training, the retention rate of CPR skill in the game group was significantly higher compared with the control (p&lt;0.05) and the average score on 4 dimensions of usability were 3.99-4.05. Overall, using 3-D CPR game in improving CPR skill retention is feasible and effective.

Dengue fever (DF) is the most serious mosquito-borne viral disease in the world and is significantly affected by temperature. Although associations between DF and temperatures have been reported repeatedly, conclusions have been inconsistent. Six databases were searched up to 23 March 2014, without language and geographical restrictions. The articles that studied the correlations between temperatures and dengue were selected, and a random-effects model was used to calculate the pooled odds ratio and 95% confidence intervals. Of 1589 identified articles, 137 were reviewed further, with 33 satisfying inclusion criteria. The closest associations were observed between mean temperature from the included studies (23.2-27.7 °C) and DF (OR 35.0% per 1 °C; 95% CI 18.3%-51.6%) positively. Additionally, minimum (18.1-24.2 °C) (29.5% per 1 °C; 20.9%-38.1%) and maximum temperature (28.0-34.5 °C) (28.9%; 10.3%-47.5%) were also associated with increased dengue transmission. The OR of DF incidence increased steeply from 22 °C to 29 °C, suggesting an inflexion of DF risk between these lower and upper limits of DF risk. This discovery is helpful for government decision-makers focused on preventing and controlling dengue in areas with temperatures within this range.

Photoautotrophic cultivation with heterotrophic cells as seeds (heterotrophic cells/photoautotrophic cultivation) is an effective way for the development of microalgal biofuel, but its development potential from the point of process optimization has not been investigated in literatures. To evaluate this, the optimizations of medium and culture conditions for Chlorella ellipsoidea were studied. In the heterotrophic stage, the biomass concentration reached 11.04 g/L with the optimized medium in flask, which were 28.0% higher than that with the original medium, and the biomass concentration reached 73.89 g/L in 5-L fermenter. In the photoautotrophic stage, the culture medium and conditions were studied in a 2-L column photobioreactor. The maximum biomass concentration, lipid content and lipid productivity reached 1.62 g/L, 36.34% and 6.1 mg/(L·h) under the optimal photoautotrophic conditions. The lipids were mainly composed of C16-C18 fatty acids, which were raw material suitable for biodiesel. After optimization, heterotrophic cells/photoautotrophic cultivation can significantly improve the capacity of biofuel production by Chlorella ellipsoidea, this method is also expected to be an efficient way for the cultivation of other microalgae that can grow heterotrophically.

As the optimal source of astaxanthin, Haematococcus pluvialis was cultured for commercial production of astaxanthin through two continuous phases: cell growth and astaxanthin induction. In this study, the efficiency of an attached system for producing astaxanthin from H. pluvialis was investigated and compared to that of the suspended system (bubble column bioreactor) under various conditions. Results showed that this attached system is more suitable for photoinduction of H. pluvialis than the suspended bioreactor. Under the optimal conditions, the astaxanthin productivity of the attached system was 65.8 mg m(-2)d(-1) and 2.4-fold of that in the suspended system. This attached approach also offers other advantages over suspended systems, such as, producing astaxanthin under a wide range of light intensities and temperatures, saving water, ease to harvest cells, resisting contamination. Therefore, the attached approach can be considered an economical, environmentally friendly and highly-efficient technology for producing astaxanthin from H. pluvialis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The multistage model of nonmelanoma skin carcinogenesis has contributed significantly to our understanding of epithelial cancer in general. We used the Krt1-15CrePR1;R26R transgenic mouse to determine the contribution of keratin 15+ cells from the hair follicle to skin tumor development by following the labeled progeny of the keratin 15 expressing cells into papillomas. We present three novel observations. First, we found that keratin 15 expressing cells contribute to most of the papillomas by 20 weeks of promotion. Second, in contrast to the transient behavior of labeled keratin 15-derived progeny in skin wound healing, keratin 15 progeny persist in papillomas, and some malignancies for many months following transient induction of the reporter gene. Third, papillomas have surprising heterogeneity not only in their cellular composition, but also in their expression of the codon 61 signature Ha-ras mutation with approximately 30% of keratin 15-derived regions expressing the mutation. Together, these results demonstrate that keratin 15 expressing cells of the hair follicle contribute to cutaneous papillomas with long term persistence and a subset of which express the Ha-ras signature mutation characteristic of initiated cells., (© 2012 Wiley Periodicals, Inc.)

Ultra-small gold nanoclusters (Au NCs) are highly promising materials for tumor imaging and therapy because of their low toxicity, intrinsic fluorescence, and the availability of multifunctional groups for covalent linkage of diverse bioactive molecules. Au NCs stabilized by bovine serum albumin (BSA) were prepared via an improved "green" synthetic routine. To ameliorate the selective affinity of Au NCs for high folate receptor (FR) expressing tumors, folic acid (FA) was immobilized on the surface of Au NCs. Subsequently, a near-infrared (NIR) fluorescent dye MPA was conjugated with Au-FA NCs for in vitro and in vivo fluorescence imaging. Similarly, Doxorubicin (DOX), a widely used clinical anticancer drug, was also conjugated to the folate-modified Au NCs to form a prodrug (Au-FA-DOX). Cellular and in vivo acute toxicity studies demonstrated the low toxicity of the Au-FA-MPA to normal cells and tissues. Additionally, in vitro and in vivo study of the dynamic behavior and targeting ability of Au-FA-MPA to different tumors validated the high selective affinity of Au-FA-MPA to FR positive tumors. With regard to the Au-FA-DOX, high anti-tumor activity was displayed by this pro-drug due to the FR mediated uptake. Herein, all of the results supported the potential of using ligand-modified Au NCs for tumor imaging and targeted therapy.

A novel cultivation strategy called "sequential heterotrophy-dilution-photoinduction" was developed for efficient algal biomass and lipid production. Three Chlorella species were first cultivated heterotrophically to achieve high cell density, then the broth was diluted to suitable concentration (2-5 g/L) and transferred to light environment for photoinduction. With this strategy, the Chlorella intracellular protein and chlorophyll increased rapidly to 50.87% and 32.97 mg/g by a 12-h illumination, which were close to the level of cells cultivated photoautotrophically. Moreover, the lipid contents were increased by 84.57%, 70.65% and 121.59% within 24-h photoinduction for C. vulgaris, C. pyrenoidosa and C. ellipsoidea, respectively. Maximum lipid content as 26.11% of biomass and maximum lipid productivity of 89.89 mg/L/d was both accomplished by C. pyrenoidosa. Further outdoor experiments showed consistent patterns. Therefore, the proposed strategy provided an effective approach for microalgal biomass production to meet the urgent need for both health food and biodiesel., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The new, single-isomer, sulfated alpha-cyclodextrin, the sodium salt of hexakis(2,3-diacetyl-6-O-sulfo)-alpha-cyclodextrin (HxDAS), was used for the first time in acidic methanol background electrolytes (BGEs) to separate the enantiomers of weak base analytes by nonaqueous capillary electrophoresis (NACE). The concentration dependence of the effective mobilities and separation selectivities followed trends similar to those observed earlier in acidic methanol background electrolytes with heptakis(2,3-diacetyl-6-O-sulfo)-beta-cyclodextrin (HDAS) and octakis(2,3-diacetyl-6-O-sulfo)-gamma-cyclodextrin (ODAS). In general, interactions between the weak base analytes and HxDAS were weaker than with HDAS and ODAS. For some of the weak base analytes, separation selectivities observed in acidic aqueous and acidic methanol background electrolytes were complementary to each other, permitting the eventual separation of enantiomers that could not be achieved otherwise.

The third, concluding member of the family of single-isomer, fully sulfated alpha-cyclodextrins, the sodium salt of hexakis(2,3-di-O-methyl-6-O-sulfo)-alpha-cyclodextrin (HxDMS), has been synthesized on the kilogram scale, completing the nine-member array of the single-isomer, 6-O-sulfo CDs now available. HxDMS was tested for the capillary electrophoretic (CE) resolution of the enantiomers of nonelectrolyte, weak acid and weak base analytes contained in our CD screening kit. HxDMS complexed differently with many of the analytes tested than either its larger-ring analogs, heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-CD (HDMS) and octakis(2,3-di-O-methyl-6-O-sulfo)-gamma-CD (ODMS) or its same-ring, but differently substituted analogs, hexakis(6-O-sulfo)-alpha-CD (HxS) and hexakis(2,3-di-O-acetyl-6-O-sulfo)-alpha-CD (HxDAS). For all analytes, the effective mobilities and separation selectivities as a function of the background electrolyte concentration of HxDMS followed the trends that were found for the other single-isomer, 6-O-sulfo CDs.

The second member of the family of single-isomer sulfated alpha-cyclodextrins, the sodium salt of hexakis(6-O-sulfo)-alpha-cyclodextrin (HxS), has been synthesized, analytically characterized, and used as the resolving agent for the capillary electrophoretic separation of the enantiomers of nonionic, weak-acid and weak-base analytes present in our initial screening kit. HxS interacted less strongly with many of the analytes tested than the larger-ring analogs, heptakis(6-O-sulfo)-beta-cyclodextrin (HS) and octakis(6-O-sulfo)-gamma-cyclodextrin (OS). For some of the analytes, the separation selectivities obtained with HxS were complementary to those observed with hexakis(2,3-di-O-acetyl-6-O-sulfo)-alpha-cyclodextrin (HxDAS), HS, and OS. For all analytes, the effective mobilities and separation selectivities as a function of the background electrolyte concentration of HxS followed the trends that were found for HxDAS, HS, and OS.

The hair follicle bulge possesses putative epithelial stem cells. Characterization of these cells has been hampered by the inability to target bulge cells genetically. Here, we use a Keratin1-15 (Krt1-15, also known as K15) promoter to target mouse bulge cells with an inducible Cre recombinase construct or with the gene encoding enhanced green fluorescent protein (EGFP), which allow for lineage analysis and for isolation of the cells. We show that bulge cells in adult mice generate all epithelial cell types within the intact follicle and hair during normal hair follicle cycling. After isolation, adult Krt1-15-EGFP-positive cells reconstituted all components of the cutaneous epithelium and had a higher proliferative potential than Krt1-15-EGFP-negative cells. Genetic profiling of hair follicle stem cells revealed several known and unknown receptors and signaling pathways important for maintaining the stem cell phenotype. Ultimately, these findings provide potential targets for the treatment of hair loss and other disorders of skin and hair.

Human neocentromeres are fully functional centromeres that provide mitotic stability to rearranged chromosomes that have separated from endogenous centromeres. A disproportionate number of neocentromeres has been observed in certain regions such as chromosome 3q (n=6), 15q (n=9) and 13q32 (n=7), suggesting that these regions contain DNA sequences with a high propensity for neocentromere formation. Therefore, we have addressed the role of primary DNA sequence in neocentromere formation by asking whether multiple independent neocentromeres that were cytologically localized to chromosome 13q32 are in fact localized to the same underlying genomic DNA. Analysis of four independent 13q32 neocentromeres using simultaneous FISH with ordered YAC probes and immunofluorescence with antibodies to CENP-C have localized three neocentromeres to a distal approximately 7 Mb domain in chromosome 13q32, and one to an overlapping proximal domain of approximately 7 Mb. DNA was obtained from three of these neocentromeres by CENP-A chromatin immunoprecipitation (ChIP) and used to screen ordered BACs using both a slot-blotted BAC pool approach and a genomic microarray that contiguously spans 13q31.3-13q33.1. The CENP-A binding domains from each of these neocentromeres was identified to distinct genomic locations of approximately 130, 215 and 275 kb within an approximately 6.5 Mb region. Thus, the lack of coincidence of these neocentromeres to the same underlying DNA sequence refutes the idea of a DNA sequence based neocentromere 'hotspot' in 13q32 and further supports the sequence-independent epigenetic formation of human neocentromeres. The screening of genomic microarrays with ChIP DNA provides a powerful method to identify mammalian DNA sequences associated with particular functional chromatin states.

The sodium salt of hexakis(2,3-di-O-acetyl-6-O-sulfo)-alpha-CD (HxDAS), the first member of the family of single-isomer, fully sulfated alpha-CDs, has been synthesized and used for the initial capillary electrophoretic separation of the enantiomers of nonionic, weak acid, weak base, and ampholytic analytes. HxDAS complexes less strongly with many of the analytes tested than the analogous beta- and gamma-cyclodextrin derivatives, namely, heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-cyclodextrin (HDAS) and octakis(2,3-di-O-acetyl-6-O-sulfo)-gamma-cyclodextrin (ODAS). Nevertheless, it facilitated the separation of the enantiomers of a large number of weak electrolyte and nonelectrolyte analytes in acidic aqueous background electrolytes. For all analytes, the effective mobilities and separation selectivities as a function of the background electrolyte concentration of HxDAS followed the trends that were found for HDAS and ODAS.

An 18-year-old woman was evaluated because of primary amenorrhea and hypogonadism. Chromosome analysis from peripheral blood lymphocytes revealed a nonmosaic 46,X,+mar constitution. The marker was shown to be a rearranged Y chromosome consisting of an inverted duplication of the long arm: rea(Y)(qter-q11::q11-qter). Deletion mapping analysis with Y-specific STS showed that the marker lacked Yp and Y-centromeric (DYZ3) sequences, but it was positive for Yq sequences tested. Fluorescence in situ hybridization analysis with Y and X chromosome centromeric and pancentromeric probes showed no hybridization signals. The marker chromosome is present in 100% of the cells; therefore, it is mitotically stable despite the absence of DYZ3 centromeric sequence. Hybridization with CENP-A and CENP-C specific antibodies localized a neocentromere close to the breakpoint., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To explore the clinical feature of benign symmetric lipomatosis (BSL) so as to improve its diagnosis and treatment., Method: 28 patients of BSL treated in our hospital were analyzed and literature was reviewed. Surgical management is used in all patients., Result: There were no patients died. All patients were satisfactory with their appearance and function improved. 28 patients were followed up for 2-15 years (average 6 years and 5 months), only 5 cases recurred., Conclusion: BSL usually occurs in middle age men. Patients have a striking appearance "hump back" because of a diffuse, symmetric distribution of the lipomatous tissue in the cervical region. The etiology is related to alcohol abuse. Operation is the most effective treatment. The radical surgical therapy should not be emphasized because the important anatomic structures may be damaged. Abstaining from alcohol may help to reduce the rate of recurrence.

We report three new cases of chromosome 13 derived marker chromosomes, found in unrelated patients with dysmorphisms and/or developmental delay. Molecular cytogenetic analysis was performed using fluorescence in situ hybridization (FISH) with chromosome-specific painting probes, alpha satellite probes, and physically mapped probes from chromosome 13q, as well as comparative genomic hybridization (CGH). This analysis demonstrated that these markers consisted of inversion duplications of distal portions of chromosome 13q that have separated from the endogenous chromosome 13 centromere and contain no detectable alpha satellite DNA. The presence of a functional neocentromere on these marker chromosomes was confirmed by immunofluorescence with antibodies to centromere protein-C (CENP-C). The cytogenetic location of a neocentromere in band 13q32 was confirmed by simultaneous FISH with physically mapped YACs from 13q32 and immunofluorescence with anti-CENP-C. The addition of these three new cases brings the total number of described inv dup 13q neocentic chromosomes to 11, representing 21% (11/52) of the current overall total of 52 described cases of human neocentric chromosomes. This higher than expected frequency suggests that chromosome 13q may have an increased propensity for neocentromere formation. The clinical spectrum of all 11 cases is presented, representing a unique collection of polysomy for different portions of chromosome 13q without aneuploidies for additional chromosomal regions. The complexity and variability of the phenotypes seen in these patients does not support a simple reductionist view of phenotype/genotype correlation with polysomy for certain chromosomal regions., (Copyright 2002 Wiley-Liss, Inc.)