Triclocarban (TCC), a widely used antibacterial agent, has aroused considerable public concern due to its potential toxicity. In the current study, we applied targeted metabolite profiling (LC/GC-MS) and untargeted 1H NMR-based metabolomics in combination with biological assays to unveil TCC exposure-induced cellular metabolic responses in murine preadipocyte and human normal hepatocytes. We found that TCC promoted adipocyte differentiation in 3T3L1 preadipocytes, manifested by marked triglyceride (TG) and fatty acids accumulation, which were consistent with significant up-regulation of mRNA levels in the key adipogenic markers Fasn, Srebp1 and Ap2. In human hepatocytes (L02), TCC exposure dose-dependently interfered with the cellular redox state with down-regulated levels of antioxidant reduced-GSH and XBP1 and further induced the accumulation of TG, ceramides and saturated fatty acid (160). We also found that TCC exposure triggered unfold protein response (UPR) and endoplasmic reticulum (ER) stress in both cells through activation of ATF4 and ATF6, resulting in toxic lipid accumulation. These findings about lipid metabolism and metabolic responses to TCC exposure in both preadipocytes and hepatocytes provide novel perspectives for revealing the mechanisms of TCC toxicity.Evacuation simulation plays an indispensable role when planning for emergencies and evaluating the consequences of disasters related to airborne toxics. Various attempts have been made to improve simulation of evacuation in toxic environments and to account for the varying concentration levels and the dynamic exposure. However, most studies neglect the reverse effect, how the exposure and dosage levels affect the physical and psychological state of an evacuee and consequently the evacuation path and process. In this work, a fully coupled exposure-response-evacuation and agent based algorithm is proposed, focusing on the H2S airborne toxic. Accordingly, the dynamically estimated exposure of the evacuee affects, non-linearly, the evacuation speed and thus the overall evacuation. This coupling is challenging and thus it depends on the available epidemiological and toxicological data. Nevertheless, the diversity and advantages of the algorithm is successfully demonstrated over three case studies including single- and multi-agent in straight-path and building evacuation scenarios. For example, the building evacuation time increased by more than 50% by inclusion of the aforementioned coupling. In conclusion, herein, a gap on the evacuation modelling is addressed by a fully coupled methodology that could be easily adapted by safety engineers and further improved by researchers as more data become available.In China, forensic age estimation in the living has become increasingly important in these few years. Due to increasing juvenile crimes, the age of 16 years has become the legal age threshold for determining whether the juvenile criminal law or adult criminal law applies to the citizen. This study aimed to assess new cut-off values of the third molar maturity index (I3M) and second molar maturity index (I2M) at the legal age threshold of 16 years in Southern Chinese population and then to compare the applicability of the cut-off values of I3M and I2M we set for discriminating whether a subject is ≥ 16 years. Orthopantomograms (OPGs) of 671 healthy Southern Chinese subjects (332 males and 339 females), aged between 10 and 20 years, were studied. Logistic regression analysis was performed with chronological age (below 16 years and over 16 years) as a dichotomous dependent variable and, I3M, I2M, and sex as predictive variables. The high p-value for sex (p = 0.861) reveals that this factor was not statistically significant in assessing the legal age of 16. The cut-off values of I3M less then 0.38 and I2M less then 0.03 were identified and used to distinguish between individuals who were or were not aged ≥ 16 years. Compared with a single predictor (I3M) alone, combining I3M and I2M can be more reliable for determining whether an individual is aged more than 16 years. We found that accuracy was 88.52% (95% confidence interval CI, 86.11-90.94%) and sensitivity and specificity were 77.96% (95% CI, 74.82-81.10%) and 97.28% (95% CI, 96.04-98.51%), respectively. The estimated Bayes post-test probability was 99.12% (95% CI, 98.41-99.83%). In conclusion, combining I3M and I2M may be useful in legal and forensic practices to determine the legal age of 16 years in Southern Chinese individuals.A search was undertaken of the Forensic Science South Australia, Australia, autopsy database over a 25-year period from 1995 to 2019 with the aim of understanding more about the role that recreational horse use not involving racing may have in mortality. Eight cases were found with an age range of 8-73 years (mean 47 years) and a malefemale ratio of 53. The major category was a fall while riding (N = 7) with the remaining case (N = 1) sustaining a lethal kicking. Blunt craniocerebral trauma was responsible for death in 4 cases with injuries following falls including acute subdural and subarachnoid haemorrhage, cerebral contusions and lacerations with associated significant cerebral edema. Skeletal injuries occurred in 2 cases with falls that had caused fractures of cervical vertebrae 2 and 4, with contusion of the underlying spinal cord (N = 1), and fracture of the pelvis with significant retroperitoneal hemorrhage from associated vascular injuries (N = 1). Lethal abdominal and chest injuries occurred in 2 cases, both with lacerated livers and multiple rib fractures. In the final case of an 8-year-old girl who was kicked by a horse there was a lacerated liver with a hematoperitoneum, and fractures of the ribs on the right side with contusion of the underlying lung. The size, strength and temperament of horses make them potentially dangerous during leisure time activities such as grooming and riding. Lethal head injuries often follow falls and kicks. Traumatic lesions identified at autopsy include fractures and blunt craniocerebral, thoracic and abdominal trauma.Curcumin has been reported to attenuate muscle atrophy. However, the underling mechanism remains unclear. The aim of this study was to investigate whether curcumin could improve chronic kidney disease (CKD)-induced muscle atrophy and mitochondrial dysfunction by inhibiting glycogen synthase kinase-3β (GSK-3β) activity. The sham and CKD mice were fed either a control diet or an identical diet containing 0.04% curcumin for 12 weeks. The C2C12 myotubes were treated with H2O2 in the presence or absence of curcumin. In addition, wild-type and muscle-specific GSK-3β knockout (KO) CKD model mice were made by 5/6 nephrectomy, and the sham was regarded as control. Curcumin could exert beneficial effects, including weight maintenance and improved muscle function, increased mitochondrial biogenesis, alleviated mitochondrial dysfunction by increasing adenosine triphosphate levels, activities of mitochondrial electron transport chain complexes and basal mitochondrial respiration and suppressing mitochondrial membrane potential. In addition, curcumin modulated redox homeostasis by increasing antioxidant activity and suppressed mitochondrial oxidative stress. Moreover, the protective effects of curcumin had been found to be mediated via inhibiting GSK-3β activity in vitro and in vivo. Importantly, GSK-3β KO contributed to improved mitochondrial function, attenuated mitochondrial oxidative damage and augmented mitochondrial biogenesis in muscle of CKD. Overall, this study suggested that curcumin alleviated CKD-induced mitochondrial oxidative damage and mitochondrial dysfunction via inhibiting GSK-3β activity in skeletal muscle.Fusarium fujikuroi species complex (FFSC) species are commonly encountered infecting rice, but knowledge of the diversity and toxigenic potential of the species is lacking in Brazil, the largest rice-producing country outside Asia. One hundred FFSC isolates obtained from national rice were identified using morphology and phylogeny of TEF, CAL and TUB genes. Eight previously known and one novel Fusarium species were identified. Three species accounted for around 60% of the strains F. fujikuroi (n = 23), F. proliferatum (n = 22) and F. verticillioides (n = 16). The less frequent species were F. volatile (n = 8), F. anthophilum (n = 6), F. pseudocircinatum (n = 4), F. sterilihyphosum (n = 2) and F. begoniae (n = 1). The novel Fusarium species was represented by 18 isolates. All species produced at least one of the analyzed mycotoxins [beauvericin (BEA), fumonisins (FBs), moniliformin (MON) and enniatins (ENNs)]. BEA was produced by all species but F. verticillioides. The FBs (mainly FB1) were produced mostly by F. fujikuroi, F. proliferatum and F. verticillioides. F. begoniae and F. verticillioides did not produce ENNs and F. sterilihyphosum and F. begoniae did not produce MON, while the other species produced MON and ENNs. Our results add new knowledge of the diversity, geographical distribution and host range of FFSC species.Background Currently, FDA-approved HIV-1 viral load (VL) assays use venipuncture-derived plasma. The Hologic Panther system uses 0.7 mL total volume for the Aptima HIV-1 Quant Assay standard (APT-Quant-std) and dilution (APT-Quant-dil) protocols. However, smaller plasma volumes from fingerstick whole blood (FSB) collected in EDTA-microtainer tubes (MCT) could provide an easier sample collection method for HIV-1 VL testing. Objectives To evaluate the performance of the APT-Quant-std compared to the Roche CAP/CTM and Abbott m2000RT VL assays and an alternative APTQuant 17 dilution protocol, the latter using 100 μL of MCT-derived plasma from FSB. Study design Linearity was determined using commercial HIV-1 RNA plasma controls. Dilutions ranging 1.56-2.95 log10 copies/mL were prepared to determine the APT-Quant-dil Limit of Quantitation (LOQ) using Probit analysis. Specificity of APT-Quant-std was calculated using 326 HIVnegative samples. To evaluate agreement, 329 plasma specimens were tested with APT-Quant-std, CAP/CTM, and m2000RT. Forty-seven matched venipuncture and MCT-derived plasma specimens were tested with APT-Quant-std and APT-Quant-dil. Results Among the RNA controls, specificity was 99.69 % for APT-Quant-std. The R2 values were 0.988 (APT-Quant-std/CAP/CTM), 0.980 (APT-Quant-std/ m2000RT), and 0.997 (APT-Quant-std/APT-Quant-dil). The APT-Quant-dil LOQ was estimated at 2.7 log10 copies/mL (500 copies/mL) (95 %CI 2.62-2.87). At 2.3 log10 copies/mL (200 copies/mL), the overall agreement was 91.0 % for APT-Quant-std/CAP/CTM, 85.7 % for APT-Quant-std/m2000RT, and 82.9 % for APT-Quant-std/APT-Quant-dil. Quantified APT-Quant-std results were on average 0.2 log10 copies/mL higher than CAP/CTM and m2000RT and 0.14 log10 copies/mL higher than APT-Quant-dil. Conclusion APT-Quant showed similar performance compared to the CAP/CTM and m2000RT assays and remains sensitive and accurate using the dilution protocol.The rising caesarean section (CS) rates have been, in part, attributed to women’s requests. Several individual studies and literature reviews have attempted to determine the degree of influence of women’s requests on overall CS rates, and the common reasons behind these requests, from women’s, midwives’ and obstetricians’ viewpoints. Despite many similarities in their findings, there is both a lack of clarity and disparity on the degree of influence women’s requests actually has on the decision to perform a CS. This paper presents a critique of a key finding from a recently published systematic review of clinicians’ (midwives’ and obstetricians’) views of factors that influenced their decision to perform a CS, which identified their belief in 'women’s request’ as a key factor. This finding is contrasted with findings from three other published reviews, which concluded that women’s request contributed minimally to the overall rising rates of CS indicating a disparity in evidence around influence and contribution of women’s request. Some of the possible reasons for this disparity can be explained by differences in views of women and clinicians, women’s decision being guided by clinicians’ beliefs of what is 'safe’ and unsafe’, and women’s concerns being interpreted as their request and preferences to birth by CS. An insight into the possible reasons for the disparity in findings can help explain whether maternal request has any influence on the rising rates of CSs.Many organizations in Europe collect data and perform research on municipal solid waste and the secondary raw materials that can be produced from them through recycling, urban mining, or landfill mining. However, the information generated and presented thereby is often highly aggregated, while research activities are many a time isolated. Both reduce the usability of the data and information generated. In order to better structure the knowledge generation on secondary raw materials production from municipal solid waste, we suggest to learn from the traditional raw materials mining industry how to perform an integrated assessment and reporting of anthropogenic resources. This is exemplarily shown for the case of the anthropogenic resource municipal solid waste incineration bottom ash and air-pollution control residues. A network of expert institutions from countries throughout Europe was build up to compile the information on legal and technological aspects for the recovery of different secondary raw materials from these residues, including construction minerals, metals, and salts. We highlight in our article the strength of the combined knowledge of an expert network not only on legal and technological, but also local and site-specific aspects of the recovery of secondary raw materials. By doing so, we hope to kick-off a discussion for how to organize and implement a structure for a better management of knowledge on anthropogenic resources, in order to provide a sustainable supply of secondary raw materials for a greener and more circular economy.Phosphorous dissolution and ensuing chemical redistribution of P in organic amendments (OA) were studied by applying a modified Hedley selective fractionation to eight water-extracted and unextracted OAs. Nine 7-day, repeated extractions were applied using a 601 waterdry OA (vw) ratio at pH 8. Eight OAs were tested including five biosolids, broiler litter, dairy manure compost and municipal solid waste compost. The average PWEP9 (percent water-extractable P following nine water-extraction cycles) for the OAs was 65 ± 9% and all of the fractions, with almost no exceptions, contributed to that figure. Organic P was depleted by mineralization (in non-stabilized sludges and broiler litter) or dissolution (stabilized composts) or both (in lime-treated biosolids) and that depletion was completed within 1-2 extraction cycles. Only the organic P of the MSWC remained undepleted. Strong linear correlations were observed between the WEP9 values of the OAs (0.8-21 g P kg-1) and several more easily determined properties, including total P content (r2 = 0.84), organic N content (r2 = 0.82), the sum of Hedley’s more easily dissolved SRP (soluble reactive P) and OP (r2 = 0.95), and the total P and SRP extracted by 16 h of shaking with the bicarbonate reagent (r2 ≥ 0.90). These findings indicate that if greater P availability is desired, the stabilization of biosolids and biowastes should be minimized. These insights into the relationships between OA characteristics and P solubility may benefit the use of OAs in agricultural systems and aid assessments of the environmental significance of their use.Agriculture is estimated to generate about 700 million tons of waste annually in the EU. Novel valorization technologies are developing continuously to recover and recycle valuable compounds and nutrients from waste materials. To close the nutrient loop, low-value agri-food wastes, co-products and by-products (AFWCBs) produced during the valorization process, need to be returned to the soil. However, knowledge on their reaction in soils that is needed to allow efficient and environmentally sound recycling is largely lacking. To this end, we set up a series of laboratory incubation experiments using 10 AFWCBs including insect frass residues made from three different feedstocks, anaerobic digestates from two feedstocks, potato-pulp, rice bran compost, duckweed and two reference crop residues (wheat straw and sugar beet) and measured net N release, C mineralization, dehydrogenase activity (DHA), microbial biomass C (MBC) and community structure. The suppressing potential of frasses and digestates against Rhizoctonia solani was determined using bean. The digestates released the highest net mineral N (50-70%) followed by rice bran compost (55%) and duckweed (30%), while frass made from general food waste and potato-pulp immobilized N like the reference straw for 91 days after incubation. All AFWCBs except digestates significantly increased MBC compared to the control while frasses, potato-pulp and duckweed increased DHA. Frasses and digestates significantly suppressed the development of Rhizoctonia solani in bean plants. AFWCBs from emerging valorizing technologies have the potential to improve microbial activities, C sequestration and may play a significant role in closing the nutrient loop.Knowledge on the material flows of engineered nanomaterials (ENMs) is crucial for assessing their environmental risks. Waste management processes constitute important parts of material flow analyses as they affect large fractions of the ENMs. Accordingly, their detailed representation could substantially improve the models. Our goal was to consider the temporal variations of wastewater and solid waste management in the dynamic probabilistic material flow analysis of carbon nanotubes (CNTs), nano-Ag, -TiO2 and -ZnO in Europe from 2000 to 2020. New input parameters included wastewater and solid waste management rates for each year. The uncertainties associated with these data were assessed based on the type of consulted source, the geographical representativeness and temporal concordance. Results show modal values of 10-27% of ENMs going from sorting to reprocessing. Large shares of environmental releases of nano-Ag and nano-ZnO end in surface water (4.9 t and 1700 t respectively in 2020), while sludge-treated soil as environmental compartment is receiving most of nano-TiO2 (22,000 t in 2020) and CNTs (8.8 t in 2020). Discharges from wastewater management to the subsurface soil make this compartment the largest environmental sink of nano-Ag and nano-ZnO (30 t and 3860 t accumulated in 2020, respectively). Landfills represent significant stocks of ENMs, with 105 t, 2077 t, 69,000 t and 1042 t of nano-Ag, nano-ZnO, nano-TiO2 and CNTs. This model includes detailed descriptions of waste management and sources of ENMs released at the European scale. However, a better understanding of the behaviour, i.e. fate and potential transformations of ENMs in reprocessing systems, is needed to complete the full assessment.Epithelial-to-mesenchymal transition (EMT) is a dynamic process that produces migratory cells from epithelial precursors. However, EMT is not binary; rather it results in migratory cells which adopt diverse strategies including collective and individual cell migration to arrive at target destinations. Of the many embryonic cells that undergo EMT, the vertebrate neural crest is a particularly good example which has provided valuable insight into these processes. Neural crest cells from different species often adopt different migratory strategies with collective migration predominating in anamniotes, whereas individual cell migration is more prevalent in amniotes. Here, we will provide a perspective on recent work toward understanding the process of neural crest EMT focusing on how these cells undergo collective and individual cell migration.Unfavorable weather conditions are one of the largest constraints to maximizing farm animal productivity. Heat stress (HS), in particular, compromises almost every metric of profitability and this is especially apparent in the grow-finish and reproductive aspects of the swine industry. Suboptimal production during HS was traditionally thought to result from hypophagia. However, independent of inadequate nutrient consumption, HS affects a plethora of endocrine, physiological, metabolic, circulatory, and immunological variables. Whether these changes are homeorhetic strategies to survive the heat load or are pathological remains unclear, nor is it understood if they temporally occur by coincidence or if they are chronologically causal. However, mounting evidence suggest that the origin of the aforementioned changes lie at the gastrointestinal tract. Heat stress compromises intestinal barrier integrity, and increased appearance of luminal contents in circulation causes local and systemic inflammatory responses. The resulting immune activation is seemingly the epicenter to many, if not most of the negative consequences HS has on reproduction, growth, and lactation. Interestingly, thermoregulatory and production responses to HS are only marginally related. In other words, increased body temperature indices poorly predict decreases in productivity. Further, HS induced malnutrition is also a surprisingly inaccurate predictor of productivity. Thus, selecting animals with a „heat tolerant” phenotype based solely or separately on thermoregulatory capacity or production may not ultimately increase resilience. Describing the physiology and mechanisms that underpin how HS jeopardizes animal performance is critical for developing approaches to ameliorate current production issues and requisite for generating future strategies (genetic, managerial, nutritional, and pharmaceutical) aimed at optimizing animal well-being, and improving the sustainable production of high-quality protein for human consumption.Background The Gymkhana Room for Education and Evaluation in Nursing Studies (GREENS©) is a pedagogical model that can be used as a learning and assessment method in nursing training workshops. This model combines the advantages of gamification, the flipped classroom and the use of low-fidelity clinical simulation, also including self-reflection and peer evaluation of the situations experienced. Objectives To evaluate the students’ perception of the implementation of GREENS© as a learning and assessment tool in an academic course at the University of Almeria. Design A cross-sectional descriptive study. Settings Academic year 2018/2019, at the University of Almeria (UAL), Spain. Participants 77 students enrolled in their 2nd year of the Nursing Degree who attended the „Health Promotion and Safety” class. Methods After completing the GREENS© activity, the perception and anxiety of students were analyzed through an online ad hoc questionnaire composed of 17 questions. Data were collected in January 2019. Results All of the questions scored above 4 out of a maximum of 5 on a Likert scale. For all the questions, >50% of the students were in total agreement with the questions answered, showing a high acceptance of the GREENS© methodology implementation. The students reported that their anxiety decreased significantly, with a score of 4.7 points on average (95% CI 4.16 to 5.33, p less then 0.001), after knowing that the assessment would be through a gamification tool, not an oral one. More than 60% of the students answered „agree” or „strongly agree” with the idea that GREENS© is useful for improving motivation, teamwork, learning, fun and knowledge assessment. Conclusions The use of GREENS© has generated a high satisfaction and motivation of the students in their learning process, and as an assessment tool, it created a lower degree of anxiety as compared to an oral examination.Pregnancy represents an immunological challenge for the maternal immune system. Pregnancy augments innate immune responses, and particularly monocytes contribute to maintaining the balance between pro- and anti-inflammatory immune responses required for the successful sequence of distinct immunological phases throughout pregnancy. Nonetheless, studies that focus on the heterogeneity of monocytes and analyze the alteration of monocyte subsets in a longitudinal approach throughout healthy pregnancies have remained scarce. In this study, we characterized the gradual phenotypic changes of monocyte subsets and the secretory potential of bulk monocytes in peripheral blood mononuclear cells of healthy pregnant women from a population-based prospective birth cohort study. Blood samples at predefined time points were analyzed using flow cytometry for in-depth characterization of monocyte subsets, which confirmed a shift from classical towards intermediate monocytes throughout pregnancy. Principal component analysis revealed characteristic phenotypic changes on monocyte subsets, especially on the intermediate monocyte subset, throughout pregnancy. Pregnancy-related hormones were measured in serum and β-human chorionic gonadotropin levels were significantly associated with expression of CD11b, CD116 and CCR2 on monocyte subsets. TLR4 and TLR7/8 stimulation of monocytes furthermore showed reduced polycytokine production towards the end of pregnancy. These data provide a comprehensive overview of phenotypic changes and secretory potential of monocytes in healthy pregnant women and establish a selective contribution of different monocyte subsets to healthy pregnancy. The results from this study therefore build a basis for future comparisons and evaluation of women with adverse pregnancy outcomes.Background and objective In avascular or hypovascular tissues, elements required for maintaining tissue functions are recruited through diffusion, which is highly related with the permeability of the extracellular matrix in health and injury. Here, we investigate the effect of collagen fibril diameter distribution of bovine Anterior Cruciate Ligament (ACL) tissue on the hydraulic permeability of the matrix. Based on the fact that the diameter distribution is significantly different between healthy and injured ACL tissues, our study aims to investigate the effect of such variability on the hydraulic permeability. Methods Simulations are carried out in 3D geometries reconstructed from actual collagen filament/fibril diameter distributions obtained from healthy and injured tissue samples (n=3). The fluid flow through the fibrous tissue is modeled based on Eringen’s theory of micropolar fluid flow to determine the effects of vortex viscosity (m) and spin gradient viscosity (N) on hydraulic permeability. Results Computational results indicate that the hydraulic permeability of models which are replicates of healthy ACL tissues is higher than that of the injured, indicating that the filament size distribution might play an important role on fluid and nutrient transport through ligament tissues. Conclusions These findings underscore the need for increased attention on replicating the diameter distribution of healthy collagens in tissue engineering scaffolds and allowing adequate supply of elements through permeation during ACL reconstruction procedures.Background and objective Most healthcare institutions are reorganizing their healthcare delivery systems based on Clinical Pathways (CPs). CPs are novel medical management plans to standardize medical activities, reduce cost, optimize resource usage, and improve the quality of service. However, most CPs are still paper-based and not fully integrated with Health Information Systems (HIS). More CP computerization research is therefore needed to fully benefit from CP’s practical potentials. A major contribution of this research is the vision that CP systems deserve to be placed at the centre of HIS, because within CPs lies the very heart of medical planning, treatment and impressions, including healthcare quality and cost factors. Methods An important contribution to the realization of this vision is to fully standardize and digitize CPs so that they become machine-readable and smoothly linkable across various HIS. To achieve this goal, this research proposes a framework for (i) CP knowledge representation and sharing using ontologies, (ii) CP standardization based on SNOMED CT and HL7, and (iii) CP digitization based on a novel coding system to encode CP data. To show the feasibility of the proposed framework we developed a prototype clinical pathway management system (CPMS) based on CPs currently in use at hospitals. Results The results show that CPs can be fully standardized and digitized using SNOMED CT terms and codes, and the CPMS can work as an independent system, performing novel CP-related functions, including useful data analytics. CPs can be compared easily for auditing and quality management. Furthermore, the CPMS was smoothly linked to a hospital EMR and CP data were captured in EMR without any loss. Conclusion The proposed framework is promising and contributes toward solving major challenges related to CP standardization, digitization, and inclusion in today’s modern computerized hospitals.Background and objectives Doxorubicin is a common apoptotic chemotherapeutic which has shown an obvious inhibitory effect in cancer chemotherapy. Here, cucurbit[n]urils (n = 7,10) have been proposed as a doxorubicin carrier, and the effects of diameter, protonation on loading and releasing of the anticancer drug doxorubicin has been studied. Methods The Density Functional Theory (DFT) calculation and Molecular Dynamics (MD) simulation are performed to study the adsorption process of the (guest) Doxorubicin molecule in the neutral and protonated states within the (host) cucurbit[n]urils (n = 7,10). Results DFT results show that the adsorption process in water is thermodynamically favorable. It is found that the binding energies for protonated drug encapsulation in cucurbit[n]urils are weaker than those of the neutral drug, implying the protonation of doxorubicin can promote the drug release from the adsorption situation. The electron density values and their Laplacian are evaluated to identify the nature of the intermolecular interactions through the topological parameters using the Bader’s theory of atoms in molecules. Furthermore, the natural bond orbital analysis shows that the electrons aretransferred from cucurbit[n]urils to drug in all complexes. MD simulation results indicate that value of drug diffusion coefficient is small, therefore, we expect DOX to be slowly released from the CB cavity. Conclusions Based on obtained results, cucurbit[n]urils may be a prominent nano-carrier to loading and release drug on to target cells.Background and objective Parkinson’s disease (PD) is a degenerative disorder of the central nervous system for which currently there is no cure. Its treatment requires long-term, interdisciplinary disease management, and usage of typical medications, including levodopa, dopamine agonists, and enzymes, such as MAO-B inhibitors. The key goal of disease management is to prolong patients’ independence and keep their quality of life. Due to the different combinations of motor and non-motor symptoms from which PD patients suffer, in addition to existing comorbidities, the change of medications and their combinations is difficult and patient-specific. To help physicians, we developed two decision support models for PD management, which suggest how to change the medication treatment. Methods The models were developed using DEX methodology, which integrates the qualitative multi-criteria decision modelling with rule-based expert systems. The two DEX models differ in the way the decision rules were defined. In the firsResults show that the DEX expert model is superior to the DEX data model. The results indicate that the constructed models are sufficiently adequate and thus fit for the purpose of making „second-opinion” suggestions to decision support users.The use of polymers such as plastic has become an important part of daily life, and in aqueous environments, these polymers are considered as pollutants. When macropolymers are reduced to the nanoscale, their small particle size and large specific surface area facilitate their uptake by plants, which has a significant impact on aquatic plants. Therefore, it is essential to study the pollution of nanoscale polymers in the aquatic environment. In this work, we prepared nanoscale polymer dots (Pdots) and explored their toxicity, uptake and transport mechanisms in penny grass. From toxicological studies, in the absence of other nutrients, the cell structure, physiological parameters (total soluble protein and chlorophyll) and biochemical parameters (malondialdehyde) do not show significant changes over at least five days. Through in vivo fluorescence and photoacoustic (PA) imaging, the transport location can be visually detected accurately, and the transport rate can be analyzed without destroying the plants. Moreover, through ex vivo fluorescence imaging, we found that different types of Pdots have various uptake and transport mechanisms in stems and blades. It may be due to the differences in ligands, particle sizes, and oil-water partition coefficients of Pdots. By understanding how Pdots interact with plants, a corresponding method can be developed to prevent them from entering plants, thus avoiding the toxicity from accumulation. Therefore, the results of this study also provide the basis for subsequent prevention work.Pollinators provide a crucial ecosystem service by pollinating commercially cultivated crops, but they are frequently exposed to various agricultural chemicals used for pest management. In this study, we assessed the potential exposure of pollinators to various systemic insecticides and a fungicide used in apple orchards. Residue levels were determined for the whole flower as well as pollen and nectar separately for pre-bloom applications of acetamiprid, imidacloprid, sulfoxaflor, thiacloprid, thiamethoxam, and myclobutanil. Very low pesticide residue levels (2-70 parts per billion, ppb) were found in the whole flower, pollen and nectar samples compared with pesticide concentrations of 60-200 parts per million (ppm) in applied foliarly only 5 days earlier. Insecticide residues from nectar and pollen samples were below the USA EPA classification of No Observable Effect Limit (NOEL) for acute toxicity to honey bees, suggesting that a single foraging visit to flowers may not cause toxicity to bees. However, cumulative acute exposure from multiple flower visits could potentially be harmful to bees, and needs to be studied further. We also examined apple flowers for residues of several systemic insecticides that were applied for brown marmorated stink bug control late in the fall of the previous season. None of the fall sprays that contained premixed insecticide active ingredients (viz., thiamethoxam + lambda-cyhalothrin, and imidacloprid + beta-cyfluthrin), including multiple applications of individual active ingredients (viz., dinotefuran, clothianidin, and sulfoxaflor), persisted until the following spring. Based on these findings, fall applications of insecticides used for controlling invasive pests such as the brown marmorated stink bug (Halyomorpha halys) and the spotted lanternfly (Lycorma delicatula) could be considered safe to pollinator species foraging in apple orchards during the spring bloom the following season.Spatiotemporal variability in seawater, spatial variation in sediment, pollution characteristics, and risks related to 16 phthalate esters (PAEs) were investigated in the Yangtze River estuary and its adjacent East China Sea. The total concentrations of ΣPAEs in surface water were 0.588-17.7 μg L-1 in summer, 2.63-22.9 μg L-1 in winter, and 1.93-20.7 μg L-1 in spring, with average values of 2.05, 10.2, and 4.89 μg L-1, respectively. PAE concentrations exhibited notable seasonal variations with the highest value in winter and the lowest value in summer. The seasonal variation in PAE concentrations may be influenced by runoff and diluted water from the Yangtze River. The chemical composition of PAEs showed that di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), and di(2-ethylhexyl) phthalate (DEHP) had significantly higher (p less then 0.05) concentrations than the other congeners and were the most abundant PAE species in sediment and seawater in all three seasons. In addition, DnBP and DiBP were the two main congeners in seawater, and DEHP concentrations were higher in sediment than in seawater. DEHP had higher potential risks to sensitive organisms in water environment than DnBP and DiBP, and DiBP and DnBP which presented high levels of risk in sedimentary environment. DMP and DEP in watery and sedimentary environments and DEHP in sedimentary environment showed no or low risks to sensitive organisms.Organisms and ecosystems are generally exposed to mixtures of chemicals rather than to individual chemicals, but there have been relatively few detailed analyses of the mixtures of pesticides that occur in surface waters. This study examined over 2600 water samples, analysed for between 21 and 47 pesticides, from 15 waterways that discharge to the lagoon of the Great Barrier Reef in Queensland, Australia between July 1, 2011 and June 30, 2015. Essentially all the samples (99.8%) contained detectable concentrations (>limit of detection) of pesticides and pesticide mixtures. Approximately, 10% of the samples contained no quantifiable (>limit of reporting) pesticides, 10% contained one quantifiable pesticide and 80% contained quantifiable mixtures of 2-20 pesticides. Approximately 82% of samples that contained quantifiable mixtures had more than two modes of action (MoAs), but only approximately 6% had five or more MoAs. The mode, average and median number of quantifiable pesticides in all the samples were 2, 5.1 and 4, respectively. The most commonly detected compounds both individually and in mixtures were the pesticides atrazine, diuron, imidacloprid, hexazinone, 2,4-D, and the degradation product desethylatrazine. The number of pesticides and modes of action of pesticides in mixtures differed spatially and were affected by land use. Waterways draining catchments where sugar cane was a major land use had mixtures with the most pesticides.Calcified cartilage extracellular matrix (ECM) is a critical interface at the osteochondral junction which plays an important role in maintaining the structural continuity between articular cartilage and subchondral bone. This mineralized network is primarily composed of glycosaminoglycans (GAGs) and collagen type II (col II) and hosts hypertrophic chondrocytes. This work aimed to investigate the effect of gel composition and collagen II content on the behavior and hypertrophic differentiation of ATDC5 cells for regeneration of calcified cartilage tissue. For this purpose, chitosan/collagen type II/nanohydroxyapatite (chi/col II/nHA) composite hydrogels were prepared to mimic the calcified cartilage ECM. ATDC5 cells were encapsulated within the composite gels and the viability, ECM production and hypertrophic gene expression were assessed during culture. All composites were favorable for ATDC5 viability and proliferation, whereas specific ECM production and hypertrophic differentiation were dependent on gel composition. Chitosan collagen II ratio had an impact on ATDC5 cell fate. Hypertrophic differentiation was best pronounced in chi/col II/nHA 7030 composition. The results obtained from this study offers a scaffold-based approach for calcified cartilage regeneration and provide an insight for biomimetic design and preparation of more complicated gradient osteochondral units.Objectives Physical capacity decline may precede physical disability. We explored age-related physical capacity decline among rural community-dwelling Taiwanese older women to provide reference values and to identify indicators of early-onset decline in physical capacity. Methods Older women aged 65-96 were recruited from rural community centers. Physical capacity was measured by handgrip strength (HS), gait speed (GS), five-times-sit-to-stand (5xSTS), timed up and go (TUG), and the Berg balance scale (BBS). Participants were stratified into four age groups 65-69, 70-74, 75-79, and ≥80 years. Results Of 137 participants, 61 % exhibited poor 5xSTS, 34-49 % showed low HS, poor TUG and BBS, and 26 % had slow GS. The mean values in GS, HS, 5xSTS, TUG, and BBS were 1.02 m/s, 17.8 kg, 14.5 s, 12.6 s, and 50 points, respectively. Abnormal mean values were first noted at age 70-74 years for 5xSTS, age 75-79 years for HS, TUG, and BBS, and age ≥80 years for GS. Also, more than half the participants exhibited the first poor 5xSTS at age 70-74 years; the first poor HS and TUG at age 75-79 years; and lastly, the first poor BBS and GS at age ≥80 years. At age 65-69 years, 14-41 % of participants reported poor performance in all measures except for GS. Conclusions Low HS and poor 5xSTS and TUG performance were more common and had earlier onset than slow GS. More attention should be directed toward the 5xSTS, TUG, and HS in rural community-dwelling Taiwanese older women.Objectives (1) To compare the frailty status between community-dwelling older adults with and without atrial fibrillation (AF) in Taiwan and (2) to test the hypothesis that AF is associated with frailty in community-dwelling older adults. Methods We conducted a cross-sectional study in several communities in Taipei. AF was confirmed by electrocardiogram recordings or medical diagnosis. Frailty status was assessed using both the Cardiovascular Health Study (CHS) frailty phenotype and Edmonton Frail Scale (EFS). Results A total of 207 community-dwelling older adults voluntarily participated in this study, and 38 had AF. There was a significantly higher percentage of frailer (prefrail and frailty) older adults in the AF group (69 % vs. 36 %, p less then 0.001) according to CHS phenotype, but no significant difference was detected by EFS criteria (92 % vs. 92 %, p = 0.966). The AF group showed significantly lower grip strength in men (26.8 ± 8.3 vs. 33.0 ± 6.9 kg, p = 0.006), walking speed (1.1 ± 0.3 vs. 1.2 ± 0.3 m/s, p = 0.003), and Timed Up and Go performance (8.8 ± 2.4 vs. 7.0 ± 1.9 s, p less then 0.001) than the control group. The multiple logistic regression model showed that AF was an independent factor associated with frailer community-dwelling older adults after adjusted for covariates (odds ratio, 3.02; 95 % confidence interval, 1.32-6.89, p = 0.009). Conclusion Community-dwelling older adults with AF showed a significantly higher percentage of frailer individuals and lower physical function than those without AF. Furthermore, AF was an independent predictor of frailer community-dwelling older adults.Purpose The progression of Parkinson’s disease causes an increase in motor dysfunctions, which makes it necessary to evaluate and monitor these changes. This integrative review aimed to gather studies – without any language restrictions – on the use, advantages and disadvantages of portable accelerometers for the evaluation of spatio-temporal gait parameters in people with Parkinson’s disease published between 2014 and 2019. Methods Articles were selected from the PubMed, Web of Science and Science Direct databases by combining descriptors from the Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH) – „accelerometry”, „accelerometer”, „ActiGraph”, „gait”, „gait analysis”, „gait rehabilitation”, „walking inertial sensors”, „Parkinson disease”, „Parkinson” and „Parkinson’s disease” – using OR and AND. The adapted Critical Appraisal Skill Program was used to analyze the methodological quality. Results All the studies used portable wearable and wireless triaxial accelerometers. Among all types of accelerometers discussed, commercial wearable devices not based on smartphones and prototypes of wearable devices based and not based on smartphones can be pointed out. There was no standardization for the protocols of use, but the sensors were more often attached to the lower back (L3/L4/L5 vertebrae). The advantages included lower cost, possibility of use in outdoor environments and less complexity of data reading for non-specialized users. However, they still seem to show reduced precision and accuracy. Conclusions Due to the still insufficient number of articles published on the subject, we consider the need for further research, which should detail protocols of evaluation, advantages and disadvantages in stages of disease.Enantioselective analysis is critically important in the pharmaceutical and agricultural industries. However, most of the methods reported were developed for the analysis of pure racemates acquired from chemical synthesis or purification. Direct analysis of chiral enantiomers in complex matrices has rarely been reported. This work demonstrated capillary electrophoresis-mass spectrometry (CE-MS) for the enantioselective analysis of botanical drugs for the first time, using a widely used botanical drug, Corydalis Rhizoma, as an example. The method was used for the simultaneous enantioselective analysis of dl-tetrahydropalmatine and (RS)-tetrahydroberberine (canadine) in Corydalis Rhizoma extract. Using (2-hydroxypropyl)-β-cyclodextrin as the chiral selector, a partial filling technique was used to avoid signal suppression and contamination of the MS detector. Post column organic modifier was used to assist with ionization in the flow through microvial CE-MS interface, therefore, organic solvents was not used in the background electrolyte. The completely aqueous background electrolyte contributed to better chiral separations. The CE-MS method established here can directly determine the analytes in their complex matrix without any pre-purification steps, while also offering high sensitivity and low operational costs (including sample, chiral selector and solvent). In the method validation process, good linearity (r > 0.993), sensitivity and accuracy (recoveries within 89.1-110.0%) were demonstrated. The CE-MS technique was shown to be able to provide good selectivity for the simultaneous chiral separation of multiple pairs of enantiomers in complex matrices.In the study, a sensitive and reproducible method for the quantitative analysis of azithromycin in broiler feather samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Feather samples were rinsed after being wrapped in medical gauze, then chopped and then added to 5% (v/v) ammonia in methanol solution for ultrasonic extraction. The extract was purified by the combination of commercial polymeric microparticles (Oasis MCX) and Fe3O4 nanoparticles. The LC separation was performed on an Agilent Eclipse plus C18 column. Multiple reaction monitoring was used for the selective detection of azithromycin. The good linearity curve of azithromycin in feather sample was in the range from 1.0 μg kg-1 to 100.0 μg kg-1 with 0.9935 of correlation coefficient. And the limit detection and limit of quantification was 0.5 μg kg-1 and 2.0 μg kg-1 in spiked feather samples. The recoveries of azithromycin were 85.2-94.7% with the relative standard deviation less than 10%. The established method is simple, rapid, sensitive and specific, and could meet the need of government and enterprises to monitor the illegal use of azithromycin in livestock and poultry breeding.Ketamine (KET) was originally developed as an anesthetic agent but has also attracted attention for further clinical applications such as medical treatment of depression or pain. The use of KET induces dissociation and emergence delirium. Due to these effects, KET has a high potential for abuse. In order to investigate metabolization of KET or to confirm misuse of KET, highly sensitive analytical methods that cover KET and its metabolites are necessary. A new analytical approach for simultaneous analysis of KET and its metabolites cis-6-hydroxynorketamine (HNK) and norketamine (NK) was established. The compounds were extracted from human blood serum by ultrafiltration and solid phase extraction with subsequent vacuum evaporation. The compounds were analyzed by non-enantioselective ultra-high performance micro-flow liquid chromatography (Waters ACQUITY UPLC® M-Class HSS T3 column, 0.1% formic acid and acetonitrile with 0.1% formic acid, 14 µL/min flow rate) coupled with tandem mass spectrometry in positive scheduled multiple reaction monitoring mode. Validation parameters such as linearity, precision, recovery, accuracy, stability, limit of detection (LOD), and limit of quantification (LOQ) were proven. LOD for KET and NK was 0.08 ng/mL and LOQ were 0.5 ng/mL and 0.6 ng/mL, respectively. For HNK, LOD was 0.1 ng/mL and LOQ 0.8 ng/mL. The method was then successfully applied to quantify KET, HNK, and NK in blood serum samples from subjects who received KET intravenously. A novel method for the simultaneous analysis of KET, NK, and HNK was established. This new method could now be used for clinical trials investigating KET and its metabolites HNK and NK or for forensic analysis in order to confirm KET abuse.In this work, we investigated the interaction of docosahexaenoic acid (DHA) with β-lactoglobulin (β-Lg) using spectroscopic and crystallographic methods. The fluorescence results showed that DHA formed complexes with β-Lg with a binding constant of 4.13 × 104 M-1. The secondary structure of β-Lg was not significantly (p > 0.05) changed after binding with DHA. Dynamic light scattering showed the particle size of β-Lg-DHA complexes was about 5 nm, the same as that of β-Lg alone. The turbidity of DHA in aqueous solution decreased after binding with β-Lg. The crystallographic results showed that DHA was bound at one site in the calyx of β-Lg and that the aliphatic chain was hidden inside the hydrophobic β-barrel while the carboxyl group was located at the calyx entrance. These findings indicate that β-Lg can act as an effective nanocarrier for DHA.This work studied the quantitation of myofibrillar protein isolated from giant squid by three methods (Bradford, biuret, and direct ultraviolet absorbance). The results were examined in relation to compositional size exclusion chromatography, static light scattering, zeta-potential and thermal analysis; comparisons between the apparent vs. the true protein concentration revealed the existence of disk-like nano protein particles (NPP) with a height of 2-3 nm, diameters ranging from several tens nm to 140 nm, and fractal dimensions df of less than 1.3. In order to probe the heterogeneity of NPP particles, their properties were studied under consecutive dilutions the df decreased from 1.265 to 1.087, the zeta-potential increased from -4.55 mV to -1.83 mV, the denaturation temperature reduced from 63.9 °C to 58.6 °C, and the endothermic enthalpy reduced from 0.529 J s-1 to 0.362 J s-1. In addition, ca. 90% protein molecules in solution were aggregated to form NPP.