tion in gut microbiota and bile acid metabolism.

The aim of this study was to investigate the association between percent contribution of ultra-processed foods to total dietary energy intake and measurements of body composition obtained using high-validity methods.

This was a cross-sectional study with 1525 adolescents 18 to 19 y of age from the second follow-up of the 1997/98 São Luís birth cohort, Brazil. To evaluate nutritional status and body composition, the body mass index (BMI)-for-age was used, along with waist circumference, total and android body fat percentage, muscle mass, and the lean mass index (LMI). Food consumption was evaluated by a food frequency questionnaire. Food items were grouped according to the level of processing as per the NOVA classification. Through semi-structured questionnaires, sociodemographic and lifestyle data were abstracted. Adjusted linear regression models were used to evaluate the associations between consumption of ultra-processed foods and body composition measurements.

Total average energy consumption was 2919.7 kcal, with 58% (1634.9 kcal) derived from natural or minimally processed foods and 37% (1136.5 kcal) from ultra-processed products. In the adjusted analyses, BMI, muscle mass, and LMI were inversely associated with consumption of ultra-processed foods. A 1% increase in the percent contribution of ultra-processed items to total dietary energy intake was associated with a 0.04 kg decrease in muscle mass (β = -0.04; 95% confidence interval [CI], -0.06 to -0.02; P < 0.001) and a 0.01 kg/m

decrease in lean body mass (β = -0.01; 95% CI, -0.02 to -0.01; P < 0.001).

The contribution of ultra-processed foods to total dietary energy intake of Brazilian adolescents was associated with body composition, especially with decreasing lean body mass.

The contribution of ultra-processed foods to total dietary energy intake of Brazilian adolescents was associated with body composition, especially with decreasing lean body mass.Despite the great promise of immune checkpoint blockade (ICB) therapy for cancer treatment, the currently available options for ICB treatment pose major clinical challenges, including the risk of severe systemic autoimmune responses. Here, we developed a novel localized delivery platform, immuno-bioglue (imuGlue), which is inspired by the intrinsic underwater adhesion properties of marine mussels and can allow the optimal retention of anti-PD-L1 drugs at tumor sites and the on-demand release of drugs in response to the tumor microenvironment. Using a triple-negative breast cancer and melanoma models, we found that imuGlue could significantly enhance anti-tumor efficacy by eliciting a robust T cell-mediated immune response while reducing systemic toxicity by preventing the rapid diffusion of anti-PD-L1 drugs into the systemic circulation and other tissues. It was also demonstrated that imuGlue could be successfully utilized for combination therapy with other immunomodulatory drugs to enhance the anti-tumor efficacy of ICB-based immunotherapy, demonstrating its versatility as a new treatment option for cancer immunotherapy.Cancer stem cells (CSCs) possess self-renewal and clonal tumor initiation capacities, which lead to drug resistance and tumor recurrence. In this work, a hypoxia-stimulated strategy based on a smart triblock vector was developed to enhance therapeutic efficacy through the inhibition of cancer stemness. The triblock precursor was designed with a fluorescence chromophore for monitoring hypoxia, a methoxy nitro-unit for biorecognition, and a poly(ethylene glycol)-folate for cancer cell targeting. As the degree of hypoxia increases, the vectors were progressively dissociated as indicated by the enhanced fluorescence intensity in hypoxic cells and compacted three-dimensional spheres. Furthermore, the expression of stem cell markers such as CD133 and SOX2 was significantly inhibited, and the serial passaging of CSCs was notably impaired after treating CSCs with the vectors. The inhibition of cancer cell stemness significantly improved the anticancer efficiency in vivo. Moreover, tumor initiation was reduced and the median survival time of xenograft tumor models was prolonged by regulating cell stemness under hypoxia. Overall, this work provides a promising approach to inhibit tumor resistance and recurrence for efficient tumor therapy.The structural plasticity of dendritic spines is considered to be essential for various forms of synaptic plasticity and, ultimately, learning and memory. The process is mediated by signaling pathways that promote the reorganization of the actin cytoskeleton and subsynaptic structures, which in turn cause structural and functional changes in dendritic spines. Recent advances in optical technologies have started to reveal the fine molecular structures and dynamic signaling occurring inside spines, providing significant insights into the molecular regulation of spines. Here, we highlight recent studies to resolve the molecular mechanisms underlying the spine actin cytoskeleton and plasticity with high spatiotemporal resolution. Moreover, we discuss new genome editing-based approaches in imaging the molecular structure and plasticity of dendritic spines.While research in previous decades demonstrated a link between the pulvinar nucleus of the thalamus and visual selective attention, the pulvinar’s specific functional role has remained elusive. However, methodological advances in electrophysiological recordings in non-human primates, including simultaneous recordings in multiple brain regions, have recently begun to reveal the pulvinar’s functional contributions to selective attention. These new findings suggest that the pulvinar is critical for the efficient transmission of sensory information within and between cortical regions, both synchronizing cortical activity across brain regions and controlling cortical excitability. These new findings further suggest that the pulvinar’s influence on cortical processing is embedded in a dynamic selection process that balances sensory and motor functions within the large-scale network that directs selective attention.Bisphenol A (BPA), an endocrine-disrupting chemical, has been used as a basic raw material for the production of polycarbonate plastics. As concern over the toxic effects of BPA grows, it is gradually being replaced in many consumer products with compounds such as bisphenol F (BPF) and bisphenol S (BPS). In this study, online solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry was used to analyze the urinary concentrations of BPA, BPF, and BPS in 2487 Korean urine samples collected between 2017 and 2018. The detection rates and geometric mean (GM) concentrations were as follows BPA (82.1 %; 0.65 μg/L), BPF (11.1 %; not calculated), and BPS (63.6 %; 0.20 μg/L), respectively. The mean daily intake based on urinary BPA concentrations was 0.013 μg/kg bw/day (95th percentile, 0.089 μg/kg bw/day), which is lower than the tolerable daily intake. This is the first study observing urinary BPA, BPF, and BPS concentrations based on a nationally representative Korean population and could contribute to the evaluation of bisphenol analogue exposure levels in risk assessments.Teen drivers are overrepresented in motor vehicle crashes, and most studies concluded it was mainly due to their lack of experiences and tendencies of risk-taking. The design of advanced driving assistance systems (ADAS) aims to provide assistance in multiple stages in human information processing during driving, including environmental sensing, information processing, decision making, and vehicle controlling, in order to improve driving safety. It is expected that novice drivers may benefit more from using ADAS than adult drivers as such technologies can compensate for their frequent errors. This study examined whether and how an integrated crash warning system impacted on drivers’ following behavior, and what were the corresponding age-related differences through an analysis of two unique naturalistic driving study datasets. Significant age-related differences in car-following behavior were found. Results showed potential negative effects of ADAS on teen drivers’ following behavior that teen drivers tended to have less controlled pedal use during treatment weeks with ADAS than during baseline weeks without ADAS, while such behavior was not observed in adult drivers. All adult drivers tended to keep longer headways when driving at night than during daytime to compensate for poor vision conditions, but no such compensation behavior was observed in the teens. In addition, teen and young-adult drivers had more aggressive following behavior (with shorter mean time headway) than middle-aged and older drivers. One limitation of this study is that the findings of this study are only addressing the short-term effect of ADAS exposure, and future studies are needed to examine the longitudinal effect. The findings of this study suggest that the design of future ADAS should consider minimizing potential negative impacts on teen driver behavior.This study developed a real-time quantitative PCR (qPCR) assay to detect L. infantum kinetoplast DNA (kDNA) in canine saliva. The qPCR showed an efficiency of 93.8%, a coefficient of correlation of 0.996 and a detection limit of 0.5 fg/reaction (0.005 parasites), although it detected until 0.25 fg/reaction (0.0025 parasites). When samples from 12 dogs experimentally infected with L. infantum were collected, L. infantum kDNA was detected at 16-weeks post-infection (wpi) in 41.7% and 91.7% of saliva and bone marrow samples, respectively, and at 47-wpi in 75% of both samples. L. infantum kDNA can be detected by qPCR in canine saliva, with lower sensitivity in the early stages of infection and a lower parasite load estimation compared to bone marrow. However, saliva had similar sensitivities to bone marrow in the later stages of the infection and could be used to detect L. infantum kDNA being aware of its limitations.

Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium.

We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo.

PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke.

Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy.

Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health.

Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health.

The objective of the study was to evaluate the indication, efficacy and safety of tocilizumab, a humanized anti-interleukin-6 receptor antibody, in patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody associated diseases (MOGAD) encountered in current neurological practice.

We conducted a retrospective analysis of an exhaustive cohort of patients with inflammatory CNS disorders at Toulouse University Hospital, France, from 2014 to 2020. Efficacy was evaluated with clinical outcome by the Annual Relapse Rate, and radiological outcome with MRI data. The other outcomes were adverse events and effectiveness according to the form of injection (intravenous or subcutaneous).

Seven patients were treated with tocilizumab four patients had NMOSD with AQP4+ antibodies (57%) and three had MOGAD (43%). Tocilizumab was administered in the presence of persistent clinical activity and/or severe side effects with other immunosuppressant medications. The median follow-up on tocilizumab was 23 months (4-50 months). All patients started with monthly intravenous injection, then three switched to a subcutaneous form. All patients were relapse-free throughout the duration of treatment with tocilizumab, and one presented with a new cervical lesion on MRI. Four patients had no adverse effect, two had a significant increase in infection rate, and one had dyslipidemia.

tocilizumab appears to be an effective therapy for patients with refractory NMOSD or MOGAD. Subcutaneous and intravenous injections appear to be equally effective.

tocilizumab appears to be an effective therapy for patients with refractory NMOSD or MOGAD. Subcutaneous and intravenous injections appear to be equally effective.Teriflunomide is an oral disease modifying therapy for relapsing-remitting multiple sclerosis (RRMS). Gastrointestinal (GI) side effects occurred in 15-17.9% of patients in the clinical trials and usually were mild and self-limiting. Few cases of inflammatory colitis related to teriflunomide and leflunomide, a prodrug which converts to teriflunomide and is used in the treatment of rheumatoid arthritis, have been reported but no clinical data is available except for a single case of lymphocytic colitis. We here report a 49-year-old man with RRMS who developed severe diarrhea and weight loss six months after starting teriflunomide and eventually was found to have multiple ulcers and inflammatory changes consistent with Crohn’s disease. After stopping teriflunomide and chelation therapy, he was started on immunotherapy for Crohn’s given the highly inflammatory degree of GI symptoms and histology findings.

Evidence from observational studies increasingly highlights the association between unhealthy diet and poor health outcomes in adults with multiple sclerosis (MS), but very few intervention trials for dietary change have been completed. Improving diet quality via a low glycemic load (GL) diet has demonstrated improvements in cardiometabolic risks, cognitive risks, and psychosocial variables in diseases other than MS. The purpose of this study was to test the feasibility of delivering a low GL dietary intervention implemented via telehealth in a sample of adults with relapsing remitting MS (RRMS). The secondary purpose was to explore the potential impact of the diet on MS outcomes and cardiometabolic risks.

Participants followed a low GL diet consisting of 100g of carbohydrate and GL of ≤45 points/1000 kcal daily for 12 weeks. Each participant received weekly calls from a telecoach, education and behavioral supports via weekly emails, and recorded all food intake on a mobile app. Feasibility was measured axiety (r=.24), pain (r=-.43), and emotional health (r=-.36) were moderately correlated with reductions in GL. Participants lost a mean of 2.93 (6.31, p=.003) kg, and had reductions in both fat and lean mass (fat mass 1.94 (2.5) kg; lean mass .72 (1.29) kg).

A low GL dietary intervention is feasible for adults with RRMS and may lead to improvements in MS outcomes and cardiometabolic risk. Additional research is needed with more tightly controlled feeding trials and larger sample sizes to further understand the impact of this dietary pattern on RRMS.

A low GL dietary intervention is feasible for adults with RRMS and may lead to improvements in MS outcomes and cardiometabolic risk. Additional research is needed with more tightly controlled feeding trials and larger sample sizes to further understand the impact of this dietary pattern on RRMS.The solid-liquid distribution coefficient (Kd) is a key input parameter in radioecological models. However, its large variability hampers its usefulness in modelling transport processes as well as its accuracy in representing soil-radionuclide interactions. For the specific case of radiocaesium, the analyses of a Cs Kd soil dataset (769 entries) showed that values varied over a five order of magnitude range, and the resulting Cs Kd best estimate (calculated as a geometric mean = 2.5 × 103 L kg-1) lacked reliability and representativity. Grouping data and creation of partial datasets based on the experimental approach (short-term ( ~1 yr)) and soil factors affecting Cs interaction (i.e., the ratio of the radiocaesium interception potential (RIP) to the potassium content in soil solution (Kss); organic matter content (OM) and soil texture) succeeded in reducing variability a few orders of magnitude, with Cs Kd best estimates also differing by one-two orders of magnitude depending on the type of soil and experimental approach. The statistical comparison of the Cs Kd best estimates and related cumulative distribution functions of the partial datasets revealed a relevant effect of the sorption dynamics on Cs Kd values (with long-term values systematically higher than short-term ones), and that the RIP/Kss ratio was an excellent predictor of Cs Kd for short-term scenarios, whereas the RIP parameter could be predicted on the basis of texture information. The OM threshold to distinguish between OM threshold to distinguish between Mineral and Organic soils subclasses, regarding Cs interaction was determined to be 50% and 90% OM for short- and long-term scenarios, respectively. It was then recommended to select the Cs Kd input data depending on the soils and scenarios to be assessed (e.g., short- vs. long-term; OM %) to improve the reliability and decrease the uncertainty of the radioecological models.In fish, the study of cholinesterases (ChEs) and carboxylesterases (CEs), apart from their involvement in neural activity and xenobiotic metabolism, respectively, requires to be further explored. The European sea bass (Dicentrarchus labrax) was the fish model used to characterise B-esterases in several matrices and organs, as well as to assess the impacts of the insecticide fipronil at two temperatures the natural temperature at the time of sampling (13 °C) and at 16 °C (based on climate change-related predictions for the Mediterranean region). Fipronil exerts harmful effects in non-target species; however, some countries are reluctant to implement regulations without additional evidence on their toxicity. A comprehensive study was performed in fish pre-acclimated to the two targeted temperatures for 15 days. B-esterases were evaluated in multiple samples after 7 and 14 day exposures to fipronil in feed (dose of 10 mg/kg) and after a 7-day depurative period. Based on hydrolysis rates, results showed that CEs were measurable in all matrices while ChEs were more abundant in muscle and, particularly, acetylcholinesterase (AChE) in the brain. A + 3 °C increase in temperature had little influence on B-esterase activity; however, fipronil caused a significant increase in brain AChE (1.5-fold) and CE (3-fold) activities. Other matrices and organs also experienced alterations in their B-esterase activities that could compromise their physiological functions.

The present study compares the local anesthetic efficacy of EMLA® cream and lidocaine injection used in the radiofrequency reduction of the inferior turbinate.

The study included a total of 124 patients with inferior turbinate hypertrophy and who underwent turbinate reduction under local anesthesia. The operations were performed 15min after a lidocaine injection and 30min after EMLA cream application. The respondent patients were asked to interpret such situations as intraoperative pain, discomfort during the procedure, choking sensation and difficulty swallowing using the Visual Analogue Scale (VAS).

The EMLA cream patients (Group A) were found to have a lower level of discomfort, choking sensation and difficulty swallowing than the lidocaine patients (Group B), while there was no substantial difference in pain between the two groups.

It is concluded that EMLA® cream is an effective alternative to lidocaine injection during inferior turbinate reduction procedures.

It is concluded that EMLA® cream is an effective alternative to lidocaine injection during inferior turbinate reduction procedures.In this Letter, we report on experimental effective coherent multiple Stokes and anti-Stokes high-order components generation by Stokes pulse injection at the process of stimulated low-frequency Raman scattering. This process can be used for effective generation the tunable spectral comb consisting of several equidistant spectral lines separated by a constant frequency spacing of several GHz.The main objectives of the study are to understand and explore critical feature wavelengths of the obtained near-infrared (NIR) data relating to dianhong black tea quality categories, we propose a multi-variable selection strategy based on the variable space optimization from big to small which is the kernel idea of a variable combination of the improved genetic algorithm (IGA) and particle swarm optimization (PSO) in this study. A rapid description based on the NIR technology is implemented to assess black tea tenderness and rankings. First, 700 standard samples from dianhong black tea of seven quality classes are scanned using a NIR system. The raw spectra acquired are preprocessed by Savitzky-Golay (SG) filtering coupled with standard normal variate transformation (SNV). Then, the multi-variable selection algorithm (IGA-PSO) is applied to compare with the single method (the IGA and PSO) and search the optimal characteristic wavelengths. Finally, the identification models are developed using a decision tree (DT), partial least-squares discriminant analysis (PLS-DA), and support vector machine (SVM) based on different kernel functions combined with the effective features from the above variables screening paths for the discrimination of black tea quality. The results show that the IGA-PSO-SVM model with a radial basis function achieves the best predictive results with the correct discriminant rate (CDR) of 95.28% based on selected four characteristic variables in the prediction process. The overall results demonstrate that NIR combined with a multi-variable selection method can constitute a potential tool to understand the most important features involved in the evaluation of dianhong black tea quality helping the instrument manufacturers to achieve the development of low-cost and handheld NIR sensors.This review summarises research on the relationship between death anxiety and religiosity. The fear of death is commonly hypothesized as a motivation for religious belief. From a Terror Management Theory perspective, religious beliefs are especially attractive because they offer both literal and symbolic immortality in the form of afterlife beliefs and belonging in venerable systems of value respectively. However, the evidence for any relationship – whether correlational or causal – between death anxiety and religious belief is weak. Indeed, evidence for death anxiety under normal (i.e. non-life threatening) circumstances is surprisingly hard to find. If the fear of death motivates religiosity, it does so subtly, weakly, and sporadically.Theranostics including imaging and therapy has become an advanced trend for cancer treatment. It is of great significance to develop new theranostics agent for precision medicine research. In this regard, structurally precise metal nanoclusters (NCs) with ultra-small diameter and potential theranostic functions are no doubt to be a priority. In this study, we firstly investigated the photothermal and photodynamic properties of structurally precise oil-soluble bimetallic NCs (Pt1Ag28) and tactfully solubilize them into the hydrophobic inner cavity of biodegradable amphiphilic chitosan derivative (ACD) micelles via hydrophobic interaction. Positively charged Pt1Ag28@ACD with suitable particle size (∼60 nm) could not only realize effectively passive targeted delivery, but also be easily uptaken by negatively charged cancer cells for increasing targeting effect. Further, the aggregation induced emission fluorescence imaging (AIE FI)-guided enhanced photothermal/photodynamic therapy (PTT/PDT) on tumor is finally nicely achieved by the micelle solubilization of ACD micelles to Pt1Ag28 NCs, which were demonstrated by in vitro and in vivo experimental results. This theranostic platform overcomes the difficulty of lipophilic NCs entering water-phase organisms, provides enlightenment for the universal study of the interaction mechanism between organisms and oil-soluble NCs at the atomic level in future precision medicine research.Persistent quadriceps strength deficits in individuals with anterior cruciate ligament reconstruction (ACLr) have been attributed to arthrogenic muscle inhibition (AMI). The purpose of the present study was to investigate the effect of vibration-induced hamstrings fatigue on AMI in patients with ACLr. Eight participants with unilateral ACLr (post-surgery time M = 46.5, SD = 23.5 months; age M = 21.4, SD = 1.4 years) and eight individuals with no previous history of knee injury (age M = 22.5, SD = 2.5 years) were recruited. A fatigue protocol, consisting of 10 min of prolonged local hamstrings vibration, was applied to both the ACLr and control groups. The central activation ratio (CAR) of the quadriceps was measured with a superimposed burst of electrical stimulation, and hamstrings/quadriceps coactivation was assessed using electromyography (EMG) during isometric knee extension exercises, both before and after prolonged local vibration. For the ACLr group, the hamstrings strength, measured by a load cell on a purpose-built chair, was significantly (P = 0.016) reduced about 14.5%, indicating fatigue was actually induced in the hamstrings. At baseline, the ACLr group showed a trend (P = 0.051) toward a lower quadriceps CAR (M = 93.2%, SD = 6.2% versus M = 98.1%, SD = 1.1%) and significantly (P = 0.001) higher hamstrings/quadriceps coactivation (M = 15.1%, SD = 6.2% versus M = 7.5%, SD = 4.0%) during knee extension compared to the control group. The fatigue protocol significantly (P = 0.001) increased quadriceps CAR (from M = 93.2%, SD = 6.2% to M = 97.9%, SD = 2.8%) and significantly (P = 0.006) decreased hamstrings/quadriceps coactivation during knee extension (from M = 15.1%, SD = 6.2% to M = 9.5%, SD = 4.5%) in the ACLr group. In conclusion, vibration-induced hamstrings fatigue can alleviate AMI of the quadriceps in patients with ACLr. This finding has clinical implications in the management of recovery for ACLr patients with quadriceps strength deficits and dysfunction.The current United States Pharmacopeia-National Formulary (USP-NF) and the British Pharmacopoeia phenoxybenzamine (PBA) hydrochloride drug substance and drug product monographs describe an HPLC procedure for the determination of a specified impurity „tertiary amine phenoxybenzamine” and use the resolution of an „unknown related substance” from PBA as a system suitability criterion; however, neither structural information of the „unknown related substance” is provided nor reference standards of the two impurities are available. The ambiguity in pharmacopeias poses difficulties in implementing the procedure for quality control. To clarify the degradation pathways, and incorporate the impurity profile of PBA into the USP monographs, the degradation of PBA was revisited. PBA undergoes rapid degradation in neutral or basic aqueous solutions to generate the „tertiary amine phenoxybenzamine” as the predominant degradation product, which was confirmed as phenoxybenzamine hydroxide (PBA-OH). In addition, the „unknown related substance” was proposed as the phenoxybenzamine nitrile (PBA-CN) on the basis of LC-MS studies. The identity of PBA-CN was unambiguously verified via chemical synthesis, HPLC and NMR analyses. A stability-indicating method was developed and validated for the determination of PBA and its impurities, and was used to support USP monograph modernization.Mango leaves (MLs) have many important medical values owing to its high contents of phytochemical compounds. Among them, phenolic compounds existing in MLs showed multiple pharmacological activities. However, there is a little information about the quality evaluation and discrimination of different varieties of MLs. In the present study, the chemical compositions of MLs were identified by using high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (HPLC-ESI-qTOF-MS/MS). Then, the quality of ten MLs varieties collected from a same plantation was assessed according to integrated HPLC fingerprinting coupled with multivariate analysis. The results revealed that Cui Yu (S5) showed the highest TPC/TFC and the strongest bio-activity, followed by Tai Long (S7) and Hong Bao Shi (S3). Among different HPLC fingerprinting, twenty compounds were selected as common characteristic peaks, and the similarity was within the range of 0.792-0.995. Meanwhile, these varieties were divided into three groups G1 (S3, S5, S7, and S10), G2 (S1 and S4) and G3 (S2, S6, S8, and S9). Two discriminant functions with the discriminant rate near 100 % were constructed. Additionally, neomangiferin, mangiferin, kaempferol-3-O-rutinoside, isoquercitrin and quercetin were found to be the key compounds in quality evaluation of MLs varieties. Pearson correlation coefficient analysis results confirmed that these key compounds directly contributed to the antioxidant activity and α-glucosidase inhibitory ability of MLs. Importantly, the possible inhibitory mechanisms of these key compounds against α-glucosidase were preliminary clarified by in silico analysis, and the analysis results provide a theoretical basis for future development and utilization of mango leaves byproducts.The orthogonal heart-cutting liquid chromatography (LC) modes coupled to high-resolution tandem mass spectrometry (HRMS/MS) provide a number of possibilities to enhance selectivity and sensitivity for the determination of targeted compounds in complex biological matricies. Here we report the development of a new fast 2D-LC-(HRMS/MS) method and its successful application for quantitative determination of the level of plasma and brain N,N-dimethyltriptamine (DMT) using α-methyltryptamine (AMT) as internal standard in an experimental model of cerebral ischemia/reperfusion using DMT administration. The 2D-LC separation was carried out by a combination of hydrophilic interaction liquid chromatography (HILIC) in the first dimension followed by second-dimensional reversed-phase (RP) chromatography within a total run time of 10 min. The enrichment of HILIC effluent of interest containing DMT was performed using a C18 trapping column. During method development several parameters of sample preparation procedures, chromatographic separation and mass spectrometric detection were optimised to achieve high DMT recovery (plasma 90 %, brain 88 %) and sensitivity (plasma 0.108 ng/mL of LOD, brain 0.212 ng/g of LOD) applying targeted analytical method with strict LC and HRMSMS confirmatory criteria. Concerning rat plasma sample, the concentration of DMT before hypoxia (49.3-114.3 ng/mL plasma) was generally higher than that after hypoxia (10.6-96.1 ng/mL plasma). After treatment, the concentration of DMT in brain was elevated up to the range of 2-6.1 ng/g. Overall, our analytical approach is suitable to detect and confirm the presence of DMT administered to experimental animals with therapeutic purpose in a reliable manner.Roots´ bark extract of Brosimum gaudichaudii Trécul (EBGT) is traditionally used for photochemotherapy of vitiligo due to the presence of furanocoumarins psoralen (PSO) and 5-methoxypsoralen (5-MOP) as major compounds. Though plant extracts may provide additional highly permeable psoralens-like substances which may act synergically on vitiligo’s therapy. Thus, the aim of this work was to develop an LC-MS/MS method for screening new highly permeable furanocoumarins from B. gaudichaudii and to compare biomarkers permeability and solubility provided as single compounds or as crude extract, according to BCS. An optimized LC-MS/MS method showed twelve permeable and bioactive compounds, among which 9 furanocoumarins, 2 pyranocoumarins and 1 dihydrocinnamic acid derivative were detected in EBGT samples. Solubility of PSO and 5-MOP was found to be, respectively, six- and eleven-fold higher in crude extract than as pure compounds. Permeability (Papp) of PSO and 5-MOP in EBGT were higher than metoprolol, the low/high BCS permeability class boundary reference compound. Hence, both biomarkers were considered as highly permeable (BCS2) compounds. Their permeability were concentration-dependent displaying values from 30.26 ± 5.13-8.21 ± 2.16 × 10-6 cm/s and 10.72 ± 1.73-6.07 ± 1.27 × 10-6 cm/s, respectively, over a wide range (2.3-200.0 mg mL-1). Thus, a carrier-mediated absorption process is suggested as the main mechanism. Accordingly, all additional permeated coumarins, identified by LC-MS/MS, showed to be at comparable amount of biomarkers in the permeated samples inferring similar high permeability rate. Moreover, biomarkers and other highly absorbable and bioactive linear furanocoumarins from EBGT may be used for vitiligo´s photochemotherapy. Taken together, these findings bring additional evidences for using crude plant extract when aiming synergistic effects of bioactive compounds on melanogenic therapies.Nucleic acid is a collective term of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), and it is an essential substance in all known life forms. As numerous of studies have shown that nucleic acids can be used as therapeutic agents and the abnormality of various nucleic acid and its modification level has been proven to be closely bound up with changes in diseases such as cancer, the development of analytical methods for the nucleic acid and its modification has become one of the research hotspots in the field of life sciences. Compared with classical nucleic acid detection methods such as Northern blotting, Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) and Polymerase Chain Reaction (PCR), novel analytical methods based on nanomaterials, nucleic acid amplification strategies and biosensors can better satisfy the needs for sensitivity and simplicity in current clinical diagnosis. Herein, the progress and trends of analysis of nucleic acid and its modification is discussed, aiming to provide guidance for the detection of nucleic acid and its modification in medical basic research and clinical diagnosis, treatment and prognosis.Comparison of Salvia miltiorrhiza polysaccharides (SMPs) from different geographical origins in China (Henan, Hebei, Shandong, Sichuan, Shaanxi) was performed using high performance size exclusion chromatography coupled with multi-angle laser light scattering and refractive index detector (HPSEC-MALLS-RID), saccharide mapping based on polysaccharide analysis by using carbohydrate gel electrophoresis (PACE) and combined with principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Based on the results of HPSEC-MALLS/RI, the relative content of SMPs showed a significant difference between different geographical origins, however, the molecular weight of SMPs showed almost no significance. SMPs can be discriminated as five regions after PACE coupled with OPLS-DA models analysis of endo-1,5-α-arabinanase hydrolysates. Moreover, all the PACE fingerprint indicated that 1,4-β-D-Galp, 1,5-α-Araf, 1,4-α-D-GalAp and 1,4-β-D-Glcp linkages existed in SMPs.A rapid, reliable and sensitive liquid chromatography quadrupole time-of-flight mass spectrometry method for the determination of tryptophan and its metabolite kynurenine in milk formulas for neonates and infants was developed and validated. Two extraction techniques based on EMR Lipid QuEChERS and liquid-liquid extraction with diethyl ether to extract lipids and methanol to precipitate the protein were tested and compared. Four different infant formula products were randomly selected and evaluated for the effect of co-extracted matrix components on the quantitative analysis results. The influence of matrix components on analytical signals was normalized by the use of stable isotope-labeled standards and matrix-matched calibration. The developed method was found to be sensitive and effective for both analytes in all the examined infant formulas with satisfactory linearity (R2 ≥ 0.9995), recovery in the range of 75.7% ± 4.5 – 99.0% ± 1.1, and intra- and inter-day precision with the coefficient of variation below 6.3% and 17.9%, respectively. The limits of detection (LOD) and quantification (LOQ) for both compounds differed significantly between the examined formulas. The LOD and LOQ values were found to be in the range of 2.18-9.85 μg/g and 6.61-29.84 μg/g for the determination of tryptophan and in the range of 0.21-2.71 μg/g and 0.63-8.23 μg/g for the determination of kynurenine, respectively. The method was proved to be suitable for the determination of tryptophan and kynurenine in infant formulas, and it can be used to study the link between tryptophan metabolism via kynurenine pathway and metabolic disorders in infants.Poultry litter is one of the main sources of fluoroquinolones (FQs) in agricultural soils. In this study, our main goal was to investigate FQ-contaminated poultry litter effects on Eisenia andrei earthworms. To achieve this, acute and chronic tests covered several endpoints, such as avoidance, biomass, lethality, reproduction and changes to immune cells. FQs (enrofloxacin and ciprofloxacin) were determined in a poultry litter sample through high performance liquid chromatography with a fluorescence detector. The avoidance test indicates that poultry litter strongly repels earthworms, even at the lowest concentration (50 g kg-1). In the acute test, the lethal concentration of poultry litter to 50% of the earthworms (LC50), was estimated at 28.5 g kg-1 and a significant biomass loss (p less then 0.05) occurred at 40 g kg-1. In the chronic test, a significant reproduction effect was observed at 20 g kg-1. Cell typing, density and feasibility indicated significant effects ranging from 5 to 20 g kg-1. A high risk quotient was estimated based on recommended poultry litter applications in field studies. Although FQ contamination in poultry litter and soils has been widely reported in previous studies, this is, to the best of our knowledge, the first toxicological assessment concerning earthworms exposed to FQ-contaminated poultry litter.Questions remain about the effects of rare earth elements (REEs) on reproductive health, and no study has explored in utero exposure to REEs and risk of orofacial clefts (OFCs). We recruited subjects from a case-control study conducted in Shanxi Province, China. Concentrations of fifteen REEs were quantified in umbilical cord samples by means of Inductively Coupled Plasma Mass Spectrometry measurements. We employed logistic regression and weighted quantile sum (WQS) regression models to estimate the association between REEs exposures and OFCs. Of 226 subjects included in our study, 34 were cleft lip only, 44 were cleft lip with cleft palate and 6 were cleft palate only. In the logistic regression model, concentrations above the median of all subjects were associated with an increased OFCs risk of 2.35-fold (95% CI 1.22, 4.53) for Lanthanum and 2.12-fold for Neodymium (95% CI 1.10, 4.10) adjusting for maternal age, BMI, gestational weeks, sex of infants and passive smoking. In WQS model, a quartile increase in the index resulting in an increase of 3.10 (95% CI 1.38, 6.96) in the odds of OFC. Lanthanum and Neodymium were suggested to be important factors. The results were largely consistent for OFC subtypes. In conclusion, in utero exposure to mixtures of REEs increased the risk of OFCs. Lanthanum and Neodymium were likely to be important factors in the development of OFCs.The evaluation on mortality displacement and distributed lag effects of airborne particulate matter (PM) on death risks is important to understand the positive association of short-term pollution from both ambient PM10 and PM2.5 with daily mortality. Herein, short-term influences of urban PM10 and PM2.5 exposure on the mortality of respiratory diseases (RD) and cardiovascular diseases (CVD) were studied at Taiyuan, China, a typical inland city suffering from heavy ambient PM loading and having high morbidity of RD and CVD. Using a time-series analysis with generalized additive distributed lag model (DLM), the potential mortality displacement was determined and the single-day and cumulative lag-day effects of PM on mortality were estimated after the daily mass concentrations of urban PM2.5 and PM10 from January 2013 to October 2015 and the daily number of non-accidental death (NAD) and cause-specific mortality in the residents aged more than 65 years old were obtained. Results showed there were significant associations of PM2.5 and PM10 with daily mortality on the current day and within one week. And a statistically significant increase (P less then 0.05) in the cumulative effect estimates of PM2.5 and PM10 on CVD, ischemic heart disease (IHD), and myocardial infarction (MI) mortality (as well as PM2.5 on NAD) was observed, while the associations of PM2.5 with RD and pneumonia mortality, PM10 with NAD and RD mortality were not statistically significant, when the exposure window was extended to lag 0-30 days. It was concluded that there were harvesting effects and cumulative effects of ambient PM2.5 and PM10 on the elderly residents’ mortality due to RD and CVD at Taiyuan and they could be estimated quantitatively when the broader time window was used, suggesting that the underestimation on the association of ambient PM with non-accidental death can be avoided using the present method in our study.The wide use of graphene oxide (GO) has raised increasing concerns about the potential risks to environmental and human health. Recent studies have shown the vital role of gut microbiome in various pathological status or even exogenous exposure, but more detailed understanding about the effects of possible gut microbiome alterations under GO exposure on reproductive toxicology evaluations in pregnant mammals remained elusive. Here we found that orally administrated GO daily during gestational day (GD) 7-16 caused dose-dependent pregnant complications of mice on the endpoint (GD19), including decreased weight of dam and live fetus, high rate of resorbed embryos and dead fetus, and skeletal development retardation. Meanwhile in placenta tissues of pregnant mice exposed to GO at dose over 10 mg/kg, the expression levels of tight junctions (Claudin1 and Occludin) and vascular endothelial growth factor (VEGFA) decreased approximately by 30%-80%, meaning impaired placenta barrier. According to the data of fecal 16s RNA sequencing in 40 mg/kg dose group and the control group, gut microbiome showed dramatically decreased α- and β-diversity, and upregulated Firmicutes/Bacteroidetes ratio owing to GO exposure. What’s more, significantly differentiated abundance of Euryarchaeota is expected to be a special biomarker for failed pregnancy caused by GO. Notably, the result of Spearman correlation analysis suggested that there was a strong link (correlation coefficient>0.6) between perturbed gut microbiome with both abnormally expressed factors of placenta barrier and adverse pregnant outcomes. In summary, the damages of GO exposure to placenta barrier and pregnancy were dose-dependent. And GO exposure was responsible for gut microbiome dysbiosis in mice with pregnant complications. These findings could provide referable evidence to evaluate reproductive risk of GO to mammals.The present study examined the relationship between perceived interparental conflict and problematic social media use (PSMU) among adolescents, as well as the mediating effects of self-esteem and maladaptive cognition toward social network sites (SNS). A sample of 688 middle school students (56.1% females; Mage = 13.44 years; SDage = 0.99) was asked to complete a survey. Surveyed items included demographics, the Children’s Perception of Interparental Conflict Scale, the Rosenberg Self-esteem Scale, the Chinese Adolescents’ Maladaptive Cognitions Scale, and the Facebook Intrusion Questionnaire. After controlling for gender and age, the results showed that (a) perceived interparental conflict was positively associated with PSMU; (b) this association was significantly mediated by maladaptive cognition toward SNS; and (c) self-esteem and maladaptive cognition toward SNS sequentially mediated this association. This study provides useful insight into the understanding of how perceived interparental conflict increases the risk of PSMU. The results further indicate that concrete approaches are required for the prevention and intervention of PSMU among adolescents.Rheumatoid arthritis (RA) is an autoimmune disease that is associated with chronic inflammation in joints, which contribute to synovial membrane hyperplasia and cartilage damage. Conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX) and leflunomide (LEF), are the common RA therapy to reduce inflammation and disease progression. Recently, drug-resistance in RA with conventional treatment has become an issue. Mutations in p53 tumor suppressor gene and overexpression of ABCB1/MDR-1/P-gp transporters may contribute to antirheumatic drug-resistance in RA. Biologic DMARDs (bDMARDs) are often prescribed, when conventional DMARDs fail to treat RA, by targeting proinflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. The efficacy of bDMARDs is affected by personal factors, for example, age, smoking, body mass index (BMI), immunogenicity, and genetic polymorphisms. This review highlights the role of p53 gene mutations, ABC family transporters and personal factors in antirheumatic drug-resistance, which may lead to new personalized therapies against RA with an increased drug-sensitivity.This work aimed to investigate the accumulation of fucoxanthin and lipids in Tisochrysis lutea during growth (N+) and nitrogen-starvation (N-) and to correlate these products with single-cell emissions using fluorescence-activated cell sorting (FACS). Fucoxanthin content decreased 52.94% from N+ to N- in batch cultivation; increased 40.53% as dilution rate changed from 0.16 to 0.55 d-1 in continuous cultivation. Total lipids (N-) were constant (~250 mg/g), but the abundance of neutral lipids increased from 4.87% to 40.63%. Nile red can stain both polar and neutral lipids. However, in vivo, this differentiation is limited due to an overlapping of signals between 600 and 660 nm, caused by neutral lipids concentrations above 3.48% (W/W). Chlorophyll autofluorescence (720 nm) was reported for the first time as a proxy for fucoxanthin (R2 = 0.90) and polar lipids (R2 = 0.98). FACS can be used in high throughput quantification of pigments and lipids and to select and sort cells with high-fucoxanthin/lipids.This work tried understanding aggregation preference of anammox bacteria from benefit-driven perspective. Aggregated anammox sludge (AGS) gained benefits in specific anammox activity (SAA) (increased by 40.47 ± 12.64%) and in toxicity resistance (enhanced by 65.41%) than scattered anammox sludge (SCS), which were verified by kinetics. The increased heme c content by 35.67 ± 5.77% and enhanced relative abundance of anammox bacteria by 9.29% supported the benefits in biological activity and improved EPS content by 1097.59 ± 43.06% (622.16 ± 61.73% for protein (PN), 2403.47 ± 162.75% for humic acid (HA) and 1145.34 ± 97.33% for polysaccharide (PS)) justified the benefits in toxicity resistance. The diverse microbial communities and organized spatial structures owned by AGS promoted interactions between species, as the intrinsic justification for obtaining the benefits. We expect our findings to provide theoretical guidance for promotions and applications of the anammox process with excellent nitrogen removal capacity and stability.Escalating environmental concerns and petroleum demands leads into the present study. In this investigation delignification of rice straw was optimized by NaOH and H2SO4 pretreatment using L16 Taguchi orthogonal array. NaOH pretreatment revealed higher delignification as compared to H2SO4 and; further subjected to separate enzymatic hydrolysis and co-fermentation (SHCF) using RSM as the SHCF demonstrated a maximum glucose and xylose yield of 575 and 205 mg/g. Further, butanol concentration of 4.32 g/L was achieved from 20 g/L of sugar loadings by co-culture of Saccharomyces cerevisiae and Pichia sp. at 72 h of incubation time which was 79.25% higher as compared to monocultures of Pichia sp. Scale-up experiments with higher sugar loadings (90 g/L) demonstrated a butanol concentration of 13.3 g/L. The release of amino acids in co-culture and monoculture systems demonstrated that the addition of S. cerevisiae promoted the butanol synthesis pathway which led to higher butanol concentration.Economical removal of fermentation inhibitors from lignocellulosic hydrolysate plays a considerable role in bioconversion of lignocellulose biomass. In this work, the textural properties of polyacrylamide/polystyrene interpenetrating polymer networks (PAM/PS IPNs) on adsorption of fermentation inhibitors from sugarcane bagasse hydrolysate (SCBH) were investigated for the first time. The results showed that, the specific surface area, pore diameter and surface polarity had important influence on its adsorption performance towards sugars, organic acids, furans and acid-soluble lignin. The PAM/PS IPNs under the optimal copolymerization situation achieved the high selectivity coefficients of 4.07, 14.9, 21.2 and 25.8 with respective to levulinic acid, furfural, hydroxymethylfurfural (HMF) and acid-soluble lignin, and had a low total sugar loss of 2.09%. Overall, this research puts forward a design and synthetic strategy for adsorbent to remove fermentation inhibitors from lignocellulosic hydrolysate.