Probiotics are dietary supplements containing viable, non-pathogenic microorganisms that interact with the gastrointestinal microflora and directly with the immune system. The possible health effects of probiotics include modulating the immune system and exerting antibacterial, anticancer, and anti-mutagenic effects. The purpose of this study was to isolate, identify, and characterize novel strains of probiotics from the faeces of Korean infants. Various assays were conducted to determine the physiological features of candidate probiotic isolates, including Gram staining, 16S rRNA gene sequencing, tolerance assays to stimulated gastric juice and bile salts, adherence ability assays, antibiotic susceptibility testing, and assays of immunomodulatory effects. Based on these morphological and biochemical characteristics, five potential probiotic isolates (Enterococcus faecalis BioE EF71, Lactobacillus fermentum BioE LF11, Lactobacillus plantarum BioE LPL59, Lactobacillus paracasei BioE LP08, and Streptococcus thermophilus BioE ST107) were selected. E. faecalis BioE EF71 and L. plantarum BioE LPL59 showed high tolerance to stimulated gastric juice and bile salts, and S. thermophilus BioE ST107 as well as these two strains exhibited stronger adherence ability than reference strain Lactobacillus rhamnosus GG. All five strains inhibited secretion of lipopolysaccharide-induced pro-inflammatory cytokines IL-6 and TNF-α in RAW264.7 macrophages in vitro. L. fermentum BioE LF11, L. plantarum BioE LPL59, and S. thermophilus BioE ST107 enhanced the production of anti-inflammatory cytokine IL-10. Overall, our findings demonstrate that the five novel strains have potential as safe probiotics and encouraged varying degrees of immunomodulatory effects.

Public-Private Partnerships (PPPs) are defined as a collaborative approach in which the public and private sector share resources, responsibilities and risks to achieve common objectives and mutual benefits in a sustainable manner. PPPs are identified as a key solution to reinforce Veterinary Services. However only limited information is available on the scope, added value and enabling factors of PPPs in this sector. The aims of this study were to develop a typology of PPPs in the veterinary field and to identify key success factors and obstacles to their implementation. A structured questionnaire was sent to all 181 World Organisation for Animal Health (OIE) Member Countries and to 47 private contacts. 36 different variables characterizing PPP initiatives were collected. 97 examples of PPPs were retrieved from 76 countries. Dimensionality reduction techniques were combined with clustering and discrimination methods to establish a typology of PPPs and to derive a set of simple rules to classify new instances of PPPs. Three clusters were identified, separated according to two main variables: the type of private partners and the type of interaction. Cluster 1, transactional PPPs, represented the traditional understanding of PPPs by Veterinary Services, initiated and funded by the public sector, giving service delivery accreditation to mostly private veterinarians; cluster 2, collaborative PPPs, included partnerships between producer associations and public Veterinary Services, driven by trade interests; cluster 3, transformational PPPs, represented joint programs initiated and funded by private companies and initially driven by business development objectives. Specific success factors and key obstacles affecting the performances and sustainability of these initiatives were identified for each cluster. This study represents the first practical attempt to develop a meaningful typology of PPPs in the field of animal health and to identify fundamental obstacles currently inhibiting the development of PPPs, and suggests ways to support national Veterinary Services in overcoming these obstacles.

Spatially heterogeneous flicker, characterized by probabilistic and locally independent luminance modulations, abounds in nature. It is generated by flames, water surfaces, rustling leaves, and so on, and it is pleasant to the senses. It affords spatiotemporal multistability that allows sensory activation conforming to the biases of the visual system, thereby generating the perception of spontaneous motion and likely facilitating the calibration of motion detectors. One may thus hypothesize that spatially heterogeneous flicker might potentially provide restoring stimuli to the visual system that engage fluent (requiring minimal top-down control) and self-calibrating processes. Here, we present some converging behavioral and electrophysiological evidence consistent with this idea. Spatially heterogeneous (multistable) flicker (relative to controls matched in temporal statistics) reduced posterior EEG (electroencephalography) beta power implicated in long-range neural interactions that impose top-down influences on sensory processing. Further, the degree of spatiotemporal multistability, the amount of posterior beta-power reduction, and the aesthetic responses to flicker were closely associated. These results are consistent with the idea that the pleasantness of natural flicker may derive from its spatiotemporal multistability that affords fluent and self-calibrating visual processing.

The application of biochar is one of the most useful methods for improving soil quality, which is of the utmost significance for the continuous production of crops. As there are no conclusive studies on the specific effects of biochar application on tobacco quality, this study aimed to improve the yield and quality of tobacco as a model crop for economic and genetic research in southern China, by such application. We used transcriptome sequencing to reveal the effects of applied biochar on tobacco development before and after topping. Our results showed that topping affected carbon and nitrogen metabolism, photosynthesis and secondary metabolism in the tobacco plants, while straw biochar-application to the soil resulted in amino acid and lipid synthesis; additionally, it affected secondary metabolism of the tobacco plants through carbon restoration and hormonal action, before and after topping. In addition to the new insights into the impact of biochar on crops, our findings provide a basis for biochar application measures in tobacco and other crops.

The intestinal microbiota plays an important role in health and disease and produces, through fermentative reactions, several metabolic products, such as lactate, that can affect the host. The microbiota also interacts with and metabolizes compounds produced by the host, such as primary bile acids. Lactate and bile acids (BA) are of particular interest in gastrointestinal diseases because they have been associated with metabolic acidosis and bile acid diarrhea, respectively. The objectives of this study were to validate an enzymatic assay to quantify D-, L-, and total lactate in canine feces, and to characterize fecal lactate and BA concentrations as well as bacterial abundances in healthy dogs and dogs with gastrointestinal diseases. Fecal samples were collected from 34 healthy dogs, 15 dogs with chronic enteropathy (CE), and 36 dogs with exocrine pancreatic insufficiency (EPI). Lactate was quantified with an enzymatic assay, BA with gas chromatography-mass spectrometry, and 11 bacterial groups with qPCR. A fecal lactate reference interval was established from 34 healthy dogs and was 0.7-1.4 mM, 0.3-6.0 mM, and 1.0-7.0 mM for D-, L-, and total lactate, respectively. The assay to measure D-, L-, and total lactate in canine fecal samples was linear, accurate, precise, and reproducible. Significant increases in fecal lactate and decreases in secondary BA concentrations were observed in dogs with CE and dogs with EPI. Dogs with EPI had an increased abundance of Escherichia coli, Lactobacillus, and Bifidobacterium; a decreased abundance of Fusobacterium and Clostridium hiranonis; and a higher Dysbiosis Index when compared to healthy dogs. Further studies are necessary to determine the clinical utility of lactate and BA quantification in canine feces. These metabolites suggest functional alterations of intestinal dysbiosis and may become promising targets for further elucidating the role of the microbiota in health and disease.

Gastrointestinal (GI)-related adverse events (AEs) are commonly observed in the clinic during cancer treatments. Citrulline is a potentially translatable biomarker of GI AEs. In this study, irinotecan-induced citrulline changes were studied for a range of doses and schedules in rats. A translational system toxicology model for GI AEs using citrulline was then developed based on new experimental data and parameters from a literature intestinal cell dynamic model. With the addition of feedback-development and tolerance-development mechanisms, the model well captured the plasma citrulline profiles after irinotecan treatment in rats. Subsequently, the model was translated to humans and predicted the observed GI AE dynamics in humans including dose-scheduling effect using the cytotoxic and feedback parameters estimated in rats with slight calibrations. This translational toxicology model could be used for other antineoplastic drugs to simulate various clinical dosing scenarios before human studies and mitigate potential GI AEs.

Most patients with Turner syndrome (TS) need hormone replacement therapy because of hypergonadotropic hypogonadism; individual outcomes, however, are highly variable. Our objective was to assess the influence of five estrogen receptor 1 gene (ESR1) polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) on adult height, breast development, uterine volume and bone mineral density (BMD). We studied 91 TS patients from a tertiary hospital using adult estrogen dose. In our group, ESR1 rs2234693 was associated with femoral neck and total hip BMD, and it accounted for around 10% of BMD variability in both sites (P < 0.01). Patients homozygous for C allele in this polymorphism had significantly lower femoral neck BMD (0.699 ± 0.065 g/cm2 vs 0.822 ± 0.113 g/cm2, P = 0.008) and total hip BMD (0.777 ± 0.118 g/cm2 vs 0.903 ± 0.098 g/cm2, P = 0.009) than patients homozygous for T allele. The other four ESR1 polymorphisms were not able to predict any of the above estrogen therapy outcomes in an isolated manner. Patients homozygous for the haplotype GCG formed by polymorphisms rs543650, rs2234693 and rs9340799 had an even more significantly lower femoral neck BMD (0.666 ± 0.049 vs 0.820 ± 0.105 g/cm2, P = 0.0047) and total hip BMD (0.752 ± 0.093 vs 0.908 ± 0.097 g/cm2, P = 0.0029) than patients homozygous for haplotypes with a T allele in rs2234693. In conclusion, homozygosity for C allele in ESR1 rs2234693 and/or for GCG haplotype appears to be associated with lower femoral neck and total hip BMD. We believe that the identification of polymorphisms related to estrogen outcomes may contribute to individualization of treatment in TS.

Meningococcal serogroup A conjugate vaccine (MACV) was introduced in Chad during 2011-2012. Meningitis surveillance has been conducted nationwide since 2003, with case-based surveillance (CBS) in select districts from 2012. In 2016, the MenAfriNet consortium supported Chad to implement CBS in 4 additional districts and real-time polymerase chain reaction (rt-PCR) at the national reference laboratory (NRL) to improve pathogen detection. We describe analysis of bacterial meningitis cases during 3 periods: pre-MACV (2010-2012), pre-MenAfriNet (2013-2015), and post-MenAfriNet (2016-2018).

Paclitaxel is a commonly used drug in the treatment of multiple solid tumors, including cancers of the breast, lung, and ovaries. Despite the established exposure-pharmacodynamic relationships for paclitaxel, treatment is associated with wide interindividual pharmacokinetic variability that leads to unpredictability of the agent's clinical activity and toxicity. We hypothesized that physiologically-based modeling approaches could be employed to predict the human pharmacokinetics of paclitaxel following administration of the approved Cremophor-based formulation (Taxol). The model was developed from tissue distribution studies performed in mice and applied to plasma concentration-time data obtained in adult cancer patients receiving Taxol at the approved dose and schedule (175 mg/m2 by a 3-hour intravenous infusion), taking into account interspecies differences in physiological parameters. The final model adequately captured the observed concentrations in patients and allowed prediction of paclitaxel distribution profiles in multiple target organs and can be applied to further refine the chemotherapeutic treatment with a clinically important agent.

Altered event-related potential (ERP) performances have been noted in attention deficit hyperactivity disorder (ADHD) patients and reflect neurocognitive dysfunction. Whether these ERP alterations and correlated dysfunctions exist in healthy parents with ADHD offspring is worth exploring.

The assessment of soil organic carbon (SOC) in mountainous karst areas is very challenging, due to the high spatial heterogeneity in SOC content and soil type. To study and assess the SOC storage in mountainous karst areas, a total of 22,786 soil samples were collected from 2,854 soil profiles in Guizhou Province in Southwest China. The SOC content in the soil samples was determined by the oxidation of potassium dichromate (K2Cr2O7), followed by titration with iron (II) sulfate (FeSO4). The SOC storage was assessed based on different land uses. The results suggested that the average SOC density in the top 1.00 m of soil associated with different land uses decreased in the following order: Croplands (9.58 kg m-2) > garden lands (9.07 kg m-2) > grasslands (8.07 kg m-2) > forestlands (7.35 kg m-2) > uncultivated lands (6.94 kg m-2). The SOC storage values in the 0.00-0.10 m, 0.00-0.20 m, 0.00-0.30 m and 0.00-1.00 m soil layers of Guizhou Province were 0.50, 0.87, 1.11 and 1.58 Pg, respectively. The SOC in the top 0.30 m of soil accounted for 70.25% of the total within the 0.00-1.00 m layer in Guizhou Province. It was concluded that assessing SOC storage in mountainous karst areas was more accurate when using land use rather than soil type. This result can supply a scientific reference for the accurate assessment of the SOC storage in the karst areas of southwestern China, the islands of Java, northern and central Vietnam, Indonesia, Kampot Province in Cambodia and in the general area of what used to be Yugoslavia, along with other karst areas with similar ecological backgrounds.

Wireless sensor networks (WSNs) are susceptible to faults in sensor data. Outlier detection is crucial for ensuring the quality of data analysis in WSNs. This paper proposes a novel improved support vector data description method (ID-SVDD) to effectively detect outliers of sensor data. ID-SVDD utilizes the density distribution of data to compensate SVDD. The Parzen-window algorithm is applied to calculate the relative density for each data point in a data set. Meanwhile, we use Mahalanobis distance (MD) to improve the Gaussian function in Parzen-window density estimation. Through combining new relative density weight with SVDD, this approach can efficiently map the data points from sparse space to high-density space. In order to assess the outlier detection performance, the ID-SVDD algorithm was implemented on several datasets. The experimental results demonstrated that ID-SVDD achieved high performance, and could be applied in real water quality monitoring.

Understanding the fundamental role of the stroma in normal development and cancer progression has been an emerging focus in recent years. The receptor tyrosine kinase (RTK) signaling pathway has been reported playing critical roles in regulating the normal and cancer microenvironment, but the underlying mechanism is still not very clear. By applying the quantitative phosphoproteomic analysis of Sprouty proteins (SPRYs), generic modulators of RTK signaling and deleted mouse mammary fibroblasts, we quantified a total of 11,215 unique phosphorylation sites. By contrast, 554 phosphorylation sites on 425 proteins had SPRY-responsive perturbations. Of these, 554 phosphosites, 362 sites on 277 proteins, were significantly increased, whereas 192 sites on 167 proteins were decreased. Among the regulated proteins, we identified 31 kinases, 7 phosphatases, and one phosphatase inhibitor that were not systematically characterized before. Furthermore, we reconstructed a phosphorylation network centered on RTK signaling regulated by SPRY. Collectively, this study uncovered a system-wide phosphorylation network regulated by SPRY, providing an additional insight into the complicated RTK signaling pathways involved in the mammary gland microenvironment.

Trastuzumab is an antibody used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers. Since trastuzumab is an internalizing antibody, two factors could play an important role in achieving high uptake and prolonged retention of radioactivity in HER2-positive tumors after radioiodination-residualizing capacity after receptor-mediated internalization and susceptibility to dehalogenation. To evaluate the contribution of these two factors, trastuzumab was radiolabeled using the residualizing reagent N-succinimidyl 4-guanidinomethyl-3-[*I]iodobenzoate ([*I]SGMIB) and the nonresidualizing reagent N-succinimidyl-3-[*I]iodobenzoate ([*I]SIB), both of which are highly dehalogenation-resistant. Paired-label uptake and intracellular retention of [125I]SGMIB-trastuzumab and [131I]SIB-trastuzumab was compared on HER2-expressing BT474 human breast carcinoma cells. Tumor uptake and normal tissue distribution characteristics for the two labeled conjugates were assessed in mice bearing BT474M1 xenografts. The internalization and intracellular retention of initially-bound radioactivity in BT474 cells was similar for the two labeled conjugates up to 4 h, but were significantly higher for [125I]SGMIB-trastuzumab at 6 and 24 h. Similarly, [*I]SGMIB labeling resulted in significantly higher uptake and retention of radioactivity in BT474M1 xenografts at all studied time points. Moreover, tumor-to-tissue ratios for [125I]SGMIB-trastuzumab were consistently higher than those for [131I]SIB-trastuzumab starting at 12 h postinjection. Thus, optimal targeting of HER2-positive breast cancers with a radioiodinated trastuzumab conjugate requires an acylation agent that imparts residualizing capacity in addition to high stability towards dehalogenation in vivo.

The plant circadian clock coordinates environmental signals with internal processes including secondary metabolism, growth, flowering, and volatile emission. Plant tissues are specialized in different functions, and petals conceal the sexual organs while attracting pollinators. Here we analyzed the transcriptional structure of the petunia (Petunia x hybrida) circadian clock in leaves and petals. We recorded the expression of 13 clock genes in petunia under light:dark (LD) and constant darkness (DD). Under light:dark conditions, clock genes reached maximum expression during the light phase in leaves and the dark period in petals. Under free running conditions of constant darkness, maximum expression was delayed, especially in petals. Interestingly, the rhythmic expression pattern of PhLHY persisted in leaves and petals in LD and DD. Gene expression variability differed among leaves and petals, time of day and photoperiod. The transcriptional noise was higher especially in leaves under constant darkness. We found that PhPRR7, PhPRR5, and PhGI paralogs showed changes in gene structure including exon number and deletions of CCT domain of the PRR family. Our results revealed that petunia petals presented a specialized clock.

Dementia is a major public health concern affecting approximately 47 million people worldwide. Mild cognitive impairment (MCI) is one form of dementia that affects an individual's memory with or without affecting their daily life. Alzheimer's disease dementia (ADD) is a more severe form of dementia that usually affects elderly individuals. It remains unclear whether MCI is a distinct disorder from or an early stage of ADD.

The dimorphic human fungal pathogen C. albicans has broad metabolic flexibility that allows it to adapt to the nutrient conditions in different host habitats. C. albicans builds large carbohydrate stores (glycogen) at the end of exponential growth and begins consumption of stored carbohydrates when nutrients become limiting. The expression of genes required for the successful transition between host environments, including the factors controlling glycogen content, is controlled by protein kinase A signaling through the transcription factor Efg1. In addition to the inability to transition to hyphal growth, C. albicans efg1 mutants have low glycogen content and reduced long-term survival, suggesting that carbohydrate storage is required for viability during prolonged culture. To test this assumption, we constructed a glycogen-deficient C. albicans mutant and assessed its viability during extended culture. Pathways and additional genetic factors controlling C. albicans glycogen synthesis were identified through the screening of mutant libraries for strains with low glycogen content. Finally, a part of the Efg1-regulon was screened for mutants with a shortened long-term survival phenotype. We found that glycogen deficiency does not affect long-term survival, growth, metabolic flexibility or morphology of C. albicans. We conclude that glycogen is not an important contributor to C. albicans fitness.

The literature suggests that high-intensity interval training (HIIT) is more effective than moderate-intensity continuous training (MICT) to improve functional ability. However, there is no evidence on including HIIT in a circuit programme (HIICT). Our objective was to determine what type of training (HIICT or MICT) induces greater adaptations in the functional ability and body mass index of middle-aged and older women. The study used a quasi-experimental randomized controlled trial with 54 participants (age = 67.8 ± 6.2 years). Participants were randomly allocated to HIICT (n = 18), MICT (n = 18) or a non-exercise control group (CG; n = 18). The participants in the HIICT or MICT groups trained twice a week (1 h/session) for 18 weeks. Forty-one subjects were analysed (HIICT; n = 17, MICT; n = 12, CG; n = 12). Five subjects presented adverse events during the study. Strength, gait, cardiorespiratory fitness, balance and body mass index were measured. A significant training x group interaction was found in the arm curl test, where HIICT was statistically better than MICT and CG. Likewise, HIICT was statistically better than the CG in the BMI interaction. In lower limb strength, gait/dynamic balance and cardiorespiratory fitness, both HIICT and MICT were statistically better than the CG. In conclusion, HIICT generated better adaptations in upper limb strength than MICT. Likewise, HIICT generated better adaptations in body mass index than CG. Finally, both HIICT and MICT had a similar influence on strength, cardiorespiratory fitness and gait/dynamic balance.

Biosynthesized silver nanoparticles (AgNPs) are widely used in Pharmacy and Medicine. In particular, AgNPs synthesized and mediated by plant extracts have shown topossess several biological activities. In the present study, AgNPs were synthesized using Picea abies L. stem bark extract as reducing agent. Factors, such as metal ion solution, pH, and time, which play a role in the AgNPs synthesis, were assessed. The synthesized AgNPs were characterized by Ultraviolet-Visible Spectrometry, Fourier transform infrared spectroscopy, and Transmission Electron Microscopy (TEM). Further, the study has been extended to evaluate the antimicrobial and antioxidant activity of AgNPs. The broad peak obtained at 411-475 nm (UV-Vis spectroscopy), and the color change pattern, confirmed the synthesis of AgNPs. TEM results showed spherical or rarely polygonal AgNPs with an average size of 44 nm at pH = 9. The AgNPs showed antioxidant activity and antibacterial effect against human pathogenic Gram-positive and Gram-negative bacteria. The results show that spruce bark extract is suitable for obtaining AgNPs, with antibacterial and antioxidant activity.

Alzheimer's disease (AD) affects not only the central nervous system, but also peripheral blood cells including neutrophils and platelets, which actively participate in pathogenesis of AD through a vicious cycle between platelets aggregation and production of excessive amyloid beta (Aβ). Platelets adhesion on amyloid plaques also increases the risk of cerebral microcirculation disorders. Moreover, activated platelets release soluble adhesion molecules that cause migration, adhesion/activation of neutrophils and formation of neutrophil extracellular traps (NETs), which may damage blood brain barrier and destroy brain parenchyma. The present study examined the effects of intermittent hypoxic-hyperoxic training (IHHT) on elderly patients with mild cognitive impairment (MCI), a precursor of AD. Twenty-one participants (age 51-74 years) were divided into three groups: Healthy Control (n = 7), MCI+Sham (n = 6), and MCI+IHHT (n = 8). IHHT was carried out five times per week for three weeks (total 15 sessions). Each IHHT session consisted of four cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Cognitive parameters, Aβ and amyloid precursor protein (APP) expression, microRNA 29, and long non-coding RNA in isolated platelets as well as NETs in peripheral blood were investigated. We found an initial decline in cognitive function indices in both MCI+Sham and MCI+IHHT groups and significant correlations between cognitive test scores and the levels of circulating biomarkers of AD. Whereas sham training led to no change in these parameters, IHHT resulted in the improvement in cognitive test scores, along with significant increase in APP ratio and decrease in Aβ expression and NETs formation one day after the end of three-week IHHT. Such effects on Aβ expression and NETs formation remained more pronounced one month after IHHT. In conclusion, our results from this pilot study suggested a potential utility of IHHT as a new non-pharmacological therapy to improve cognitive function in pre-AD patients and slow down the development of AD.