Infant milk formula (IMF) is designed to mimic the composition of human milk (9-11 g protein/L); however, the standard protein content of IMF (15 g/L) is still a matter of controversy. In contrast to breastfed infants, excessive protein in IMF is associated with overweight and symptoms of metabolic syndrome in formula-fed infants. Moreover, the beta-lactoglobulin (β-Lg) content in cow milk is 3-4 g/L, whereas it is not present in human milk. It is considered to be a major reason for cow milk allergy in infants. In this respect, to modify protein composition, increasing the ratio of alpha-lactalbumin (α-Lac) to β-Lg would be a pragmatic approach to develop a hypoallergenic IMF with low protein content. Such a formula would ensure the necessary balance of essential amino acids, as 123 and 162 amino acid residues are available in α-Lac and β-Lg, respectively. Hence, in this study, a pasteurized form of hypoallergenic and low-protein ready-to-feed (RTF) formula, a new product, is developed to retain heat-sensitive bioactives and other components. Therefore, the effects of high pressure processing (HPP) under 300-600 MPa at approximately 20-40 °C and HTST pasteurization (72 °C for 15 and 30 s) were investigated and compared. The highest ratio of α-Lac to β-Lg was achieved after HPP (600 MPa for 5 min applied at 40.4 °C), which potentially explains the synergistic effect of HPP and heat on substantial denaturation of β-Lg, with significant retention of α-Lac in reconstituted IMF. Industrial relevance: This investigation showed the potential production of a pasteurized RTF formula, a niche product, with a reduced amount of allergenic β-Lg.

With the growing concern about the health impacts associated with airborne particles, there is a pressing need to design an effective filter device. The objective of this study is to investigate the effect of plasma-based surface modifications on static charges of electrospun filter media and their resulting filtration performance. Polystyrene (PS) electrospun web (ES) had inherent static charges of ~3.7 kV due to its electric field-driven process, displaying effective filtration performance. When oxygen species were created on the surface by the oxygen plasma process, static charges of electret media decreased, deteriorating the filter performance. When the web surface was fluorinated by the plasma-enhanced chemical vapor deposition (PECVD), the filtration efficiency against oily aerosol significantly increased due to the combined effect of decreased wettability and strong static charges (~-3.9 kV). Solid particles on the charged media formed dendrites as particles were attracted to other layers of particles, building up a pressure drop. The PECVD process is suggested as a facile functionalization method for effective filter design, particularly for capturing oily aerosol.

One of the basic needs of professional athletes is the real-time and non-invasive monitoring of their activities. The use of these kind of data is necessary to develop strategies for specific tailored training in order to improve performances. The sensor system presented in this work has the aim to adopt a novel approach for the monitoring of physiological parameters, and athletes' performances, during their training. The anaerobic threshold is herein identified with the monitoring of the lactate concentration and the respiratory parameters. The data collected by the sensor are used to build a model using a supervised method (based on the partial least squares method, PLS) to predict the values of the parameters of interest. The sensor is able to measure the lactate concentration from a sample of saliva and it can estimate a respiratory parameter, such as maximal oxygen consumption, maximal carbon dioxide production and respiratory rate from a sample of exhaled breath. The main advantages of the device are the low power; the wireless communication; and the non-invasive sampling method, which allow its use in a real context of sport practice.

6'-Sialyllactose (6SL) displays a wide range of the bioactive benefits, such as anti-proliferative and anti-angiogenic activities. However, the therapeutic effects of 6SL on benign prostatic hyperplasia (BPH) remain unknown.

Influenza virus infection predisposes to secondary bacterial pneumonia. Currently licensed influenza vaccines aim at the induction of neutralizing antibodies and are less effective if the induction of neutralizing antibodies is low and/or the influenza virus changes its antigenic surface. We investigated the effect of suboptimal vaccination on the outcome of post-influenza bacterial superinfection.

For the full use of Spanish mackerel (Scomberomorous niphonius) muscle to produce antioxidant peptides, the proteins of Spanish mackerel muscle were separately hydrolyzed under five kinds of enzymes and in vitro gastrointestinal digestion, and antioxidant peptides were isolated from the protein hydrolysate using ultrafiltration and multiple chromatography methods. The results showed that the hydrolysate (SMPH) prepared using in vitro GI digestion showed the highest degree of hydrolysis (27.45 ± 1.76%) and DPPH radical scavenging activity (52.58 ± 2.68%) at the concentration of 10 mg protein/mL among the six protein hydrolysates, and 12 peptides (SMP-1 to SMP-12) were prepared from SMPH. Among them, SMP-3, SMP-7, SMP-10, and SMP-11 showed the higher DPPH radical scavenging activities and were identified as Pro-Glu-Leu-Asp-Trp (PELDW), Trp-Pro-Asp-His-Trp (WPDHW), and Phe-Gly-Tyr-Asp-Trp-Trp (FGYDWW), and Tyr-Leu-His-Phe-Trp (YLHFW), respectively. PELDW, WPDHW, FGYDWW, and YLHFW showed high scavenging activities on DPPH radical (EC50 1.53, 0.70, 0.53, and 0.97 mg/mL, respectively), hydroxyl radical (EC50 1.12, 0.38, 0.26, and 0.67 mg/mL, respectively), and superoxide anion radical (EC50 0.85, 0.49, 0.34, and 1.37 mg/mL, respectively). Moreover, PELDW, WPDHW, FGYDWW, and YLHFW could dose-dependently inhibit lipid peroxidation in the linoleic acid model system and protect plasmid DNA (pBR322DNA) against oxidative damage induced by H2O2 in the tested model systems. In addition, PELDW, WPDHW, FGYDWW, and YLHFW could retain their high activities when they were treated under a low temperature (<60 °C) and a moderate pH environment (pH 5-9). These present results indicate that the protein hydrolysate, fractions, and isolated peptides from Spanish mackerel muscle have strong antioxidant activity and might have the potential to be used in health food products.

Amyloid beta-peptide is produced by the cleavage of amyloid precursor protein by two secretases, a β-secretase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and a γ-secretase. It has been hypothesised that partial inhibition of BACE1 in individuals with a high risk of developing Alzheimer's disease may be beneficial in preventing cognitive decline. In this study, we report the development of a novel antisense oligonucleotide (AO) that could efficiently downregulate the BACE1 transcript and partially inhibit BACE1 protein. We designed and synthesised a range of 2'-OMethyl-modified antisense oligonucleotides with a phosphorothioate backbone across various exons of the BACE1 transcript, of which AO2, targeting exon 2, efficiently downregulated BACE1 RNA expression by 90%. The sequence of AO2 was later synthesised with a phosphorodiamidate morpholino chemistry, which was found to be not as efficient at downregulating BACE1 expression as the 2'-OMethyl antisense oligonucleotides with a phosphorothioate backbone variant. AO2 also reduced BACE1 protein levels by 45%. In line with our results, we firmly believe that AO2 could be used as a potential preventative therapeutic strategy for Alzheimer's disease.

Obesity is associated with several comorbid disorders, ranging from cardiovascular diseases to insulin resistance. In this context, visceral adipose tissue (VAT) seems to have a close connection with insulin resistance. In our study, we hypothesized that the expression profile of key adipogenic genes, such as proliferator-activated receptor γ type 2 (PPAR-γ2), CCAAT/enhancer-binding protein type α (C/EBP-α), and forkhead box protein class O type 1 (FOXO1) in VAT should shed light on their association with obesity-related insulin resistance.

Liposomal nanotechnology has a great potential to overcome the current major problems of chemotherapy. However, the lack of penetrability and targetability retards the successful delivery of liposomal carriers. Previously, we showed that BR2 peptide modification endowed cantharidin-loaded liposomes with intracellular penetration that enhanced the drug cytotoxic effects. Here, we aimed to improve the targeting delivery of drugs into cancer cells via highly expressed carbonic anhydrase IX (CA IX) receptors by modifying our previous catharidin-loaded BR2-liposomes with anti-CA IX antibody. A higher cellular uptake of dual-functional liposomes (DF-Lp) than other treatments was observed. Induction of CA IX over-expressing resulted in a higher cellular binding of DF-Lp; subsequently, blocking with excess antibodies resulted in a decreased cancer-cell association, indicating a specific targeting property of our liposomes towards CA IX expressed cells. After 3h tracking, most of the liposomes were located around the nucleus which confirmed the involvement of targeting intracellular delivery. Cantharidin loaded DF-Lp exhibited enhanced cytotoxicity in vitro and was most effective in controlling tumor growth in vivo in an orthotopic hepatocellular carcinoma model compared to other groups. Collectively, our results presented the advantage of the BR2 peptide and CA IX antibody combination to elevate the therapeutic potential of cantharidin loaded DF-liposomes.

The rat grimace scale (RGS) is a measure of spontaneous pain that evaluates pain response. The ability to characterize pain through a non-invasive method has considerable utility for numerous animal models of disease, including mucositis, a painful, self-limiting side-effect of chemotherapy treatment. Preclinical studies investigating novel therapeutics for mucositis often focus on pathological outcomes and disease severity. These investigations fail to measure pain, in spite of reduction of pain being a key clinical therapeutic goal. This study assessed the utility of the RGS for pain assessment in a rat model of mucositis, and whether changes in disease activity index (DAI) and open field test (OFT) reflected the grimace responses recorded. Sixty tumor-bearing female Dark Agouti rats were injected with either saline or 5-Fluourouracil alone, or with co-administration of opioid analgesics. Whilst differences in DAI were observed between treatment groups, no difference in RGS scores or OFT were demonstrated. Significant increases in grimace scores were observed across time. However, whilst a statistically significant change may have been noted, the biological relevance is questionable in terms of practical usage, since an observer is only able to score whole numbers. Development of effective pain assessment methods in animal models is required to improve welfare, satisfy regulatory requirements, and increase translational validity of the model to human patients.

An expansion of effector/activated Vδ2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of Vδ2 T-cells against ZIKV-infected cells. The Vδ2 T-cells expansion and their cytotoxic activity against ZIKV-infected cells were tested in vitro and analyzed by RT-PCR and flow cytometry. We found that ZIKV infection was able to induce Vδ2 T-cells expansion and sensitized A549 cells to Vδ2-mediated killing. Indeed, expanded Vδ2 T-cells killed ZIKV-infected cells through degranulation and perforin release. Moreover, ZIKV infection was able to increase the expression on A549 cells of NKG2D ligands (NKG2DLs), namely MICA, MICB, and ULBP2, at both the mRNA and protein levels, suggesting the possible involvement of these molecules in the recognition by NKG2D-expressing Vδ2 T-cells. Indeed, the killing of ZIKV-infected cells by expanded Vδ2 T-cells was mediated by NKG2D/NKG2DL interaction as NKG2D neutralization abrogated Vδ2 cytotoxicity. Our data showed a strong antiviral activity of Vδ2 T-cells against ZIKV-infected cells, suggesting their involvement in the protective immune response. Other studies are necessary to investigate whether the lack of Vδ2 T-cells expansion in vivo may be associated with disease complications.

The larvae of the black soldier fly (Hermetia illucens L., BSFL) have received increased industrial interest as a novel protein source for food and feed. Previous research has found that insects, including BSFL, are capable of metabolically converting aflatoxin B1 (AFB1), but recovery of total AFB1 is less than 20% when accounting for its conversion to most known metabolites. The aim of this study was to examine the conversion of AFB1 by S9 extracts of BSFL reared on substrates with or without AFB1. Liver S9 of Aroclor-induced rats was used as a reference. To investigate whether cytochrome P450 enzymes are involved in the conversion of AFB1, the inhibitor piperonyl butoxide (PBO) was tested in a number of treatments. The results showed that approximately 60% of AFB1 was converted to aflatoxicol and aflatoxin P1. The remaining 40% of AFB1 was not converted. Cytochrome P450s were indeed responsible for metabolic conversion of AFB1 into AFP1, and a cytoplasmic reductase was most likely responsible for conversion of AFB1 into aflatoxicol.

Exosomes play a crucial role in the progression of infectious diseases, as exosome release and biogenesis are affected by external factors, such as pathogenic infections. Pyrogens may aide in the progression of diseases by triggering inflammation, endothelial cell injury, and arterial plaque rupture, all of which can lead to acute coronary disease, resulting in cardiac tissue death and the onset of a cardiac event (CE). To better understand the effects of Gram-negative bacterial infections on exosome composition and biogenesis, we examined exosome characteristics after treatment of AC16 human cardiomyocytes with lipopolysaccharide (LPS), which served as a model system for Gram-negative bacterial infection. Using increasing doses (0, 0.1, 1, or 10 µg) of LPS, we showed that treatment with LPS substantially altered the composition of AC16-derived exosomes. Both the relative size and the quantity (particles/mL) of exosomes were decreased significantly at all tested concentrations of LPS treatment compared to the untreated group. In addition, LPS administration reduced the expression of exosomal proteins that are related to exosomal biogenesis. Conversely, we observed an increase in immunomodulators present after LPS administration. This evaluation of the impact of LPS on cardiac cell death and exosome composition will yield new insight into the importance of exosomes in a variety of physiological and pathological processes as it relates to disease progression, diagnosis, and treatment.

Composite nanoparticles were used in solid phase micro membrane tip extraction and capillary electrophoresis to determine phenol and p-amino-phenol in wastewater. The optimized conditions were 100 g/L concentration, 40 min contact time, 11 pH, 5 mg/mL nanoparticles amounts, 60 min desorption time, 9 desorption pH and 298 K temperature. Capillary electrophoresis conditions were phosphate buffer (15 mM, pH 7.0) background electrolyte, 18 kV applied voltage, 214 nm UV detection, 30 s sample loading at 23 ± 1 °C. The maximum percent uptakes of p-amino-phenol and phenol were 80.0 and 85.0%. High ratio recoveries of p-amino-phenol and phenol from nanomaterial were 99.0 and 98. Consequently, the actual extractions of p-amino-phenol and phenol from wastewater were 79.2 and 83.30 percent. The migration times of phenol and p-amino-phenol and were 9.0 and 12.0 min. The detection limits of phenol and p-amino-phenols were 0.1 and 0.2 µg/L after extraction and CE. Therefore, this combination of solid phase micro membrane tip extraction and capillary electrophoresis may be considered as the ideal one for monitoring of toxic phenol and p-amino-phenol in water sample.

The International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus nephritis (LN) classification is under reconsideration, given challenges with inter-rater reliability and resultant inconsistent relationship with treatment response. Integration of molecular classifiers into histologic evaluation can improve diagnostic precision and identify therapeutic targets. This study described the relationship between histological and molecular phenotypes and clinical responses in LN. Renal compartmental mRNA abundance was measured in 54 biopsy specimens from LN patients and correlated to ISN/RPS classification and individual histologic lesions. A subset of transcripts was also evaluated in sequential biopsies of a separate longitudinal cohort of 36 patients with paired samples obtained at the time of flare and at follow up. Unsupervised clustering based on mRNA abundance did not demonstrate a relationship with the (ISN/RPS) classification, nor did univariate statistical analysis. Exploratory analyses suggested a correlation with individual histologic lesions. Glomerular FN1 (fibronectin), SPP1 (secreted phosphoprotein 1), and LGALS3 (galectin 3) abundance correlated with disease activity and changed following treatment. Exploratory analyses suggested relationships between specific transcripts and individual histologic lesions, with the important representation of interferon-regulated genes. Our findings suggested that the current LN classification could be refined by the inclusion of molecular descriptors. Combining molecular and pathologic kidney biopsy phenotypes may hold promise to better classify disease and identify actionable treatment targets and merits further exploration in larger cohorts.

Zika virus (ZIKV) is an emerging mosquito-borne virus of medical concern. ZIKV infection may represent a serious disease, causing neonatal microcephaly and neurological disorders. Nowadays, there is no approved antiviral against ZIKV. Several indigenous or endemic medicinal plants from Mascarene archipelago in Indian Ocean have been found able to inhibit ZIKV infection. The purpose of our study was to determine whether essential oil (EO) from Reunion Island medicinal plant Ayapana triplinervis, whose thymohydroquinone dimethyl ether (THQ) is the main component has the potential to prevent ZIKV infection in human cells. Virological assays were performed on human epithelial A549 cells infected with either GFP reporter ZIKV or epidemic viral strain. Zebrafish assay was employed to evaluate the acute toxicity of THQ in vivo. We showed that both EO and THQ inhibit ZIKV infection in human cells with IC50 values of 38 and 45 µg/mL, respectively. At the noncytotoxic concentrations, EO and THQ reduced virus progeny production by 3-log. Time-of-drug-addition assays revealed that THQ could act as viral entry inhibitor. At the antiviral effective concentration, THQ injection in zebrafish does not lead to any signs of stress and does not impact fish survival, demonstrating the absence of acute toxicity for THQ. From our data, we propose that THQ is a new potent antiviral phytocompound against ZIKV, supporting the potential use of medicinal plants from Reunion Island as a source of natural and safe antiviral substances against medically important mosquito-borne viruses.

Burnout is a common and growing phenomenon in the health care setting. The objective of the present study is to examine contextual factors in the workplace associated with burnout among primary care providers (PCPs) in Shandong Province, China. A cross-sectional survey was conducted among 951 PCPs nested within 48 primary health institutions (PHIs). Burnout was measured using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). We used two-level random intercept linear regression models to examine individual- versus workplace-level risk factors for burnout. The result revealed that 33.12%, 8.83% and 41.43% PCPs were experiencing a high degree of emotional exhaustion (EE), depersonalization (DP) and low personal accomplishment (PA). In multilevel analysis, the most significant and common individual-level predictors of burnout were lack of perceived work support and autonomy. At the institutional level, workload was positively related to EE (odds ratio (OR): 6.59; 95% confidence interval (CI): 3.46-9.72), while work support was related to higher PA (OR: 3.49; 95% CI: 0.81-6.17). Greater attention should be paid to the influence of the work environment factors (workload and work support) to prevent burnout. Strategies such as increasing human resources allocated to PHIs and establishing a supportive work environment are encouraged to prevent and reduce burnout among PCPs in China.

The hyperbranched epoxy resins (HBE) composed of bisphenol A (BPA) and polyethylene glycol (PEG) as reactants and pentaerythritol as branching point were successfully synthesized via A2 + B4 polycondensation reaction at various BPA/PEG ratios. The 13C NMR spectra revealed that the synthesized HBE mainly had a dendritic structure as confirmed by the high degree of branching (DB). The addition of PEG in the resin enhanced degree of branching (DB) (from 0.82 to 0.90), epoxy equivalent weight (EEW) (from 697 g eq-1 to 468 g eq-1) as well as curing reaction. Adding 5-10 wt.% PEG in the resin decreased the onset and peak curing temperatures and glass transition temperature; however, adding 15 wt.% PEG in the resin have increased these thermal properties due to the lowest EEW. The curing kinetics were evaluated by fitting the experimental data of the curing behavior of all resins with the Šesták-Berggren equation. The activation energy increased with the increase of PEG in the resins due to HBE's steric hindrance, whereas the activation energy of HBE15P decreased due to a large amount of equivalent active epoxy group per mass sample. The curing behavior and thermal properties of obtained hyperbranched BPA/PEG epoxy resin would be suitable for using in electronics application.

CD73, a cell-surface protein encoded by the gene NT5E, is overexpressed in glioblastoma (GBM), where it contributes to the tumor's pathophysiology via the generation of immunosuppressive adenosine. Adenosinergic signaling, in turn, drives immunosuppression of natural killer (NK) cells through metabolic and functional reprogramming. The correlation of CD73 with patient survival in relation to GBM pathology and the intratumoral infiltration of NK cells has not been comprehensively studied before. Here, we present an analysis of the prognostic relevance of CD73 in GBM based on transcriptional gene expression from patient data from The Cancer Genome Atlas (TCGA) database. Utilizing bioinformatics data mining tools, we explore the relationship between GBM prognosis, NT5E expression, and intratumoral presence of NK cells. Our analysis demonstrates that CD73 is a negative prognostic factor for GBM and that presence of NK cells may associate with improved prognosis. Moreover, the interplay between expression of NT5E and specific NK genes hints to potential functional effects of CD73 on NK cell activation.

High performance Mg-6Al-3Sn-0.25Mn-xZn alloys (x = 0, 0.5, 1.0, 1.5, and 2.0 wt %) without rare earth were designed. The effects of different Zn contents on the microstructure and mechanical properties were systematically investigated. The addition of Zn obviously refines the as-cast alloys dendritic structure because of the increase in the number in the second phase. For the as-extruded alloys, an appropriate amount of Zn promotes complete recrystallization, thus increasing the grain size. As the Zn content increases, the texture gradually evolves into a typical strong basal texture, which means that the basal slip is difficult to initiate. Meanwhile, the addition of Zn promotes the precipitation of small-sized second phases, which can hinder the dislocation movement. The combination of texture strengthening and precipitation strengthening is the main reason for the improvement of alloys' strength.