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S2 Open Access 2017
pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms

Lin Liu, Wendong Yao, Yuefeng Rao et al.

Abstract Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

316 sitasi en Medicine
S2 Open Access 2016
Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique?

E. A. Miller, D. Beasley, R. Dunn et al.

The human vaginal microbiome is dominated by bacteria from the genus Lactobacillus, which create an acidic environment thought to protect women against sexually transmitted pathogens and opportunistic infections. Strikingly, lactobacilli dominance appears to be unique to humans; while the relative abundance of lactobacilli in the human vagina is typically >70%, in other mammals lactobacilli rarely comprise more than 1% of vaginal microbiota. Several hypotheses have been proposed to explain humans' unique vaginal microbiota, including humans' distinct reproductive physiology, high risk of STDs, and high risk of microbial complications linked to pregnancy and birth. Here, we test these hypotheses using comparative data on vaginal pH and the relative abundance of lactobacilli in 26 mammalian species and 50 studies (N = 21 mammals for pH and 14 mammals for lactobacilli relative abundance). We found that non-human mammals, like humans, exhibit the lowest vaginal pH during the period of highest estrogen. However, the vaginal pH of non-human mammals is never as low as is typical for humans (median vaginal pH in humans = 4.5; range of pH across all 21 non-human mammals = 5.4–7.8). Contrary to disease and obstetric risk hypotheses, we found no significant relationship between vaginal pH or lactobacilli relative abundance and multiple metrics of STD or birth injury risk (P-values ranged from 0.13 to 0.99). Given the lack of evidence for these hypotheses, we discuss two alternative explanations: the common function hypothesis and a novel hypothesis related to the diet of agricultural humans. Specifically, with regard to diet we propose that high levels of starch in human diets have led to increased levels of glycogen in the vaginal tract, which, in turn, promotes the proliferation of lactobacilli. If true, human diet may have paved the way for a novel, protective microbiome in human vaginal tracts. Overall, our results highlight the need for continuing research on non-human vaginal microbial communities and the importance of investigating both the physiological mechanisms and the broad evolutionary processes underlying human lactobacilli dominance.

341 sitasi en Biology, Medicine
S2 Open Access 2018
Effect of pH, temperature and freezing-thawing on quantity changes and cellular uptake of exosomes

Yirui Cheng, Qingyu Zeng, Qing Han et al.

Exosomes are cup-shaped small (30–150 nm) extracellular vesicles with the structure of lipid bilayer membrane (Tkach and Thery, 2016) containing proteins, mRNAs and microRNAs that mediate intercellular communication (Valadi et al., 2007). Unlike other extracellular vesicles, exosomes are released into the extracellular space when the multivesicular bodies (MVBs) fuse with the plasma membrane (Colombo et al., 2014). Almost all cell types can secret exosomes and exosomes exist in diverse biological fluids, such as blood, urine, saliva, hydrothorax and breast milk (Thery et al., 2006). Up to now, a number of studies have demonstrated the functions of exosomes in disease development and the potential clinical applications in diagnosis and therapy (Shao et al., 2016). To conduct reproducible studies on exosomal content and function, storage conditions need to have minimal impact on exosomes. There have been a few studies providing partial confirmation of the effect of different storage conditions on exosomes currently. Using exosomes from urine (Zhou et al., 2006) and conditioned medium (Lee et al., 2016) respectively to investigate the influence of storage temperature on exosomes as measured by Western blot, both groups have concluded that storage below −70 °C for a long time is the best temperature for the recovery of exosomes. On the other hand, Sokolova et al. (2011) applied nanoparticle tracking analysis (NTA) to measure the size changes of exosomes at different temperatures, revealing that storage at 37 °C led to more reduction in exosome sizes than that at 4 °C. However, in this study no information about changes in the particle concentration was reported. Some other studies revealed the effect of pH, storage temperature and cycles of freezing and thawing only on the yield of exosome isolation, but not on quantity changes during storage (Akers et al., 2016; Ban et al., 2015; Zhao et al., 2017). Therefore, the standard criterion of exosomal preservation condition is still undefined. Herein, we used HEK 293T cells and ExtraPEG method (Rider et al., 2016) to investigate the influence of multiple storage conditions (temperature, cycles of freezing and thawing, pH) on the quantity changes and cellular uptake of exosomes. ExtraPEG is a new polyethylene glycol (PEG) precipitation method for the purification exosomes without affecting their biological activity. Generally, ultracentrifugation (UC) (Mincheva-Nilsson et al., 2016) is most reliable but time-consuming; and precipitation methods such as ExoQuick (patent number: US20130337440 A1) and ExtraPEG can obtain higher yields of exosomes but with impurity of coprecipitated proteins. First, exosomes from the conditioned medium were extracted by ExtraPEG or UC method. After isolation, transmission electron microscope (TEM), NTA and Western blot were performed to analyze exosomes. Exosomes extracted by UC or ExtraPEG were similar in cupshaped structure (Fig. S1A and S1B), size distribution (Fig. S1C and S1D). And as representative exosome biomarkers, ALG-2-interacting protein X (ALIX), heat shock protein 70 (HSP70) and tumor susceptibility gene 101 (TSG101) were detected in exosomal protein while β-tubulin, widely used as an internal reference to analyze intracellular protein levels, was not detected in exosome samples (Fig. S1E and S1F). These data indicated exosomes were successfully isolated by ExtraPEG method and suitable for the following experiments. After isolation, the exosome pellets were divided equally into several portions and each portion was stored at different temperatures (−80 °C, −20 °C, 4 °C, 37 °C and 60 °C), or through 1–5 cycles of freezing to −80 °C and thawing, or at different pH levels (pH 4, pH 7 and pH 10). After 24 h, NTA and Western blot were performed to measure the remaining quantity of exosomes. Regarding temperatures, the exosomes stored at 4 °C had the highest concentration (Fig. 1A). Consistent with the NTA results, the exosomes stored at 4 °C showed higher levels of representative exosome markers ALIX, HSP70 and TSG101 (Fig. 1B). With the increasing cycles of freezing and thawing, the exosomal concentration and protein levels of ALIX, HSP70 and TSG101 all decreased (Fig. 1D and 1E). For different pH levels, the loss of exosomal concentration and three exosome markers ALIX, HSP70 and TSG101 at pH 4 and pH 10 was more than that at pH 7 (Fig. 1E and 1F). Interestingly, exosomes stored at pH 4 decreased more sharply than that at pH 10 (Fig. 1F and 1G), suggesting that acidic

265 sitasi en Chemistry, Medicine
arXiv Open Access 2025
Women in Physics in the United Kingdom: A Review of Recent Policy and Initiatives

Sally Jordan, Sarah Bakewell, Holly Jane Campbell et al.

Across the United Kingdom, initiatives designed to increase the participation and outcomes for women in physics continue, working with children of various ages as well as with adults. Improvements have been achieved by a combination of these initiatives and an accompanying strengthening of policy, but significant gender imbalances remain.

en physics.soc-ph, physics.ed-ph
S2 Open Access 2018
Sorption of ammonium and nitrate to biochars is electrostatic and pH-dependent

Rivka B. Fidel, D. Laird, K. Spokas

Biochars are potentially effective sorbents for NH4+ and NO3− in water treatment and soil applications. Here we compare NH4+ and NO3− sorption rates to acid-washed biochars produced from red oak (Quercus rubra) and corn stover (Zea mays) at three pyrolysis temperatures (400, 500 and 600 °C) and a range of solution pHs (3.5–7.5). Additionally, we examined sorption mechanisms by quantification of NH4+ and NO3− sorption, as well as Ca2+ and Cl− displacement for corn stover biochars. Solution pH curves showed that NH4+ sorption was maximized (0.7–0.8 mg N g−1) with low pyrolysis temperature (400 °C) biochar at near neutral pH (7.0–7.5), whereas NO3− sorption was maximized (1.4–1.5 mg N g−1) with high pyrolysis temperatures (600 °C) and low pH (3.5–4). The Langmuir (r2 = 0.90–1.00) and Freundlich (r2 = 0.81–0.97) models were good predictors for both NH4+ (pH 7) and NO3− (pH 3.7) sorption isotherms. Lastly, NH4+ and NO3− displaced Ca2+ and Cl−, respectively, from previously CaCl2-saturated corn stover biochars. Results from the pH curves, Langmuir isotherms, and cation displacement curves all support the predominance of ion exchange mechanisms. Our results demonstrate the importance of solution pH and chemical composition in influencing NH4+ and NO3− sorption capacities of biochar.

189 sitasi en Chemistry, Medicine
S2 Open Access 2018
The pH behavior of seventeen deep eutectic solvents

A. Škulcová, A. Russ, M. Jablonský et al.

Deep eutectic solvents (DESs) are a unique category of green solvents that have gained attention in biomass processing due to their distinctive properties not offered by traditional solvents. The pH behavior of 17 selected DESs along with their temperature dependence on pH were evaluated in this study. For all investigated DESs, a temperature increase caused a decrease in pH value.

146 sitasi en Chemistry

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