Hasil untuk "physics.gen-ph"

J. Rousk, J. Rousk, E. Bååth et al.

K. Caldeira, M. Wickett

E. Slessarev, Yang Lin, N. Bingham et al.

Hong-Jun Li, Jin-Zhi Du, Jing Liu et al.

Boeun Lee, Hyoree Seo, Hae Ri Lee et al.

L. Giordano, B. Han, M. Risch et al.

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.

W. Dang, Libu Manjakkal, W. Navaraj et al.

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.

T. Cheng, Lu Wang, B. Merinov et al.

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

Xiaorong Fan, Zhong Tang, Yawen Tan et al.

Mam Y Mboge, B. Mahon, R. McKenna et al.

The pH of the tumor microenvironment drives the metastatic phenotype and chemotherapeutic resistance of tumors. Understanding the mechanisms underlying this pH-dependent phenomenon will lead to improved drug delivery and allow the identification of new therapeutic targets. This includes an understanding of the role pH plays in primary tumor cells, and the regulatory factors that permit cancer cells to thrive. Over the last decade, carbonic anhydrases (CAs) have been shown to be important mediators of tumor cell pH by modulating the bicarbonate and proton concentrations for cell survival and proliferation. This has prompted an effort to inhibit specific CA isoforms, as an anti-cancer therapeutic strategy. Of the 12 active CA isoforms, two, CA IX and XII, have been considered anti-cancer targets. However, other CA isoforms also show similar activity and tissue distribution in cancers and have not been considered as therapeutic targets for cancer treatment. In this review, we consider all the CA isoforms and their possible role in tumors and their potential as targets for cancer therapy.

Salime Bazban-Shotorbani, M. M. Hasani-Sadrabadi, A. Karkhaneh et al.

A. Abuhelwa, Desmond B. Williams, R. Upton et al.

S. Nakata, Mao Shiomi, Yusuke Fujita et al.

Sandeep J. Sonawane, Rahul S. Kalhapure, T. Govender

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.

Haoran Wei, Eric P. Vejerano, Weinan Leng et al.

Significance Aerosols with high water content (aerosol droplets) are ubiquitous and play a significant role in atmospheric chemistry and meteorology. However, directly measuring the pH of an individual aerosol droplet remains challenging due to its inaccessibility to pH electrodes. In this study, nanometer-sized pH probes were dispersed in droplets to report pH via surface-enhanced Raman spectroscopy. The droplet core exhibits higher pH than the bulk solution, suggesting the presence of a stable pH gradient. This in situ technique extends pH characterization to confined water environments and deepens our understanding of aerosol chemistry and the air/water interface. Suspended aqueous aerosol droplets (<50 µm) are microreactors for many important atmospheric reactions. In droplets and other aquatic environments, pH is arguably the key parameter dictating chemical and biological processes. The nature of the droplet air/water interface has the potential to significantly alter droplet pH relative to bulk water. Historically, it has been challenging to measure the pH of individual droplets because of their inaccessibility to conventional pH probes. In this study, we scanned droplets containing 4-mercaptobenzoic acid–functionalized gold nanoparticle pH nanoprobes by 2D and 3D laser confocal Raman microscopy. Using surface-enhanced Raman scattering, we acquired the pH distribution inside approximately 20-µm-diameter phosphate-buffered aerosol droplets and found that the pH in the core of a droplet is higher than that of bulk solution by up to 3.6 pH units. This finding suggests the accumulation of protons at the air/water interface and is consistent with recent thermodynamic model results. The existence of this pH shift was corroborated by the observation that a catalytic reaction that occurs only under basic conditions (i.e., dimerization of 4-aminothiophenol to produce dimercaptoazobenzene) occurs within the high pH core of a droplet, but not in bulk solution. Our nanoparticle probe enables pH quantification through the cross-section of an aerosol droplet, revealing a spatial gradient that has implications for acid-base–catalyzed atmospheric chemistry.

P. Salvo, B. Melai, N. Calisi et al.