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Diet of the crab-eating monkey (Macaca fascicularis) consists of both plants and animals, including chitin-containing organisms such as crabs and insects. This omnivorous monkey has a high expression of acidic chitinase (CHIA) in the stomach and here, we report on its enzymatic properties under different conditions. When we compared with Mus musculus CHIA (Mm-CHIA), Macaca fascicularis CHIA (Mf-CHIA) exhibits higher chitinolytic activity at broad pH (1.0–7.0) and temperature (30–70 ℃) range. Interestingly, at its optimum pH (5.0), Mf-CHIA showed the highest activity at 65 °C while maintaining it at robust levels between 50 and 70 °C. The degradation efficiency of Mf-CHIA was superior to Mm-CHIA toward both polymeric chitin as well as an artificial chromogenic substrate. Our results show that unique features of Mf-CHIA including its thermostability warrant the nomination of this enzyme for potential agricultural and biomedical applications. [ABSTRACT FROM AUTHOR]

Radiotherapy-related caries is a complication of radiotherapy for nasopharyngeal carcinoma; however, factors influencing the occurrence, accurate prediction of onset, and protective factors of radiotherapy-related caries remain unclear. This study analyzed risk factors, disease predictors, and protective factors for radiotherapy-related caries in nasopharyngeal carcinoma. This prospective study included 138 nasopharyngeal carcinoma patients receiving radical radiotherapy at our hospital during June 2012–December 2016 and were followed up for dental caries. Patients' clinical data on radiotherapy were collected, dynamic monitoring was performed to assess changes in oral pH values, and a questionnaire survey was administered to collect patients' lifestyle habits. Time-dependent cox regression trees, event-free Kaplan–Meier curve, Mann–Whitely U test were used to analysis the results. The median follow-up time was 30 (12–60) months. Radiotherapy-related caries occurred in 28 cases (20.3%). Univariate analyses showed that radiotherapy-related caries was associated with patient's age, oral saliva pH value, green tea consumption, and radiation dose to sublingual glands, but not with the radiation dose to the parotid and submandibular glands. Multivariate analysis showed that oral saliva pH value [hazard ratio (HR) = 0.390, 95% confidence interval = 0.204–0.746] was an independent prognostic factor for radiotherapy-related caries. Patients with oral saliva pH values ≤ 5.3 in the 9th month after radiotherapy represented a significantly higher risks for radiotherapy-related caries (p < 0.001). Green tea consumption was associated with the occurrence of radiotherapy-related caries, and oral saliva pH values could predict the occurrence of radiotherapy-related caries. Limiting radiation doses to sublingual glands can reduce the occurrence of radiotherapy-related caries. [ABSTRACT FROM AUTHOR]

Nervous necrosis virus (NNV) is a pathogenic fish-virus belonging to the genus Betanodavirus (Nodaviridae). Surface protrusions on NNV particles play a crucial role in both antigenicity and infectivity. We exposed purified NNV particles to different physicochemical conditions to investigate the effects on antigenicity and infectivity, in order to reveal information regarding the conformational stability and spatial relationships of NNV neutralizing-antibody binding sites and cell receptor binding sites. Treatment with PBS at 37 °C, drastically reduced NNV antigenicity by 66–79% on day one, whereas its infectivity declined gradually from 107.6 to 105.8 TCID50/ml over 10 days. When NNV was treated with carbonate/bicarbonate buffers at different pHs, both antigenicity and infectivity of NNV declined due to higher pH. However, the rate of decline with respect to antigenicity was more moderate than for infectivity. NNV antigenicity declined 75–84% after treatment with 2.0 M urea, however, there was no reduction observed in infectivity. The antibodies used in antigenicity experiments have high NNV-neutralizing titers and recognize conformational epitopes on surface protrusions. The maintenance of NNV infectivity means that receptor binding sites are functionally preserved. Therefore, it seems highly likely that NNV neutralizing-antibody binding sites and receptor binding sites are independently located on surface protrusions. [ABSTRACT FROM AUTHOR]

Abstract The mechanisms of membrane defence by lysylphosphatidylglycerol (LPG), were investigated using synthetic biomimetic mono- and bilayer models of methicillin resistant S. aureus ST239 TW, based on its lipid composition in both pH 7.4 (28% LPG) and pH 5.5 (51% LPG) cultures. These models incorporated a stable synthetic analogue of LPG (3adLPG) to facilitate long-duration biophysical studies, which were previously limited by the lability native LPG. Both increased 3adLPG content and full headgroup ionization at pH 5.5, increased bilayer order and dampened overall charge, via the formation of neutral ion pairs with anionic lipids. Ion pair formation in air/liquid interface lipid monolayers elicited a significant condensing effect, which correlated with the inhibition of subphase-injected magainin 2 F5W partitioning. In fluid phase lipid vesicles, increasing the proportion of 3adLPG from 28 to 51 mol% completely inhibited the adoption of the membrane-active α‑helical conformation of the peptide, without the need for full headgroup ionization. Neutron reflectivity measurements performed on biomimetic PG/3adLPG fluid floating bilayers, showed a significant ordering effect of mild acidity on a bilayer containing 30 mol% 3adLPG, whilst peptide binding/partitioning was only fully inhibited in a bilayer with 55 mol% 3adLPG at pH 5.5. These findings are discussed with respect to the roles of LPG in resistance to human epithelial defences in S. aureus and the continued evolution of this opportunistic pathogen's virulence. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract Escherichia coli β-lactamase TEM-1 is potentially useful in the antibody-directed enzyme/prodrug therapy (ADEPT), converting nontoxic prodrugs to toxic agents. The produced toxin would kill cancer cells, when the enzyme is attached to a tumor-antigen-specific antibody. However, the off-site reaction possibly occurring in the blood or normal tissues raises safety concern. In the present study, we engineered TEM-1 variants preferentially active at pH 5.8–6.2, near the pH of the acidic microenvironment of tumor. A library of randomly mutagenized variants was screened for the ability to confer an antibiotic resistance on E. coli cells in acidic growth media and not in neutral media, to isolate a variant with a Thr-to-Ile substitution at position 160. An extensive mutagenesis study was then conducted in the proximity of this position, to show that a Leu162Glu mutation also causes the acid preference. Kinetic analyses indicated that the overall activity of the wild-type TEM-1 hardly changes over a pH range from 5.8 to 7.0, whereas TEM-1(T160I) is 1.5-times as active at pH 6.2 than pH 7.0, and TEM-1(T160I) is 3.1-fold as active at pH 5.8 than pH 7.0. A further mutagenesis study suggested that a change in the overall structure of the enzyme underlies the pH dependency of the variants. Highlights • Genetic screening is useful for obtaining β-lactamases with altered pH dependency. • A few mutations each suppress the activity of a β-lactamase at pH 7.0. • The engineered β-lactamase variants are more active under the acidic conditions. • The relevant amino acid substitutions are located far from the catalytic site. [ABSTRACT FROM AUTHOR]

Background: Due to concerns about long-term PPI use in patients with acid reflux, we aimed at minimizing PPI use, either by avoiding initiating therapy, downscaling to other therapies, or introducing endoscopic or surgical options.Aims: To examine the role of esophageal ambulatory pHmetry in minimizing PPI use in patients with heartburn and acid regurgitation.Methods: Retrospective cohort analysis of patients with reflux symptoms, who underwent endoscopy, manometry, and ambulatory pHmetry to define the need for PPI. Patients were classified as: (1) never users; (2) partial responders to PPI; (3) users with complete response to PPI. Patients were then managed as: (1) PPI non-users; (2) PPI-initiated, and (3) PPI-continued.Results: Of 286 patients with heartburn and regurgitation, 103 (36%) were found to have normal and 183 (64%) abnormal esophageal acid exposure (AET). In the normal AET group, 44/103 had not been treated and were not initiated on PPI. Of the 59 who had previously received PPI, 52 stopped and 7 continued PPI. Hence, PPI were avoided in 96/103 patients (93%). In the abnormal AET group, 61/183 had not been treated and 38 were initiated on PPI and 23 on other therapies. In the 122 patients previously treated with PPI, 24 were not treated with PPI, but with H2RAs, prokinetics, endoscopic, or surgical therapy. Hence, PPI therapy was avoided in 47/183 patients (26%).Conclusions: In patients with GER symptoms, esophageal pHmetry may avert PPI use in 50%. In the era of caution regarding PPIs, early testing may provide assurance and justification. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: The association between urine pH and abnormal glucose tolerance in men and women is unclear; therefore, we carried out a community‐based, cross‐sectional study to investigate sex‐specific associations between these values, possible indicators of prediabetes and type 2 diabetes. Materials and Methods: We enrolled 4,945 Japanese individuals (2,490 men and 2,455 women), who had undergone annual health checkups. To investigate the relationship between low urine pH and abnormal glucose tolerance, participants were divided into three groups based on their fasting plasma glucose levels (<6.11 mmol/L, 6.11–6.99 mmol/L and ≥6.99 mmol/L), and three groups based on their glycated hemoglobin levels (≤44.3 mmol/mol, 44.3–47.5 mmol/mol and ≥47.5 mmol/mol). To examine the effects of urine pH on abnormal glucose tolerance, participants were categorized into five groups based on their urine pH (5.0, 5.5, 6.0, 6.5 and ≥7.0). Results: Multivariate analysis adjusted for age, body mass index, systolic blood pressure, triglycerides, high‐density lipoprotein cholesterol, uric acid, creatinine and antidiabetic agent use showed significant associations between low urine pH and both high fasting plasma glucose and high glycated hemoglobin levels (P for trend = 0.0260, 0.0075) in men. Furthermore, after the same adjustments, prevalence rates of abnormal glucose tolerance (≥6.11 mmol/L and ≥6.99 mmol/L), increased significantly as urine pH levels decreased (P for trend = 0.0483, 0.0181) in men. In women, a similar trend was observed without a significant difference. Conclusions: Low urine pH is significantly associated with abnormal glucose tolerance; therefore, measuring urine pH might prove useful for identifying patients at high risk for diabetes. [ABSTRACT FROM AUTHOR]

Aims After oral administration, naproxen generates several side-effects related to stomach malfunction. Undoubtedly, the enteric dosage forms with naproxen can be considered as safer. Moreover, since it has been evidenced that development and growth of colorectal cancer is related to the presence of cyclooxygenase, naproxen is investigated in terms of the tumor prevention. The aim of the present work was to formulate and evaluate the properties of novel naproxen-loaded macrobeads, made on the basis of low-acyl gellan gum and its blends with carrageenans, guar gum, cellulose sulfate, and dextran sulfates. Method Seven formulations were prepared by ionotropic gelation. The morphology of the dried beads was evaluated by scanning electron microscopy. The next step focused on Raman spectroscopy and thermal analysis of naproxen, polymers, and the beads. Next, the swelling behavior was examined in three acceptor fluids at pH = 1.2; 4.5, and 7.4. The beads were evaluated regarding naproxen content and encapsulation efficiency. The last stage of the work concerned the drug release studies. Results Addition of any other polysaccharide than gellan resulted in flattening of the beads upon drying. Differential scanning calorimetry confirmed the crystalline form of naproxen. Raman spectra showed that no apparent interactions occurred. In the acidic environment, all the beads revealed the tendency to absorb water. The beads swelled to the greatest extent at pH = 4.5. Naproxen was released from the beads at a varied rate. At pH = 7.4, the most prolonged release was observed for the beads containing carrageenans. Conclusions We have proved that blending of gellan with various polysaccharides can change the pH-dependent properties of the beads loaded with naproxen. We believe that the information enclosed in the paper will be of particular importance regarding the development and characteristics of novel oral dosage forms based on natural polymers. [ABSTRACT FROM AUTHOR]

Conditions leading to unrepaired DNA double‐stranded breaks are potent inducers of genetic instability. Systemic conditions may lead to fluctuation of hydrogen ions in the cellular microenvironment, and we show that small variations in extracellular pH, termed suboptimal pHe, can decrease the efficiency of DNA repair in the absence of intracellular pH variation. Recovery from bleomycin‐induced DNA double‐stranded breaks in fibroblasts proceeded less efficiently at suboptimal pHe values ranging from 7.2 to 6.9, as shown by the persistence of repair foci, reduction of H4K16 acetylation, and chromosomal instability, while senescence or apoptosis remained undetected. By allowing escape from these protective mechanisms, suboptimal pHe may therefore enhance the genotoxicity of double‐stranded breaks, leading to genetic instability. [ABSTRACT FROM AUTHOR]

During transit through the female reproductive tract, sperm encounter metabolites and environmental conditions that modulate various processes leading to fertilization. Intracellular Ca 2+ dynamics regulate the acrosome reaction (AR), which involves exocytosis of the acrosomal granule, a prerequisite for successful fertilization. We explored the ability of progesterone, prostanglandin-E1, and GABA to induce Ca 2+ mobilization and AR in single human spermatozoa capacitated under external pH (pH e ) conditions found in different regions of the female reproductive tract (pH e 6.5, 7.4 and 8.0). The highest percentage of AR induction, regardless of the inducer, occurred when sperm were capacitated at pH e 7.4. Interestingly, at pH e 6.5 a high percentage of cells exhibit Ca 2+ oscillations, which prevent AR. These oscillations involve extracellular and intracellular Ca 2+ channels. Pharmacological inhibition of Ca 2+ oscillations restores the ability of spermatozoa to undergo the AR when exposed to progesterone, even if capacitated at pH e 6.5. [ABSTRACT FROM AUTHOR]

During the growth of Japanese cows, the ruminal pH value is an important physiological parameter, which remarkably affects their nutritional status. To monitor the health condition of the cows and help farmers efficiently manage their livestock, a clear need exists to develop a novel method to efficiently sense the daily range of the rumen pH. Thus, we developed a solid-state pH sensor for real-time monitoring of the rumen pH value of Japanese cows. The indium tin oxide and field-effect transistor-based pH sensor was fabricated and well packaged, and its performance was comprehensively evaluated. The isolation resistance and waterproofing of the packaged sensor were measured, and the functional features fully satisfied the specific requirements. The power consumption of the developed sensor was measured and calculated. The compact pH sensor only incurred a power consumption of 8.2 × 10 mA h, which is a low value for a cell battery-powered system. Stability test of the packaged pH sensor was performed, and the developed sensor could well measure an acid solution with a stable output for a relatively long time. The output characteristic of the pH sensor and its field measurement were also presented in this paper. [ABSTRACT FROM AUTHOR]

Vanadium-substituted polyoxometalate clusters of type HPMoVO and reduced graphene oxide (rGO) were incorporated into a multilayer composite film via combining layer-by-layer self-assembly (using polyethyleneimine) and in-situ UV photoreduction. The growth of the multilayer film was monitored by UV-vis spectroscopy. The UV-induced conversion of graphene oxide to rGO in the multilayer film is due to the photocatalytic activity of PMoV and was proven by X-ray photoelectron spectroscopy. The material was placed on a glassy carbon electrode (GCE) where it displayed good electrocatalytic activity towards oxidation of folic acid (FA) as demonstrated by cyclic voltammetry and differential pulse voltammetry. The modified GCE (best operated at a working voltage of 0.75 V vs Ag/AgCl and a scan rate of 50 mV s) compared to films containing either PMoV or rGO only. The effects of the number of bilayers and of pH values on the electro-oxidation were investigated. The modified GCE was applied to selective determination of FA even in the presence of dopamine (DA) and uric acid (UA) at physiological pH. In fact, the modified GCE may also be applied to the simultaneous determination of DA, UA and FA. The amperometric response to FA increases linearly in the 10 nM to 0.8 mM FA concentration range, with a 0.28 nM detection limit. The sensor was successfully applied to the determination of FA in spiked human serum samples. [ABSTRACT FROM AUTHOR]

The unusual rate and extent of environmental changes due to human activities may exceed the capacity of marine organisms to deal with this phenomenon. The identification of physiological systems that set the tolerance limits and their potential for phenotypic buffering in the most vulnerable ontogenetic stages become increasingly important to make large-scale projections. Here, we demonstrate that the differential sensitivity of non-calcifyingAmbulacraria (echinoderms and hemichordates) larvae towards simulated ocean acidification is dictated by the physiology of their digestive systems. Gastric pH regulation upon experimental ocean acidification was compared in six species of the superphylum Ambulacraria. We observed a strong correlation between sensitivity to ocean acidification and the ability to regulate gut pH. Surprisingly, species with tightly regulated gastric pH were more sensitive to ocean acidification. This study provides evidence that strict maintenance of highly alkaline conditions in the larval gut of Ambulacraria early life stages may dictate their sensitivity to decreases in seawater pH. These findings highlight the importance of identifying and understanding pH regulatory systems in marine larval stages that may contribute to substantial energetic challenges under near-future ocean acidification scenarios. [ABSTRACT FROM AUTHOR]

A supramolecular ligand for the specific detection of Cd 2+ ions, [pyridine-2,6-diylbis (methyleneimino-2,1-phenylene)]bis(phenyl methanone) ( L ) was synthesized, and characterized by various spectral techniques and single crystal X-ray crystallography. The L exhibits “turn-on” fluorescence and excellent selectivity towards Cd 2+ ions in acetonitrile/HEPES buffer medium (1:5 v/v). The lowest quantum yield and shorter emission lifetime of L (Φ = 0.0293, τ = 9.98 ns) was corroborated by the operation of PET process. This PET is quenched during the complex formation between L and Cd 2+ leads to high quantum yield and longer emission lifetime (Φ = 0.1770, τ = 13.46 ns). The L forms 1:1 complex with Cd 2+ is confirmed by Job’s plot and ESI-Mass techniques. The binding of L with Cd 2+ was studied by UV–vis and NMR. The reversible of L.Cd 2+ with EDTA establishes the reuse of L. The lower detection limit of L was found to be 10.21 nM. The impact of fluorescence with respect to pH, time, temperature and solvent concentrations was investigated to find its practical applications. The sensor was applied for the determination of Cd 2+ ions in water samples. DFT studies explain the binding mechanism between the L and Cd 2+ . The cell imaging studies established that L has been used to detect the intracellular Cd 2+ ions in HeLa cells. [ABSTRACT FROM AUTHOR]

Hemipholis cordifera and Microphiopholis gracillima are burrowing brittlestars that differ in burrow architecture and oxygen obtaining strategies: M. gracillima actively ventilates a gallery while H. cordifera has a simple chamber and instead relies on oxygen being transported from arms exposed to the overlying water using hemoglobin in its water vascular system. To determine the possible effects of near future climate change on both species, in terms of metabolism and regeneration, they were exposed to current (25 °C & 28 °C) and elevated (32 °C) temperatures, as well as normal (8.1) and hypercapnia/lowered pH (7.8 & 7.6) in all combinations for six weeks. Oxygen uptake was measured weekly during this period. As expected, M. gracillima had a higher overall oxygen uptake rate than H. cordifera . Both species had highly variable oxygen uptake and were significantly affected by the week was measured. H. cordifera experienced increased oxygen uptake at the higher temperature (32 °C) and as a result of interactive effects of time and pH 7.6. Both species experienced interactive effects of pH and temperature, but there was no clear pattern. Increased temperature positively affected arm regeneration in H. cordifera , increasing both length and percent recovery. There were no effects on disc regeneration observed in M gracillima , however lower pH decreased the dry weight in both intact and regenerating animals. Calcification, measured as percent inorganic content, was not affected in either species by regeneration, temperature or pH. Despite the minor effects on its physiology, M. gracillima experienced lower percent survivorship than H. cordifera . Temperature had the most effect, with survivorship higher at 28 °C, than at 25 °C or 32 °C. These results indicate that both species are operating near or at their physiological limits and may be unable to cope with future drastic changes. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop an artificial stomach-duodenum (ASD) dissolution model as an in vitro evaluation tool that would simulate the gastrointestinal physiology of gastric pH-reduced dogs as a method to assess formulations for a poorly soluble free acid compound with ng/mL solubility. After establishing the ASD model with well-controlled duodenum pH, 5 formulations each applying different solubilization principles were developed and their performance in the ASD model and in vivo in dogs was evaluated. Excellent correlations were obtained between dog area under the curve (AUC) and ASD AUC of 5 formulations evaluated with simulated intestinal fluid (r 2 = 0.987) and fasted-state simulated intestinal fluid (r 2 = 0.989) as the duodenum dissolution medium, indicating that the approach of infusing NaOH into duodenum compartment to maintain duodenum pH of an ASD worked properly in simulating gastric pH–reduced dog. Raman spectroscopy was used to study drug dissolution kinetics associated with different solubilization principles and the results suggested that the solubilization principles performed as designed. Spectroscopic results also identified that the compound formed a gel during dissolution and hypromellose maintained the drug-gelled state to avoid further solid form conversion. The implication of the compound physical gelation to drug dissolution kinetics and in vivo exposure are discussed. [ABSTRACT FROM AUTHOR]

Design of DNA self-assembly with reversible responsiveness to external stimuli is of great interest for diverse applications. We for the first time develop a pH-responsive, fully reversible hybridization chain reaction (HCR) assembly that allows sensitive sensing and imaging of pH in living cells. Our design relies on the triplex forming sequences that form DNA triplex with toehold regions under acidic conditions and then induce a cascade of strand displacement and DNA assembly. The HCR assembly has shown dynamic responses in physiological pH ranges with excellent reversibility and demonstrated the potential for in vitro detection and live-cell imaging of pH. Moreover, this method affords HCR assemblies with highly localized fluorescence responses, offering advantages of improving sensitivity and better selectivity. The proton-fueled, reversible HCR assembly may provide a useful approach for pH-related cell biology study and disease diagnostics. [ABSTRACT FROM AUTHOR]

Improving the catalytic activity of heterogeneous photocatalysts has become a hot topic recently. To this end, considerable progress has been made in the efficient separation of photogenerated charge carriers by e.g. the realization of heterojunction photocatalysts. V–VI–VII compound semiconductors, namely, bismuth oxyhalides, are popular photocatalysts. However, results on antimony oxyhalides [SbxOyXz (X = Br, Cl, I)], the very promising alternatives to the well-known BixOyXz photomodifiers, are scarce. Here, we report the successful decoration of titanium oxide nanostructures with 8–11 nm diameter SbxOyXz nanoparticles for the first time ever. The product size and stoichiometry could be controlled by the pH of the reactant mixture, while subsequent calcination could transform the structure of the titanate nanotube (TiONT) support and the prepared antimony oxychloride particles. In contrast to the ease of composite formation in the SbxOyXz/TiONT case, anatase TiO2 could not facilitate the formation of antimony oxychloride nanoparticles on its surface. The titanate nanotube-based composites showed activity in a generally accepted quasi-standard photocatalytic test reaction (methyl orange dye decolorization). We found that the SbxOyClz/TiONT synthesized at pH = 1 is the most active sample in a broad temperature range. [ABSTRACT FROM AUTHOR]

A novel biomimetic drug delivery system (BDDS) inspired by the pH-dependent ferric ion-transport and release manner of transferrin (Tf) was developed for combating multidrug-resistant breast cancer. Tf-inspired carrier was synthesized by modifying bovine serum albumin (BSA) with histamine (HA) through amide reaction to provide superior specific coordination sites for ferric ion-drug complexes, and self-assembled into nanoparticles (NPs) induced by coordination bond. Tf-inspired NPs were prepared via environment-friendly method, and well redispersed in saline after lyophilization. When internalized into tumor cells by SPARC (secreted protein acidic and rich in cysteine) mediated endocytosis, Tf-inspired NPs bypassed and decreased the P-glycoprotein-mediated drug efflux and led to more effective treatment of multidrug-resistant breast cancer compared with free drugs both in vitro and in vivo due to the enhanced cellular uptake and rapid pH-responsive drug release. Moreover, Tf-inspired NPs exhibited good biocompatibility and low systemic toxicity. Thus, our results demonstrate that Tf-inspired NPs based on coordination bond represent as a smart drug delivery strategy to combat multidrug-resistant cancer and have great potential for clinical applications in cancer therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine salivary pH, buffering capacity and calcium levels in caries-free and caries-active children. We examined 80 children of both genders, 15 years of age. Subjects were divided into four groups as follows: caries-free females, caries-active females, caries-free males, caries-active males; each group consisted of 20 subjects. The unstimulated saliva sample was collected by the spitting method and then pH, buffering capacity and calcium in saliva was measured. The results showed that mean level of buffering capacity of saliva was decreased significantly in the caries-active group as compared to caries-free group. The obtained data showed that the mean levels of pH and calcium were decreased in the caries-active group as compared to the caries-free group, but the difference was not statistically significant. The saliva with its constituents plays an important role in maintaining oral and especially dental health. Salivary pH values were found to be higher in the caries-free group. In our study, there was no significant correlation of pH values and caries activity with gender. Buffer capacity values were significantly lower in the caries-active group than in the caries-free group. There were significant differences when the groups were compared in the caries-active group where buffer capacity values were higher in boys than in girls. Calcium content of saliva was higher in the caries-free group. The results obtained in this study related to the values of the pH, buffering capacity and calcium in saliva, may serve as parameters for determining the caries risk patients, and accordingly to plan and carry appropriate caries preventive measures. [ABSTRACT FROM AUTHOR]

A novel nanobiopolymer film was electrodeposited on the surface of glassy carbon through cyclic voltammetry from dopamine, β -cyclodextrin, and phosphate buffer solution in physiological pH (7.40). The electrochemical behavior of polydopamine-Beta-cyclodextrin modified glassy carbon electrode was investigated for electro-oxidation and determination of some amino acids ( l -Cysteine, l -Tyrosine, l -Glycine, and l -Phenylalanine). The modified electrode was applied for selected amino acid detection at physiological pH using cyclic voltammetry, differential pulse voltammetry and chronoamperometry, chronocoulometery. The linear concentration range of the proposed sensor for the l -Glycine, l -Cysteine, l -Tyrosine, and l -Phenylalanine were 0.2–70, 0.06–0.2, 0.01–0.1, and 0.2–10 μM, while low limit of quantifications were 0.2, 0.06, 0.01, and 0.2 μM, respectively. The modified electrode shows many advantages as an amino acid sensor such as simple preparation method without using any specific electron transfer mediator or specific reagent, good sensitivity, short response time, and long term stability. [ABSTRACT FROM AUTHOR]

Aim To develop and validate pH-cycling model for primary enamel, which was then used to evaluate the anti-caries potential of fluoride toothpastes. Design Human primary enamel slabs were subjected to pH-cycling model for 10 days and maintained for 6 h in demineralizing solution and 18 h in remineralizing solution daily. Twice/day, the slabs were treated. To validate it, the treatments were water or solutions containing 62.5, 125, 250, and 375 μg F/mL. Commercial toothpastes containing no fluoride, 500, 1100, and 1450 μg F/g were evaluated. Demineralization was assessed by percentage of surface hardness loss (% SHL) and cross-sectional hardness (ΔS). Fluoride dose-response effect was analysed by quadratic regression and the effects of toothpastes by Tukey's test. Results Dose-response effect was found between fluoride concentration and % SHL ( R2 = 0.7047; P < 0.01) or ΔS ( R2 = 0.4465; P < 0.01). % SHL and ΔS (mean ± SD) for the group treated with 500 μg F/g toothpaste was 36.6 ± 8.0 and 6298.5 ± 1221.3, respectively, which were significantly higher than those treated with 1100 (25.2 ± 8.7; 4565.7 ± 1122) and 1450 μg F/g (24.2 ± 5.2; 2339.1 ± 879.7) toothpastes. Conclusion The developed pH-cycling model may be used to evaluate and compare the anti-caries potential of toothpaste formulations with low fluoride concentration because it presents dose-response effects on the reduction of primary enamel demineralization. [ABSTRACT FROM AUTHOR]

Psychrotrophic strains of the foodborne pathogen Bacillus cereus can multiply during the refrigerated storage of food products. The aim of this study was to determine the impact of anaerobiosis on the growth of two psychrotrophic B. cereus strains exposed to acidic pH at a cold temperature in a laboratory medium. At 10 °C, growth occurred at pH values equal to or higher than 5.7 during anaerobiosis, whereas aerobic growth was observed from pH 5.4. Growth rates during aerobiosis were similar at pH 5.4 and pH 7. No growth was observed for the two tested strains at 8 °C without oxygen regardless of the pH; however, both strains grew at this temperature from pH 5.4 in the presence of oxygen. These pH growth limits in aerobiosis are consistent with those reported for different strains and different foods or media, but no other studies have described anaerobic growth at acidic pH values. The maximal B. cereus concentration was approximately 6.0 log 10 CFU/ml for cultures in the absence of oxygen and approximately 8.0 log 10 CFU/ml for cultures in the presence of oxygen. In conclusion, we found that the combination of anaerobiosis, pH < 5.7 at 10 °C, or anaerobiosis and temperatures ≤8 °C prevent psychrotrophic B. cereus growth. [ABSTRACT FROM AUTHOR]

The regulation of the luminal pH of each organelle is crucial for its function and must be controlled tightly. Nevertheless, it has been assumed that the nuclear pH is regulated by the cytoplasmic proton transporters via the diffusion of H+ across the nuclear pores because of their large diameter. However, it has been demonstrated that ion gradients exist between cytosol and nucleus, suggesting that the permeability of ions across the nuclear pores is restricted. Vacuolar H+-ATPase (V-H+-ATPase) is responsible for the creation and maintenance of trans-membrane electrochemical gradient. We hypothesize that V-H+-ATPase located in the nuclear membranes functions as the primary mechanism to regulate nuclear pH and generate H+ gradients across the nuclear envelope. We studied the subcellular heterogeneity of H+ concentration in the nucleus and cytosol using ratio imaging microscopy and SNARF-1, a pH indicator, in prostate cells. Our results indicate that there are proton gradients across the nuclear membranes that are generated by V-H+-ATPase located in the outer and inner nuclear membranes. We demonstrated that these gradients are mostly dissipated by inhibiting V-H+-ATPase. Immunoblots and V-H+-ATPase activity corroborated the existence of V-H+-ATPase in the nuclear membranes. This study demonstrates that V-H+-ATPase is functionally expressed in nuclear membranes and is responsible for nuclear H+ gradients that may promote not only the coupled transport of substrates, but also most electrochemically driven events across the nuclear membranes. This study represents a paradigm shift that the nucleus can regulate its own pH microenvironment, providing new insights into nuclear ion homeostasis and signaling. [ABSTRACT FROM AUTHOR]

Purpose: The influence of short-term exposure to an acidic environment on the radiosensitivity of tumor cells has been extensively explored, but the implication of chronic exposure to an acidic environment for the response of tumor cells to radiation has not been fully elucidated. This study aimed to investigate the effects of chronic pre- and post-irradiation exposure of tumor cells to an acidic environment on the radiation-induced clonogenic death. Materials and methods: Rat gliosarcoma cells were used throughout the in vitro study. Cells were exposed to pH 6.6 medium for varying durations of up to 4 days before and after X-irradiation. Cell viability, apoptosis, clonogenic cell death and cell cycle distribution were observed. Results: Incubation of tumor cells in pH 6.6 medium for 2 or 4 days extended cell cycle, decreased cell viability, and induced apoptotic and clonogenic cell death. The radiation-induced clonogenic death was increased by 2- or 4-day pre-irradiation exposure of tumor cells to pH 6.6 medium, whereas it was reduced by 4-day post-irradiation exposure to an acidic medium. Conclusion: Prolonged exposure to an acidic environment enhanced the sensitivity of tumor cells to subsequent X-irradiation. However, the radiosensitization by pre-irradiation exposure was almost completely nullified by prolonged post-irradiation exposure to an acidic environment. [ABSTRACT FROM AUTHOR]

Uric acid may be a risk factor for atherosclerotic cardiovascular disease, although the data conflict and the mechanism by which it may cause cardiovascular disease is uncertain. This study was performed to test the hypothesis that uric acid, an anion at physiologic pH, can cause erythrocyte aggregation, which itself is associated with cardiovascular disease. Normal erythrocytes and erythrocytes with a positive direct antiglobulin test for surface IgG were incubated for 15 minutes in 14.8 mg/dL uric acid. Erythrocytes without added uric acid were used as controls. Erythrocytes were then examined microscopically for aggregation. Aggregates of up to 30 erythrocytes were noted when normal erythrocytes were incubated in uric acid. Larger aggregates were noted when erythrocytes with surface IgG were incubated in uric acid. Aggregation was negligible in controls. These data show that uric acid causes erythrocyte aggregation. The most likely mechanism is decreased erythrocyte zeta potential. Erythrocyte aggregates will increase blood viscosity at low shear rates and increase the risk of atherothrombosis. In this manner, hyperuricemia and decreased zeta potential may be risk factors for atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Cryopreservation techniques are expected to evolve further to preserve biomaterials and foods in a fresh state for extended periods of time. Long-term cryopreservation of living materials such as food and biological tissue is generally achieved by freezing; thus, intracellular freezing occurs. Intracellular freezing injures the cells and leads to cell death. Therefore, a dream cryopreservation technique would preserve the living materials without internal ice crystal formation at a temperature low enough to prevent bacterial activity. This study was performed to investigate the effect of micro electrical current loading during cooling as a new cryopreservation technique. The behavior of intracellular ice crystal formation in plant tissues with or without an electric current load was evaluated using the degree of supercooling, degree of cell deformation, and grain size and growing rate of intracellular ice crystal. Moreover, the transition of intracellular pH during plant tissue cooling with or without electric current loading was also examined using the fluorescence intensity ratio to comprehend cell activity at lower temperatures. The results indicated that micro electric current load did not only decrease the degree of cell deformation and grain size of intracellular ice crystal but also reduced the decline in intracellular pH due to temperature lowering, compared with tissues subjected to the same cooling rate without an electric current load. Thus, the effect of electric current load on cryopreservation and the potential of a new cryopreservation technique using electric current load were discussed based on these results. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of different conditions, including temperature (37 °C, 22 °C, and 4 °C), NaCl concentrations (2.5%, 4%, and 8%), and acidity (pH = 5), on the growth response of persistent and non-persistent isolates of Listeria monocytogenes . The resistance to two common sanitizers (benzalkonium chloride and hydrogen peroxide) was also investigated. A selected group of 41 persistent and non-persistent L . monocytogenes isolates recovered from three cheese processing plants during a previous longitudinal study was assembled. Average lag time was similar for persistent and non-persistent isolates grown at 37 °C, 22 °C and 4 °C but significantly shorter (p < 0.05) for persistent isolates grown at 2.5%, 4% and 8% NaCl, and at pH 5. Average growth rates were significantly higher (p < 0.05) for persistent than for non-persistent isolates when grown at 22 °C, 2.5%, 4% and 8% NaCl, and at pH 5. These results suggest that persistent strains may be better adapted to grow under stressful conditions frequently encountered in food processing environments than non-persistent strains. No relation between persistence and resistance to the tested sanitizers was found. [ABSTRACT FROM AUTHOR]

Amyloidoses are clinical disorders where deposition of β-sheet rich, misfolded protein aggregates called amyloid occurs in vital organs like brain, kidney, liver or heart etc. Aggregation of several proteins such as immunoglobulin light chain, fibrinogen Aα chain (FGA) and lysozyme have been found to be associated with renal amyloidosis. Fibrinogen amyloidosis (AFib) is predominantly familial and is associated with the deposition of mutant FGA amyloid, primarily in kidneys. Over ten substitution and frame-shift mutations in FGA have been identified from AFib patients. Whether wild-type FGA is also involved in AFib is yet unknown. The affected tissues from AFib patients usually show ∼10 kDA peptide from C-terminal 80 amino acid residues of mutant FGA. Notably, this region also encompasses all known disease-related mutations. Whether these point mutations increase the amyloidogenicity of FGA leading to disease progression, have not been studied yet. Here, we have investigated the role of two disease-related mutations in affecting amyloidogenic propensity of an FGA(496-581) fragment. We found that at physiological pH, the wild-type FGA(496-581) fragment remains monomeric, whereas its E540V mutant forms amyloid-like fibrils as observed by AFM. Also, FGA(496-581) harbouring another familial mutation, R554L, converts in vitro into globular, β-sheet rich aggregates, showing amyloid-like properties. These findings suggest that familial mutations in FGA may have role in renal amyloidosis via enhanced amyloid formation. [ABSTRACT FROM AUTHOR]

The SAR of brain penetration for a series of heteroaryl piperazinyl- and piperadinyl-urea fatty acid amide hydrolase (FAAH) inhibitors is described. Brain/plasma (B/P) ratios ranging from >4:1 to as low as 0.02:1 were obtained through relatively simple structural changes to various regions of the heteroaryl urea scaffold. It was not possible to predict the degree of central nervous system (CNS) penetration from the volumes of distribution ( V d ) obtained from pharmacokinetic (PK) experiments as very high V d s did not correlate with high B/P ratios. Similarly, calculated topological polar surface areas (TPSAs) did not consistently correlate with the degree of brain penetration. The lowest B/P ratios were observed for those compounds that were significantly ionized at physiological pH. However, as this class of compounds inhibits the FAAH enzyme through covalent modification, low B/P ratios did not preclude effective central target engagement. [ABSTRACT FROM AUTHOR]

Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr protein kinase family. It is regulated by the calcium-calmodulin dependent signal through a secondary messenger, Ca2+, which leads to the activation of its autoinhibited form. The over-expression and mutation in CAMKIV as well as change in Ca2+ concentration is often associated with numerous neurodegenerative diseases and cancers. We have successfully cloned, expressed, and purified a functionally active kinase domain of human CAMKIV. To observe the effect of different pH conditions on the structural and functional properties of CAMKIV, we have used spectroscopic techniques such as circular diachroism (CD) absorbance and fluorescence. We have observed that within the pH range 5.0-11.5, CAMKIV maintained both its secondary and tertiary structures, along with its function, whereas significant aggregation was observed at acidic pH (2.0-4.5). We have also performed ATPase activity assays under different pH conditions and found a significant correlation between the structure and enzymatic activities of CAMKIV. In-silico validations were further carried out by modeling the 3-dimensional structure of CAMKIV and then subjecting it to molecular dynamics (MD) simulations to understand its conformational behavior in explicit water conditions. A strong correlation between spectroscopic observations and the output of molecular dynamics simulation was observed for CAMKIV. [ABSTRACT FROM AUTHOR]

The symbiosis of chickpea-mesorhizobia is often affected by various constraints abiotic in particular the salinity and phosphate deficiency. Thirty six of native rhizobial strains from southern Morocco were studied. The results showed that most of isolated rhizobia have capacity solubilize inorganic phosphate (TCP) in the PVK and NBRIP medium. By comparing the halo zone of these strains, it was observed that mesorhizobia has strong PS activity and therefore classified as PSB. Only one strain MC0415 have capacity to solubilize inorganic and organic (pNPP), whereas 1.66% of the strains were able to survive under conditions of strong salinity (520mM). This work determined the percentage of mesorhizobia isolated having capacity to survive in conditions of phosphate deficiency, salinity and pH [ABSTRACT FROM AUTHOR]

The aim of this work was to understand the effect of pH and chelators on free iron (Fe2+/Fe3+)-mediated oxidation in liposome dispersions made of marine phospholipids. Consumption of dissolved oxygen was used to follow lipid oxidation. The highest oxygen uptake rates were found at pH 4-5. The increase in pH (>5.7) enhanced autoxidation rate of Fe2+ to Fe3+ and lowered solubility of Fe3+ causing decrease in oxygen uptake rates. Simultaneously, the negative charge on the liposome vesicles increased with increasing pH improving the attraction between iron and liposomes. The retention of Fe3+ ions by phospholipids is suggested to prevent complete precipitation of Fe3+ at pH > 5, which facilitates a pro-oxidative activity of iron even at higher pH. The tested chelators reduced Fe2+ (10 μM) mediated oxidation at pH 5.5 and at 2:1 chelator-to-iron ratio in the following order: EDTA ∼ casein > citric acid > oxalic acid. However, when pH was reduced below the pKa of the EDTA carboxylic groups, EDTA lost its chelating abilities. The stability constants for complexes between the chelators and iron followed the same sequence as efficacy of the chelators at pH 5.5, making it an additional factor determining the efficacy of chelators. This study shows that the final oxidation rate is dependent on the overall dissolved iron in the system and the degree of attraction between iron and the surface of liposome vesicles at a given pH. Practical applications For successful addition of marine polyunsaturated lipids into emulsified food, it is important to understand how physicochemical conditions affect the pro-oxidative activity of iron and the antioxidant activity of metal chelators. This work addresses the role of pH in oxidation of marine liposomes, and the knowledge may help to characterise effective hurdles for lipid oxidation. This study shows that pH has an impact on iron solubility and attraction between iron and the liposome surface and also affects the efficacy of EDTA. This study also shows that by quantification of the dissolved oxygen consumption, it is possible to screen and evaluate the impact of surrounding conditions (pH, chelators) on iron-mediated oxidation in a water-based system. The study shows that oxidation rate is dependent on the overall dissolved iron in the system and the degree of attraction between iron and the surface of liposome vesicles at a given pH. [ABSTRACT FROM AUTHOR]

Caries is caused by acid production in biofilms on dental surfaces. Preventing caries therefore involves control of microorganisms and/or the acid produced. Here, calcium-phosphate-osteopontin particles are presented as a new approach to caries control. The particles are made by co-precipitation and designed to bind to bacteria in biofilms, impede biofilm build-up without killing the microflora, and release phosphate ions to buffer bacterial acid production if the pH decreases below 6. Analysis of biofilm formation and pH in a five-species biofilm model for dental caries showed that treatment with particles or pure osteopontin led to less biofilm formation compared to untreated controls or biofilms treated with osteopontin-free particles. The anti-biofilm effect can thus be ascribed to osteopontin. The particles also led to a slower acidification of the biofilm after exposure to glucose, and the pH always remained above 5.5. Hence, calcium-phosphate-osteopontin particles show potential for applications in caries control. [ABSTRACT FROM PUBLISHER]

Evoking tumor cellular senescence, an irreversible status of cell growth quiescence, has been recently proposed as a potential strategy to improve the efficacy of cancer treatment. In the current study, all-trans retinal, the precursor of all-trans retinoic acid, was conjugated to dextran via hydrazone bond to generate amphiphilic dextran-retinal (DR) conjugates, which self-assembled into pH-sensitive DR micelles. Our results showed that DR micelles moderately inhibited MCF-7 breast cancer cell growth through inducing p21-associated cellular senescence, which relied on retinoic acid receptors (RARs) and was accompanied by significant G0/G1 cell cycle arrest. Moreover, DR micelles were capable of encapsulating doxorubicin (DOX) to generate DOX-loaded DD micelles, facilitating the uptake and release of DOX in cancer cells. Compared with free DOX, DD micelles more effectively suppressed tumor growth and prolonged survival time of mouse xenograft model through inducing tumor apoptosis and cellular senescence. However, blocking cellular senescence diminished DD-caused apoptosis in MCF-7 cells by 40–50%. Therefore, pH-sensitive DR micelles not only served as a potent platform for DOX delivery, but also enhanced the anti-tumor effect of DOX by inducing tumor cellular senescence. These data reveal a great potential of evoking tumor senescence with retinal-conjugated micelles for boosting breast cancer chemotherapy. [ABSTRACT FROM AUTHOR]

To efficiently deliver anti-cancer drug to tumor site and reduce its toxic side effects on normal tissues, a polyethylene glycol (PEG) shielding and tumor microenvironment triggering cascade pH-responsive hollow mesoporous silica nanoparticles (HMSNs) drug delivery system was fabricated. 3-(3, 4-dihydroxyphenyl) propionic acid (DHPA) functionalized beta-cyclodextrin (β-CD) was grafted onto the surfaces of HMSNs via boronic acid-catechol ester bonds. Then, PEG conjugated adamantane (Ada) was anchored on HMSNs-β-CD nanocarrier via host-gust interaction. Various techniques proved the successful fabrication of the system. The in vitro tests confirmed that the system was biocompatible. After the system permeating into tumor via enhanced permeability and retention (EPR) effect, the benzoic-imine bonds between the PEG and Ada were cleaved under weak acid condition in tumor microenvironment (pH 6.8), while the dissociated PEG protective layer facilitating cellular uptake of HMSNs system. Subsequently, the boronic acid-catechol ester bonds linkers further hydrolyzed under even low endosomal pH (4.5–6.5) condition for intracellular drug delivery, leading to efficient cell apoptosis. The in vivo results demonstrated that drug loaded HMSNs significantly inhibited tumor growth while only with minimal toxic side effects. The strategy provides new insight into the development of new generation of drug delivery carriers triggering by tumor microenvironment. [ABSTRACT FROM AUTHOR]

Background: The presence of dilated intercellular spaces in the stratified squamous lining of the esophagus is the pathognomonic feature of reflux esophagitis secondary to gastroesophageal reflux disease (GERD). In addition to stomach acid, bile salts are major constituents of gastroesophageal refluxate. The aim of our study was to determine the effect of bile salts cocktail at different pHs on epithelial junctions in an in vitro transwell model of stratified esophageal squamous epithelium.Discussion: Human telomerase reverse transcriptase (hTERT) immortalized primary esophageal EPC1 cells were grown on polyester transwell surfaces in calcium-enriched media. The cells exhibited gradual stratification into an 11-layered squamous epithelium over 7 days, together with epithelial barrier function as indicated by increased transepithelial electrical resistance (TEER). This stratified epithelium demonstrated well-formed tight junctions, adherens junctions, and desmosomes as visualized by immunofluorescence and electron microscopy. When exposed to short pulses of bile salts at pH 5, but not either condition alone, there was loss of stratification and decrease in TEER, concomitant with disruption of adherens junctions, tight junctions, and desmosomes, leading to the appearance of dilated intercellular spaces. At the cellular level, bile salts at pH 5 activated the Wnt pathway (indicated by increased β-catenin Ser552 phosphorylation).Conclusion: In conclusion, in our in vitro transwell model bile salts at pH 5, but not bile salts or media at pH 5 alone, modulate Wnt signaling, disrupt different junctional complexes, and cause increased permeability of stratified squamous esophageal epithelium. These changes approximate the appearance of dilated intercellular space similar to that found in GERD patients. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) is widely used to treat various cancers. However, its distribution to normal tissues causes serious adverse effects. For this study, we synthesized a complex of styrene-maleic acid copolymer (SMA) and CDDP (SMA–CDDP), which formed polymeric micelles, to achieve tumor-selective drug delivery based on the enhanced permeability and retention (EPR) effect. SMA–CDDP is obtained by regulating the pH of the reaction solution of SMA and CDDP. The mean SMA-CDDP particle size was 102.5 nm in PBS according to electrophoretic light scattering, and the CDDP content was 20.1% (w/w). The release rate of free CDDP derivatives from the SMA–CDDP complex at physiological pH was quite slow (0.75%/day), whereas it was much faster at pH 5.5 (4.4%/day). SMA–CDDP thus had weaker in vitro toxicity at pH 7.4 but higher cytotoxicity at pH 5.5. In vivo pharmacokinetic studies showed a 5-fold higher tumor concentration of SMA–CDDP than of free CDDP. SMA–CDDP had more effective antitumor potential but lower toxicity than did free CDDP in mice after i.v. administration. Administration of parental free CDDP at 4 mg/kg × 3 caused a weight loss of more than 5%; SMA–CDDP at 60 mg/kg (CDDP equivalent) × 3 caused no significant weight change but markedly suppressed S-180 tumor growth. These findings together suggested using micelles of the SMA–CDDP complex as a cancer chemotherapeutic agent because of beneficial properties-tumor-selective accumulation and relatively rapid drug release at the acidic pH of the tumor-which resulted in superior antitumor effects and fewer side effects compared with free CDDP. [ABSTRACT FROM AUTHOR]

The highly permeable integument of amphibians renders them vulnerable to chemical characteristics of their environment, especially during the aquatic larval stage. As the cane toad ( Rhinella marina, Bufonidae) invades southwards along the east coast of Australia, it is encountering waterbodies with highly variable conditions of temperature, pH, and salinity. Understanding the tolerance of toads to these conditions can clarify the likely further spread of the invader, as well as the adaptability of the species to novel environmental challenges. We measured salinity in waterbodies in the field and conducted laboratory trials to investigate the impacts of salinity on toad viability. Eggs and tadpoles from the southern invasion front tolerated the most saline conditions we found in potential spawning ponds during surveys [equivalent to 1200 ppm (3.5 % the salinity of seawater)]. Indeed, high-salinity treatments increased tadpole body sizes, accelerated metamorphosis, and improved locomotor ability of metamorphs (but did not affect metamorph morphology). At very low salinity [40 ppm (0.1 % seawater)], eggs hatched but larvae did not develop past Gosner stage 37. Our study shows that the egg and larval life stages of cane toads can tolerate wide variation in the salinity of natal ponds and that this aspect of waterbody chemistry is likely to facilitate rather than constrain continued southward expansion of the toad invasion front in eastern Australia. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the release profile andin vivohypoglycemic effect of insulin (INS)-loaded pH-sensitive hydrogel (INS-TPM950) administrated by oral route. TPM950 was fabricated via a free polymerization method and its inner morphology was observed with a scanning electron microscope (SEM). INS was encapsulated into TPM950 by an adsorption method, and thein vitrorelease profiles of INS from INS-TPM950 were revealed in pH 1.2 and 6.8. To investigate the hypoglycemic effect of INS-TPM950, Male Wistar rats were used in modeling of diabetes mellitus by multiple intraperitoneal injection of alloxan. Thein vivohypoglycemic effect of oral INS-TPM950 was studied, and the optimal dosage was also determined. SEM photograph showed that abundant 3D meshes were distributed in the inner of TPM950 hydrogel. INS release profile suggested that only 18.2 ± 11.3% INS was released in pH 1.2, but over 88.8 ± 4.9% was delivered into phosphate buffer solution in pH 6.8. After injection to the diabetic rats, the released INS solution from INS-TPM950 exhibited an obvious hypoglycemic effect. Oral administration of 50.0 I.U./kg of INS-TPM950 showed a slow but effective hypoglycemic effect, and the lowest blood glucose level was reached to 47.5 ± 5.5% of the original level. Therefore, this formulation had a potential application in diabetes treatment via oral ingestion. [ABSTRACT FROM PUBLISHER]

During the fermentative production of xylitol the following environmental parameters have a controlling effect on the xylitol yield: concentration of monosaccharides, temperature, aeration and pH. The purpose of the present work was to evaluate xylitol production by four yeast strains at different pH values and oxygen transfer rates (OTRs). The highest xylitol yields were obtained under the following conditions: Candida parapsilosis: pH 5.0, OTR 6.1 mmol L-1 h-1; Candida guilliermondii: pH 4.5, OTR 5.7 mmol L-1 h-1; Candida boidinii: pH 6.0, OTR 5.7 mmol L-1 h-1; Hansenula anomala: pH 4.5, OTR 2.8 mmol L-1 h-1 using 50 g L-1 initial xylose concentration. [ABSTRACT FROM AUTHOR]

Fertilization is a key reproductive event in which sperm and egg fuse to generate a new individual. Proper regulation of certain parameters (such as intracellular pH) is crucial for this process. Carbonic anhydrases (CAs) are among the molecular entities that control intracellular pH dynamics in most cells. Unfortunately, little is known about the function of CAs in mammalian sperm physiology. For this reason, we re-explored the expression of CAI, II, IV and XIII in human and mouse sperm. We also measured the level of CA activity, determined by mass spectrometry, and found that it is similar in non-capacitated and capacitated mouse sperm. Importantly, we found that CAII activity accounts for half of the total CA activity in capacitated mouse sperm. Using the general CA inhibitor ethoxyzolamide, we studied how CAs participate in fundamental sperm physiological processes such as motility and acrosome reaction in both species. We found that capacitated human sperm depend strongly on CA activity to support normal motility, while capacitated mouse sperm do not. Finally, we found that CA inhibition increases the acrosome reaction in capacitated human sperm, but not in capacitated mouse sperm. [ABSTRACT FROM AUTHOR]

The objective is to identify changes in the milk yield and pH and temperature of reticulorumen content after omentopexy. The research was performed in a dairy farm with 550 cows on December 2014--January 2015. The sample consisted of 10 cows. The left-sided displacement of the abomasums was diagnosed in 5 of them, which was treated by lateral omentopexy according to Dirksen; the rest 5 were used for control. Additional treatment was not applied. A special bolus for measuring pH and temperature was administered to the reticulorumen of healthy cows and cows after the operation. The milk yield was registered with the help of herd management program Westfalia DP C21. Rectal temperature of all cows was measured. All data were recorded once a week for four weeks. Statistically reliable difference in the milk yield (p< 0.05) between the research groups was observed during the entire research. The major difference was recorded on Week 1 after the treatment (29.18 kg/d); in Week 4, the difference was 13.97 kg/d. During the entire research, the reticulorumen pH of the Test group was lower than that of the Control group. Statistically reliable difference between the groups was identified on Week 1 (p< 0.05). During the period mentioned, the pH of the reticulorumen content of the Test group was lower by 0.42 than that of the Control group. In Week 3, the difference increased up to 0.84. In Weeks 1, 2, and 3, statistically reliable (p< 0.05) higher temperature was observed in the Test group. Major differences of temperature, 1.81 °C, were recorded in Week 1. In Week 4, the temperature of the reticulorumen in the Test group became equal to that of the Control group. The first four weeks after omentopexy treatment showed the following results: statistically reliable difference in the milk yield remained most obvious in Week 1 after the treatment; cows with left-sided displacement of abomasums were exposed to greater risk of acidosis; they indicated lower pH of reticulorumen content; the first two weeks after omentopexy, reticulorumen content has increased temperature, especially obvious in Week 1. [ABSTRACT FROM AUTHOR]

Nauplii of brine shrimp that hatched within 24 h were collected, homogenized, centrifuged and the supernatant was used as the crude enzyme preparation. In the reaction mixture for the amylase assay, various volumes of the enzyme preparation and the effect of reaction time on the initial velocity of amylase were determined. Also, the effects of pH and temperature on amylase activity and stability were investigated. Several metal ions were added to the amylase reaction to determine if they inhibited or enhanced the brine shrimp amylase activitiy. Results showed that homogenization with 20 times the buffer (w/v) was enough to produce linear relationship of the volume of the enzyme preparation and progress time with the initial activity of amylase. Maximal (and also optimal) temperature and pH were determined to be 40°C and pH 7.5, respectively. Thermal and pH stabilities ranged from 0°C to about 50°C and pH 6.0-7.5, respectively. The Michaelis-Menten constant (Km) for starch of the Artemia nauplii amylase was estimated using Lineweaver-Burk plot to be 0.11 µM maltose mg protein-1 (equivalent to 1.98 mg mL-1 glucose). Conclusion: The initial activity of the brine shrimp amylase could be measured using the enzyme volume and reaction time covered by the linear curves. Artemia amylase activity was optimal at 40°C and pH 7.5; it demonstrated high thermal and wide pH stability. Ca2+, Fe2+, Li+, Mn2+, Mg2+, Na+ and Zn2+ inhibited amylase of the Artemia nauplii, retaining only 20% or less of the maximal activity. By the Km value, the physiological concentration of complex carbohydrates in the newly hatched Artemia nauplii was near the value equivalent to 0.11 µM maltose mg protein-1. [ABSTRACT FROM AUTHOR]

The marine environment is changing and becoming less stable as a result of direct (e.g. lower pH) and indirect (e.g. salinity fluctuations from changing rainfall) effects of climate change. The larval stages may be a bottleneck for reproductive success and recruitment, therefore the potential for environmental stressors to impact upon larval recruitment is high; the ability to tolerate environmental stress in early life history is crucial to an individual's overall fitness. This study investigated the effect of hypercapnia and salinity stress on the early life stages of the Norway Lobster Nephrops norvegicus . Sensitivity to hypercapnia was shown to be highly brood specific with large differences in mortality between broods under hypercapnic stress. Furthermore, this environmental stressor was demonstrated to increase the energetic demand on the larvae, which could potentially have a negative effect later in development. Salinity stress experiments were not designed to test brood specific effects but did demonstrate increased energy usage (higher MR and lower weight) under salinity stress. Although the larvae were tolerant to present levels of salinity stress future changes in this stressor may alter species distribution. This study demonstrated that environmental stressors have the potential to have a large effect on future recruitment. Further, future studies need to consider mechanisms that affect an individual's tolerance from conception, such as epigenetics, maternal provisioning and genetic factors, to determine what makes some individuals tolerant where others are not. [ABSTRACT FROM AUTHOR]

The development of a marine phytoplankton community was studied in a series of mesocosm tanks exposed to different levels of nutrient inputs. Key ecosystem variables such as phytoplankton species development, ecosystem net production (NEP), pH and bacteria production were measured. The overall aim was to mimic the consequences of extreme weather events by applying nutrients in either repeated (pulse treatment) versus a single inputs (full treatment). Regardless of treatment type, pH increased steadily, until nutrients became exhausted. During the experiment, potentially nuisance dinoflagellates developed and became dominant whereas diatoms became rare as compared to the parallel controls. At pH > 9, a shift from the presence of the potential nuisance Alexandrium pseudogonyaulax towards high pH tolerant Prorocentrum species was observed. Diatoms disappeared when A. pseudogonyaulax became dominant. The NEP was significantly higher (ca. 2500 μg C L − 1 d − 1 ) in the nutrient amended tanks than in the control tanks (ca. 500 μg C L − 1 d − 1 ). NEP dropped substantially as nutrients became depleted whereas bacterial communities maintained a high production likely driven by easy access to carbohydrates, turning the ecosystem net heterotrophic. This study suggests that a single nutrient dose drives pH higher than multiple smaller nutrient doses injected albeit the total amount of nutrient injected to the treatments was similar. Such changes affect pH, species composition and rates of pelagic production ultimately uncoupling high bacterial production from primary production, leading to severe oxygen consumption following ephemeral blooms. [ABSTRACT FROM AUTHOR]

In case of diarrhea calves are treated with oral rehydration solutions ( ORS), which are known to increase abomasal pH and inhibit milk clotting in vitro. Nevertheless, recent studies have shown that ORS with HCO3- ≤ 62 mmol/L do not interfere with abomasal milk clotting in healthy calves. However, in diarrheic calves, feeding ORS and milk simultaneously may disturb abomasal curd formation and exacerbate diarrhea due to faster abomasal passage of ingesta. Therefore, the aim of the present study was to ultrasonographically examine abomasal milk clotting and diameter after feeding milk and milk replacer ( MR) with and without ORS to healthy and diarrheic calves. Abomasal curd formation and diameter in healthy and diarrheic calves were ultrasonographically imaged before and after feeding milk, MR and ORS prepared in milk or MR. Feeding mixtures of milk or MR with ORS did not cause any remarkable differences in the ultrasonographic images of abomasal content. Moreover, abomasal milk clotting was not disturbed due to diarrhea. Statistically significant differences of abomasal diameter after feeding between healthy and diarrheic calves indicated that abomasal emptying is delayed in diarrheic calves. Hence, further studies are needed to determine reasons for decelerated abomasal passage in calves suffering from diarrhea. [ABSTRACT FROM AUTHOR]

Oral colon-specific drug delivery is of great interest for ulcerative colitis (UC) therapy. Here, an emulsion-solvent evaporation method was used to fabricate microparticles (MPs) with pH-sensitive Eudragit S100 (ERS100) and poly(lactide-co-glycolide) (PLGA), and the MPs were loaded with curcumin (an efficient anti-inflammatory agent). The resultant spherical MPs had a desirable particle size ranging from 1.52 to 1.91 μm. Their loading efficiency could be regulated by changing the weight ratios of ERS100 and PLGA, with some MPs exhibiting loading efficiencies over 80%. It was observed that the fast release of curcumin from MPs in buffers (pH 1.2 and 6.8) could be significantly decreased by increasing the PLGA content. ERS100/PLGA MPs with a weight ratio of 1:2 (MPs-4) were able to maintain sustained release of curcumin, releasing ∼48% of the initial drug load at pH 7.2–7.4 during a 20 h-incubation. Most importantly, in vivo experiments revealed that orally administered MPs-4 had a superior therapeutic efficiency in alleviating colitis in a UC mouse model, compared to curcumin. Collectively, our one-step-fabricated curcumin-loaded MPs have the properties of pH-sensitivity, controlled drug release and colon targeting, and thus, may hold promise as a readily scalable drug carrier for the efficient clinical treatment of UC. [ABSTRACT FROM AUTHOR]

The pH-triggered intracellular drug delivery platforms have attracted great interest in malignancy therapy. Herein, a pH-responsive polyion complex (PIC) micelle from anionic acid-sensitive methoxy poly(ethylene glycol)- block -poly( N (ϵ)-((1-carboxy-cis-cyclohexene)-2-carbonyl)-L-lysine) (mPEG- b -PCLL) and cationic doxorubicin (DOX), a model anthracycline antitumor drug, was constructed by electrostatic interaction for directional intracellular drug delivery in malignancy chemotherapy. The PIC micelle kept constant diameter at physiological condition ( i.e. , pH 7.4), while gradually swelled and finally disassembled at mimicking intratumoral pH ( i.e. , 6.8) and especially intracellular endo/lysosomal pH ( i.e. , 5.5). The DOX release from the PIC micelle at pH 7.4 was slow, whereas obviously accelerated at the intracellular acidic condition of pH 5.5. These results should be related to the rapid cleavage of the side amide bond of mPEG- b -PCLL in an acidic environment. The PIC micelle exhibited satisfactory tumor suppression toward the H22 hepatoma-bearing BALB/c mouse model compared with free DOX, which was demonstrated by the upregulated tumor inhibition rate, and the increased necrotic and apoptosis areas in tumor tissue. Furthermore, the enhanced security was also observed in the PIC micelle group in relation to that of free DOX. The above results strongly supported that the acid-sensitive PIC micelle was promising for selective intracellular drug delivery along with upregulated malignancy inhibition. [ABSTRACT FROM AUTHOR]

Objectives: This laboratory study aimed to (a) compare the fluoride dose-response of different caries lesions created in human and bovine enamel (HE/BE) under pH-cycling conditions and (b) investigate the suitability of Knoop and Vickers surface microhardness (K-SMH/V-SMH) in comparison to transverse microradiography (TMR) to investigate lesion de- and remineralization. Materials and methods: Caries lesions were formed using three different protocols (Carbopol, hydroxyethylcellulose-HEC, methylcellulose-MeC) and assigned to 24 groups using V-SMH, based on a 2 (enamel types) × 3 (lesion types) × 4 (fluoride concentrations used during pH-cycling-simulating 0/250/1100/2800 ppm F as sodium fluoride dentifrices) factorial design. Changes in mineral content and structural integrity of lesions were determined before and after pH-cycling. Data were analyzed using three-way ANOVA. Results: BE was more prone to demineralization than HE. Both enamel types showed similar responses to fluoride with BE showing more remineralization (as change in integrated mineral loss and lesion depth reduction), although differences between tissues were already present at lesion baseline. Carbopol and MeC lesions responded well to fluoride, whereas HEC lesions were almost inert. K- and V-SMH correlated well with each other and with the integrated mineral loss data, although better correlations were found for HE than for BE and for MeC than for Carbopol lesions. Hardness data for HEC lesions correlated only with surface zone mineral density data. Conclusion: BE is a suitable surrogate for HE under pH-cycling conditions. Clinical relevance: The in vitro modeling of dental caries is complex and requires knowledge of lesion behavior, analytical techniques, and employed hard tissues. [ABSTRACT FROM AUTHOR]