A Microtiter Plate Assay at Acidic pH to Identify Potentiators that Enhance Pyrazinamide Activity Against Mycobacterium tuberculosis.

Pyrazinamide (PZA) is a key component of chemotherapy for the treatment of drug-susceptible tuberculosis (TB) and is likely to continue to be included in new drug combinations. Potentiation of PZA could be used to reduce the emergence of resistance, shorten treatment times, and lead to a reduction in the quantity of PZA consumed by patients, thereby reducing the toxic effects. Acidified medium is required for the activity of PZA against Mycobacterium tuberculosis. In vitro assessments of pyrazinamide activity are often avoided because of the lack of standardization, which has led to a lack of effective in vitro tools for assessing and/or enhancing PZA activity.We have developed and optimized a novel, robust, and reproducible, microtiter plate assay, that centers around acidity levels that are low enough for PZA activity. The assay can be applied to the evaluation of novel compounds for the identification of potentiators that enhance PZA activity. In this assay, potentiation of PZA is demonstrated to be statistically significant with the addition of rifampicin (RIF), which can, therefore, be used as a positive control. Conversely, norfloxacin demonstrates no potentiating activity with PZA and can be used as a negative control. The method, and the associated considerations, described here, can be adapted in the search for potentiators of other antimicrobials.

Physical properties of soft contact lens multipurpose solutions commercially available in Ghana.

Purpose: To investigate the physical properties of commercially available multipurpose soft contact lens solutions in Ghana. Methods: pH (Kelilong ICL-099 pH meter, China), osmolality (OSMOMAT 3000, GONOTEC, Germany), surface tension (Sigma 700 Tensiometer, Sweden), and viscosity (CFOC-200 Viscometer, Cannon Company, USA) of various soft contact lens multipurpose solutions (MPS) were measured in triplicates at room temperature. Viscosity measurements were also taken at 34 °C ocular surface temperature. The solutions examined were Opti-Free Replenish (OFR), Trufresh (TF), Avizor (AV), Freshlook (FL), and Refresh (RF). Results: Several solutions were largely hypo-osmotic in the range of 108-231 mOsm/kg, the exception being Avizor, which had osmolality values that were closer to human tears (301 ± 0.58 mOsm/kg). The range of pH values of the solutions (6.33-8.24, mean (SD) = 7.53 ± 0.18) fell within the reported tolerable range for the ocular surface (6.20-9.00). Surface tension values ranged from 35.86 to 42.27 mNm with a mean of 38.49 ± 2.32 mNm. The average viscosity of most solutions at room temperature (25 °C) was 1.44 ± 0.49 cP with a range of 1.04-2.15 cP. Significantly lower values ranging from 0.79 to 1.58 cP were obtained at ocular surface temperature (34 °C), p = 0.0001). Conclusions: The physical properties of many of the solutions used as MPS in Ghana are markedly variable. Nevertheless, pH, surface tension, and viscosity fall within the acceptable limits of ocular physiological tolerance; except for osmolality, which majority were outside the reported tolerable range for the ocular surface. This information may partly explain the reason some patients exhibit strong preferences for certain care systems and should aid clinical decision-making when prescribing eye care systems to patients.

Advances in pH Sensing: From Traditional Approaches to Next-Generation Sensors in Biological Contexts.

pH has been considered one of the paramount factors in bodily functions because most cellular tasks exclusively rely on precise pH values. In this context, the current techniques for pH sensing provide us with the futuristic insight to further design therapeutic and diagnostic tools. Thus, pH-sensing (electrochemically and optically) is rapidly evolving toward exciting new applications and expanding researchers' interests in many chemical contexts, especially in biomedical applications. The adaptation of cutting-edge technology is subsequently producing the modest form of these biosensors as wearable devices, which are providing us the opportunity to target the real-time collection of vital parameters, including pH for improved healthcare systems. The motif of this review is to provide insight into trending tech-based systems employed in real-time or in-vivo pH-responsive monitoring. Herein, we briefly go through the pH regulation in the human body to help the beginners and scientific community with quick background knowledge, recent advances in the field, and pH detection in real-time biological applications. In the end, we summarize our review by providing an outlook; challenges that need to be addressed, and prospective integration of various pH in vivo platforms with modern electronics that can open new avenues of cutting-edge techniques for disease diagnostics and prevention.

Spectral Characteristics of Water-Soluble Rhodamine Derivatives for Laser-Induced Fluorescence.

We present a comprehensive fluorescence characterization of seven water-soluble rhodamine derivatives for applications in laser-induced fluorescence (LIF) techniques. Absorption and emission spectra for these dyes are presented over the visible spectrum of wavelengths (400 to 700 nm). Their fluorescence properties were also investigated as a function of temperature for LIF thermometry applications. Rhodamine 110 depicted the least fluorescence emission sensitivity to temperature at -0.11%/°C, while rhodamine B depicted the most with a -1.55%/°C. We found that the absorption spectra of these molecules are independent of temperature, supporting the notion that the temperature sensitivity of their emission only comes from changes in quantum yield with temperature. Conversely, these rhodamine fluorophores showed no change in emission intensities with pH variations and are, therefore, not suitable tracers for pH measurements. Similarly, fluorescent lifetime, which is also a property sensitive to local environmental changes in temperature, pH, and ion concentration, measurements were conducted for these fluorophores. It was found that rhodamine B and kiton red 620 have shorter fluorescence timescales compared to those of the other five rhodamine dyes, making them least suitable for applications where temporal changes in emission are monitored. Lastly, we conducted experiments to assess the physicochemical absorption characteristics of these dyes' molecules into polydimethylsiloxane (PDMS), the most common material for microfluidic devices. Rhodamine B showed the highest diffusion into PDMS substrates as compared to the other derivative dyes.

Controlled assembly of superparamagnetic iron oxide nanoparticle into nanoliposome for Pickering emulsion preparation.

There has been a surge in effort in the development of various solid nanoparticles as Pickering emulsion stabilizers in the past decades. Regardless, the exploration of stabilizers that simultaneously stabilize and deliver bioactive has been limited. For this, liposomes with amphiphilic nature have been introduced as Pickering emulsion stabilizers but these nano-sized vesicles lack targeting specificity. Therefore in this study, superparamagnetic iron oxide nanoparticles (SPION) encapsulated within liposomes (MLP) were used as Pickering emulsion stabilizers to prepare pH and magnetic-responsive Pickering emulsions. A stable MLP-stabilized Pickering emulsion formulation was established by varying the MLP pH, concentration, and oil loading during the emulsification process. The primary stabilization mechanism of the emulsion under pH variation was identified to be largely associated with the MLP phosphate group deprotonation. When subjected to sequential pH adjustment to imitate the gastrointestinal digestion pH environment, a recovery in Pickering emulsion integrity was observed as the pH changes from acidic to alkaline. By incorporating SPION, the Pickering emulsion can be guided to the targeted site under the influence of a magnetic field without compromising emulsion stability. Overall, the results demonstrated the potential of MLP-stabilized Pickering emulsion as a dual pH- and magnetic-responsive drug delivery carrier with the ability to co-encapsulate hydrophobic and hydrophilic bioactive.

The application of pH-responsive hyaluronic acid-based essential oils hydrogels with enhanced anti-biofilm and wound healing.

pH could play vital role in the wound healing process due to the bacterial metabolites, which is one essential aspect of desirable wound dressings lies in being pH-responsive. This work has prepared a degradable hyaluronic acid hydrogel dressing with wound pH response-ability. The aldehyde-modified hyaluronic acid (AHA) was obtained, followed by complex mixture formation of eugenol and oregano antibacterial essential oil in the AHA-CMCS hydrogel through the Schiff base reaction with carboxymethyl chitosan (CMCS). This hydrogel composite presents pH-responsiveness, its disintegration mass in acidic environment (pH = 5.5) is 4 times that of neutral (pH = 7.2), in which the eugenol release rate increases from 37.6 % to 82.1 %. In vitro antibacterial and in vivo wound healing investigations verified that hydrogels loaded with essential oils have additional 5 times biofilm removal efficiency, and significantly accelerate wound healing. Given its excellent anti-biofilm and target-release properties, the broad application of this hydrogel in bacteria-associated wound management is anticipated.

Interrupting marine fouling with active buffered coatings.

Biofouling on marine surfaces causes immense material and financial harm for maritime vessels and related marine industries. Previous reports have shown the effectiveness of amphiphilic coating systems based on poly(dimethylsiloxane) (PDMS) against such marine foulers. Recent studies on biofouling mechanisms have also demonstrated acidic microenvironments in biofilms and stronger adhesion at low-pH conditions. This report presents the design and utilization of amphiphilic polymer coatings with buffer functionalities as an active disruptor against four different marine foulers. Specifically, this study explores both neutral and zwitterionic buffer systems for marine coatings, offering insights into coating design. Overall, these buffer systems were found to improve foulant removal, and unexpectedly were the most effective against the diatom Navicula incerta.

Novel theranostic wounds dressing based on pH responsive alginate hydrogel/graphene oxide/levofloxacin modified silk.

Integrating pH sensor with controlled antibiotic release is fabricated on silk to create a theranostic wound dressing. Alginate (ALG) hydrogel and graphene oxide (GO) loaded with levofloxacin (LVX) and a pH indicator are applied to fabricate a pH-responsive theranostic wound dressing. The modified silk color changes from yellow to green in response to elevated skin pH, indicating the skin infection. The semi-quantitative analysis was conducted using ImageJ, revealing significant color changes across the wide range. At elevated pH levels, the ionization of the COOH bonds within ALG induces repulsion among the COO- groups, thereby accelerating the release of the incorporated drug compared to release under lower pH. At an infected pH of 8, ALG hydrogel triggers LVX releasing up to 135.86 ± 0.3 µg, while at a normal pH of 7, theranostic silk releases 123.13 ± 0.26 µg. Incorporating GO onto silk fibers enhances LVX loading and sustains LVX release. Furthermore, these modified silks possess antimicrobial abilities without causing irritation or allergies on the human skin. This theranostic silks represents a major step forward in smart wound care, introducing a versatile platform of smart wound care.

The multistressor effect of pH reduction, microplastic and lanthanum on sea urchin Arbacia lixula.

pH reduction (Low pH), microplastic (MP), and lanthanum (La) are substantial stressors due to their increasing trends in marine ecosystems and having adverse effects on marine species. This study investigates the single and combined effects of those stressors (Low pH: 7.45, polyethylene MP: 26 µg L-1, and La: 9 µg L-1) on the physiology and histology of sea urchin Arbacia lixula. Regarding physiological results, while the coelomocytes' quantity was slightly affected by stressors, their viability was significantly affected. The coelomocyte count and viability were suppressed most in Low pH-MP-La treatment. The stressors did not impact the respiration rate. According to the histological examination results, the crypt (villi-like structure) was shorter, and epithelial layers were thinner in single and dual stress treatments like MP, Low pH, Low pH-La, and MP-La. Overall, we suggest that the combination of variable types of those stressors causes negative effects on sea urchin's physiology and histology.

Fe7S8 coupled with VS4 heterogeneous interface engineering driven by FeV bimetallic MOFs: An efficient all-pH and durable hydrogen evolution.

Rational design and preparation of a multiphase electrocatalyst for hydrogen evolution reaction (HER) has become a hot research topic, while applicable and pH versatility of vanadium tetrasulfide (VS4) and heptairon octasulfide (Fe7S8) composites have rarely been reported. Here, the facile topological sulfide self-template sacrifice method using FeV bimetallic MOFs is designed to obtain Fe7S8 coupled with VS4 heterostructures, enhancing the electron precipitation in the catalysts and attracts electrons to migrate. According to DFT simulations, the electronic coupling at the atomic orbital level and the modulation of interfacial electrons among various interfaces play a crucial role in enhancing the intermediate state process of the hydrogen evolution reaction (HER) across the entire pH range, promoting the optimal d-band centroid value (εd). Reassuringly, the prepared 3D Fe7S8/VS4 electrodes possessed excellent performances of η10 = 53 mV, η10 = 135 mV and η10 = 38 mV in a conventional three-electrode configuration in a 1 M KOH, 1 M Na2SO4, and 0.5 M H2SO4, and the stabilized currents can all be maintained for 48 h. This innovative design of in situ heterostructured materials constructed from dual transition metal sulfides provides inspiring ideas for the preparation of all-pH catalysts.

In Operando Imaging Electrostatic-Driven Disassembly and Reassembly of Collagen Nanostructures.

Collagen is the most abundant protein in tissue scaffolds in live organisms. Collagen can self-assemble in vitro, which has led to a number of biotechnological and biomedical applications. To understand the dominant factors that participate in the formation of collagen nanostructures, here we study in real time and with nanoscale resolution the disassembly and reassembly of collagens. We implement a high-speed force microscope, which provides in situ high spatiotemporal resolution images of collagen nanostructures under changing pH conditions. The disassembly and reassembly are dominated by the electrostatic interactions among amino-acid residues of different molecules. Acidic conditions favor disassembly by neutralizing negatively charged residues. The process sets a net repulsive force between collagen molecules. A neutral pH favors the presence of negative and positively charged residues along the collagen molecules, which promotes their electrostatic attraction. Molecular dynamics simulations reproduce the experimental behavior and validate the electrostatic-based model of the disassembly and reassembly processes.

Response of N, P, and metal ions in deep soil layers to long-term cultivation of rubber and rubber-based agroforestry systems.

The growing demand for natural rubber products has driven the expansion of rubber plantations in recent decades. While much attention has been given to studying the long-term effects of rubber and rubber-based agroforestry systems on surface soil properties, there has been a tendency to overlook changes in soil properties in deeper layers. Our study addresses this gap by examining alterations in nitrogen (N), phosphorus (P), and metal ion levels in deep soil layers resulting from the prolonged cultivation of rubber and rubber-based agroforestry systems. We found notable shifts in soil NH4+ and NO3- concentrations within the 0-30 cm soil layer across different-aged rubber and rubber-based agroforestry systems. Particularly in mature systems, NO3- and available P levels were close to zero below 30 cm soil depth. Introducing Flemingia macrophylla into young rubber plantations increased soil NH4+ and NO3- in the 0-90 cm soil layer and available P in the 0-10 cm soil layer. Over the long term, cultivation of rubber plantations increased the depletion of total P in the 0-50 cm soil layer, available iron (Fe) and manganese (Mn) in the 30-90 cm soil layer, available copper (Cu) and zinc (Zn) in the 0-90 cm soil layer, accompanied by a decrease in soil pH and increase in exchangeable aluminum (Al) in the 0-90 cm soil layer. Notably, soil exchangeable Al levels exceeding 2.0 cmol kg-1 appeared to induce aluminum toxicity. Furthermore, soil pH below 5.2 triggered a sharp release of exchangeable Al within the 0-90 cm soil layer of rubber plantations, with soil available P nearing zero when exchangeable Al levels assed 7.3 cmol kg-1. Our findings underscore the profound impact of long-term rubber plantation cultivation on surface and deep soil properties. Addressing soil degradation in these deep soil layers poses significant challenges for future soil restoration efforts.

Fluctuations in equine cutaneous pH and transepidermal water loss with time of day and ambient conditions.

Cutaneous pH and transepidermal water loss (TEWL) are commonly utilized measures in dermatological research as they provide information concerning barrier function. The importance of dermal health has become more evident in recent years. Accordingly, the aim of this work was to identify natural fluctuations in the biophysical parameters of healthy equine skin. Cutaneous pH and TEWL was collected on nine mares at 6:00 AM, 12:00 PM, and 6:00 PM daily for five days on the nose, withers, girth area, mid-back, and base of tail. Ambient temperature and humidity were measured at each collection. Statistical analysis was completed using SAS On Demand. Tests included repeated measures, ANOVA, and regression analysis. Mean cutaneous pH significantly differed by day (P = 0.0052) and time (P = 0.0073) but was unaffected by anatomical location (P = 0.2841). Interestingly, cutaneous pH had a significant interaction of day and location (P = 0.0004). Mean TEWL measures significantly differed by day (P < 0.0001), time (P < 0.0001), and anatomical location (P = 0.0231). Interaction of day and time had a significant effect on TEWL (P < 0.0001) and resulted in a three-way interaction of day, time, and location (P = 0.0167). There were no significant associations of pH with temperature and humidity. All measures of TEWL across all locations were significantly correlated with temperature and humidity (P < 0.0001). Cutaneous pH and TEWL measures are affected by environmental conditions which should be considered in future models and work using dermal characteristics of horses.

The effect of an acidic environment during the hydrothermal carbonization of sewage sludge on solid and liquid products: The fate of heavy metals, phosphorus and other compounds.

The pH of sewage sludge is a crucial factor during the hydrothermal carbonization process that influences the characteristics of the resulting products and migration of certain compounds from the solid to liquid phase. Accordingly, this work is focused on examining the pH impact during the HTC process, in particular, pH equals 2, 3, 4, 5 and 6 on the individual hydrothermally carbonized products generated at 200 °C and 2 h residence time. For this reason, the chemical and physical indicators describing the post-processing liquid and hydrochar were determined. For instance, it was observed that the phosphorus content detected in the liquid, derived at pH2, rose significantly by 80%. Furthermore, decreasing the pH of sewage sludge had a significant impact on the ash content and the calorific value of the hydrochar. Additionally, changes in the specific surface area of hydrochar were noticed: pH = 5 and pH = 6 showed an increase of 20-30%, while for lower pH values a decrease of c.a. 26% was achieved. The distribution of heavy metals between the obtained fractions in the HTC process (solid and liquid) indicated that 92 to almost 100% of the tested heavy metals were transferred to the hydrochar. A significant effect of pH on the distribution between these fractions was observed only for Zn and Ni. For instance, for pH = 2, Zn and Ni in post-processing liquid were 34% and 29%, respectively. In addition, the sequential extraction of heavy metals from hydrochar was also performed in order to identify mobile and non-mobile phases. It was noticed that the acidic environment favours a higher amount of mobile heavy metals in hydrochar. The largest effect was observed for Cd, Pb, Cr and Cu, for which, at pH = 2, their respective amounts in the mobile fraction were 2.7; 3.6; 1.8; 6.2 times higher, compared to the hydrochar without pH correction.

Solid-liquid partitioning and speciation of Pb(II) and Cd(II) on goethite under high pH conditions, as examined by subnanomolar heavy metal analysis, X-ray absorption spectroscopy, and surface complexation modeling.

The adsorption of heavy metals on iron oxides generally increases with pH and is almost complete at neutral to slightly alkaline pH. However, almost complete adsorption on a linear scale does not imply sufficient removal of the heavy metals in terms of their toxicity. Here, we elucidated the chemical reactions that determine the solid-liquid partitioning of Pb(II) and Cd(II) on goethite at high pH. While the removal of both heavy metals was almost complete on a linear scale above pH 7 for Pb(II) and pH 9 for Cd(II), the dissolved metal concentrations decreased on a logarithmic scale with pH, reaching minima at around pH 10 for Pb(II) and pH 10-11 for Cd(II), and then they increased with pH thereafter. The XAFS spectra of Pb(II)- or Cd(II)-adsorbed goethite prepared at pH > 11 were almost the same as those at neutral pH, suggesting that removal of the heavy metals from solution was achieved by a single adsorption reaction over the entire pH range. Based on the observed macroscopic and microscopic adsorption behaviors at high pH, a robust surface complexation model was developed to predict the solid-liquid partitioning of divalent heavy metals over the entire pH range.

Combined transcriptomic and metabolomic analysis revealed that pH changes affected the expression of carbohydrate and ribosome biogenesis-related genes in Aspergillus niger SICU-33.

The process of carbohydrate metabolism and genetic information transfer is an important part of the study on the effects of the external environment on microbial growth and development. As one of the most significant environmental parameters, pH has an important effect on mycelial growth. In this study, the effects of environmental pH on the growth and nutrient composition of Aspergillus niger (A. niger) filaments were determined. The pH values of the medium were 5, 7, and 9, respectively, and the molecular mechanism was further investigated by transcriptomics and metabolomics methods. The results showed that pH 5 and 9 significantly inhibited filament growth and polysaccharide accumulation of A. niger. Further, the mycelium biomass of A. niger and the crude polysaccharide content was higher when the medium's pH was 7. The DEGs related to ribosome biogenesis were the most abundant, and the downregulated expression of genes encoding XRN1, RRM, and RIO1 affected protein translation, modification, and carbohydrate metabolism in fungi. The dynamic changes of pargyline and choline were in response to the oxidative metabolism of A. niger SICU-33. The ribophorin_I enzymes and DL-lactate may be important substances related to pH changes during carbohydrate metabolism of A.niger SICU-33. The results of this study provide useful transcriptomic and metabolomic information for further analyzing the bioinformatic characteristics of A. niger and improving the application in ecological agricultural fermentation.

pH-Responsive, Wide Color Gamut Dynamic Color Display Enabled by PDMAEMA Brush-Based Fabry-Perot Resonant Cavity.

Dynamic color-changing materials have attracted broad interest due to their widespread applications in visual sensing, dynamic color display, anticounterfeiting, and image encryption/decryption. In this work, we demonstrate a novel pH-responsive dynamic color-changing material based on a metal-insulator-metal (MIM) Fabry-Perot (FP) cavity with a pH-responsive poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brush layer as the responsive insulating layer. The pH-responsive PDMAEMA brush undergoes protonation at a low pH value (pH < 6), which induces different swelling degrees in response to pH and thus refractive index and thickness change of the insulator layer of the MIM FP cavity. This leads to significant optical property changes in transmission and a distinguishable color change spanning the whole visible region by adjusting the pH value of the external environment. Due to the reversible conformational change of the PDMAEMA and the formation of covalent bonds between the PDMAEMA molecular chain and the Ag substrate, the MIM FP cavity exhibits stable performance and good reproducibility. This pH-responsive MIM FP cavity establishes a new way to modulate transmission color in the full visible region and exhibits a broad prospect of applications in dynamic color display, real-time environment monitoring, and information encryption and decryption.

Rapid intracellular pH measurement based on electroporation- surface-enhanced Raman scattering.

In this study, electroporation-surface-enhanced Raman scattering (SERS) was applied to rapidly measure intracellular pH. The generation of a sensitive SERS probe for measuring pH in the range of 6.0-8.0 was accomplished through the conjugation of the pH-sensitive molecule 4-mercaptobenzoic acid (4-MBA) to the surface of gold nanoparticles (Au NPs) through its thiol functional group. This bioprobe was then rapidly introduced into nasopharyngeal carcinoma CNE-1 cells by electroporation, followed by SERS scanning and the fitting of intensity ratios of each detection point's Raman peaks at 1423 cm-1 and 1072 cm-1, to create the pH distribution map of CNE-1 cells. The electroporation-SERS assay introduces pH bioprobes into a living cell in a very short time and disperses the nanoprobe throughout the cytoplasm, ultimately enabling rapid and comprehensive pH analysis of the entire cell. Our work demonstrates the potential of electroporation-SERS for the biochemical analysis of live cells.

pH-responsive chitosan copolymer synthesized via click chemistry for design of polymeric nanoparticles for targeted drug delivery.

The polymeric nanoparticles (PNPs) loaded with prednisolone were developed to exhibit pH-responsive properties owing to the attachment of a hydrazone linkage between the copolymer chitosan and mPEG. In the diseased cellular environment, the hydrazone bond tends to break due to reduced pH, leading to the release of the drug from the PNPs at the required site of action. The fabricated PNPs exhibit spherical morphology, optimum size (∼200 nm), negative surface charge, and monodispersed particle size distribution. The encapsulation efficiency of the PNPs was determined to be 71.1 ± 0.79 % and two experiments (polymer weight loss and drug release) confirmed the pH-responsive properties of the PNPs. The cellular study cytotoxicity assay showed biocompatibility of PNPs and drug molecule-mediated toxicity to A549 cells. The ligand atrial natriuretic peptide-attached PNPs internalized into A549 cells via natriuretic peptide receptor-A to achieve target specificity. The PNPs cytotoxicity and pH-response medicated inflammation reduction functionality was studied in inflammation-induced RAW264.7 cell lines. The study observed the PNPs effectively reduced the inflammatory mediators NO and ROS levels in RAW264.7. The results showed that pH-responsive properties of PNPs and this novel fabricated delivery system effectively treat inflammatory and cancer diseases.