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Abstract\nNovelty statementCoal mine drainage (CMD) is an environmental threat due to its high volume, low pH, presence of toxic metals, and absence of biodegradable organics. The present study aims to treat CMD in a horizontal sub-surface flow constructed wetland (CW) using dairy wastewater as an organic source. CW was planted with Typha angustifolia. Characteristics of synthetic CMD were (except pH, all unit mg/L) pH 1.9; Fe: 100, SO42−: 1,000, Mn: 6, Zn: 5, Co: 1, Ni: 1, and Cr: 1. CMD was mixed with synthetic dairy wastewater (pH: 5.05, COD: 2,700 mg/L, BOD: 1,600 mg/L) in the ratio of 3:1. Alkalinity of 120–190 mg/L CaCO3 was generated and effluent pH improved from 2.2 to 6.6. Metals precipitated as metal sulfide or hydroxide. Sulfate removal was hindered due to the synergistic toxicity of several metals. Except for Mn, all other effluent parameters were within the discharge limit for disposal in inland surface water.There is limited information available on the advantages of using organic rich wastewater as a substrate for treatment of low carbon coal mine drainage (CMD). Coal mine drainage was mixed with dairy wastewater and treated in horizontal flow constructed wetland. Organic removal, metal removal, sulfate removal, and pH improvement of mixed wastewater are investigated in the present study. [ABSTRACT FROM AUTHOR]

The effects of four initial culture pH values (3, 4, 5, and 6) and nitrogen limitation on growth, TAG accumulation, lipid production, fatty acid profile, and estimated biodiesel quality of Starmerella magnoliae X3 were investigated. TAG and lipid levels were measured by Nile Red fluorescence and sulfo-phospho-vanilin (SPV) techniques, respectively. The results showed that a combination of nitrogen limitation and acidic pH significantly (p < 0.05) increased TAG accumulation, total lipid contents, and lipid productivity in Starmerella magnoliae X3 compared to the control group. Under nitrogen limitation, the highest TAG accumulation was achieved at initial pHs of 3 and 5 after 72 h of cultivation, and the highest lipid productivity (0.306 g L−1 d−1) was observed after 48 h at pH 3; the major fatty acids at the four pH values were oleic acid (63.6%–64%), palmitoleic acid (11.3%–12.5%), stearic acid (9.7%–11.4%), and palmitic acid (9.4%–10%). In addition, both stresses were associated with lower iodine value and higher cetane number of the biodiesel compared to the control. These findings suggest that cultivation in a low-nitrogen medium at an initial pH of 3 or 5 holds promise in increasing TAG production in Starmerella magnoliae X3. [ABSTRACT FROM AUTHOR]

The release of cadmium into the environment is a significant global concern due to its toxicity, non-biodegradability, and persistence in nature. There is an urgent need for effective, eco-friendly, and cost-effective systems for removing Cd because of the many drawbacks of conventional physicochemical techniques. This study investigated the ability of the extremophile red microalgal strain Galdieria sulphuraria CCMEE 5587.1 to tolerate and remove Cd (II) ions at acidic pH in a controlled laboratory environment. Three distinct concentrations of Cd (1.5 mg L−1, 3 mg L−1, and 6 mg L−1) were introduced to the cyanidium medium, and G. sulphuraria cells were introduced in the medium and grown for ten days. Four distinct aspects were identified regarding Cd removal: time course Cd removal, total Cd removal, extracellular Cd removal, and intracellular Cd removal. The inhibitory effects of Cd on G. sulphuraria growth were observed using a daily growth profile. Initial incubation days showed an inhibition of G. sulphuraria growth. In addition, increasing the Cd concentration in the medium decreased the growth rate of G. sulphuraria. Rapid Cd removal occurred on the first day of the experiment, followed by a steady removal of Cd until the last day. The highest total removal efficiency occurred in a medium containing 3 mg L−1 of Cd ions, which was 30%. In contrast, the highest sorption capacity occurred in a medium containing 6 mg L−1 of Cd ions, which was 1.59 mg g−1 of dry biomass. In all media compositions, a major fraction (>80%) of Cd removal occurred via adsorption on the cell surface (extracellular). These results showed that G. sulphuraria cells can remove Cd ions from aqueous solution, which makes them a potential bioremediation option for heavy metal removal. [ABSTRACT FROM AUTHOR]

Introduction: The integrity of the stratum corneum (SC) is crucial for the skin's barrier function, protecting against environmental stressors and minimizing transepidermal water loss. Advances in skincare formulations have introduced multilamellar systems designed to emulate the SC's lipid composition and organization. This study hypothesizes that the application of a multilamellar cream will significantly impact the SC's lipid content and lamellar structure, thereby enhancing the epidermal barrier. Methods: A saturated phosphatidylcholine‐based multilamellar cream was applied to a cohort of adult subjects with very dry skin. Electron microscopy was utilized to analyse the micro‐morphology of the cream and its integration into the lipid‐depleted SC. Lipid analysis was conducted to quantify changes in the intercellular lipid matrix. Results: Transmission‐electron microscopy (TEM) imaging demonstrated that the multilamellar cream possesses a structured arrangement comparable to the natural SC architecture. Short‐term application revealed a time‐dependent restoration of lipid bilayers, while a 14‐day regimen showed a marked increase in lipid lamellae density and length within the SC. Lipid analysis indicated a significant increase in total lipid content, with notable enhancements in ceramide and free fatty acid levels, without altering cholesterol levels. Lipid ratio analysis further confirmed the rebalancing of the SC's lipid composition. Discussion: The multilamellar cream selectively increased specific lipids critical for barrier function, suggesting an action mechanism that aligns with the skin's natural regulatory processes. This selective augmentation indicates the potential of the formulation to not only restore but also enhance the epidermal barrier, with the maintenance of physiological lipid ratios suggesting compatibility with intrinsic repair mechanisms. Conclusion: The study confirms that a multilamellar cream can significantly improve the SC's lipid composition and structural integrity, indicating enhanced barrier function. They are pivotal for skincare professionals, dermatologists, and product developers, enriching the understanding of multilamellar creams' benefits and applications in improving epidermal barrier function. [ABSTRACT FROM AUTHOR]

Introduction: Stratum corneum (SC) is essential for skin barrier function, mitigating water loss and shielding against potentially harmful substances and allergens. The SC's lipid matrix, arranged in a lamellar structure, is integral to its protective role. Our study explores the restoration effects of a multilamellar cream with an acidic pH compared to a basic placebo cream on skin physiology and its interaction with the skin microbiome after stress induction via tape stripping (TS). Materials and Methods: In this double‐blind study, 14 healthy participants aged 21–58 years were assessed pre‐ and post‐tape stripping, followed by a 14 days application of a multilamellar test cream and a placebo cream with evaluations on days 7, 14 and 17 for sustained effects. Skin physiology was analysed in terms of epidermal barrier function, SC hydration and surface pH. The microbiome was analysed by 16S rRNA amplicon sequencing the 16S rRNA gene using Illumina MiSeq, with subsequent species identification. Results: Our study showed significant improvements in skin barrier repair and SC hydration with verum, particularly after 14 days of application, while both creams initially enhanced stratum corneum hydration. No significant changes in surface‐pH were detected. The skin microbiome analysis revealed that TS slightly decreased alpha diversity, a trend that verum significantly reversed, enhancing diversity beyond baseline levels after 14 days. Overall, while both creams contributed to a broader microbial phyla diversity over time, no significant changes in the abundance of specific genera or species were noted between treatments. Discussion and Conclusion: Our study delineates the efficacy of a pH‐optimized multilamellar cream in enhancing epidermal barrier recovery and SC hydration post‐sequential TS, in contrast to an unstructured basic placebo. Verum cream significantly improved skin barrier function and SC hydration at day 14, with sustained effects evident beyond the treatment period. Furthermore, the multilamellar formulation facilitated the restitution of cutaneous microbiome diversity, a key indicator of healthy skin ecology, underscoring the symbiotic relationship between barrier integrity and microbial composition. These findings underscore the importance of multilamellar emollient structures in dermatological therapeutics, with potential implications for the design of advanced skincare interventions that holistically support cutaneous resilience and homeostasis. [ABSTRACT FROM AUTHOR]

The number of antibiotic-resistant microbial infections is dramatically increasing, while the discovery of new antibiotics is significantly declining. Furthermore, the activity of antibiotics is negatively influenced by the ability of bacteria to form sessile communities, called biofilms, and by the microenvironment of the infection, characterized by an acidic pH, especially in the lungs of patients suffering from cystic fibrosis (CF). Antimicrobial peptides represent interesting alternatives to conventional antibiotics, and with expanding properties. Here, we explored the effects of an acidic pH on the antimicrobial and antibiofilm activities of the AMP Esc(1-21) and we found that it slightly lost activity (from 2- to 4-fold) against the planktonic form of a panel of Gram-negative bacteria, with respect to a ≥ 32-fold of traditional antibiotics. Furthermore, it retained its activity against the sessile form of these bacteria grown in media with a neutral pH, and showed similar or higher effectiveness against the biofilm form of bacteria grown in acidic media, simulating a CF-like acidic microenvironment, compared to physiological conditions. [ABSTRACT FROM AUTHOR]

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In order to improve the emulsifying properties of soy protein around isoelectric point, soy protein isolate (SPI) and γ‐polyglutamic acid (γ‐PGA) complexes were prepared by electrostatic interaction. The formation of SPI–γ‐PGA electrostatic complex and emulsifying properties were investigated by monitoring turbidity, zeta potential, intrinsic fluorophores, emulsion characterization, and microstructure observation. The results showed that the formation of SPI–γ‐PGA electrostatic complex was identified through turbidimetric analysis and zeta‐potential measurement. Intrinsic fluorescence spectrum indicated internal structure changes of electrostatic complexes. Furthermore, SPI–γ‐PGA complex–stabilized emulsions showed better stability with small droplet sizes and slow growth as well as the uniform microstructure around the isoelectric point (pH 4.0–5.0) than SPI‐formed emulsions. Under the different thermal treatments and ionic strengths, emulsions stabilized by SPI–γ‐PGA‐soluble complex resulted in improved emulsion stability to environmental stresses. This may be attributed to the increased steric repulsion and electrostatic repulsion by SPI–γ‐PGA complexes at oil–water interfaces. The findings derived from this research would provide theoretical reference about SPI–γ‐PGA electrostatic complex that can be applied in acid beverages and developed a novel plant‐based sustainable stabilizer for emulsions. Practical Application: The electrostatic interaction between SPI and γ‐PGA improved the emulsifying characteristics of soy protein around isoelectric point. The results derived from this research would expand applications of SPI–γ‐PGA‐soluble electrostatic complex that can be applied in acid beverages, as well as a novel plant‐based sustainable stabilizer for emulsions. [ABSTRACT FROM AUTHOR]

The release of cadmium into the environment is a significant global concern due to its toxicity, non-biodegradability, and persistence in nature. There is an urgent need for effective, eco-friendly, and cost-effective systems for removing Cd because of the many drawbacks of conventional physicochemical techniques. This study investigated the ability of the extremophile red microalgal strain Galdieria sulphuraria CCMEE 5587.1 to tolerate and remove Cd (II) ions at acidic pH in a controlled laboratory environment. Three distinct concentrations of Cd (1.5 mg L−1, 3 mg L−1, and 6 mg L−1) were introduced to the cyanidium medium, and G. sulphuraria cells were introduced in the medium and grown for ten days. Four distinct aspects were identified regarding Cd removal: time course Cd removal, total Cd removal, extracellular Cd removal, and intracellular Cd removal. The inhibitory effects of Cd on G. sulphuraria growth were observed using a daily growth profile. Initial incubation days showed an inhibition of G. sulphuraria growth. In addition, increasing the Cd concentration in the medium decreased the growth rate of G. sulphuraria. Rapid Cd removal occurred on the first day of the experiment, followed by a steady removal of Cd until the last day. The highest total removal efficiency occurred in a medium containing 3 mg L−1 of Cd ions, which was 30%. In contrast, the highest sorption capacity occurred in a medium containing 6 mg L−1 of Cd ions, which was 1.59 mg g−1 of dry biomass. In all media compositions, a major fraction (>80%) of Cd removal occurred via adsorption on the cell surface (extracellular). These results showed that G. sulphuraria cells can remove Cd ions from aqueous solution, which makes them a potential bioremediation option for heavy metal removal.

The number of antibiotic-resistant microbial infections is dramatically increasing, while the discovery of new antibiotics is significantly declining. Furthermore, the activity of antibiotics is negatively influenced by the ability of bacteria to form sessile communities, called biofilms, and by the microenvironment of the infection, characterized by an acidic pH, especially in the lungs of patients suffering from cystic fibrosis (CF). Antimicrobial peptides represent interesting alternatives to conventional antibiotics, and with expanding properties. Here, we explored the effects of an acidic pH on the antimicrobial and antibiofilm activities of the AMP Esc(1-21) and we found that it slightly lost activity (from 2- to 4-fold) against the planktonic form of a panel of Gram-negative bacteria, with respect to a ≥ 32-fold of traditional antibiotics. Furthermore, it retained its activity against the sessile form of these bacteria grown in media with a neutral pH, and showed similar or higher effectiveness against the biofilm form of bacteria grown in acidic media, simulating a CF-like acidic microenvironment, compared to physiological conditions.

ABSTRACT Functional genomics analysis of Mycobacterium abscessus clinical isolates from chronically infected patients to identify genes under strong evolutionary pressure during lung adaptation identified phoR as one of the most frequently mutated. phoR encodes the histidine kinase (HK) of the two-component regulatory system (TCS) PhoPR. While PhoPR has been extensively studied in Mycobacterium tuberculosis for its role in virulence, little is known about the function of this TCS and the signals governing its activation in M. abscessus. We here show that acidic pH leads to the upregulation of phoP in M. abscessus and that clinically relevant non-synonymous mutations identified in PhoR exacerbate this response. PhoR modulates the ability of its cognate response regulator, PhoP, to autoregulate itself by controlling its dephosphorylation. At low pH, the phosphatase activity of PhoR is reduced and the build-up of phospho-PhoP that ensues results in the upregulation of phoP that accompanies the induction of a defined set of genes, many of which are thought to play a role in virulence and host adaptation. In line with the idea that M. abscessus isolates expressing clinically relevant PhoR variants may be better prepared for survival within the host, we find these strains to be less efficiently internalized by macrophages and to display enhanced intracellular survival. IMPORTANCE Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the Mycobacterium abscessus group have been steadily increasing in the USA and globally. Owing to the relatively recent recognition of M. abscessus as a human pathogen, basic and translational research to address critical gaps in diagnosis, treatment, and prevention of diseases caused by this microorganism has been lagging behind that of the better-known mycobacterial pathogen, Mycobacterium tuberculosis. To begin unraveling the molecular mechanisms of pathogenicity of M. abscessus, we here focus on the study of a two-component regulator known as PhoPR which we found to be under strong evolutionary pressure during human lung infection. We show that PhoPR is activated at acidic pH and serves to regulate a defined set of genes involved in host adaptation. Accordingly, clinical isolates from chronically infected human lungs tend to hyperactivate this regulator enabling M. abscessus to escape macrophage killing.

ABSTRACT Burkholderia cenocepacia is an opportunistic pathogen correlated with increased disease severity and mortality in cystic fibrosis (CF) patients. One major difficulty when treating these infections in CF is the poor relationship between in vitro susceptibility and clinical outcome. Previous analysis of CF sputum samples showed elevated levels of zinc and iron ions and an acidic pH (2.9–6.5) compared to healthy individuals. Additionally, B. cenocepacia grows at an acidic pH (~3.5) in vitro and persists for 24 h in the intracellular acid compartments of amoebas and macrophages. We seek to understand the impact of acidic pH and increased zinc and iron concentrations on antibiotic susceptibility in the CF nutritional environment. The Synthetic Cystic Fibrosis sputum Media (SCFM) was modified to represent the acidic pH and increased zinc and iron concentrations found in CF sputum (SCFM-FeZn). We found that the nutritional environment modulated B. cenocepacia susceptibility to antimicrobials, and more strikingly, acidic pH decreased susceptibility to most antimicrobials used clinically to treat these infections. Finally, we assessed susceptibility against a custom compound library of antimicrobials using SCFM-FeZn agar plates. Out of 591 antibiotics, only 18 were active against B. cenocepacia at both neutral and acidic pH. Four of these compounds (novobiocin, coumermycin, mitomycin C, and streptonigrin) were selected for susceptibility assays in liquid culture. Here, we show that acidic pH modulates antimicrobial susceptibility in the CF nutritional environment and that susceptibility testing in media that mimic the host nutritional environment could pave the way to finding new therapies against infections in CF. IMPORTANCE Burkholderia cenocepacia causes severe infections in cystic fibrosis (CF) patients. CF patients are prone to reoccurring infections due to the accumulation of mucus in their lungs, where bacteria can adhere and grow. Some of the antibiotics that inhibit B. cenocepacia in the laboratory are not effective for CF patients. A major contributor to poor clinical outcomes is that antibiotic testing in laboratories occurs under conditions that are different from those of sputum. CF sputum may be acidic and have increased concentrations of iron and zinc. Here, we used a medium that mimics CF sputum and found that acidic pH decreased the activity of many of the antibiotics used against B. cenocepacia. In addition, we assessed susceptibility to more than 500 antibiotics and found four active compounds against B. cenocepacia. Our findings give a better understanding of the lack of a relationship between susceptibility testing and the clinical outcome when treating B. cenocepacia infections.

Monitoring the microenvironment within specific cellular regions is crucial for a comprehensive understanding of life events. Fluorescent probes working in different ranges of pH regions have been developed for the local imaging of different pH environments. Especially, rhodamine-based fluorescent pH probes have been of great interest due to their ON/OFF fluorescence depending on the spirolactam ring's opening/closure. By introducing the N-alkyl-hydroxamic acid instead of the alkyl amines in the spirolactam of rhodamine, we were able to tune the pH range where the ring opening and closing of the spirolactam occurs. This six-membered cyclic hydroxamate spirolactam ring of rhodamine B proved to be highly fluorescent in acidic pH environments. In addition, we could monitor pH changes of lysosomes in live cells and zebrafish. [ABSTRACT FROM AUTHOR]

The strain of red microalgae Galdieria sulphuraria CCMEE 5587.1 was evaluated in a controlled laboratory environment for its ability to tolerate and remove two heavy metal (HM) ions: cadmium [Cd(II)] and lead [Pb(II)] in aqueous solutions as a single metal species. Various concentrations (0 mg L−1 to 5 mg L−1) of Cd and Pb ions were added to the Cyanidium medium in which the chosen microalgae strain G. sulphuraria CCMEE 5587.1 was grown at an acidic pH of 2.5. The effectiveness of G. sulphuraria CCMEE 5587.1 in tolerating and removing these two metal ions was measured by analyzing its growth profile, growth rate, nutrient removal, and metal ion removal efficiency. The growth of G. sulphuraria CCMEE 5587.1 was inhibited during the initial days of incubation, and the growth rate decreased when the HM concentration in the media was increased. Nutrient removal in the HM-containing media is comparable to that in the control media at low metal concentrations but decreases as the metal concentration rises. G. sulphuraria CCMEE 5587.1 has the highest removal efficiency for Cd and Pb in a medium containing 2.5 mg L−1 of metal ions, which is 49.80% and 25.10%, and the corresponding sorption capacity is 1.45 mg g−1 and 0.53 mg g−1 of dry biomass, respectively. These findings suggest that G. sulphuraria CCMEE 5587.1 holds potential as a viable bioremediation solution for extracting Cd and Pb from wastewater, alongside its capacity to remove nutrients concurrently. The study underscores the dual advantage of G. sulphuraria CCMEE 5587.1, making it a promising candidate for addressing heavy metal pollution in wastewater treatment processes. [ABSTRACT FROM AUTHOR]

Iron (Fe) toxicity in plant species depends on the availability of Fe in the soil, uptake ability by the root system, and translocation rate to other parts of the plant. The aim of this study was to assess Fe uptake by root tissues of Catharanthus roseus, translocation rate to leaf tissues, and the impairment of plant physio-morphological characteristics. Fe uptake by the roots (~ 700 µg g−1 DW) of C. roseus was observed during the early exposure period (1 week), and translocation factor from root to shoot was fluctuated as an independent strategy. A high level of Fe content in the root tissues significantly inhibited root length and root dry weight. Under acidic pH condition, an enrichment of Fe in the shoots (~ 400 µg g−1 DW) led to increase in leaf temperature (> 2.5 °C compared to control) and crop stress index (> 0.6), resulting in stomatal closure, subsequently decreasing CO2 assimilation rate and H2O transpiration rate. An increment of CSI in Fe-stressed plants was negatively related to stomatal conductance, indicating stomatal closure with an increase in Fe in the leaf tissues. High Fe levels in the leaf tissues directly induced toxic symptoms including leaf bronzing, leaf spotting, leaf necrosis, leaf chlorosis, and leaf senescence in C. roseus plants. In summary, C. roseus was identified as a good candidate plant for Fe phytoextraction, depending on Fe bioaccumulation, therefore 50 mM Fe treatment was designated as an excess Fe to cause the growth inhibition, especially in the prolonged Fe incubation periods. [ABSTRACT FROM AUTHOR]

ABSTRACT This work aimed to examine the germination and initial growth of Zeyheria tuberculosa (Vell.) Bureau ex Verl. seedlings at different pH values. pH of the deionized water was adjusted with hydrochloric acid and/or sodium hydroxide to 4.7, 5.7, 6.7, 7.7 and 8.7. The following parameters were evaluated: final germination percentage (GP), germination speed index, time required for 50% germination, germination rate, viability of the remaining seeds and length of the radicle. All parameters were reduced in alkaline pH. Maximum germination of 94% was reached in the treatment control, followed by pH 4.7. At alkaline pH (7.7 - 8.7), GP was 43 and 31%, respectively. Therefore, at these pHs, germination was reduced. We provided direct evidence that pH is a limiting factor for germination and for the radicle growth of Z. tuberculosa seedlings. In addition, we show experimental evidence of why this species is widely distributed in the Cerrado biome, where the soils are more acidic, and the relationship between soil composition and high germination in acidic medium was corroborated with this study. We suggest that the germination test at different pHs be included in reforestation programs with native species to predict the establishment of seedlings in soils with different pH.

Abstract Semiconductor-based visible light active photo-catalyst has been synthesized through microwave-assisted chemical precipitation method under acidic pH with minimal time of reaction using microwave irradiation. The monoclinic crystal phase of the material with no impurity is confirmed with XRD data. We can observe slight left shift after doping with copper (Cu) in 2Θ peak of XRD data. SEM analysis exhibits a gradual change in morphology with the increase in doping concentration. UV–Vis data confirms an improvement in absorption with the increase in dopant concentration. PL analysis further clarifies the change in recombination rate of photo-induced charge carriers. Photocatalysis has been tested with methylene blue (MB) synthetic dye. The maximum percentage of degradation was determined to be 61.08% and it is obtained for 0.25% Cu-doped BiVO4. It is also observed that 0.25% Cu-doped BiVO4 has lower energy band gap value, i.e., 2.03 eV and lesser PL intensity than pure un-doped BiVO4. The HRTEM analysis proves that 0.25% Cu-BiVO4 is well crystalline in nature with the d spacing corresponding to (121) plane of BiVO4. [ABSTRACT FROM AUTHOR]

Tissue acidification causes sustained activation of primary nociceptors, which causes pain. In mammals, acid-sensing ion channels (ASICs) are the primary acid sensors; however, Na+/H+ exchangers (NHEs) and TRPV1 receptors also contribute to tissue acidification sensing. ASICs, NHEs, and TRPV1 receptors are found to be expressed in nociceptive nerve fibers. ASIC inhibitors reduce peripheral acid-induced hyperalgesia and suppress inflammatory pain. Also, it was shown that pharmacological inhibition of NHE1 promotes nociceptive behavior in acute pain models, whereas inhibition of TRPV1 receptors gives relief. The murine skin-nerve preparation was used in this study to assess the activation of native polymodal nociceptors by mild acidification (pH 6.1). We have found that diminazene, a well-known antagonist of ASICs did not suppress pH-induced activation of CMH-fibers at concentrations as high as 25 μM. Moreover, at 100 μM, it induces the potentiation of the fibers' response to acidic pH. At the same time, this concentration virtually completely inhibited ASIC currents in mouse dorsal root ganglia (DRG) neurons (IC50 = 17.0 ± 4.5 μM). Non-selective ASICs and NHEs inhibitor EIPA (5-(N-ethyl-N-isopropyl)amiloride) at 10 μM, as well as selective NHE1 inhibitor zoniporide at 0.5 μM induced qualitatively the same effects as 100 μM of diminazene. Our results indicate that excitation of afferent nerve terminals induced by mild acidification occurs mainly due to the NHE1, rather than acid-sensing ion channels. At high concentrations, diminazene acts as a weak blocker of the NHE. It lacks chemical similarity with amiloride, EIPA, and zoniporide, so it may represent a novel structural motif for the development of NHE antagonists. However, the effect of diminazene on the acid-induced excitation of primary nociceptors remains enigmatic and requires additional investigations. [ABSTRACT FROM AUTHOR]

Seed germination is a complex process involving several stages, starting with the imbibition of water and ending with the emergence of the radicle. In the current study, we address the observation of an unexpected pH shift during the imbibition of maize grains. We used direct pH measurements of soak water, the pH indicator methyl red, and anatomical analysis to shed light on the acidification associated with maize (Zea mays L.) germination, a largely overlooked phenomenon. Our work shows that acidification during imbibition of maize grains is a two-step process: (i) early, rapid acidification (pH values up to 4.4), in which protons stored in the (dead) pericarp/testa are mobilised and rapidly diffuse into the surrounding medium, and (ii) late, delayed acidification (pH values just below 6), starting hours after contact of grains with water, representing an active transport process caused by living cells of the seed. We discuss the physiological mechanisms and ecological relevance of environmental acidification during maize grain germination. [ABSTRACT FROM AUTHOR]

The present study proposed the synthesis of low-toxicity and eco-friendly spherically shaped manganese oxides (α-MnO2, Mn2O3, and Mn3O4) by using the chemical precipitation method. The unique variable oxidation states and different structural diversity of manganese-based materials have a strong effect on fast electron transfer reactions. XRD, SEM, and BET analyses were used to confirm the structure morphology, higher surface area, and excellent porosity. The catalytic activity of as-prepared manganese oxides (MnOx) was investigated for the rhodamine B (RhB) organic pollutant with peroxymonosulfate (PMS) activation under the condition of control pH. In acidic conditions (pH = 3), complete RhB degradation and 90% total organic carbon (TOC) reduction were attained in 60 min. The effects of operating parameters such as solution pH, PMS loading, catalyst dosage, and dye concentration on RhB removal reduction were also tested. The different oxidation states of MnOx promote the oxidative–reductive reaction under acidic conditions and enhance the SO4•−/•OH radical formation during the treatment, whereas the higher surface area offers sufficient absorption sites for interaction of the catalyst with pollutants. A scavenger experiment was used to investigate the generation of more reactive species that participate in dye degradation. The effect of inorganic anions on divalent metal ions that genuinely occur in water bodies was also studied. Additionally, separation and mass analysis were used to investigate the RhB dye degradation mechanism at optimum conditions based on the intermediate's identification. Repeatability tests confirmed that MnOx showed superb catalytic performance on its removal trend. [ABSTRACT FROM AUTHOR]

This study determined the in vitro activity of finafloxacin against panels of bacterial strains, representative of those associated with infection in cystic fibrosis patients and predominately isolated from clinical cases of respiratory disease. Many of these isolates were resistant to various antimicrobials evaluated including the aminoglycosides, cephalosporins, carbapenems and fluoroquinolones. Broth microdilution assays were performed at neutral and acidic pH, to determine antimicrobial activity. Finafloxacin demonstrated superior activity at reduced pH for all of the bacterial species investigated, highlighting the requirement to determine the activity of antimicrobials in host-relevant conditions. [ABSTRACT FROM AUTHOR]

Euglena is a microalga with the potential to be an environmentally friendly renewable energy resource. The pH value is a crucial factor in micro-algal cultivation. Changes in pH affect the growth and development of microalgae, including the production of biomass and primary metabolites, such as proteins, carbohydrates, and lipids. In this study, Euglena sp. was grown on Cramer-Myers medium and subjected to various acidic conditions. This study aimed to determine the effect of pH on the growth kinetics, biomass, carbohydrate, lipid, and protein contents of Euglena sp. The Euglena sp. culture was optimized at various pH values of 2.5, 3.5, and 4.5. The results were analyzed by one-way analysis of variance at a 95% confidence level, followed by Duncan's multiple range test. As results, Euglena sp. had the best growth rate, the greatest biomass, and the highest carbohydrate, protein, and lipid contents at pH 3.5 compared to the other pH conditions. The average biomass in the pH 3.5 treatment was 1.600 ± 0.229 g/L, and the carbohydrate, protein, and lipid contents were 5.983 ± 0.056 g/L, 0.196 ± 0.023 µg/mL, and 0.300 ± 0.020 g/L, respectively. [ABSTRACT FROM AUTHOR]

Dye‐decolorizing peroxidases (DyPs), a type of heme‐containing oxidoreductase enzymes, catalyze the peroxide‐dependent oxidation of various industrial dyes as well as lignin and lignin model compounds. In our previous work, we have recently reported the crystal structures of class A‐type DyP from Bacillus subtilis at pH 7.0 (BsDyP7), exposing the location of three binding sites for small substrates and high redox‐potential substrates. The biochemical studies revealed the optimum acidic pH for enzyme activity. In the present study, the crystal structure of BsDyP at acidic pH (BsDyP4) reveals two‐monomer units stabilized by intermolecular salt bridges and a hydrogen bond network in a homo‐dimeric unit. Based on the monomeric structural comparison of BsDyP4 and BsDyP7, minor differences were observed in the loop regions, that is, LI (Ala64‐Gln71), LII (Glu96‐Lys108), LIII (Pro117‐Leu124), and LIV (Leu295‐Asp303). Despite these differences, BsDyP4 adopts similar heme architecture as well as three substrate‐binding sites to BsDyP7. In BsDyP4, a shift in Asp187, heme pocket residue discloses the plausible reason for optimal acidic pH for BsDyP activity. This study provides insight into the structural changes in BsDyP at acidic pH, where BsDyP is biologically active. [ABSTRACT FROM AUTHOR]

Cancer cells are highly heterogeneous to adapt to extreme tumor microenvironments (TMEs). TMEs challenge cancer cells via hypoxia, nutrition starvation, and acidic pH, promoting invasion and metastasis concomitant with genetic, epigenetic, and metabolic alterations. Metabolic adaptation to an extreme TME could allow cancer cells to evade cell death and immune responses, as well as resulting in drug resistance, recurrence, and poor patient prognosis. Therefore, elucidation of the metabolic adaptation of malignant cancer cells within TMEs is necessary, however, most are still elusive. Recently, adaptation of cancer cells within the TME can be analyzed via cell–cell interactions at the single‐cell level. In addition, information into organelle–organelle interactions has recently been obtained. These cell–cell, and organelle–organelle interactions demonstrate the potential as new cancer therapy targets, as they play essential roles in the metabolic adaptation of cancer cells to the TME. In this manuscript, we review (1) metabolic adaptations within tumor microenvironments through (2) cell‐to‐cell, and (3) organelle–organelle metabolic interactions. [ABSTRACT FROM AUTHOR]

ABSTRACT Pseudomonas aeruginosa is a versatile pathogen that resists environmental stress, such as suboptimal pH. As a result of exposure to environmental stress, P. aeruginosa shows an altered virulence-related phenotype. This study investigated the modifications that P. aeruginosa undertakes at a mildly low pH (pH 5.0) compared with the bacteria grown in a neutral medium (pH 7.2). Results indicated that in a mildly acidic environment, expression of two-component system genes (phoP/phoQ and pmrA/pmrB), lipid A remodeling genes such as arnT and pagP and virulence genes, i.e., pqsE and rhlA, were induced. Moreover, lipid A of the bacteria grown at a mildly low pH is modified by adding 4-amino-arabinose (l-Ara4N). Additionally, the production of virulence factors such as rhamnolipid, alginate, and membrane vesicles is significantly higher in a mildly low-pH environment than in a neutral medium. Interestingly, at a mildly low pH, P. aeruginosa produces a thicker biofilm with higher biofilm biomass. Furthermore, studies on inner membrane viscosity and permeability showed that a mildly low pH causes a decrease in the inner membrane permeability and increases its viscosity. Besides, despite the importance of PhoP, PhoQ, PmrA, and PmrB in Gram-negative bacteria for responding to low pH stress, we observed that the absence of each of these two-component systems does not meaningfully impact the remodeling of the P. aeruginosa envelope. Given that P. aeruginosa is likely to encounter mildly acidic environments during infection in its host, the alterations that the bacterium undertakes under such conditions must be considered in designing antibacterial strategies against P. aeruginosa. IMPORTANCE P. aeruginosa encounters environments with acidic pH when establishing infections in hosts. The bacterium develops an altered phenotype to tolerate a moderate decrease in the environmental pH. At the level of the bacterial envelope, modified lipid A composition and a reduction of the bacterial inner membrane permeability and fluidity are among the changes P. aeruginosa undergoes at a mildly low pH. Also, the bacterium is more likely to form biofilm in a mildly acidic environment. Overall, these alterations in the P. aeruginosa phenotype put obstacles in the way of antibacterial activities. Thus, considering physiological changes in the bacterium at low pH helps design and implement antimicrobial approaches against this hostile microorganism.

Tissue acidification causes sustained activation of primary nociceptors, which causes pain. In mammals, acid-sensing ion channels (ASICs) are the primary acid sensors; however, Na+/H+ exchangers (NHEs) and TRPV1 receptors also contribute to tissue acidification sensing. ASICs, NHEs, and TRPV1 receptors are found to be expressed in nociceptive nerve fibers. ASIC inhibitors reduce peripheral acid-induced hyperalgesia and suppress inflammatory pain. Also, it was shown that pharmacological inhibition of NHE1 promotes nociceptive behavior in acute pain models, whereas inhibition of TRPV1 receptors gives relief. The murine skin-nerve preparation was used in this study to assess the activation of native polymodal nociceptors by mild acidification (pH 6.1). We have found that diminazene, a well-known antagonist of ASICs did not suppress pH-induced activation of CMH-fibers at concentrations as high as 25 μM. Moreover, at 100 μM, it induces the potentiation of the fibers’ response to acidic pH. At the same time, this concentration virtually completely inhibited ASIC currents in mouse dorsal root ganglia (DRG) neurons (IC50 = 17.0 ± 4.5 μM). Non-selective ASICs and NHEs inhibitor EIPA (5-(N-ethyl-N-isopropyl)amiloride) at 10 μM, as well as selective NHE1 inhibitor zoniporide at 0.5 μM induced qualitatively the same effects as 100 μM of diminazene. Our results indicate that excitation of afferent nerve terminals induced by mild acidification occurs mainly due to the NHE1, rather than acid-sensing ion channels. At high concentrations, diminazene acts as a weak blocker of the NHE. It lacks chemical similarity with amiloride, EIPA, and zoniporide, so it may represent a novel structural motif for the development of NHE antagonists. However, the effect of diminazene on the acid-induced excitation of primary nociceptors remains enigmatic and requires additional investigations.

Background: Pediocin PA-1 is a bacteriocin of recognized value with applications in food bio-preservation and the medical sector for the prevention of infection. To date, industrial manufacturing of pediocin PA-1 is limited by high cost and low-performance. The recent establishment of the biotechnological workhorse Corynebacterium glutamicum as recombinant host for pediocin PA-1 synthesis displays a promising starting point towards more efficient production. Results: Here, we optimized the fermentative production process. Following successful simplification of the production medium, we carefully investigated the impact of dissolved oxygen, pH value, and the presence of bivalent calcium ions on pediocin production. It turned out that the formation of the peptide was strongly supported by an acidic pH of 5.7 and microaerobic conditions at a dissolved oxygen level of 2.5%. Furthermore, elevated levels of CaCl2 boosted production. The IPTG-inducible producer C. glutamicum CR099 pXMJ19 Ptac pedACDCg provided 66 mg L−1 of pediocin PA-1 in a two-phase batch process using the optimized set-up. In addition, the novel constitutive strain Ptuf pedACDCg allowed successful production without the need for IPTG. Conclusions: The achieved pediocin titer surpasses previous efforts in various microbes up to almost seven-fold, providing a valuable step to further explore and develop this important bacteriocin. In addition to its high biosynthetic performance C. glutamicum proved to be highly robust under the demanding producing conditions, suggesting its further use as host for bacteriocin production. [ABSTRACT FROM AUTHOR]

The hydrangea (Hydrangea macrophylla (Thunb). Ser.), an ornamental plant, has good marketing potential and is known for its capacity to change the colour of its inflorescence depending on the pH of the cultivation media. The molecular mechanisms causing these changes are still uncertain. In the present study, transcriptome and targeted metabolic profiling were used to identify molecular changes in the RNAome of hydrangea plants cultured at two different pH levels. De novo assembly yielded 186,477 unigenes. Transcriptomic datasets provided a comprehensive and systemic overview of the dynamic networks of the gene expression underlying flower colour formation in hydrangeas. Weighted analyses of gene co-expression network identified candidate genes and hub genes from the modules linked closely to the hyper accumulation of Al3+ during different stages of flower development. F3′5′H, ANS, FLS, CHS, UA3GT, CHI, DFR, and F3H were enhanced significantly in the modules. In addition, MYB, bHLH, PAL6, PAL9, and WD40 were identified as hub genes. Thus, a hypothesis elucidating the colour change in the flowers of Al3+-treated plants was established. This study identified many potential key regulators of flower pigmentation, providing novel insights into the molecular networks in hydrangea flowers. [ABSTRACT FROM AUTHOR]

• Peptide separation selectivity have been evaluated for ZIC-HILIC, XBridge Amide, ZIC-cHILIC columns at acidic pH using ∼30,000 peptides datasets. • Peptide retention at pH 2.7 HILIC increases in order of ZIC-cHILIC < XBridge amide < ZIC-HILIC. • Composition and sequence-dependent retention factors contributing to peptide retention on HILIC at acidic pH have been elucidated. • The peptide separation orthogonality for HILIC-RPLC 2D LC combinations was found higher at pH 4.5 compared to pH 2.7. Peptide separation selectivity was evaluated for hydrophilic interaction liquid chromatography (HILIC) ZIC-HILIC, ZIC-cHILIC, and XBridge Amide sorbents using formic acid as eluent additive (pH 2.7). Sequence-specific retention prediction algorithms were trained using retention datasets of ∼30,000 peptides for each column. Our retention models were able to attain ∼0.98 R2-value and yielded retention coefficients that can be probed to understand peptide-stationary phase interaction. Overall, the hydrophilicity for these columns decreased when the mobile phase changed pH from 4.5 to 2.7, when using 0.1 % formic acid in the mobile phase. The acidic residues became protonated, and the resultant hydrophilic interaction is dampened at the lower pH, leaving only the basic residues as the primary hydrophilic interactors. Hence, peptides of increasing charge have higher retention. In this comparison between the three columns, ZIC-HILIC has the highest chromatographic resolution between groups of peptides of different charge. From the position-dependent retention coefficients for ZIC-HILIC at pH 2.7, we found that the amino acids at the terminal positions of the peptide modulate the basicity of the N-terminal amino group or the C-terminal Arg/Lys for tryptic peptides. With respect to the separation orthogonality between HILIC and acidic pH RPLC for two dimensional separations, the orthogonality values were lower at pH 2.7 than operating HILIC at pH 4.5 for the first dimension. We also demonstrate that ZIC-HILIC was able to distinguish citrullinated and deamidated peptides based on predicted retention values. [ABSTRACT FROM AUTHOR]

Heavy metals (HMs) are extensively used in various industrial processes, and releasing them into the environment, is a significant concern due to their persistence and non-biodegradability nature. Therefore, there is a strong need for efficient, environment-friendly, and cost-effective methods for removing HMs from contaminated sites. The ability of the living cells of the extremophile red microalgal strain Galdieria sulphuraria (G. sulphuraria) to tolerate and remove Cd (II), Pb (II), Ni (II), and Zn (II) from acidic aqueous medium in both single and mixed metal systems was assessed in this study. HM ions were introduced at different concentrations to the Cyanidium medium in which G. sulphuraria was cultivated at an acidic pH of 2.5 for seven days. Growth, nutrient removal, and metal ion removal efficiency were assessed during seven-day incubation periods. Cd (II) and Pb (II) added medium inhibited growth on the initial days, whereas no initial growth inhibition was detected in the medium supplemented with Ni (II) and Zn (II). Moreover, the exponential growth phase begins on day one in the Zn (II) added medium. The highest removal efficiencies for Cd (II), Pb (II), Ni (II), and Zn (II) in a single metal system are 45.90 %, 25.15 %, 6.56 %, and 28.44 %, respectively, and these efficiencies are achieved at lower initial metal concentrations. The highest sorption capacity is 1.45, 0.53, 0.75, and 2.46 mg g−1 of dry biomass for Cd (II), Pb (II), Ni (II), and Zn (II) in a single metal system, respectively. The experiment conducted in a mixed metal system observed a decline in removal efficiency for Cd (II), Pb (II), and Zn (II). In addition, higher removal efficiency was achieved in a mixed metal system when higher concentrations of HM were used. There was an effect in nitrogen removal with the presence of HM ions, where the presence of modest quantities of HMs does not significantly impact the removal of phosphorus. These results indicate that G. sulphuraria has the ability to remove HMs and nutrients simultaneously from aqueous solution, making a promising bioremediation solution for the combined treatment of industrial and municipal wastewater at acidic pH conditions. • Demonstrated Galdieria sulphuraria 's ability to withstand higher concentrations of Ni (II) and Zn (II) in the aqueous samples. • Demonstrated effective removal of Cd (II), Pb (II), Ni (II), and Zn (II) along with nutrient removal at the end of the cultural periods. • Demonstrated the potential of an algal-based system for heavy metal and nutrient removal from synthetic heavy metal samples. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel ratiometric fluorescent probe TZTF for the recognition of acidic pH was synthesized from camphor. • TZTF exhibited good selectivity and sensitivity to acidic pH with a pKa of 5.41. • TZTF was successfully applied to monitor the freshness of food samples. • TZTF was also utilized to imaging acid pH in living cells and zebrafish. In this research, a high-efficiency ratiometric fluorescent probe TZTF for sensitive detecting the fluctuations of acidic pH was synthesized. The fluorescent color changed from bright blue to orange in the pH values range from 8.0 to 1.0 with the pKa value of 5.41. Meanwhile, the probe demonstrated excellent selectivity, good anti-interference ability, prominent reversibility, outstanding photostability, and low cytotoxicity. The detection mechanism of TZTF towards acidic pH was verified through 1H NMR analysis and DFT calculation. Additionally, probe TZTF was also applied to evaluate the freshness of meat samples, as the pH value of meat samples may decrease if they are not stored properly, and the subsequent acid-catalyzed denaturation of proteins may pose a threat to human health through the food chain. More importantly, fluorescence imaging experiments confirmed that TZTF is appropriate for real-time tracking of pH variations in living cells and living zebrafish. [ABSTRACT FROM AUTHOR]

Acidic soil is a serious harmful problem for rice crop productivity. Approximately 50% of the world’s potentially arable soils are acidic, whereas in North East (NE) India 80% of arable soils are effected. In nature, it exists synergistically with other metal stresses. Hence most of the studies to date were performed in combinations. This paper highlights the detrimental effect of acidity on plants to differentiate between the effect of acidity on plant growth to that of stress in combinations. We depict it through a cascade of morphological and physiological assays, including growth, reactive oxygen species (ROS), and photosynthesis-related parameters under acidic and non-acidic rhizospheric conditions in rice seedlings of Disang and Joymati. Up to 31% root length reduction was observed in Joymati, and up to 17% reduction in Disang variety; whereas, root-relative water content was observed to reduce by 3% in Disang and 9% was recorded in Joymati cultivars. Overall, we observed limited effect on morphometric parameters like root length, biomass, and chlorophyll content irrespective of variety analyzed. On the contrary, ROS accumulation was observed to be significantly increased; more in Joymati (sensitive variety) when compared to Disang (tolerant variety). Although there was not much decrease in chlorophyll content, photosynthesis was affected immensely as depicted from chlorophyll fluorescence parameters. Hence through this study, we hypothesize that the response of plants to acid stress is rather slow.

The intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits host macrophage as a crucial survival and replicative niche. To minimize host immune response stimulated by flagellin, the expression of flagellar genes is downregulated during S. Typhimurium growth within host macrophages. However, the underlying mechanisms are largely unknown. In this study, we show that STM14_1285 (named AsiR), a putative RpiR-family transcriptional regulator, which is downregulated within macrophages as previously reported and also confirmed here, positively regulates the expression of flagellar genes by directly binding to the promoter of flhDC. By generating an asiR mutant strain and a strain that persistently expresses asiR gene within macrophages, we confirmed that the downregulation of asiR contributes positively to S. Typhimurium replication in macrophages and systemic infection in mice, which could be attributed to decreased flagellar gene expression and therefore reduced flagellin-stimulated secretion of pro-inflammatory cytokines IL-1β and TNF-α. Furthermore, the acidic pH in macrophages is identified as a signal for the downregulation of asiR and therefore flagellar genes. Collectively, our results reveal a novel acidic pH signal-mediated regulatory pathway that is utilized by S. Typhimurium to promote intracellular replication and systemic pathogenesis by repressing flagellar gene expression.

In acidic secretory granules of mammalian cells, peptide hormones including the parathyroid hormone are presumably stored in the form of functional amyloid fibrils. Mature PTH, however, is considerably positively charged in acidic environments, a condition known to impede unassisted self‐aggregation into fibrils. Here, we studied the role of the polyanion heparin on promoting fibril formation of PTH. Employing ITC, CD spectroscopy, NMR, SAXS, and fluorescence‐based assays, we could demonstrate that heparin binds PTH with submicromolar affinity and facilitates its conversion into fibrillar seeds, enabling rapid formation of amyloid fibrils under acidic conditions. In the absence of heparin, PTH remained in a soluble monomeric state. We suspect that heparin‐like surfaces are required in vivo to convert PTH efficiently into fibrillar deposits. [ABSTRACT FROM AUTHOR]

Seed germination is a complex process involving several stages, starting with the imbibition of water and ending with the emergence of the radicle. In the current study, we address the observation of an unexpected pH shift during the imbibition of maize grains. We used direct pH measurements of soak water, the pH indicator methyl red, and anatomical analysis to shed light on the acidification associated with maize (Zea mays L.) germination, a largely overlooked phenomenon. Our work shows that acidification during imbibition of maize grains is a two-step process: (i) early, rapid acidification (pH values up to 4.4), in which protons stored in the (dead) pericarp/testa are mobilised and rapidly diffuse into the surrounding medium, and (ii) late, delayed acidification (pH values just below 6), starting hours after contact of grains with water, representing an active transport process caused by living cells of the seed. We discuss the physiological mechanisms and ecological relevance of environmental acidification during maize grain germination.

This study determined the in vitro activity of finafloxacin against panels of bacterial strains, representative of those associated with infection in cystic fibrosis patients and predominately isolated from clinical cases of respiratory disease. Many of these isolates were resistant to various antimicrobials evaluated including the aminoglycosides, cephalosporins, carbapenems and fluoroquinolones. Broth microdilution assays were performed at neutral and acidic pH, to determine antimicrobial activity. Finafloxacin demonstrated superior activity at reduced pH for all of the bacterial species investigated, highlighting the requirement to determine the activity of antimicrobials in host-relevant conditions.

Objective: To investigate the antibacterial activity of calcium silicate–based sealers (CSBSs) against Enterococcus faecalis biofilm in a neutral or acidic condition. Materials and methods: Dentin cylinders (4 mm length) were prepared and infected with 3-week-old E. faecalis. The samples were filled with BioRoot RCS (BR), EndoSequence BC (ES), and NeoMTA Plus (NMTA) and incubated in either neutral or acidic conditions for 7 days (n=10/group). Sterile or infected samples alone were used as the positive and negative control. The root canal sealers were removed after 7 days, and the remaining bacteria on dentinal walls were determined by colony-forming units (CFUs/ml), and three samples from each group were visualized under a confocal laser scanning microscope (CLSM). The pH was also measured (n=3/group) after 4 h and 7 days of incubation at 37°C in both conditions. Results: In the neutral condition, all sealers significantly decreased the log-CFU values (p<0.05), while in the acidic condition, the log-CFU reduction was less for ES and NMTA, but a higher reduction was observed in BR (p<0.05). The antibacterial activity of CSBSs was similar in neutral conditions (p>0.05), and BR showed a greater antibacterial effect than ES and NMTA in the acidic condition (p<0.05). The pH of BR, ES, and NMTA ranged from 8.2 to 8.8 in the neutral condition in the presence of dentin after 7 days. However, acidic conditions reduced the pH values to 7.8 for BR, 6.0 for ES, and 5.8 for NMTA. Conclusions: All CSBSs showed similar antibacterial activity in neutral conditions, while acidic pH had a reducing antibacterial effect on CSBSs. Clinical relevance: Inflammatory pH decreased the antibacterial properties of CSBSs depending on the sealer type. [ABSTRACT FROM AUTHOR]

Background: Aminoacyl-phosphatidylglycerol (aaPG) synthases are bacterial enzymes that usually catalyze transfer of aminoacyl residues to the plasma membrane phospholipid phosphatidylglycerol (PG). The result is introduction of positive charges onto the cytoplasmic membrane, yielding reduced affinity towards cationic antimicrobial peptides, and increased resistance to acidic environments. Therefore, these enzymes represent an important defense mechanism for many pathogens, including Staphylococcus aureus and Mycobacterium tuberculosis (Mtb), which are known to encode for lysyl-(Lys)-PG synthase MprF and LysX, respectively. Here, we used a combination of bioinformatic, genetic and bacteriological methods to characterize a protein encoded by the Mtb genome, Rv1619, carrying a domain with high similarity to MprF-like domains, suggesting that this protein could be a new aaPG synthase family member. However, unlike homologous domains of MprF and LysX that are positioned in the cytoplasm, we predicted that the MprF-like domain in LysX2 is in the extracytoplasmic region. Results: Using genetic fusions to the Escherichia coli proteins PhoA and LacZ of LysX2, we confirmed this unique membrane topology, as well as LysX and MprF as benchmarks. Expression of lysX2 in Mycobacterium smegmatis increased cell resistance to human β-defensin 2 and sodium nitrite, enhanced cell viability and delayed biofilm formation in acidic pH environment. Remarkably, MtLysX2 significantly reduced the negative charge on the bacterial surface upon exposure to an acidic environment. Additionally, we found LysX2 orthologues in major human pathogens and in rapid-growing mycobacteria frequently associated with human infections, but not in environmental and non-pathogenic mycobacteria. Conclusions: Overall, our data suggest that LysX2 is a prototype of a new class within the MprF-like protein family that likely enhances survival of the pathogenic species through its catalytic domain which is exposed to the extracytoplasmic side of the cell membrane and is required to decrease the negative charge on the bacterial surface through a yet uncharacterized mechanism. [ABSTRACT FROM AUTHOR]

The intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits host macrophage as a crucial survival and replicative niche. To minimize host immune response stimulated by flagellin, the expression of flagellar genes is downregulated during S. Typhimurium growth within host macrophages. However, the underlying mechanisms are largely unknown. In this study, we show that STM14_1285 (named AsiR), a putative RpiR-family transcriptional regulator, which is downregulated within macrophages as previously reported and also confirmed here, positively regulates the expression of flagellar genes by directly binding to the promoter of flhDC. By generating an asiR mutant strain and a strain that persistently expresses asiR gene within macrophages, we confirmed that the downregulation of asiR contributes positively to S. Typhimurium replication in macrophages and systemic infection in mice, which could be attributed to decreased flagellar gene expression and therefore reduced flagellin-stimulated secretion of pro-inflammatory cytokines IL-1β and TNF-α. Furthermore, the acidic pH in macrophages is identified as a signal for the downregulation of asiR and therefore flagellar genes. Collectively, our results reveal a novel acidic pH signal-mediated regulatory pathway that is utilized by S. Typhimurium to promote intracellular replication and systemic pathogenesis by repressing flagellar gene expression. [ABSTRACT FROM AUTHOR]

Background: To gain patient compliance, pediatric medication preparations are made palatable by adding sugars such as sucrose, glucose, or fructose. These readily fermentable carbohydrates can significantly increase dental caries potential in the young and chronically sick children. Objectives: To evaluate acidogenic potential of commonly used pediatric liquid medicaments (PLMs). Materials and Methods: The acidogenic potential is assessed by estimating the endogenous pH of PLM. Results: The mean endogenous pH was higher in Azomycin (9.16 ± 0.25) and lowest in Lorinase (3.16 ± 0.15). Conclusion: Of nine, eight PLMs were acidic in nature.

Introduction: Stratum corneum (SC) is essential for skin barrier function, mitigating water loss and shielding against potentially harmful substances and allergens. The SC's lipid matrix, arranged in a lamellar structure, is integral to its protective role. Our study explores the restoration effects of a multilamellar cream with an acidic pH compared to a basic placebo cream on skin physiology and its interaction with the skin microbiome after stress induction via tape stripping (TS)., Materials and Methods: In this double-blind study, 14 healthy participants aged 21-58 years were assessed pre- and post-tape stripping, followed by a 14 days application of a multilamellar test cream and a placebo cream with evaluations on days 7, 14 and 17 for sustained effects. Skin physiology was analysed in terms of epidermal barrier function, SC hydration and surface pH. The microbiome was analysed by 16S rRNA amplicon sequencing the 16S rRNA gene using Illumina MiSeq, with subsequent species identification., Results: Our study showed significant improvements in skin barrier repair and SC hydration with verum, particularly after 14 days of application, while both creams initially enhanced stratum corneum hydration. No significant changes in surface-pH were detected. The skin microbiome analysis revealed that TS slightly decreased alpha diversity, a trend that verum significantly reversed, enhancing diversity beyond baseline levels after 14 days. Overall, while both creams contributed to a broader microbial phyla diversity over time, no significant changes in the abundance of specific genera or species were noted between treatments., Discussion and Conclusion: Our study delineates the efficacy of a pH-optimized multilamellar cream in enhancing epidermal barrier recovery and SC hydration post-sequential TS, in contrast to an unstructured basic placebo. Verum cream significantly improved skin barrier function and SC hydration at day 14, with sustained effects evident beyond the treatment period. Furthermore, the multilamellar formulation facilitated the restitution of cutaneous microbiome diversity, a key indicator of healthy skin ecology, underscoring the symbiotic relationship between barrier integrity and microbial composition. These findings underscore the importance of multilamellar emollient structures in dermatological therapeutics, with potential implications for the design of advanced skincare interventions that holistically support cutaneous resilience and homeostasis., (© 2024 The Authors. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Pseudomonas aeruginosa is the most prevalent bacterial species that contribute to cystic fibrosis (CF) respiratory failure. The impaired function of CF transmembrane conductance regulator leads to abnormal epithelial Cl–/HCO3– transport and acidification of airway surface liquid. However, it remains unclear why the CF lung is most commonly infected by Pseudomonas aeruginosa versus other pathogens. We carried out studies to investigate if lower pH helps Pseudomonas aeruginosa adapt and thrive in the CF-like acidic lung environment. Our results revealed that Pseudomonas aeruginosa generally forms more biofilm, induces antibiotic resistance faster in acidic conditions, and can be reversed by returning the acidic environment to physiologically neutral conditions. Pseudomonas aeruginosa appears to be highly adaptive to the CF-like acidic pH environment. By studying the effects of an acidic environment on bacterial response, we may provide a new therapeutic option in preventing chronic Pseudomonas aeruginosa infection and colonization. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is the most prevalent bacterial species that contribute to cystic fibrosis (CF) respiratory failure. The impaired function of CF transmembrane conductance regulator leads to abnormal epithelial Cl–/HCO3– transport and acidification of airway surface liquid. However, it remains unclear why the CF lung is most commonly infected by Pseudomonas aeruginosa versus other pathogens. We carried out studies to investigate if lower pH helps Pseudomonas aeruginosa adapt and thrive in the CF-like acidic lung environment. Our results revealed that Pseudomonas aeruginosa generally forms more biofilm, induces antibiotic resistance faster in acidic conditions, and can be reversed by returning the acidic environment to physiologically neutral conditions. Pseudomonas aeruginosa appears to be highly adaptive to the CF-like acidic pH environment. By studying the effects of an acidic environment on bacterial response, we may provide a new therapeutic option in preventing chronic Pseudomonas aeruginosa infection and colonization.

[Display omitted] Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells. However, little is known about its regulatory roles in gene expression and cell fate determination. Here, we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embryonic stem cells (mESCs). Importantly, acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions. Furthermore, acidic pH partially blocks the differentiation of human ESCs (hESCs). Mechanistically, acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs. Interestingly, AGO1 protein is also downregulated by acidic pH in cancer cells. Altogether, this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells (PSCs). [ABSTRACT FROM AUTHOR]

Sulfate-reducing microbial communities remain a suitable option for the remediation of acid mine drainage using several types of carrier materials and appropriate reactor configurations. However, acetate prevails as a product derived from the incomplete oxidation of most organic substrates by sulfate reducers, limiting the efficiency of the whole process. An established sulfate-reducing consortium, able to degrade acetate at initial acidic pH (3.0), was used to develop biofilms over granular activated carbon (GAC), glass beads, and zeolite as carrier materials. In batch assays using glycerol, biofilms successfully formed on zeolite, glass beads, and GAC with sulfide production rates of 0.32, 0.26, and 0.14 mmol H2S/L·d, respectively, but only with glass beads and zeolite, acetate was degraded completely. The planktonic and biofilm communities were determined by the 16S rRNA gene analysis to evaluate the microbial selectivity of the carrier materials. In total, 46 OTUs (family level) composed the microbial communities. Ruminococcaceae and Clostridiaceae families were present in zeolite and glass beads, whereas Peptococcaceae was mostly enriched on zeolite and Desulfovibrionaceae on glass beads. The most abundant sulfate reducer in the biofilm of zeolite was Desulfotomaculum sp., while Desulfatirhabdium sp. abounded in the planktonic community. With glass beads, Desulfovibrio sp. dominated the biofilm and the planktonic communities. Our results indicate that both materials (glass beads and zeolite) selected different key sulfate-reducing microorganisms able to oxidize glycerol completely at initial acidic pH, which is relevant for a future application of the consortium in continuous bioreactors to treat acidic streams. Key points: • Complete consumption of glycerol and acetate at acidic pH by sulfate reduction. • Glass beads and zeolite are suitable materials to form sulfate-reducing biofilms. • Acetotrophic sulfate-reducing bacteria attached to zeolite preferably. [ABSTRACT FROM AUTHOR]

Trefoil factor family member 2 (Tff2) is significantly involved in intestinal tumor growth in ApcMin/+ mice, which can be used as a human colon cancer model. TFF2, which encodes TFF2 (spasmolytic protein 1) is highly expressed in human cancer tissues, including the pancreas, colon and bile ducts, as well as in normal gastric and duodenum tissues. By contrast, TFF2 exhibits low expression levels in other normal tissues, including the small and large intestine. Furthermore, TFF2 expression has not been detected in DLD-1 cells, a cell line derived from human colon cancer. What induces TFF2 expression in normal and tumor cells is still unknown. Highly malignant tumor tissues are characterized by higher temperatures and lower pH (6.2–6.9) than in normal tissues, where normal pH ranges from 7.2 to 7.4. This microenvironment exacerbates malignancy by promoting the acquisition of cell death resistance, drug resistance and immune escape. Therefore, the present study examined how TFF2 expression is affected in cultured cells that imitate the tumor tissue microenvironment. The incubation temperature was increased from 37 to 40°C, but no expression of TFF2 was induced. Subsequently, a culture solution with an acidic pH was prepared to simulate the Warburg effect in tumors. TFF2 expression was increased by 42.8- and 5.8-fold in cells cultured in acidic medium at pH 6.5 and 6.8 compared with at pH 7.4, respectively, as determined using the relative quantification method following quantitative polymerase chain reaction. The present study also analyzed fluctuations in the expression levels of genes other than TFF2, under acidic conditions. Acidic conditions upregulated the expression of genes related to cell membranes and glycoproteins, based on the Database for Annotation, Visualization, and Integrated Discovery. In conclusion, TFF2 was highly expressed under acidic conditions, implying that it may have an important function in protecting the plasma membrane from acidic environments in both normal and cancer cells. These findings warrant further investigation of TFF2 as a target of cancer therapy and diagnosis. [ABSTRACT FROM AUTHOR]

While purifying a regular monospecific antibody, we found that the Protein A step yield was much lower than expected. Further studies revealed that the antibody formed large-size aggregates that did not bind to the Protein A resin, hence leading to dropped recovery. In an attempt to solve this low yield issue, we found that mildly acidic pH or ammonium sulfate treatment can partially convert the aggregates into monomers. In addition, when acidic pH treated culture harvest was processed by Protein A chromatography, the yield was restored to the normal range, suggesting that the monomers recovered from aggregates regained Protein A binding capability. Thus, low pH treatment of culture harvest can be potentially used as a general approach for improving Protein A step yield in cases where non-binding antibody aggregates are formed through noncovalent interactions. • SEC-HPLC analysis of culture harvest of a monospecific antibody disclosed formation of large- and small-size aggregates. • The large-size aggregates are predominant and did not bind to the Protein A resin, leading to lower-than-expected step yield. • Upon mildly acidic pH or ammonium sulfate treatment, the non-binding aggregates were partially converted into monomers. • Low pH treatment of culture harvest restored normal Protein A yield, suggesting recovered monomers regained binding ability. [ABSTRACT FROM AUTHOR]