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AbstractRheumatoid arthritis (RA) is characterized by increased joint pain and stiffness, particularly in the morning, which requires medication for treatment. Our research described here was aimed to develop, evaluate, and optimize coated naproxen pellets for colon-specific delivery using the carboxymethyl Leucaena leucocephala gum for the chronotherapy of RA. The extrusion-spheronization process was used for the preparation of the pellets followed by coating in a fluidized bed processor with materials such as Eudragit® S 100 and L 100. An 11-run, 2-factor, 3-level, randomized full factorial design was used to analyze the impact on the responses by varying the levels of independent factors to obtain the optimized formulation. The drug release of all the formulation batches at the 4th hour varied from 1.24 to 17.22% in the upper gastrointestinal (GI) tract; while the release of the drug at the 10th hour varied from 76.87 to 98.39% at the colonic pH. Furthermore, it was observed that the optimized formulation exhibited an increased release of naproxen in the presence of cecal matter collected from rats. We suggest that the prepared optimized formulation of the coated pellets of naproxen shows promise for the chronotherapeutic treatment of early morning symptoms associated with RA. [ABSTRACT FROM AUTHOR]

The current budesonide formulations are inadequate for addressing left-sided colitis, and patients might hesitate to use an enema for a prolonged time. This study focuses on developing a single-layer coating for budesonide pellets targeting the descending colon. Pellets containing budesonide (1.5%w/w), PVP K30 (5%w/w), lactose monohydrate (25%w/w) and Avicel pH 102 (68.5%w/w) were prepared using extrusion spheronization technique. Coating formulations were designed using response surface methodology with pH and time-dependent Eudragits. Dissolution tests were conducted at different pH levels (1.2, 6.5, 6.8, and 7.2). Optimal coating formulation, considering coating level and the Eudragit (S + L) ratio to the total coating weight, was determined. Budesonide pellets were coated with the optimized composition and subjected to continuous dissolution testing simulating the gastrointestinal tract. The coating, with 48% S, 12% L, and 40% RS at a 10% coating level, demonstrated superior budesonide delivery to the descending colon. Coated pellets had a spherical shape with a uniform 30 µm thickness coating, exhibiting pH and time-dependent release. Notably, zero-order release kinetics was observed for the last 9 h in colonic conditions. The study suggests that an optimized single-layer coating, incorporating pH and time-dependent polymers, holds promise for consistently delivering budesonide to the descending colon. [ABSTRACT FROM AUTHOR]

The clinical use of anti-EGFR antibody-based cancer therapy has been limited by antibody-EGFR binding in normal tissues, so developing pH-dependent anti-EGFR antibodies that selectively bind with EGFR in tumors—by taking advantage of the acidity of tumor microenvironment relative to normal tissues—may overcome these limitations. Here, we generated pH-dependent anti-EGFR antibodies with cross-species reactivity for human and mouse EGFR, and we demonstrate that pH-dependent antibodies exhibit tumor-selective binding by binding strongly to EGFR under acidic conditions (pH 6.5) but binding weakly under neutral (pH 7.4) conditions. Based on screening a non-immune human antibody library and antibody affinity maturation, we initially generated antibodies with cross-species reactivity for human and mouse EGFR. A structure model was subsequently constructed and interrogated for hotspots affecting pH-dependent binding, which supported development of a cross-reactive pH-dependent anti-EGFR antibody, G532. Compared with its non-pH-dependent antibody variant, G532 exhibits improved tumor selectivity, tumor penetration, and antitumor activity. Thus, beyond showing that pH-dependent anti-EGFR antibodies can overcome multiple limitations with antibody-based cancer therapies targeting EGFR, our study illustrates a structure-guided antibody-antigen binding pH-dependency engineering strategy to enhance antibody tumor selectivity and tumor penetration, which can inform the future development of antibody-based cancer therapies targeting other ubiquitously expressed molecules.

HadA monooxygenase catalyses the detoxification of halogenated phenols and nitrophenols via dehalogenation and denitration respectively. C4a‐hydroperoxy‐FAD is a key reactive intermediate wherein its formation, protonation and stabilization reflect enzyme efficiency. Herein, transient kinetics, site‐directed mutagenesis and pH‐dependent behaviours of HadA reaction were employed to identify key features stabilizing C4a‐adducts in HadA. The formation of C4a‐hydroperoxy‐FAD is pH independent, whereas its decay and protonation of distal oxygen are associated with pKa values of 8.5 and 8.4 respectively. These values are correlated with product formation within a pH range of 7.6–9.1, indicating the importance of adduct stabilization to enzymatic efficiency. We identified Arg101 as a key residue for reduced FAD (FADH−) binding and C4a‐hydroperoxy‐FAD formation due to the loss of these abilities as well as enzyme activity in HadAR101A and HadAR101Q. Mutations of the neighbouring Asn447 do not affect the rate of C4a‐hydroperoxy‐FAD formation; however, they impair FADH− binding. The disruption of Arg101/Asn447 hydrogen bond networking in HadAN447A increases the pKa value of C4a‐hydroperoxy‐FAD decay to 9.5; however, this pKa was not altered in HadAN447D (pKa of 8.5). Thus, Arg101/Asn447 pair should provide important interactions for FADH− binding and maintain the pKa associated with H2O2 elimination from C4a‐hydroperoxy‐FAD in HadA. In the presence of substrate, the formation of C4a‐hydroxy‐FAD at the hydroxylation step is pH insensitive, and it dehydrates to form the oxidized FAD with pKa of 7.9. This structural feature might help elucidate how the reactive intermediate was stabilized in other flavin‐dependent monooxygenases. [ABSTRACT FROM AUTHOR]

Extracting uranium from water is crucial for environmental protection and the sustainable nuclear power industry. However, high-efficiency extraction and mild desorption condition still poses significant challenges. Herein, a polyoxometalate-based metal-organic framework (POMOF) for high-performance uranium extraction is prepared by in situ confined encapsulating H 3 [PW 12 O 40 ] (PW 12) into MIL-101(Cr). The highly dispersed PW 12 enables adsorption sites to be sufficiently exposed, supports the pore structure of MIL-101(Cr), while being protected by spatial confinement. Furthermore, its abundant oxygen groups form high-affinity coordination with uranium and provide the pH-dependent conformation switch to achieve selective adsorption and instantaneous structural transformation. The assembly of structure and function makes POMOF exhibit substantial synergistic stability and adsorption capacity. Consequently, the constructed MIL-101(Cr)@PW 12 exhibits excellent uranium adsorption ability of 461.88 mg/g, as well as superior selectivity towards a wide variety of metal ions. Remarkably, instantaneous desorption can be achieved in 2 s under mild desorption conditions of 0.005 mol/L HCl, and the adsorption capacity remained at 94.30 % after 8 adsorption cycles. POMOF demonstrates the vast potential for uranium capture from water and offers new insight into designing structure and functional synergistic materials for the selective adsorption and instantaneous desorption of uranium. [Display omitted] • POMOF is prepared by in situ confined encapsulating kegging-POM into MOF. • POMOF exhibits substantial synergistic stability and adsorption capacity. • pH-dependent conformation switch achieves selective adsorption and structural transformation. • Instantaneous desorption can be achieved in 2 s under mild desorption conditions. [ABSTRACT FROM AUTHOR]

Carbonate (CO 3 2−/HCO 3 −) have a significant impact on advanced oxidation processes (AOPs) by consuming reactive free radicals such as HO• to generate CO 3 •-. However, research on the mechanisms and kinetics of CO 3 •- remains limited. This study investigates the degradation mechanism and kinetics of sulfonamide antibiotics (SAs) by CO 3 •- through theoretical calculations. The calculation results revealed that the effect of CO 3 •- on SAs degradation is pH-dependent due to the dissociable sulfonamide group (-SO 2 NH-) of SAs in the common water treatment pH range (3–8). The main reaction type of CO 3 •- with both neutral and anionic molecules of SAs is single electron transfer reaction. Frontier molecular orbital theory (FMO) illustrated that deprotonation of the sulfonamide group of SAs decreases the charge density on the heterocyclic ring, facilitating the electrophilic addition of CO 3 •-. The second-order rate constants of the neutral and anionic molecules of SAs with CO 3 •- were calculated as 7.57 × 101∼1.84 × 108 and 1.81 × 107∼7.94 × 109 M−1 s−1, respectively, resulting in an increase in the apparent reaction rate constants with pH. Stepwise multiple linear regression was employed to predict reactivity with anionic sulfonamide antibiotics (SAs−). Two models with outstanding prediction and stability were developed with coefficients of determination R2 of 0.660 and 0.681, respectively. The degradation kinetics simulation indicated that in the UV/H 2 O 2 process in the presence of carbonate, the degradation rate of SAs increased with pH. Furthermore, the contribution of CO 3 •- to SMX degradation increased while that of HO• decreased. This study highlights the contribution of carbonates to the micropollutant degradation in the UV/H 2 O 2 process as the model, providing theoretical insights into the development of carbonate-based AOPs. [Display omitted] • The main pathway of carbonate radical react with 19 sulfonamide antibiotics was single electron transfer. • The reactivities of most neutral and anionic sulfonamide antibiotics were significantly different. • QSAR models were developed to predict the reactivity of carbonate radical with anionic sulfonamide antibiotics. • The effects of carbonate on the degradation of sulfonamides were pH-dependent. [ABSTRACT FROM AUTHOR]

[Display omitted] • PVDF-supported N, S-semicoke (SC) membrane was prepared for persulfate activation. • A binary NOR and CIP mixture was used for their simultaneous degradation. • Mechanisms of pH-dependent species mediating degradation pathways were revealed. • N, S-SC-PVDF/PS had degradation efficiencies of 97.4 % for NOR and 96.8 % for CIP. • N, S-SC-PVDF/PS showed high tolerance at pH 3.0–9.0 and common Cl−/HCO 3 − at 5–20 mM. In persulfate-based advanced oxidation processes (PS-AOPs), pH is the most important factor affecting the degradation efficiency. However, the mechanism of pH-dependent generation of active species to mediate degradation pathways in PS-AOPs is currently unclear. In this study, N, S-modified semi-coke (N, S-SC) was first prepared by pyrolysis, and then poly (vinylidene fluoride) (PVDF) was used as support to obtain N, S-SC-PVDF membrane. Subsequently, N, S-SC-PVDF was used to activate peroxomonosulfate for the construction of N, S-SC-PVDF/PS system to promote the co-degradation of a binary mixture of norfloxacin (NOR) and ciprofloxacin (CIP) in water. Under optimized conditions of 0.4 g/L PS, pH = 7.0 and T = 30 °C, N, S-SC-PVDF/PS showed the degradation efficiencies of 97.4 % for NOR and 96.8 % for CIP within 240 min. Also, this system exhibited high resistance to Cl−/HCO 3 − at 5–20 mM and humic acid at 10–40 mg/L, with a wide pH tolerance of 3.0–9.0 and excellent cycle stability. Combining electron spin resonance and fluorescence quantification analysis, hydroxyl radicals (·OH) were the dominant species with a small amount of singlet oxygen (1O 2) at pH = 3.0, whereas radicals (·OH, SO 4 ·−) and non-radicals (1O 2) co-dominated at pH = 7.0. LC-MS analysis was used to identify the degradation products under different pH conditions, and different reactive oxygen species selected different sites to attack, resulting in different degradation pathways for the target binary pollutants. This study combines carbon-based catalyst and membrane separation process to construct an N, S-SC-PVDF/PS system for simultaneous degradation of binary NOR and CIP, and the relevant findings can not only provide a theoretical basis towards high-efficiency degradation of multi-component mixed antibiotics, but also new insights into pH-dependent degradation mechanism for the development of carbon-based PS-AOPs system in practical wastewater treatment. [ABSTRACT FROM AUTHOR]

Target of Myb1 (TOM1) facilitates the transport of endosomal ubiquitinated proteins destined for lysosomal degradation; however, the mechanisms regulating TOM1 during this process remain unknown. Here, we identified an adjacent DXXLL motif-containing region to the TOM1 VHS domain, which enhances its affinity for ubiquitin and can be modulated by phosphorylation. TOM1 is an endosomal phosphatidylinositol 5-phosphate (PtdIns5P) effector under Shigella flexneri infection. We pinpointed a consensus PtdIns5P-binding motif in the VHS domain. We show that PtdIns5P binding by TOM1 is pH-dependent, similarly observed in its binding partner TOLLIP. Under acidic conditions, TOM1 retained its complex formation with TOLLIP, but was unable to bind ubiquitin. S. flexneri infection inhibits pH-dependent endosomal maturation, leading to reduced protein degradation. We propose a model wherein pumping of H+ to the cytosolic side of endosomes contributes to the accumulation of TOM1, and possibly TOLLIP, at these sites, thereby promoting PtdIns5P- and pH-dependent signaling, facilitating bacterial survival. [Display omitted] • Binding of TOM1 VHS to ubiquitin is enhanced by an internal DXXLL motif • Binding of TOM1 to PtdIns5P is maximal under acidic conditions • TOLLIP's binding to PtdIns5P also increases as pH acidifies • A tight TOM1-TOLLIP complex binds to PtdIns5P under acidic conditions Xiong and Roach et al. report a DXXLL motif in TOM1 that increases its affinity for ubiquitin binding. They identify a PtdIns5P-binding site in TOM1 and demonstrate that its binding is maximal under acidic conditions. Furthermore, under these conditions, the TOM1-TOLLIP complex also interacts with the phosphoinositide. [ABSTRACT FROM AUTHOR]

Triclosan (TCS) has been widely employed as active ingredient in household products and has received attention for its hepatotoxicity, endocrine disruption and disturbance on immune function. Polylactic acid (PLA) has been highlighted as an alternative biodegradable microplastic, and the knowledge about the adsorption affinity towards TCS is limited. In this study, the ability to act as carrier of TCS by PLA and non-biodegradable microplastics, including polystyrene (PS), polyvinyl chloride (PVC) and polyethylene (PE) with different particle sizes were explored. The influence factors (e.g., dosage, pH and salinity), adsorption kinetics and isotherms were also investigated. Batch experiment results indicated that the TCS adsorption onto PLA and non-biodegradable microplastics exhibited a pronounced pH-dependent pattern (pH of 4, 7 and 10), and the adsorption capacity decreased gradually as pH increased. Furthermore, the adsorption capacity of TCS on PS, PVC and PE decreased as salinity increased from 0 to 3.5%, while no significant inhibition for the sorption capacity of PLA was observed. The adsorption kinetic data of TCS was best fitted with the pseudo-second order model. The Freundlich model with R2 (0.999) was suitable to describe the adsorption isotherms of TCS on PLA, while the isotherms data of TCS on PS, PVC and PE was fitted by linear and Freundlich model. The higher adsorption capacity of PLA (38.6 mg g−1) compares to those of PS, PVC and PE (31.3, 11.4 and 9.64 mg g−1, respectively), illustrated by the fact that the physicochemical properties of microplastics have a noticeable impact on adsorption process, and the biodegradable PLA is a stronger vector than the non-biodegradable microplastics. [ABSTRACT FROM AUTHOR]

• High specific surface area and C, O co-doped carbon nitride (UCN) was synthesized. • Enhanced light absorption and e–- h+ separation with increased doping levels. • pH-dependent generation of singlet oxygen and superoxide radicals in UCN system. • The flexible tunability of UCN can cope with complex water matrix. The metal-free, non-toxic, and highly tunable structure of carbon nitride confers unique advantages in photocatalytic advanced oxidation processes. Regulating the generation of radical and non-radical species during photocatalysis to maintain high degradation efficiency across different water matrices is of great practical significance for the application of carbon nitride. In this study, a C and O co-doped modified carbon nitride (UCN) with a high specific surface area was developed for efficient photodegradation of p -chlorophenol (p-Cl) without exogenous oxidants. Characterizations demonstrated that UCN in higher specific surface area exposed more active sites. Additionally, with rising doping levels, UCN exhibited enhanced light absorption capability and a narrower bandgap, which favored the separation of photogenerated electron-hole pairs. The primary active species were identified as holes, accompanied by the generation of superoxide radicals (·O 2 –) and singlet oxygen (1O 2) depending on the pH value. Under acidic conditions, 1O 2 was predominantly generated, whereas ·O 2 – dominated under alkaline conditions. As a result, the removal efficiency of p-Cl was enhanced under both strongly acidic and alkaline conditions. The pseudo-first-order rate constants for p-Cl removal at pH 3, 7, and 11 were 0.0558, 0.0354, and 0.0443 min−1, respectively. Moreover, combining DFT calculations and LC-MS data, analysis on the intermediate products of p-Cl degradation revealed unique characteristics at different pH values, further proving the flexible tunability and providing insights into the practical application of modified carbon nitride. [ABSTRACT FROM AUTHOR]

The heterogeneous catalytic ozonation with natural iron oxides has been proven to be a powerful technology for the removal of recalcitrant organics in water due to the involvement of reactive oxygen species. However, little information can be obtained about the performance of Ferrihydrite in catalytic ozonation especially the relavant reaction mechanism. In this study, Ferrihydrite was synthesized via a simple precipitation method and 2,4-Dichlorophenoxyacetic acid (2,4-D) degradation was used to evaluate its catalytic ozonation performance. Compared with sole ozonation, Ferrihydrite had an excellent activity in catalytic ozonation and 2,4-D was always efficiently degraded (>90%) at a wide pH range (3.0–8.0). Electron spin resonance (ESR) and radical scavenging tests proved that •OH and O 2 •- were the dominant reactive oxygen species (ROS) in 2,4-D degradation (92.33% vs. 77.4% in ozone alone) and mineralization (63% vs. 16.2% in ozone alone). Based on a series of characterizations, Ferrihydrite processed a higher BET area and surface -OH groups than other iron oxides such as FeOOH, Fe 2 O 3 and Fe 3 O 4. The efficiently exposed surface -OH group with a high density was the reactive centers for the generation of ROS. Importantly, pH PZC of Ferrihydrite (6.3) and pKa of 2,4-D (2.73) induced a pH-dependent 2,4-D removal patterns (surface reaction at pH < 6.3 and reaction in bulk solution at pH > 6.3) were proposed via the electrostatic attraction or repulsion between the hydrogenated/hydroxylated surface of Ferrihydrite and negative charged 2,4-D. [Display omitted] • Ferrihydrite had an excellent ozonation activity towards 2,4-D degradation at pH 3-8. • Exposed surface -OH was the active site in catalytic ozonation and.•OH/O 2 •- formation • Surface charge of Ferrihydrite due to pH PZC can affect the 2,4-D degradation patterns. • 2,4-D removal at solid-water interface or in bulk solution depends on the solution pH. • A pH dependent and surface -OH involved catalytic ozonation mechanism was proposed. [ABSTRACT FROM AUTHOR]

Food effect (FE) and gastric pH-dependent drug-drug interactions (DDIs) are both absorption-related. Here, we evaluated if Biopharmaceutics Classification System (BCS) classes may be correlated with FE or pH-dependent DDIs. Trends in FE data were investigated for 170 drugs with clinical FE studies from the literature and new drugs approved from 2013 to 2019 by US Food and Drug Administration. A subset of 38 drugs was also evaluated to determine whether FE results can inform the need for a gastric pH-dependent DDI study. The results of FE studies were defined as no effect (AUC ratio 0.80–1.25), increased exposure (AUC ratio ≥1.25), or decreased exposure (AUC ratio ≤0.8). Drugs with significantly increased exposure FE (AUC ratio ≥2.0; N=14) were BCS Class 2 or 4, while drugs with significantly decreased exposure FE (AUC ratio ≤0.5; N=2) were BCS Class 1/3 or 3. The lack of FE was aligned with the lack of a pH-dependent DDI for all 7 BCS Class 1 or 3 drugs as expected. For the 13 BCS Class 2 or 4 weak base drugs with an increased exposure FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). Among the 16 BCS Class 2 or 4 weak base drugs with no FE, 6 had a pH-dependent DDI (AUC ratio ≤0.8). FE appears to have limited correlation with BCS classes except for BCS Class 1 drugs, confirming that multiple physiological mechanisms can impact FE. Lack of FE does not indicate absence of pH-dependent DDI for BCS Class 2 or 4 drugs. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system.

[Display omitted] • Interaction kinetics of anthocyanin species were examined at different pH values. • Pigmented monomers decreased over time, while self-associated species increased. • Simulations showed that anthocyanin self-association occurs nonlinearly. • Self-association stabilises red, purple and blue colouration in plants. • Predictive modelling can increase anthocyanin use in food and beverage industries. Anthocyanins are polyphenolic compounds that provide pigmentation in plants as reflected by pH-dependent structural transformations between the red flavylium cation, purple quinonoidal base, blue quinonoidal anion, colourless hemiketal, and pale yellow chalcone species. Thermodynamically stable conditions of hydrated plant cell vacuoles in vivo correspond to the colourless hemiketal, yet anthocyanin colour expression appears in an important variety of hues within plant organs such as flowers and fruit. Moreover, anthocyanin colour from grape berries is significant in red winemaking processes as it plays a crucial role in determining red wine quality. Here, nonlinear ordinary differential equations were developed to represent the evolution in concentration of various anthocyanin species in both monomeric (chemically reactive) and self-associated (temporally stable) forms for the first time, and simulations were verified experimentally. Results indicated that under hydrating conditions, anthocyanin pigmentation is preserved by self-association interactions, based on pigmented monomeric anthocyanins experiencing colour loss whereas colour-stable self-associated anthocyanins increase in concentration nonlinearly over time. In particular, self-association of the flavylium cation and the quinonoidal base was shown to influence colour expression and stability within Geranium sylvaticum flower petals and Vitis vinifera grape skins. This study ultimately characterises fundamental mechanisms of anthocyanin stabilisation and generates a quantitative framework for anthocyanin-containing systems. [ABSTRACT FROM AUTHOR]

A novel colorimetric and fluorogenic probe L based on hydrazine carbothioamide and 1,8-naphthalimide moieties has been designed and synthesized for the hypersensitive detection of Hg2+ or Ag+ ions. The observed probe L showed colorimetric and fluorometric responses for these studies when Hg2+ or Ag+ was added to the DMSO - HEPES buffer solution (pH = 7). An interference test with other metal ions was determined, and the high selectivity of Hg2+ and Ag+ did not interfere with other metal ions in colorimetric and fluorogenic methods. The possible mechanism of binding of these metal ions and the probe L 1:1 complex was determined by H1 NMR. Additionally, the reversibility of the affinity of probe L with mercury (Hg2+) and silver (Ag+) ions was investigated by adding Na2EDTA. The naked eye detected the “Off-On” type fluorescence sensor in the presence of Hg2+ and EDTA. The tested test strip kits provided a strong probability of probe L with high response and rapid, sensitive detection with Hg2+ ion, which may be suitable for practical use. [ABSTRACT FROM AUTHOR]

This study employs density functional theory to explore the interaction between ibuprofen (IBU) and silica, emphasizing the influence of the trimethylsilyl (TMS) functional group for designing pH-responsive drug carriers. The surface (S) and drug (D) molecules' neutral (0) or deprotonated (−1) states were taken into consideration during the investigation. The likelihood of these states was determined based on the pKa values and the desired pH conditions. To calculate the pH-dependent interaction energy (E int p H ), four different situations have been identified: S0D0, S0D−1, S−1D0, and S−1D−1.The electrostatic component of interaction energy aligns favorably with its theoretical value in both the Debye-Hückel and Grahame models. The investigation has gathered first-hand experimental data on the drug loading and release of pH-responsive mesoporous silica nanoparticles. Effective drug loading was observed in the acidic environment of the stomach (pH 2–5), followed by a release in the slightly basic to neutral pH of the small intestine (pH 7.4), These findings align with existing literature. The results revealed horizontal drug adherence on silica surfaces, improving binding capabilities. Comparisons were made with combinations involving carboxylated carbon nanotubes and ibuprofen, silica, and sulfasalazine, and silica and alendronate, exploring drug loading/release dynamics associated with positive/negative interaction energies. The investigation, supported by experimental data, contributes valuable insights into pH-responsive mesoporous silica nanoparticles, offering new design possibilities for drug carriers. [Display omitted] • Loading of drugs onto silica nanoparticles (MSNs) is significantly influenced by pH. • Controlled release of the drug in the slightly basic pH in the small intestine. • Molecular Insights: Drug-Silica Interactions at Varying pH. • QM calculations on the energy and stability aspects of the drug-silica system. • Comparing pH-dependent Drug-Surface Interaction energies. [ABSTRACT FROM AUTHOR]

Developing efficient and recyclable membranes for water contaminant removal still remains a challenge in terms of practical applications. Herein, a recyclable membrane constituted of polyacrylonitrile-graphene and oxide-polydopamine was fabricated and demonstrated efficient adsorption capacities with respect to heavy metal ions (62.9 mg g−1 of Cu2+ ion, CuSO4 50 mg L−1) and organic dye molecules (306.7 mg g−1 of methylene blue and 339.6 mg g−1 of eriochrome black T, MB/EBT 50 mg L−1). The polyacrylonitrile fibers provide the skeleton of the membrane, while the graphene oxide and polydopamine endow the membrane with hydrophilicity, which is favorable for the adsorption of pollutants in water. Benefitting from the protonation and deprotonation effects of graphene oxide and polydopamine, the obtained membrane demonstrated promotion of the selective adsorption or desorption of pollutant molecules. This guarantees that the adsorbed pollutant molecules can be desorbed promptly from the membrane through simple pH adjustment, ensuring the reusability of the membrane. After ten adsorption–desorption cycles, the membrane could still maintain a desirable adsorption capacity. In addition, compared with other, similar membranes reported, this composite membrane displays the highest mechanical stability. This work puts forward an alternative strategy for recyclable membrane design and expects to promote the utilization of membrane techniques in practical wastewater treatment.

Chloroquine and its derivatives have been used since ages to treat malaria and have also been approved by the FDA to treat autoimmune diseases. The drug employs pH-dependent inhibition of functioning and signalling of the endosome, lysosome and trans-Golgi network, immunomodulatory actions, inhibition of autophagy and interference with receptor binding to treat cancer and many viral diseases. The ongoing pandemic of COVID-19 has brought the whole world on the knees, seeking an urgent hunt for an anti-SARS-CoV-2 drug. Chloroquine has shown to inhibit receptor binding of the viral particles, interferes with their replication and inhibits “cytokine storm”. Though multiple modes of actions have been employed by chloroquine against multiple diseases, viral diseases can provide an added advantage to establish the anti–SARS-CoV-2 mechanism, the in vitro and in vivo trials against SARS-CoV-2 have yielded mixed results. The toxicological effects and dosage optimization of chloroquine have been studied for many diseases, though it needs a proper evaluation again as chloroquine is also associated with several toxicities. Moreover, the drug is inexpensive and is readily available in many countries. Though much of the hope has been created by chloroquine and its derivatives against multiple diseases, repurposing it against SARS-CoV-2 requires large scale, collaborative, randomized and unbiased clinical trials to avoid false promises. This review summarizes the use and the mechanism of chloroquine against multiple diseases, its side-effects, mechanisms and the different clinical trials ongoing against “COVID-19”.

Peptide-based self-assembled nanostructures are emerging vehicles for nutrient delivery and interface engineering. The present study screened eight β-lactoglobulin (β-Lg) derived peptides and found that two reducing peptides [EQSLVCQCLV (EV-10) and VCQCLVR (VR-7)] demonstrated pH-dependent reversible fibrilization. EV-10 formed fibrils at pH 2.0 but became unordered aggregates at pH 7.0. VR-7 showed the opposite trend. Both peptides could undergo repetitive transitions between fibrils and unordered aggregates during consecutive pH-cycling. Fibrilization of both peptides was dominated by charges carried by N- and C-terminals. Both fibrils were characterized by a cross-β sheet structure where the β-sheet was arranged in an antiparallel manner. Fe 3+ was reduced by Cys and EV-10 (pH 5.0 and 7.0) simultaneously upon mixing. In contrast, EV-10 fibrils released Fe 3+ reducing capacity progressively, which were beneficial to long-term protection Fe 2+ . The EV-10 fibrils remained intact after simulated gastric digestion and finally dissociated after intestinal digestion. The results shed light on the mechanisms of fibrilization of β-Lg derived peptides. This study was beneficial to the rational design of smart pH-responsive materials for drug delivery and antioxidants for nutrients susceptible to oxidation.

Layered/two‐dimensional covalent organic frameworks (2D COF) are crystalline porous materials composed of light elements linked by strong covalent bonds. Interlayer force is one of the main factors directing the formation of a stacked layer structure, which plays a vital role in the stability, crystallinity, and porosity of layered COFs. The as‐developed new way to modulate the interlayer force of imine‐linked 2D TAPB‐PDA‐COF (TAPB = 1,3,5‐tris(4‐aminophenyl)benzene, PDA = terephthaldehyde) by only adjusting the pH of the solution. At alkaline and neutral pH, the pore size of the COF decreases from 34 Å due to the turbostratic effect. Under highly acidic conditions (pH 1), TAPB‐PDA‐COF shows a faster and stronger turbostratic effect, thus causing the 2D structure to exfoliate. This yields bulk quantities of an exfoliated few/single‐layer 2D COF, which was well dispersed and displayed a clear Tyndall effect (TE). Furthermore, nanopipette‐based electrochemical testing also confirms the slipping of layers with increase towards acidic pH. A model of pH‐dependent layer slipping of TAPB‐PDA‐COF was proposed. This controllable pH‐dependent change in the layer structure may open a new door for potential applications in controlled gas adsorption/desorption and drug loading/releasing. [ABSTRACT FROM AUTHOR]

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Amygdalin, despite possessing anticancerous properties, has been viewed as a controversial choice due to the presence of the cyanide group. Here, we synthesise and investigate the potential of alginate–chitosan nanoparticles (ACNPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer cells. Amygdalin loaded ACNPs were made with both anionic and cationic outer layer to further investigate charge dependency on drug delivery and cytotoxicity. ACNPs encapsulating amygdalin were monodisperse, colloidally stable with ~90% drug encapsulation efficiency and were entirely made from natural materials. The nanoparticles exhibited sustained drug release for a duration of 10 h and significant swelling rates in neutral and slightly acidic environments. The ACNPs successfully adhered to porcine mucin type II when assessed for its mucoadhesion and shown to transmigrate with an average velocity of 1.68 μm/s in uncoated channels, under biomimicked flow conditions. To investigate charge dependency on drug delivery and cytotoxicity, amygdalin loaded ACNPs were made with both anionic and cationic outer layer and assessed. ACNPs demonstrated greater yet sustained anti-cancerous effect on H1299 cell lines in a dose-dependent manner than free amygdalin suggesting greater cellular uptake of the former. In conclusion, biocompatible and biodegradable alginate–chitosan nanoparticles can be used as an effective drug delivery system for sustained and controlled amygdalin release with its improved cytotoxic effect on cancerous cells while protecting normal cells and tissues. Unlabelled Image [ABSTRACT FROM AUTHOR]

A series of Gemini surfactants N,N″‐dialkyl‐N,N′,N″‐tripropionate diethylenetriamine (referred as DTPDT‐n, where n is the length of the hydrocarbon chain, n = 10, 12, 14) were synthesized, which have three carboxylic head‐groups and two hydrophobic alkane chains. The products were characterized by means of nuclear magnetic resonance and mass spectrometry. The physicochemical properties of DTPDT‐n surfactants with different hydrocarbon chain lengths were studied such as isoelectric point, surface activities, emulsifying properties, and foam properties. It is showed that these compounds exhibit pH‐dependent protonation‐deprotonation behavior. The isoelectric points of DTPDT‐n surfactants are between 3.40 and 10.90. The critical micellar concentration (cmc) of all three surfactants are lower than the corresponding monomeric surfactants (single head group, single‐chain), especially DTPDT‐14, whose cmc can reach 2.29 × 10−5 mol/L. With an increase in the length of the alkyl chain, the solubility of the surfactants decreases and the surface tension of the three surfactants at cmc increases. In consideration of pH, all of three surfactants appear better emulsifying capacity and foaming property under weak alkaline conditions. DTPDT‐14 has the best performance of emulsifying capacity among the three surfactants. DTPDT‐10 has excellent foaming ability and foam stability. [ABSTRACT FROM AUTHOR]

For wounds with heavy exudate levels, a dressing that can help to absorb wound exudate and improve the wound healing process is highly desired. Hydrogen sulfide (H 2 S) has been recognized as an important gasotransmitter that can improve angiogenesis which is crucial for wound healing. In this study, a functional sodium alginate (SA) dressing with H 2 S-releasing property (SA/JK-1) was fabricated by incorporating JK-1 molecule, a pH-dependent H 2 S donor, into SA sponge. The resultant SA/JK-1 sponge provided a moist and protective healing environment and was capable of releasing H 2 S consistently under acidic pH condition by absorbing exudate at the wound interface. The H 2 S release of JK-1 donor was prolonged by the SA sponge compared with JK-1 in solution. Cell study in vitro indicated that SA/JK-1 not only exhibited good cyto-compatibility, but also improved fibroblast proliferation and migration. In addition, the effects of the SA/JK-1 dressing on wound healing was evaluated using an in vivo full thickness dermal defect model, which revealed that SA/JK-1 can significantly improve wound healing process with enhanced granulation tissue formation, re-epithelialization, collagen deposition and angiogenesis, due to the H 2 S released from JK-1. Taken together, our results showed that SA dressing doped with H 2 S donor could potentially serves as an effective wound healing strategy. The gasotransmitter H 2 S has been proven to improve the wound healing process in nanofibrous dressing due to its biological functions on angiogenesis. However, for non-healing wounds with heavy exudates, a wound dressing that can absorb wound exudates and controlled gasotransmitter release to improve the wound healing process is still in urgent need. Here we fabricated a sodium alginate (SA) sponge incorporated with H 2 S donor JK-1 (SA/JK-1), which showed strong water uptake capability, and released H 2 S under acidic condition. The SA/JK-1 sponge exhibited biocompatibility to fibroblasts and promoted cell migration in vitro , and exhibited obviously positive influence on wound healing in vivo. This H 2 S donor doped alginate wound dressing represents a promising strategy for treatment of non-healing wound. Image, graphical abstract [ABSTRACT FROM AUTHOR]

This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system. [ABSTRACT FROM AUTHOR]

Background/Aim: One of the most studied bacterial resistance mechanisms is the resistance related to multidrug efflux pumps. In our study the pump activity of the Escherichia coli K-12 AG100 strain expressing the AcrAB-TolC pump system was investigated at pH 7 and pH 5 in the presence of the efflux pump inhibitor (EPI) promethazine (PMZ). Materials and Methods: The EPI activity was assessed by real-time fluorimetry. The influence of PMZ treatment on the relative expression of the pump genes acrA, acrB and their regulators marA, marB, marR, the stress genes soxS, rob, as well as the bacterial growth control genes ftsI, and sdiA were determined by RT-qPCR. Results: The EPI activity of PMZ was more effective at neutral pH. The PMZ treatment induced a significant stress response in the bacterium at acidic pH by the up-regulation of genes. Conclusion: The genetic system that regulates the activity of the main efflux pump is pH-dependent. [ABSTRACT FROM AUTHOR]

Whitlockite (WK) is a hierarchically self-assembled and second most abundant biomineral in a naturally occurring complex bone at the nanoscale. Most of the properties at the nanoscale are size and shape-dependent. However, single-phase synthesis of WK is challenging and is pH and temperature-dependent. This work reports the different shapes and sizes of a novel bone-regenerative mineral (whitlockite) in a one-solvent system. We designed and investigated the synthetic conditions to achieve morphologically different WK nanostructures by fine-tuning the precursor's proportion, pH, temperature, and ageing. By manipulating the pH to 5.4, we successfully synthesised irregular plates of pure WK nanostructures. Conversely, through temperature control within the range of 90 °C–100 °C, various morphologies of pure whitlockite, such as cubes, irregular plates, clusters, and spheres, were attained. However, elongated clusters of WK structures were obtained after ageing the solution for three days at 90 °C. A broader particle size distribution was achieved within the 76.4 nm to 1 μm range. The purity, crystallinity, formation of auxiliary phases, functional groups, shapes, sizes, and elemental composition were investigated through correlative analytical approaches encompassing XRD, FTIR, Raman, SEM and EDS. [Display omitted] • This work reports the different shapes and sizes of a novel bone-regenerative mineral, whitlockite (WK) in a one-solvent system. • We designed and investigated the synthetic conditions to achieve morphologically different WK nanostructures by fine-tuning the precursor's proportion, pH, temperature, and ageing. • By manipulating the pH to 5.4, we successfully synthesised irregular plates of pure WK nanostructures. • Conversely, through temperature control within the range of 90 °C–100 °C, various morphologies of pure whitlockite, such as cubes, irregular plates, clusters, and spheres, were attained. • Elongated clusters of WK structures were obtained after ageing the solution for three days at 90 °C. A broader particle size distribution was achieved within the 76.4 nm to 1 μm range. • The purity, crystallinity, formation of auxiliary phases, functional groups, shapes, sizes, and elemental composition were investigated through correlative analytical approaches encompassing XRD, FTIR, Raman, SEM and EDS. [ABSTRACT FROM AUTHOR]

• First leaching assessment of cement activated fly ash and slag treated soils. • Promoting cement activation for safer use of fly ash and slag in soil stabilization. • Cement addition yielded lower Al leaching at a wide pH range. • Al, Cu, Zn and dissolved organic carbon followed an amphoteric leaching pattern. • Fe and SO 4 concentrations decreased monotonically with an increase in effluent pH. The use of industrial by-products such as fly ash and slag have become very prevalent in soil stabilization owing to its suitable physical and mechanical properties, and economical advantages. However, fly ash and slag have been identified as the potential source of toxic substances, and may pose environmental risk by leaching heavy and trace metals into soil, surface and groundwater. Toxicity characteristic leaching procedure (TCLP) tests were conducted to investigate the environmental hazards associated with the leaching of aluminum (Al), copper (Cu), iron (Fe) and zinc (Zn) from fly ashes, slag, type I/II cement and cement activated fly ash and slag stabilized soils. Sulfate (SO 4), dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) concentrations were also quantified to evaluate their influence on metal leaching. To understand the effect of pH on the leaching behavior, pH-dependent leach tests were conducted at the pH ranges of 2–14. Results indicated that an increase in fly ash or slag content may not necessarily increase the effluent metal concentrations. Al, Cu, Zn and DOC followed an amphoteric leaching pattern where concentrations increased in both acidic and basic conditions. In contrast, maximum DIC concentrations occurred at neutral or near neutral pH values. Fe and SO 4 showed cationic leaching behavior where concentrations decreased with an increase in effluent pH. Additionally, the leaching controlling mechanisms of the metals were identified by implementing geochemical modeling program Visual MINTEQ. The geochemical analyses indicated that the solubility of Al3+ and Fe3+ were controlled by precipitation/dissolution reactions of oxide/hydroxide minerals at all pH values. Leaching of Cu2+ was only solubility controlled at pH higher than 7, whereas Zn2+ leaching was solubility controlled in the pH range of 8–12. [ABSTRACT FROM AUTHOR]

Sulfolobus solfataricus β-glycosidase (SS-βGly) belongs to Glycosyl Hydrolase family1 (GH1) with broad substrate specificity. SS-βGly catalyzes both hydrolysis and transglycosylation reactions. SS-βGly is commonly used to synthesize variety of galacto-oligosaccharides. A comparison of SS-βGly with bacterial and eukaryotic homologs, using DALI search, revealed unique inserts. Free enzyme molecular dynamics (MD) simulation was performed under two different pH conditions (pH 6.5 and 2.5) at a constant temperature of 65 °C using GROMACS. A probable active-site loop (residues 331–364) in SS-βGly was identified. Dynamics of substrate binding cavity revealed that it was buried and inaccessible during most timeframes at pH 6.5 whereas open and accessible at pH 2.5. New cavities identified during both simulations may act as probable water channel or product egress path. Analyses of docked complexes of 3D structures obtained at every 1ns interval with compounds, involved in hydrolysis and tranglycosylation reactions, demonstrated that conformational states sampled by SS-βGly during free enzyme dynamics mimic the stages in enzyme catalysis thereby providing a mechanistic perspective. Current study revealed that conformational changes were conducive for hydrolysis at pH 6.5 and multiple cycles of transglycosylation at pH 2.5. Probable role of salt-bridge interactions in determining the type of reaction mechanism was also explored. Image 1 • Three unique insert regions were identified in SS-βGly. • Free enzyme dynamics of SS-βGly was performed at pH 6.5 and pH 2.5. • Probable active-site loop (residues 331–364) in SS-βGly was identified. • SS-βGly sampled conformations conducive to hydrolysis and transglycosylation. [ABSTRACT FROM AUTHOR]

Cement-solidification and chelator-stabilisation of municipal solid waste incineration fly ash (MSWI-FA) are two main treatment techniques to immobilise heavy metals. Differences in the long-term stabilities of those two methods of heavy-metal immobilisation were explored to aid in determining the better MSWI-FA treatment. However, few comparative studies have been conducted on 6-year-old cement-solidified FA (Ce-6-FA) and chelator-stabilised FA (Ch-6-FA). In this study, we compared the physicochemical and heavy metal leaching characteristics of Ce-6-FA and Ch-6-FA. The chemical speciation of heavy metals was modelled using geochemical software to assess long-term stability. The results showed weaker long-term stability in Pb immobilisation under the chelating system. The leaching concentrations of target heavy metals, acetic acid leaching tests, acid neutralising capacity, and pH-dependent leaching results indicated that Ce-6-FA had higher long-term stability than Ch-6-FA. A column experiment indicated that the cumulative release rates of Pb in Ce-6-FA and Ch-6-FA were 2.49% and 4.72%, respectively. The phase-controlled leaching of Pb in Ce-6-FA mainly occurred through Pb 2 (OH) 3 Cl and chloropyromorphite (Pb 5 (PO 4) 3 Cl), whereas that in Ch-6-FA mainly occurred through Pb 5 (PO 4) 3 Cl. The decomposition of heavy metal chelates in Ch-6-FA and salt generation in this process led to the release of Pb via the inorganic complex. Image 1 • We compared heavy metal leaching characteristics of 6 years aged cement-solidified FA and chelator-stabilised FA. • The leaching concentration of Pb and Cd in Ch-6-FA exceeds the MSW landfill thresholds. • We compared the difference of chemical speciation of heavy metal between Ce-6-FA and Ch-6-FA. • Poorer long-term stability in Pb immobilisation under the chelating system. [ABSTRACT FROM AUTHOR]

Two new polyoxometalate-based coordination polymers have been synthesized at different pHs under identical hydrothermal conditions, (Hbib)[Cu2(bib)2(PMo12O40)] (1) and (Hbib)2[Cu(bib) (PMo12O40)]·2H2O (2) (bib = 4-bis(imidazol-1-yl) benzene). Their structures were determined by single crystal X-ray diffraction analyses and characterized by routine methods. When the pH was adjusted to 2.0 − 2.5, 1 was obtained, which exhibits a 1-D rail-like chain. Compound 2 was obtained at pH of 2.5 − 3.2 and exhibits a 2-D layer with (44) sql net. The pH of the reaction plays a key role in the assembly of the polyoxometalate-based coordination polymer. The electrochemical experiments indicate that 2-based carbon paste electrode possesses high catalytic efficiency and high stability towards reduction of iodate and oxidation of ascorbic acid. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Monoclinic bismuth vanadate (c-BVO) was prepared via simple calcination of solvothermally processed tetrahedral BiVO 4. The physicochemical and morphological properties of c-BVO demonstrated the successful synthesis of the photoactive monoclinic phase from the tetrahedral phase, which has low photoactivity properties. The photoactivities of c-BVO were investigated using the photodegradation of methylene blue (MB) and photoelectrochemical (PEC) measurements in acidic (pH = 2.5), neutral (pH = 6.5) and basic (pH = 9.5) media. The photocatalytic activity of c-BVO was increased with increasing pH, achieved 99% MB degradation in the basic condition, compared with 70 and 45% in the neutral and acidic media, respectively. Although the tetrahedral BiVO 4 showed mainly adsorption with negligible photodegradation, c-BVO demonstrated both good adsorption and photodegradation activities. The PEC results indicated that the photocurrent density was affected by both pH and applied voltage. Impedance measurements showed faster charge transfer in the neutral condition than in the acidic and basic electrolytes. The incident photon conversion efficiency (IPCE) showed very low activity for tetrahedral BiVO 4 , but in comparison it was enhanced by 20- and 10-fold for c-BVO in the visible and simulated solar light, respectively. [ABSTRACT FROM AUTHOR]

In this paper we have studied the density functional theory of four drugs ibuprofen, alendronate, Sulfasalazine and paracetamol with quartz, propylamine, trimethylamine functionalized quartz and carboxyl modified carbon nanotube. The attractive and repulsive interaction energies between drugs and quartz is obtained at various pH values. The attractive and repulsive energies are well correlated with experimental drug loading and releasing behavior by mesoporous silica nanoparticles. Further, a theoretical model is developed that accounts the electrostatic interaction between silica and drug and the model can predict the drug loading and releasing behavior by silica nanoparticles at various pH values. Sulfasalazine can be taken orally and loaded with trimethyl ammonium functionalized mesoporous silica nanoparticles, which keeps the drug in tact with the carrier in the acidic environment of the stomach and releases it into the neutral or basic medium of the small intestine. Alendronate may be loaded and released from propylamine functionalized mesoporous silica nanoparticles in the ranges of 1–5 and > 8, respectively. Ibuprofen is absorbed in an acidic environment and released in basic conditions for carboxyl modified carbon nanotube. The loading and releasing pH ranges for paracetamol in trimethylammonium functionalized mesoporous silica nanoparticles are 4–8 and >8, respectively. We also convert the pH-dependent variant of the diffusion-controlled Higuchi equation. We have changed the original Higuchi equation to produce the pH-dependent variation by incorporating the Nernst-Planck equation into Flick's first law. The updated equation could be used to forecast when medication particles with varying release times will emerge from a nanoparticles matrix. [ABSTRACT FROM AUTHOR]

The pH-sensitive and magnetic-triggered release ensures the effective delivery of drugs. Chitosan carries amine pendants that encourage the fabrication of pH-responsive carriers. Montmorillonite (MMt), an attractive nano-clay in drug delivery possessing high encapsulation properties, was magnetized through the co-precipitation of Fe3+/Fe2+ ions. The study aimed to integrate the magnetic montmorillonite (mMMt) into the chitosan matrix and crosslinked by citric acid (CA) to achieve the nanocomposite carrier with double-responsive features for effective drug delivery. The release evaluation revealed that coating the mMMt with CA-crosslinked chitosan prevented the burst release of Ciprofluxcacin (Cip). The nanocomposite showed a high sustained release, and the release rate in the neutral environment (pH 7.4) was remarkably higher than in acidic media (pH 5.8). The new nanocomposite carrier showed high encapsulation efficiency to Cip (about 98 %). The study was developed by investigating external magnetic effects on the release rate, which lead to an increase in the release rate. The kinetics studies confirmed the diffusion mechanism for Cip release in all experimental media. The Cip-loaded nanocomposite carriers showed antibacterial activity against E. coli and S. aureus. • The prepared core-shells showed high encapsulation efficiency to Cip. • The release amount was higher in the neutral environment than in acidic media. • Using an external magnetic field increased the release amount of Cip. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) irradiation is considered an energy source for the prebiotic chemical synthesis of life’s building blocks. However, it also results in photodegradation of biology-related organic compounds on early Earth. Thus, it is important to find a process to protect these compounds from decomposition by UV irradiation. Herein, pH effects on both the adsorption of peptides on montmorillonite (MMT) and the abilities of peptides to resist UV irradiation due to this adsorption were systematically studied. We found that montmorillonite (MMT) can adsorb peptides effectively under acidic conditions, while MMT-adsorbed peptides can be released under basic conditions. Peptide adsorption is positively correlated with the length of the peptide chains. MMT’s adsorption of peptides and MMT-adsorbed peptide desorption are both rapid-equilibrium, and it takes less than 30 min to reach the equilibrium in both cases. Furthermore, compared to free peptides, MMT-adsorbed peptides under acidic conditions are well protected from UV degradation even after prolonged irradiation. These results indicate amino acid/peptides are able to concentrate from aqueous solution by MMT adsorption under low-pH conditions (concentration step). The MMT-adsorbed peptides survive under UV irradiation among other unprotected species (storage step). Then, the MMT-adsorbed peptides can be released to the aqueous solution if the environment becomes more basic (releasing step), and these free peptides are ready for polymerization to polypeptides. Hence, a plausible prebiotic concentration–storage–release cycle of amino acids/peptides for further polypeptide synthesis is established.

In this work, poly[1-vinyl-3(2-carboxyethyl) imidazolium betaine] (PVCIB), as a zwitterionic polyelectrolyte, was tethered onto a commercial thin film composite polyamide (TFC PA) membrane. First, polyvinyl imidazole (PVI) was grafted onto the TFC PA membrane surface by free radical graft polymerization method at various grafting times. Afterwards, one of PVI-modified membranes was betainized using 3-bromopropionic acid to obtain PVCIB brushes on the membrane surface. Evaluation of membrane performance through desalination process indicated that despite decrease of salt rejection, water flux increased from 73.4 L/m 2 h in the PA membrane to 91.6 L/m 2 h in the PA-PVCIB membrane. Antimicrobial assessment using Escherichia coli showed that the PVCIB-modified membrane was able to inhibit bacterial growth by about 98.8%. Antifouling and cleaning abilities of membranes were investigated using BSA and lysozyme at various pH values. It was revealed that hydrophilic PVCIB brushes considerably improved protein-resistant property of the TFC PA membrane. However, by considering pH-dependent behavior of PVCIB (zwitterionic at alkaline pH or polyelectrolyte at acidic pH), it was found that hydration repulsion or electrostatic repulsive forces also made a major contribution to the fouling mitigation. Accordingly, the PA-PVCIB membrane exhibited remarkable antifouling ability to resist non-specific protein adsorption at neutral and alkaline pHs, whereas both PA-PVI and PA-PVCIB membranes exhibited high resistance to the positively charged lysozyme adhesion at acidic pH. [ABSTRACT FROM AUTHOR]

Highlights • We characterized the cement-solidified FA after 6 years of natural aging (FA-6). • The leaching concentration of lead in FA-6 exceeds the landfill thresholds. • We determined the distribution of heavy metal in minerals and non-minerals in FA-6. • The carbonates, HFO, DOC in FA-6 influence the chemical speciation of heavy metals. • Pb 5 (PO 4) 3 Cl and Pb 2 (OH) 3 Cl were the major phase controlling the lead leaching. Abstract Solidification/stabilization (S/S) is the most common treatment for municipal solid waste incineration fly ash (MSWI-FA), and is widely applied in developed countries but has a history barely longer than 10 years in China. However, our understanding of the physicochemical characteristics of the solidified FA body after long-term natural aging is comparatively poor. Focusing on cement-solidified FA that was naturally aged for 6 years (hereafter referred to as FA-6), the physicochemical characteristics including elemental composition, mineral composition, microstructure, thermogravimetry, distribution of heavy metals in mineral phases, and leaching characteristics of inorganic salts (Na, K, Ca), anions (Cl and SO 4) and heavy metals (Cd, Cr, Cu, Pb, Zn) were investigated in this study. By combining pH-dependent leaching results with the geochemical model LeachXS, the chemical forms of heavy metals in the FA solid phase was determined. The main conclusion was as follows: (1) soluble salts of FA-6 decreased by more than 92% compared with fresh FA. (2) In FA-6, the proportions of Pb, Cd and Zn in the non-mineral phase were 100%, 100% and 58%, respectively, which may cause potential environmental risk of heavy metal release. The leaching concentration of Pb was 4007.37 μg/L according to compliance batch test of HJ300, which was far higher than the landfill requirement of 250 μg/L. (3) The controlling phase for Pb in FA-6 was Pb 5 (PO 4) 3 Cl (pH 2–12) and Pb 2 (OH) 3 Cl (pH > 12). (4) Carbonates, hydrous Fe oxides (HFO) and dissolved organic carbon (DOC) in FA-6 also affected the phase-controlled leaching of heavy metals. The carbonate fraction partly controlled the leaching of Cd, Cu and Zn. For example, smithsonite (ZnCO 3) controlled the release of Zn (pH 2–13). Adsorption to solid humic acid (SHA) controlled the Cr leaching at pH < 7 and the Cu leaching except pH > 12. [ABSTRACT FROM AUTHOR]

Bismuth oxyiodides have exhibited high potential for applications in visible-light photocatalytic environmental remediation and solar energy conversion. In this work, a series of iodine-deficient bismuth oxyiodides (Bi 4 O 5 I 2 , Bi 7 O 9 I 3 , Bi 5 O 7 I) can be simply prepared through a pH-dependent aqueous procedure with feeding Bi/I ratio of 2:1. The compositions of the Bi-based oxyiodides are closely related to acid-base circumstances, with Bi 4 O 5 I 2 formed in weakly acidic medium (pH = 5) and Bi 7 O 9 I 3 , Bi 5 O 7 I in basic medium (pH = 8 and 11). Morphology differences of nanosheet-assembled Bi 4 O 5 I 2 , Bi 7 O 9 I 3 architectures and rod-like Bi 5 O 7 I microstructures demonstrate different crystalline characters and construction of Bi-based oxyiodide crystals. UV–vis DRS results revealed good visible-light absorptions of Bi 4 O 5 I 2 and Bi 7 O 9 I 3 architectures and appropriate band structures for photocatalytic reactions, on comparison to Bi 5 O 7 I microrods. Low electrochemical impedance of Bi 7 O 9 I 3 microflowers with sheet-like units further facilitated the separation of e − –h + carriers in the degradation process. Accordingly, among the bismuth oxyiodide samples, Bi 7 O 9 I 3 displayed prominent visible-light degradation performance for colorless bisphenol-A (BPA) due to the direct photoexcitation process. [ABSTRACT FROM AUTHOR]

Coatings for corrosion protection usually contain pigments that constantly release substances actively inhibiting corrosion. However, this constant leaching places an important limitation on the protection lifetime of the coating. An intelligent release system may improve the long-term function of a coating, as uncontrolled loss by leaching is inhibited. This ensures that high amounts of inhibitors are still present when needed. Furthermore, this is also favourable for the environment, as no inhibitor is unnecessarily released into it. In this sense, smart mesoporous systems are excellent candidates thanks to their ability to provide more efficient and longer lasting anticorrosive protection by responding quickly to external stimuli such as local environmental changes (temperature, pH, local defects, humidity, etc.). A change in pH is a particularly interesting stimulus since, as is well known, corrosion activity leads to local pH changes in cathodic and anodic areas. In the present paper an environmentally friendly corrosion inhibitor, sodium phosphomolybdate, has been loaded into mesoporous silica nanoparticles. One of the main goals has been to study whether this corrosion inhibitor compound can offer controlled release as a function of pH, even in the absence of encapsulation. The results have shown that the polymerisation processes experienced by molybdenum species, as well as the different phosphate ions present as a function of pH, prevent their release into the environment in the absence of an outer capsule within the pH 3–9 range, thus avoiding the need to carry out an encapsulation stage. [ABSTRACT FROM AUTHOR]

After more than two decades of research and development, adeno-associated virus (AAV) has become one of the dominant delivery vectors in gene therapy. Despite the focused research, the cell entry pathway for AAV is still not fully understood. Universal AAV receptor (AAVR) has been identified to be involved in cellular entry of different AAV serotypes. With the unveiling of the high-resolution AAV-AAVR complex structure by cryogenic electron microscopy, the atomic level interaction between AAV and AAVR has become the focus of study in recent years. However, the serotype dependence of this binding interaction and the effect of pH have not been studied. Here, orthogonal approaches including bio-layer interferometry (BLI), size-exclusion chromatography coupled to multi-angle laser scattering (SEC-MALS) and sedimentation velocity analytical ultracentrifugation (SV-AUC) were utilized to study the interaction between selected AAV serotypes and AAVR under different pH conditions. A robust BLI method was developed and the equilibrium dissociation binding constants (K D) between different AAV serotypes (AAV1, AAV5 and AAV8) and AAVR was measured. The binding constants measured by BLI together with orthogonal methods (SEC-MALS and SV-AUC) all confirmed that AAV5 has the strongest binding affinity followed by AAV1 while AAV8 binds the weakest. It was also observed that lower pH promotes the binding between AAV and AAVR and neutral or slightly basic conditions lead to very weak binding. These data indicate that for certain serotypes, AAVR may play a prominent role in trafficking AAV to the Golgi rather than acting as a host cell receptor. Information obtained from these combinatorial biophysical methods can be used to engineer future generations of AAVs to have better transduction efficiency. • Orthogonal methods (BLI, AUC and SEC-MALS) were used to study AAV-AAVR interaction. • Robust bio-layer interferometry method developed to measure binding affinities for AAV-AAVR interaction. • Different AAV serotype (AAV1, AAV5 or AAV8) showed different binding affinities for AAVR. • Lower pH promotes AAV-AAVR interaction. [ABSTRACT FROM AUTHOR]

The in vitro solubility of poorly water-soluble drugs is one of the key parameters required for the development of the oral delivery system, but the determination of the solubility often relies on extensive experiments, which are time-consuming and costly. Therefore, it is meaningful to accurately model and predict the solubility of drugs in biorelevant media. Two insoluble drugs, oxaprozin and irbesartan, were selected and their solubilities in surfactant solutions, buffer solutions and biorelevant media were measured in this work. The thermodynamic phase behaviors of oxaprozin and irbesartan were modeled and predicted using Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) combined with pH-dependent and micellar solubilization models. The good agreement between the experimental results and the predicted values indicates the success of the model predictions, which provides the solubility database and good theoretical guidance for drug development and formulation selection. [ABSTRACT FROM AUTHOR]

Iron-modified biochar (Fe-biochar) has been widely developed to attenuate Cr(VI) pollution in both acid and alkaline environments. However, there are few comprehensive studies on how the iron speciation in Fe-biochar and chromium speciation in solution influencing the removal of Cr(VI) and Cr(III) under varying pH. Here, multiple Fe-biochar containing Fe 3 O 4 or Fe(0) were prepared and applied to remove aqueous Cr(VI). Kinetics and isotherms suggested that all Fe-biochar could efficiently remove Cr(VI) and Cr(III) via adsorption-reduction-adsorption. The Fe 3 O 4 -biochar immobilized Cr(III) by forming FeCr 2 O 4 , while amorphous Fe–Cr coprecipitate and Cr(OH) 3 was formed when using Fe(0)-biochar. Density functional theory (DFT) analysis further indicated that pH increase caused more negative adsorption energies between Fe(0)-biochar and the pH-dependent Cr(VI)/Cr(III) species. Consequently, the adsorption and immobilization of Cr(VI) and Cr(III) species by Fe(0)-biochar was more favored at higher pH. In comparison, Fe 3 O 4 -biochar exhibited weaker adsorption abilities for Cr(VI) and Cr(III), which were in consistent with their less negative adsorption energies. Nonetheless, Fe(0)-biochar merely reduced ∼70% of adsorbed Cr(VI), while ∼90% of adsorbed Cr(VI) was reduced by Fe 3 O 4 -biochar. These results unveiled the importance of iron and chromium speciation for chromium removal under varying pH, and might guide the application-oriented design of multifunctional Fe-biochar for broad environmental remediation. [Display omitted] • Fe-biochar efficiently removed aqueous Cr via adsorption-reduction-adsorption. • Fe speciation altered the contribution of adsorption and reduction to Cr removal. • The role of Fe speciation in Cr removal process was dependent on pH. • The interaction between Cr species and Fe-biochar at varying pH was analyzed by DFT. [ABSTRACT FROM AUTHOR]

[Display omitted] • Three novel lamotrigine-acid salts with enhanced solubility are reported. • Lamotrigine salts show pH-dependent solubility behavior. • The pH-solubility window is beneficial to understand the solubility changes. Lamotrigine (LAM), a Biopharmaceutics Classification System (BCS) class II drug, is widely used to treat epilepsy, bipolar disorder and neuropathic pain. However, its low solubility and dissolution rate limit its absorption and bioavailability. This study aims to enhance the solubility of LAM by forming salts with different acids and elucidate the mechanism underlying the solubility changes. Herein, three new salt forms as lamotrigine-2, 5-dihydroxybenzoic acid (LAM-DA), lamotrigine-isonicotinic acid (LAM-IA), and lamotrigine-shikimic acid (LAM-SA) were discovered and characterized. We investigated and compared the intrinsic dissolution rate (IDR) and solubility between LAM and its corresponding salts. Significantly improved solubility was observed for all three LAM salts, which were 3.37 (LAM-DA), 6.44 (LAM-IA), and 7.90 (LAM-SA)-fold greater than LAM in water, respectively. Accordingly, the IDR parameters of all the salts exhibit a similar pattern, indicating an overall improvement over LAM. In order to investigate the solubility mechanism, solution were prepared at different pH values (1.2, 3.0, 5.0, 6.8 buffered solutions, and water) and their changes were measured. Our findings indicated that the solubility of LAM salts was influenced by the pH. The results demonstrate that the solubility of LAM salts is pH-dependence. The solubility of salts was negatively correlated with the pH of the solution. In this regard, the solubility of LAM-DA, LAM-IA and LAM-SA increased from 326.7, 330.8, and 320.1 μg/mL at pH = 6.8 to 1238.2, 6527.9, and 7854.9 μg/mL at pH = 3.0, respectively. Analyzing the pH-dependent curves can help to comprehend the mechanisms underlying the solubility changes of LAM salts. Overall, this approach can serve as a valuable tool in predicting their potential oral bioavailability. [ABSTRACT FROM AUTHOR]

In this study, the magnetite nanoparticles were immobilized on the sepiolite needles via co-precipitation of iron ions. Then, the resulted magnetic sepiolite (mSep) nanoparticles were coated with chitosan biopolymer (Chito) in the presence of citric acid (CA) to prepare mSep@Chito core-shell drug nanocarriers (NCs). TEM images showed magnetic Fe 3 O 4 nanoparticles with small sizes (less than 25 nm) on the sepiolite needles. Sunitinib anticancer drug loading efficiencies were ⁓45 and 83.7 % for the NCs with low and high content of Chito, respectively. The in-vitro drug release results exhibited that the mSep@Chito NCs have a sustained release behavior with high pH-dependent properties. Cytotoxic results (MTT assay) showed that the sunitinib-loaded mSep@Chito2 NC had a significant cytotoxic effect on the MCF-7 cell lines. Also, the in-vitro compatibility of erythrocytes, physiological stability, biodegradability, and antibacterial and antioxidant activities of NCs was evaluated. The results showed that the synthesized NCs had excellent hemocompatibility, good antioxidant properties, and were sufficiently stable and biocompatible. Based on the antibacterial data, the minimal inhibitory concentration (MIC) values for mSep@Chito1, mSep@Chito2, and mSep@Chito3 were obtained as 125, 62.5, and 31.2 μg/mL towards S. aureus , respectively. All in all, the prepared NCs could be potentially used as a pH-triggered system for biomedical applications. • Co-precipitation of iron ions was performed for the preparation of magnetic sepiolite. • pH-responsive nanocarriers were synthesized by the combination of magnetic sepiolite and chitosan. • Non-toxic citric acid as a crosslinker was used to attain magnetic carriers. • High loading capacity and sustained release of sunitinib into carriers were obtained. • The nanocarriers showed cytotoxicity to the cancer cell line (MCF-7). [ABSTRACT FROM AUTHOR]

M-type phospholipase A2 receptor (M-PLA2R) is a member of the mannose receptor family and known as the receptor of secretory phospholipase A2s. It has also been identified as the major autoantigen of idiopathic membranous nephropathy, one of the most common causes for nephrotic syndrome in adults. Here we determine the structure of human M-PLA2R ectodomain by cryo-electron microscopy. The results show that the ectodomain has high internal flexibility and forms a compact dual-ring-shaped conformation at acidic pH and adopts extended conformations at basic pH. The inter-domain interactions of human M-PLA2R are explored by the binding studies with individual domains, showing the mechanism of the conformational change. In addition, the biochemical data suggest that mouse M-PLA2R recognizes mouse secretory phospholipase A2-G1B only at physiological or basic pH, rather than at acidic pH. These results suggest that the pH-dependent conformational change might play important roles in the functional activities of M-PLA2R such as ligand binding and release, and may also be relevant to the immunogenicity in membranous nephropathy. [ABSTRACT FROM AUTHOR]

Polymers are essential tools in the research and development of new therapeutic devices. The diversity and flexibility of these materials have generated high expectations in the composition of new materials with extraordinary abilities, especially in the design of new systems for the modified release of pharmaceutically active ingredients. The natural polymer rosin features moisture protection and pH-dependent behavior (i.e., it is sensitive to pH > 7.0), suggesting its possible use in pharmaceutical systems. The synthetic polymer Eudragit® RS PO is a low-permeability material, the disintegration of which depends on the time of residence in the gastrointestinal tract. The present study developed a polymeric material with desirable physicochemical characteristics and synergistic effects that resulted from the inherent properties of the associated polymers. Isolated films were obtained by solvent evaporation and subjected to a water vapor transmission test, scanning electron microscopy, calorimetry, Fourier transform-infrared (FT-IR) spectroscopy, micro-Raman spectroscopy, and mechanical analysis. The new polymeric material was macroscopically continuous and homogeneous, was appropriately flexible, had low water permeability, was vulnerable in alkaline environments, and was thermally stable, maintaining an unchanged structure up to temperatures of ∼400°C. The new material also presented potentially suitable characteristics for application in film coatings for oral solids, suggesting that it is capable of carrying therapeutic substances to distal regions of the gastrointestinal tract. These findings indicate that this new material may be added to the list of functional excipients. [ABSTRACT FROM AUTHOR]

The development of efficient photocatalysts is of paramount significance for sustainable availability of solar energy. Herein, hollow α-Ag 3 VO 4 photocatalysis crystallites were successfully synthesized via a facile one-pot hydrothermal approach without modifier. The morphology, phase composition and crystal structure of α-Ag 3 VO 4 crystallites are strongly dependent on the pH values of the precursor solution, and the formation of hollow α-Ag 3 VO 4 nanospheres merely occurs at pH = 10. Furthermore, hollow α-Ag 3 VO 4 nanospheres exhibit superior photocatalytic activities compared with bulk α-Ag 3 VO 4 for the degradation of Rhodamine B (Rh B) under the simulated solar light, achieving up to 97% degradation in 2 h irradiation. This improved photocatalytic performance of hollow α-Ag 3 VO 4 nanospheres is primarily attributed to the synergistic effect of the improved electron-transfer efficiency, the extended light absorption range and effective separation of electron-hole pairs. [ABSTRACT FROM AUTHOR]

A polyampholytic superabsorbent polymer (PASAP), sodium alginate-g-(polyacrylic acid-co-allyltrimethylammonium chloride) (SA-g-(PAA-co-PTM)), was prepared by free-radical graft copolymerization and characterized. The polymer exhibited pH-dependent swelling behaviors with extremely high swelling ratios, and was saline tolerant. The dye adsorption properties of SA-g-(PAA-co-PTM) were investigated using methylene blue (MB) as a cationic dye model. It was found that its dye adsorption capacity was significantly affected by the TM content in PASAP and pH of dye solution. The dye adsorption kinetics and isotherm obey the pseudo-second-order kinetic model and the Langmuir isotherm model, respectively, and the adsorption process is chemisorption in nature. In addition, SA-g-(PAA-co-PTM) exhibited high MB adsorption capacities in a wide pH range and reusability in at least five adsorption-desorption cycles, indicating its great application potentials as the adsorbent for dye removals from effluents.