Acidic pHs Research Articles

A New Enzyme for Biodiesel Production and Food Applications: Lipase of Bacillus megateriumF25 Isolated From an Aquatic Insect Rhantus suturalis

ABSTRACTThis study aimed to isolate, purify, and characterize a lipase from the gut symbiont Bacillus megaterium F25 (GenBank accession: MF597792) of the aquatic insect Rhantus suturalis, with a focus on its potential applications in biodiesel and food industries. Under optimized culture conditions, B. megaterium F25 could produce 583 U/L of lipase in shaking flask culture. The purified lipase (PL) exhibited a specific activity with 113.89 U/mg, and its molecular weight was determined as 34 kDa. The activity of PL was enhanced by methanol, ethanol, Tween‐80, Triton X‐100, Ca2+, and Mg2+, while β‐mercaptoethanol, EDTA, SDS, Fe2+, Mn2+, and Cu2+ were inhibitory. PL showed optimal activity and stability at neutral and slightly acidic pHs, as well as in a temperature range of 20°C–30°C. PL displayed strong hydrolytic activity toward plant oils and animal fats, indicating its potency for both the food industry and the remediation of oil‐contaminated environments. When tested as a catalyst, PL provided biodiesel production with a transesterification yield of 86.8% under optimized conditions (36 h reaction time, 4 mL enzyme solution, 30°C, pH 7.0, and waste cooking oil:methanol ratio of 10 mL/40 mL). This is the first report on the lipase‐producing potential of gut microbial symbionts of aquatic insects. Furthermore, B. megaterium lipase was tested for the first time as a biocatalyst for biodiesel production.

Hydrogen‐Bonded Organic Frameworks as a Carrier for Nanodrugs with Host–Guest Interaction for Smart Wound Dressing Applications

AbstractThis study introduces surface modification to conventional dressings utilizing adducts of a hydrogen‐bonded organic framework (HOF) with curcumin, curcumin–silver, curcumin‐zinc oxide nanoparticles, and citric acid drugs. Accordingly, eight HOF‐AMs and dressings modified with them were studied. The synthesized structures underwent characterization using various methods, including IR, 1H NMR, XRD, FE‐SEM, and EDX. FE‐SEM results show that the hexagonal morphology is maintained along with the crystal growth in the form of hexagonal tubes. In order to confirm the nanoscale nature of the structures, TEM analysis was conducted specifically for curcumin‐Ag nanoparticles and curcumin–ZnO nanoparticles which confirms the particle size smaller than 50 nm. Knowing the sensitivity of the release of the incorporated substances to temperature and pH, the controlled release of the drugs at two different temperatures (37 °C and 40 °C) and pH levels of 5.5, 7.4, and 9 at the modified dressings was investigated. Investigating the release of HOF‐AMs particles and modified dressings indicates that these products in both cases provide the possibility of drug release in alkaline and acidic pHs. Also, the results showed that increasing the temperature increases the release of curcumin particles in all its types. The modified dressings showed a loading capacity of more than 50 mg g−1.

Characteristics and properties of co-precipitated protein and film based on Bambara groundnut protein isolate and fish skin acid-soluble collagen

Co-precipitated protein (CPP) from Bambara groundnut protein isolate (BGPI) and fish skin acid-soluble collagen (ASC) at different BGPI/ASC ratios (100:0, 75:25, 50:50, 25:75 and 0:100 (v/v)) were prepared and characterized. CPP of BGPI/ASC at ratio of 75:25 had higher solubility at acidic and alkaline pHs, compared to other CPP samples. All CPPs had good emulsifying properties. Based on protein patterns, the combination of major bands from BGPI and ASC in the resulting CPP sample was observed. CPP with BGPI/ASC at ratio of 75:25 showed higher surface hydrophobicity than those of other CPP samples. When the films from CPPs were fabricated, similar tensile strength (p > 0.05) was observed, regardless of BGPI/ASC ratios. Nevertheless, film from CPP with BGPI/ASC ratio of 25:75 had higher elongation at break along with lower water vapor permeability (p < 0.05), compared to other CPP films. All CPP films had bright-yellowish color. Increasing ASC ratio augmented (p < 0.05) light transmission of resulting CPP films. FTIR spectra revealed that all CPP films had the similar pattern and functional groups. Therefore, the co-precipitated BGPI and ASC at appropriate ratio could improve properties of resulting proteins, especially for film forming ability.

A novel catalyst based on zero-valent iron nanoparticles for assisting electro-fenton process applied to a toxic wastewater

A catalyst based on zero-valent iron nanoparticles (nZVI) supported by zeolite Y (zeolite Y-nZVI) was synthesized to improve the performance of the heterogeneous electro-Fenton-like process for treating a toxic pesticide wastewater with pH of 6. Central Composite Design (CCD) under Response Surface Methodology (RSM) was applied to design the experiments and find the optimal parameters including time, current intensity, hydrogen peroxide volume (or concentration) and the synthesized catalyst dosage. The results showed that the chemical oxygen demand (COD) removal under the optimal conditions (time of 125 min, current intensity of 272 mA, hydrogen peroxide volume (or concentration) of 0.19 ml (8.102 × 10−3 M), and zeolite Y-nZVI catalyst dosage of 1.78 g) was at 83.69 % for treating a wastewater with pH of 6 although this increased to 91.26 % at pH of 3 under the Fenton reactions. In fact, the synthesized catalyst could properly treat wastewater in a pH close to neutral one. Since electro-Fenton is as efficient technique for treating the hazardous pollutants such as pesticide, it can successfully be used by their manufacturing factories. Since it properly works in the acidic pHs, it is not as applied technique for most of industries. Therefore, catalytic electro-Fenton process can be performed in (or near) a neutral pH. Since electro-Fenton is basically associated with iron, a catalyst based on it (such as Fe°) was chosen and supported on an abundant and suitable material such as zeolite. The synthesized catalyst was initially synthesized and characterized, and then successfully applied in the electro-Fenton process to treat a real pesticide containing wastewater obtained from industry.

Pomegranate Peel Flour as a Co-encapsulant Improves the Survival of Lactic Acid Bacteria to Thermal Treatment and Simulated Gastrointestinal Conditions

AbstractPomegranate peel flour was employed as a co-encapsulant of two lactic acid bacteria, by alginate emulsion templated microencapsulation, to enhance their resistance to thermal treatment, acidic pHs, and gastric conditions. Samples with pomegranate peel flour increased the tolerance to heat treatment, results consistent with thermal properties related to higher denaturation enthalpy of microcapsules. Co-encapsulated microcapsules also enhanced the survival to low pHs and enhanced almost 60% up the tolerance to bile salts. There was also an increase in survival rate against in vitro gastric acid conditions due to use of the co-encapsulant. In scanning electron microscopy, the incorporation of pomegranate peel flour resulted in a rough and porous structure, probably due to certain interference with the formation of spherical microcapsules, although it presented similar mean diameter, plus higher cell viability as confirmed by confocal laser microscopy. The obtained results indicate that co-encapsulation with a prebiotic ingredient represents a reinforcement of the physical microcapsule integrity to tolerate food process temperatures, besides retarding the adverse effect of acidic, bile salts, and simulated gastrointestinal conditions. The micro alginate co-encapsulation by ionic gelation with a prebiotic as pomegranate peel flour is a suitable alternative to develop thermal processed functional foods.

Factors governing attachment of Rhizobium leguminosarum to legume roots at acid, neutral, and alkaline pHs.

The first step by which bacteria interact with plant roots is by attachment. In this study, we use a combination of insertion sequencing and biochemical analysis to determine how bacteria attach to pea roots and how this is influenced by pH. We identify several key adhesins, which are molecules that enable bacteria to stick to roots. This includes a novel filamentous hemagglutinin which is needed at all pHs for attachment. Overall, 115 proteins are required for attachment at one or more pHs.

Proline substitutions in the ASIC1 β11-12 linker slow desensitization

Desensitization is a prominent feature of nearly all ligand-gated ion channels. Acid-sensing ion channels (ASICs) undergo desensitization within hundreds of milliseconds to seconds upon continual extracellular acidification. The ASIC mechanism of desensitization is primarily due to the isomerization or “flipping” of a short linker joining the 11th and 12th β sheets in the extracellular domain. In the resting and active states this β11-12 linker adopts an “upward” conformation while in the desensitized conformation the linker assumes a “downward” state. It is unclear if a single linker adopting the downward state is sufficient to desensitize the entire channel, or if all three are needed or some more complex scheme. To accommodate this downward state, specific peptide bonds within the linker adopt either trans-like or cis-like conformations. Since proline-containing peptide bonds undergo cis-trans isomerization very slowly, we hypothesized that introducing proline residues in the linker may slow or even abolish ASIC desensitization, potentially providing a valuable research tool. Proline substitutions in the chicken ASIC1 β11-12 linker (L414P and Y416P) slowed desensitization decays approximately 100- to 1000-fold as measured in excised patches. Both L414P and Y416P shifted the steady-state desensitization curves to more acidic pH values while activation curves and ion selectivity were largely unaffected (except for a left-shifted activation pH50 of L414P). To investigate the functional stoichiometry of desensitization in the trimeric ASIC, we created families of L414P and Y416P concatemers with zero, one, two, or three proline substitutions in all possible configurations. Introducing one or two L414P or Y416P substitutions only slightly attenuated desensitization, suggesting that conformational changes in the single remaining faster wild-type subunits were sufficient to desensitize the channel. These data highlight the unusual cis-trans isomerization mechanism of ASIC desensitization and support a model where ASIC desensitization requires only a single subunit.

Exploring photocatalytic tetracycline removal performance under simulated sunlight irradiation: Milling time effect on metallic reduction of MnO/ZrO2 mixed oxide

In the present research, it is reported that ball milling technique can be applied to enhance the photocatalytic properties of MnO and ZrO2 metal oxide powders (MZOx) furthermore the fabricated photocatalyst can be used for the degradation of tetracycline (TTC). XRD analyses revealed that increasing the milling time resulted in the formation of a pure metallic Mn crystal phase, which boosted the antibiotic degradation rate. It was confirmed by SEM technique that the morphological structures of the particles were generally small and uniform. The band gap energy was calculated as 3.70 eV for the hybrid metal oxide. Additionally, the adsorptive and photoluminescence features were illuminated via DRS and PL analyses. The effect of milling time had a major impact on the photodegradation rate of TTC, and the 8 h milling sample (MZOx-8h) exhibited the highest catalytic degradation activity (79.4 %). Low photocatalytic activity was obtained at acidic pHs and increased at alkaline pHs. The presence of H2O2 sharply decreased photocatalytic process time (60 min) and 94.3 % of the TTC was degraded at 7.5 mM H2O2. The photocatalytic degradation process proceeded through superoxide radicals and was supported by holes. The stability of MZOx-8h almost remained constant (70.02 %) even after seven cycles. It was determined that the presence of oxalic acid positively affected the progress of TTC degradation reactions. Further, practical application areas were investigated and MZOx-8h doped on support materials was found to be suitable for such applications in proportion to the doping ratio. Finally, it was demonstrated that MZOx-8h exhibited remarkable performance in photocatalytic reactions of different types of organic pollutants. The synergistic nature of MnO and ZrO2 with the contribution of ball milling time effect resulted in high photocatalytic activity.

Reducing oil and grease on-site in real offshore oilfield-produced water through feasible adsorption-desorption cycling

Although produced water treatment is witnessing an increasing demand worldwide, conventional treatments are limited, marginally aiming at water-soluble pollutants. Here, we develop a cycling adsorption process, targeting water-soluble compounds and mapping the conditions to yield oils and grease content in real water matrix below the legislation requirements, allowing full adsorbent reuse through a feasible offshore route. The adsorption performance was evaluated in terms of pH, adsorbent concentration, and contact time, while the desorption performance was assessed in terms of eluent type, concentration, and contact time. The polymeric resin MN 202 presents an excellent ability to remove oil and grease from the real produced water matrix, and acid pHs favored the process. The adsorption equilibrium is reached after 12 h, with an oil and grease removal of 92 % at pH 5, presenting multilayer adsorption during the process, with an influence of external diffusion governed by hydrophobic and electrostatic interactions. In the desorption process, CH3O− species, originated by NaOH's solubilization in methanol, enables complete adsorbent regeneration in 2 h. The adsorption-desorption cycling is stable, and the adsorbent microstructure assessment indicates no significant changes in the resin surface due to adsorption-desorption runs.

In-Situ structural and Adsorbate Induced Surface Evolutions Monitored By Electrochemical Stress Measurements

We report on in-situ electrochemical stress measurements of well-defined surfaces during electrochemical reactions in aqueous media. Electrochemical stress measurements during hydrogen evolution reaction (HER) on Pt surfaces shows distinct pH-dependent features which we assign to anion adsorption/desorption and hydrogen adsorption/desorption. Our surface stress analysis shows higher hydrogen induced stresses at alkaline environments than stresses observed at acidic pHs. This observation is consistent with the monotonic change in apparent hydrogen binding energy with pH, most likely due to the changes in water interactions with surface. However, H-induced surface stress shows a dramatic increase around neutral pH. We will present our analysis of how interfacial water may explain this effect. Additionally, we will show how in-situ underpotential deposition of Cu on Pt and Ni on Au changes Had induced effects on these surfaces.We will also discuss the structural and compositional evolution of Sr2Fe2O6-δ thin films during oxygen evolution reaction (OER). Interestingly, in-situ electrochemical stress measurements show a tensile stress response during OER which is different from Au model surfaces. We will present our analysis of how potential controlled formation of iron (oxy)hydorxides may explain in-situ stress response and structural evolution of perovskite type structures during OER.In summary, our analysis shows how adsorbate-induced effects can be used to explain surface reactions, and particularly explain and provide insight into interfacial structural changes and water interactions at different pHs.

PH Sensitivity of YFPs is Reduced Upon AlphaRep Binding: Proof of Concept in Vitro and in Living Cells.

Yellow fluorescent proteins (YFPs) are commonly used in biology to track cellular processes, particularly as acceptors in experiments using the Förster Resonant Energy Transfer (FRET) phenomenon. However, their fluorescence intensity is strongly pH-dependent, limiting their utility in acidic environments. Here, we explore the pH sensitivity of YFPs upon binding with an artificial repeat protein (αRep) both in vitro and in living cells. We show that αRep binds to Citrine, with high affinity in the nanomolar range at physiological and acidic pHs, leading to increased thermal stability of the complex. Moreover, αRep binding reduces Citrine's pKa by 0.75 pH units, leading to a decreased sensitivity to pH fluctuations. This effect can be generalized to other YFPs as Venus and EYFP in vitro. An efficient binding of αRep to Citrine has also been observed in living cells both at pH 7.4 and pH 6. This interaction leads to reduced variations of Citrine fluorescence intensity in response to pH variations in cells. Overall, the study highlights the potential of αReps as a tool to modulate the pH sensitivity of YFPs, paving the way for future exploration of biological events in acidic environments by FRET in combination with a pH-insensitive cyan donor.

Bio-inspired conductive ink: Harnessing plant based binder for customizing electrochemical, rheological and printing applications

The search for environmentally friendly electronic materials has become more intense in recent years, encouraged by the need to limit the hazards of electronic waste. Conductive inks are crucial in printed electronics. However, challenges like toxic metals, low throughput, and complex fabrication processes hindered their widespread use and spurred the exploration of natural material-based alternatives. This research explores the development of a natural Rosin and Carbon-based Conductive (RoCa) ink, focusing on optimizing the composition and its in-depth electrochemical, rheological, spectroscopic, and morphological characterization. The developed RoCa ink presented shear thinning behavior with a conductivity range between 500 and 1500 S/m and sheet resistance between 14 and 7.82 Ω/sq. The ink coatings were hydrophobic and stable to acid, basic and neutral pHs. The ink was characterized using Raman spectroscopy to understand carbon allotropes and their disordered forms with layers of graphite. FTIR was used to study the functional groups of the ink and XRD and SEM were used to study crystallite size, particle morphology and blending. The customisable electrochemical and mechanical properties of the RoCa ink paved the way towards sustainable and green printing as an environmentally benign alternative to traditional conductive inks in electronic applications.

Electrochemical Behaviour and Sensing of Chlorpromazine at Polymer‐Free Kaolin‐Based Nanosodalite and Nanosodalite‐Graphene Foam Film modified Glassy Carbon Electrodes

AbstractA nanosodalite (SOD) was synthesized utilizing Cameroonian kaolin and then used to prepare a nanocomposite (SOD‐GF) with graphene foam (GF). The as‐synthesized materials were characterized using X‐ray diffractometry (XRD), Fourier transform‐infrared (FT‐IR) spectroscopy, N2 adsorption‐desorption and scanning electron microscopy coupled with emission dispersive X‐ray (SEM/EDX). The results show a pure sodalite with high degree of crystallinity with crystallite size and BET surface area of 38.3 nm and 22 m2/g, respectively. The composite's characterization revealed a well‐integrated material in which the structural integrity of each material is maintained, its surface area being 4‐fold that of pristine SOD. Stable SOD and SOD‐GF modified glassy carbon electrode (GCE) were prepared by drop coating without a binder and utilized to study the electrochemistry of chlorpromazine (CPZ) in acidic, neutral and basic pHs. It appeared that (i) CPZ's electrochemical oxidation was a two‐step one‐electron process at SOD/GCE and a one‐step two‐electron process at SOD‐GF/GCE and (ii) the electrochemical reaction mechanism was an EEC mechanism at SOD/GCE while at SOD‐GF/GCE the mechanism was EEC at pH&lt;4 and EC for greater pH. SOD/GCE and SOD‐GF/GCE were used to sense CPZ within CPZ's concentration ranging from 0.5‐30 μM with low detection limits.

ZIF-8 nanoparticles synthesis for pH-sensitive release of corrosion inhibitor

Zeolite imidazole framework-8 (ZIF-8), with porous structure and pH sensitivity, is an ideal stimulus-response nanocarrier for delivering molecules. Choosing the appropriate synthesis conditions for achieving the accessible porosity volume is the main challenge in creating ZIF-8. This study synthesized new micro-mesoporous ZIF-8 nanoparticles with a 3.11 nm pore size using an ultrasonic bath in a methanol-dimethylformamide mixed solvent. The response surface methodology was used to explore the impact of the synthesis environments. It was found that the optimized conditions were 8.38 ligand-to-metal ion ratio, 100 % power, 64 min, and 6.11 methanol/dimethylformamide. The optimized particles loaded with a corrosion inhibitor, 2-mercaptobenzothiazole, demonstrated a faster inhibitor release in acidic pHs due to the breakdown of the ZIF-8 structure. This research concluded that blending solvents with varying strengths can yield superior physicochemical properties, facilitating micro-mesoporous ZIF-8 production with high pore volume. This discovery holds promise for producing ZIF-8-based materials that benefit various applications.

Trace Ce(III) boosted acidic peroxone (O3/H2O2) process for efficient water treatment: Essential role of oxalic acid complexation

The peroxone (O3/H2O2) process has long suffered from inefficient performance for water decontamination at acidic pHs. Herein, we find the evident capability of trace Ce(III) to boost the acidic peroxone process. In contrast to the negligible degradation (∼6% in 60 min) of oxalic acid (OA) as a recalcitrant compound in the O3/H2O2 system, efficient removal of OA (∼95 %) was achieved by introducing trace Ce(III) (0.30 µM). OA was identified as an effective ligand activating Ce(III) by forming the Ce(III)-OA complex, which served as the catalytic active component to accelerate the decomposition of O3 and H2O2 to produce •OH and promote the co-degradation of refractory pollutant atrazine and ibuprofen. The remarkable catalytic activity of trace Ce(III) for peroxone reaction resulted from the efficient interconversion of Ce(III/IV) relying on both the favorable electron transfer from the ternary Ce(III)-OA-hydroperoxo complex to O3 and the rapid reduction of Ce(IV) back to Ce(III) mainly by H2O2. Furthermore, the catalytic performance of Ce(III) for peroxone process outperformed Fe(II), Cu(II), and Co(II). This study puts forward an effective method to extrapolate the applicability of the peroxone (O3/H2O2) process to the acidic range and enlightens the development of Ce-catalyzed peroxone processes.

Local Structure and Crystallization Transformation of Hydrous Ferric Arsenate in Acidic H2O-Fe(III)-As(V)-SO42- Systems: Implications for Acid Mine Drainage and Arsenic Geochemical Cycling.

Hydrous ferric arsenate (HFA) is a common thermodynamically metastable phase in acid mine drainage (AMD). However, little is known regarding the structural forms and transformation mechanism of HFA. We investigated the local atomic structures and the crystallization transformation of HFA at various Fe(III)/As(V) ratios (2, 1, 0.5, 0.33, and 0.25) in acidic solutions (pH 1.2 and 1.8). The results show that the Fe(III)/As(V) in HFA decreases with decreasing initial Fe(III)/As(V) at acidic pHs. The degree of protonation of As(V) in HFA increases with increasing As(V) concentrations. The Fe K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure results reveal that each FeO6 is linked to more than two AsO4 in HFA precipitated at Fe(III)/As(V) < 1. Furthermore, the formation of scorodite (FeAsO4·2H2O) is greatly accelerated by decreasing the initial Fe(III)/As(V). The release of As(V) from HFA is observed during its crystallization transformation process to scorodite at Fe(III)/As(V) < 1, which is different from that at Fe(III)/As(V) ≥ 1. Scanning electron microscopy results show that Oswald ripening is responsible for the coarsening of scorodite regardless of the initial Fe(III)/As(V) or pH. Moreover, the formation of crystalline ferric dihydrogen arsenate as an intermediate phase at Fe(III)/As(V) < 1 is responsible for the enhanced transformation rate from HFA to scorodite. This work provides new insights into the local atomic structure of HFA and its crystallization transformation that may occur in AMD and has important implications for arsenic geochemical cycling.

Abstract CT068: Interim results of the ongoing phase 1-2 clinical trial of KVA12123, an engineered IgG1 targeting VISTA, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors

Abstract V-domain Ig Suppressor of T-cell Activation (VISTA), a promising immuno-oncology target, is primarily expressed by immunosuppressive myeloid cells that infiltrate solid tumors. VISTA may contribute to resistance to anti-PD-(L)1 and anti-CTLA-4 therapies and correlates with a poor prognosis. KVA12123 is a human IgG1 monoclonal antibody that specifically binds to VISTA at neutral and acidic pHs. It was designed to improve pharmacokinetic (PK) characteristics as well as reduce the risk of cytokine release syndrome (CRS). KVA12123 exhibited strong anti-tumor activity alone and in combination with anti-PD1 in preclinical studies. It demonstrated an excellent safety profile in non-human primates. The VISTA-101 clinical trial is a first-in-human, Phase 1/2, multicenter, open-label, safety, PK and pharmacodynamic (PD) evaluation of KVA12123, both as monotherapy and in combination with pembrolizumab, in adult patients with advanced solid tumors (NCT05708950). METHODS: The phase 1 of VISTA-101 is an accelerated Bayesian Optimal Interval Design consisting of two arms: Part A) KVA12123 monotherapy dose escalation from 3 mg to 1000 mg including 6 cohorts and Part B) KVA12123 dose escalation from 30 mg to 1000 mg in combination with 400 mg fixed dosing of pembrolizumab including 4 cohorts. The primary objectives are safety, tolerability and to define a recommended phase 2 dose. Safety, PK and receptor occupancy data were considered during dose escalation. VISTA-101 is also assessing PD and predictive biomarkers of response. Patient tumor response is evaluated by iRECIST. RESULTS: Forty-two patients have been enrolled in the dose escalation monotherapy arm of the study. KVA12123 was administered at doses ranging from 3 to 1000 mg every 2 weeks over a 6-week cycle. KVA12123 was well tolerated at all dose levels and no DLTs were observed. The most frequently observed adverse events were grade 1 or 2 transient infusion-related reactions. No evidence of CRS-associated cytokines were detected. PK analysis demonstrated greater than dose-proportional exposure consistent with target-mediated metabolism. A VISTA receptor occupancy assay demonstrated full target engagement at doses of 30 mg and above. PD analysis indicated a dose-dependent induction of pro-inflammatory myeloid derived cytokines and chemokines involved in immune cell activation and recruitment to the tumor microenvironment including CCL2, CCL3, CCL4 and CXCL10. Increases in nonclassical monocytes, NK cells, CD4+ and CD8+ T cells were also demonstrated, consistent with observations made in preclinical models and indicative of VISTA target engagement. Patient tumor response evaluations in the monotherapy arm will be reported. The study continues to evaluate KVA12123 both as a monotherapy and in combination with pembrolizumab to define the recommended phase 2 dose. Citation Format: Evan Y. Yu, Jason Henry, Manish R. Patel, Paul Swiecicki, Ida Micaily, Benjamin Garmezy, Kalyan Banda, Vinny Hayreh, Kurt Lustig, Yulia Ovechkina, Shawn P. Iadonato, Thierry Guillaudeux, Lee Rosen. Interim results of the ongoing phase 1-2 clinical trial of KVA12123, an engineered IgG1 targeting VISTA, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT068.

Sorption of Antibiotics in Agricultural Soils as a Function of pH

This study aims to understand the adsorption/desorption process in six agricultural soils of two antibiotics, Ciprofloxacin (CIP) and Trimethoprim (TRI), widely used today and the influence of pH on this process. Antibiotics can reach the soil through the application of sludge and effluents from wastewater treatment plants and are directly influenced by changes in pH, once in the soil. Therefore, this study with batch experiments allows us to know the adsorption process in a pH range between 2 and 12, in six soils with different organic carbon content, between 1% and 7.7%. The results obtained show that the adsorption of CIP has its maximum at pH between 5 and 7; above and below this range, the adsorption decreases. The soils with the highest organic carbon content (between 4.4% and 7.7%) are those with the highest adsorption. The values for each forms in which the CIP molecule is found are: for KdCIP+, between 0.887 and 8.289 L kg−1; for KdCIP−, between 0.670 and 5.440 L kg−1, while for KdCIP0, the values do not differ from 0, except soils 1 and 3, whose values are 0.206 and 0.615 L kg−1, respectively. Regarding TRI, the maximum adsorption takes place at acidic pHs, below 6 for all soils. Above these values, desorption decreases. The Kd values for each of the species vary between 0.085 and 0.218 L kg−1 for KdTRI+, between 0.011 and 0.056 L kg−1 for KdTRI0, and between 0.092 and 0.189 L kg−1 for KdTRI−. For both antibiotics, the highest adsorption was achieved in the soil with the highest organic carbon content (7.7%). Comparing both antibiotics, we see that CIP presents the highest adsorption, and in the case of desorption, for CIP, it varies between 3.7% and 75.8%, with the maximum desorption at basic pHs. In the case of TRI, desorption is higher, varying between 9.4% and 99.1%, with the maximum around neutrality, except for two soils, whose maximums are at pH of 4.3 and 9.5. These results should be taken into account, as once they reach the soil, pH will be a determining factor in their behaviour and fate.

On the potential role of naturally occurring carboxylic organic acids as anti-infective agents: opportunities and challenges

Carboxylic organic acids are intermediates of central carbon metabolic pathways (e.g. acetic, propionic, citric, and lactic acid) long known to have potent antimicrobial potential, mainly at acidic pHs. The food industry has been leveraging those properties for years, using many of these acids as preservatives to inhibit the growth of pathogenic and/or spoilage fungal and bacterial species. A few of these molecules (the most prominent being acetic acid) have been used as antiseptics since Hippocratic medicine, mainly to treat infected wounds in patients with burns. With the growth of antibiotic therapy, the use of carboxylic acids (and other chemical antiseptics) in clinical settings lost relevance; however, with the continuous emergence of multi-antibiotic/antifungal resistant strains, the search for alternatives has intensified. This prospective article raises awareness of the potential of carboxylic acids to control infections in clinical settings, considering not only their previous exploitation in this context (which we overview) but also the positive experience of their safe use in food preservation. At a time of great concern with antimicrobial resistance and the slow arrival of new antimicrobial therapeutics to the market, further exploration of organic acids as anti-infective molecules may pave the way to more sustainable prophylactic and therapeutic approaches.

Alterations in network robustness upon simultaneous temperature and pH perturbations.

Nervous systems have evolved to function consistently in the face of the normal environmental fluctuations experienced by animals. The stomatogastric nervous system (STNS) of the crab, Cancer borealis, produces a motor output that has been studied for its remarkable robustness in response to single global perturbations. Changes in environments, however, are often complex and multifactorial. Therefore, we studied the robustness of the pyloric network in the stomatogastric ganglion (STG) in response to simultaneous perturbations of temperature and pH. We compared the effects of elevated temperatures on the pyloric rhythm at control, acid, or base pHs. In each pH recordings were made at 11°C, and then the temperature was increased until the rhythms became disorganized ("crashed"). Pyloric burst frequencies and phase relationships showed minor differences between pH groups until reaching close to the crash temperatures. However, the temperatures at which the rhythms were disrupted were lower in the two extreme pH conditions. This indicates that one environmental stress can make an animal less resilient to a second stressor.NEW & NOTEWORTHY Resilience to environmental fluctuations is important for all animals. It is common that animals encounter multiple stressful events at the same time, the cumulative impacts of which are largely unknown. This study examines the effects of temperature and pH on the nervous system of crabs that live in the fluctuating environments of the Northern Atlantic Ocean. The ranges of tolerance to one perturbation, temperature, are reduced under the influence of a second, pH.