Acidic pH Levels Research Articles

Three Strategies in Engineering Nanomedicines for Tumor Microenvironment-Enabled Phototherapy.

Canonical phototherapeutics have several limitations, including a lack of tumor selectivity, nondiscriminatory phototoxicity, and tumor hypoxia aggravation. The tumor microenvironment (TME) is characterized by hypoxia, acidic pH, and high levels of H2 O2 , GSH, and proteases. To overcome the shortcomings of canonical phototherapy and achieve optimal theranostic effects with minimal side effects, unique TME characteristics are employed in the development of phototherapeutic nanomedicines. In this review, the effectiveness of three strategies for developing advanced phototherapeutics based on various TME characteristics is examined. The first strategy involves targeted delivery of phototherapeutics to tumors with the assistance of TME-induced nanoparticle disassembly or surface modification. The second strategy involves near-infrared absorption increase-induced phototherapy activation triggered by TME factors. The third strategy involves enhancing therapeutic efficacy by ameliorating TME. The functionalities, working principles, and significance of the three strategies for various applications are highlighted. Finally, possible challenges and future perspectives for further development are discussed.

Boron-assisted abiotic polypeptide synthesis

The emergence of proteins and their interactions with RNAs were a key step in the origin and early evolution of life. The abiotic synthesis of peptides has been limited in short amino acid length and is favored in highly alkaline evaporitic conditions in which RNAs are unstable. This environment is also inconsistent with estimated Hadean Earth. Prebiotic environments rich in boron are reportedly ideal for abiotic RNA synthesis. However, the effects of boron on amino acid polymerization are unclear. We report that boric acid enables the polymerization of amino acids at acidic and near-neutral pH levels based on simple heating experiments of amino acid solutions containing borate/boric acid at various pH levels. Our study provides evidence for the boron-assisted synthesis of polypeptides in prebiotically plausible environments, where the same conditions would allow for the formation of RNAs and interactions of primordial proteins and RNAs that could be inherited by RNA-dependent protein synthesis during the evolution of life.

Phosphorylated walnut protein/chitosan nanocomplexes as promising carriers for encapsulation of caffeic acid phenethyl ester.

Walnut proteins have poor solubility and dispersity under acidic pH conditions, which limits their application in acidic beverages and foods. The present study aimed to fabricate stable nanocomplexes between phosphorylated walnut protein (PWPI) and chitosan (CS) at acidic pH and investigate the encapsulation capacity of the complexes. PWPI/CS nanocomplexes prepared at a mass ratio of 2:1 showed small Z-average sizes (approximately 285 nm at pH 5.5 and 222 nm at pH 3.5) with a narrow particle distribution (polydispersity index < 0.3). Caffeic acid phenethyl ester (CAPE) can be effectively encapsulated into PWPI/CS with improved solubility. Circular dichroism analysis indicated that PWPI/CS and CAPE-loaded PWPI/CS (PWPI/CS-CAPE) had a reduced α-helical content and increased β-sheet content. Fourier transform infrared spectroscopy analysis further identified the different driving forces for the complexation of PWPI and CS at pH 3.5 and 5.5 and confirmed the successful encapsulation of CAPE. Rheological results revealed that the PWPI/CS and PWPI/CS-CAPE formed at pH 3.5 (PWPI/CS-CAPE-3.5) had a higher apparent viscosity and better viscoelasticity than the complexes formed at pH 5.5. PWPI/CS-CAPE-3.5 also showed good stability under heat treatment, salt treatment, and long-term storage. Moreover, PWPI/CS-CAPE complexes showed controlled release of CAPE. PWPI/CS nanocomplexes prepared at acidic pH were stable and promising carriers for CAPE, which would expand the application of walnut proteins in the food industry. This article is protected by copyright. All rights reserved.

Removal of Methylene Blue and Congo Red Using a Chitosan-Graphene Oxide-Electrosprayed Functionalized Polymeric Nanofiber Membrane.

Untreated textile effluent may contain toxic organic pollutants that can have negative impacts on the ecosystem. Among the harmful chemicals present in dyeing wastewater, there are two frequently used organic dyes: methylene blue (cationic) and congo red (anionic). The current study presents investigations on a novel two-tier nanocomposite membrane, i.e., a top layer formed of electrosprayed chitosan-graphene oxide and a bottom layer consisting of an ethylene diamine functionalized polyacrylonitrile electrospun nanofiber for the simultaneous removal of the congo red and methylene blue dyes. The fabricated nanocomposite was characterized using FT-IR spectroscopy, scanning electron microscopy, UV-visible spectroscopy, and Drop Shape Analyzer. Isotherm modeling was used to determine the efficiency of dye adsorption for the electrosprayed nanocomposite membrane and the confirmed maximum adsorptive capacities of 182.5 mg/g for congo red and 219.3 mg/g for methylene blue, which fits with the Langmuir isotherm model, suggesting uniform single-layer adsorption. It was also discovered that the adsorbent preferred an acidic pH level for the removal of congo red and a basic pH level for the removal of methylene blue. The gained results can be a first step for the development of new wastewater cleaning techniques.

Peptide Models of the Cytoplasmic Tail of Influenza A/H1N1 Virus Hemagglutinin Expand Understanding its pH-Dependent Modes of Interaction with Matrix Protein M1.

Influenza A virus hemagglutinin (HA) is a major virus antigen. No cryo-electron microscopy or X-ray data can be obtained for the HA intraviral (cytoplasmic) domain (CT) post-translationally modified with long fatty acid residues bound to three highly conserved cysteines. We recently proposed a model of HA CT of Influenza A/H1N1 virus possessing an antiparallel beta structure based on the experimental secondary structure analysis of four 14-15 amino acid long synthetic peptides, corresponding to the HA CT sequence, with free or acetaminomethylated cysteines. To dispel doubts about possible non-specific "amyloid-like" aggregation of those synthetic peptides in phosphate buffer solution, we have determined the order of oligomers based on blue native gel electrophoresis, membrane filtration, fluorescence spectroscopy and molecular modeling approaches. We have found that unmodified peptides form only low molecular weight oligomers, while modified peptides form both oligomers of low order similar to those found for unmodified peptides and high order conglomerates, which however are not of beta-amyloid-like fold. This study confirms that the beta structure previously detected by circular dichroism spectroscopy analysis is more likely the result of intrinsic propensity of the HA CT amino acid sequence than the consequence of aggregation. The structures of low order oligomers of the synthetic peptides were used for in silico experiments on modeling of HA CT interactions with matrix protein M1 at physiological and acidic pH levels and revealed two different areas of binding. Finally, tripeptides capable of blocking interactions between HA CT and M1 were proposed.

Isotherm and kinetic studies of acid yellow 11 dye adsorption from wastewater using Pisum Sativum peels microporous activated carbon

In this study, Pea Peels-Activated Carbon (PPAC), a novel biochar, was created from leftover pea peels (Pisum sativum) by wet impregnation with ZnCl2 and subsequent heating to 600, 700, and 800 °C in a CO2 atmosphere. Investigated how the newly acquired biochar affected the capacity to extract the AY11 dye from the aqueous solution. Through the use of FTIR, XRD, SEM, BJH, BET, DSC, EDX, and TGA studies, the prepared PPAC was identified. It was found that a pH of 2 is optimum for the AY11 dye elimination. The highest removal percentage of AY11 dye was 99.10% using a beginning AY11 dye concentration of 100 mg/L and a 1.0 g/L dose of PPAC. The highest adsorption capacity (Qm) of the PPAC was 515.46 mg/g. Freundlich (FIM), Halsey (HIM), Langmuir (LIM), Tempkin (TIM), and Gineralize (GIM) isotherm models were useful in examining the adsorption results. A variety of error functions, including the average percent errors (APE), root mean square errors (RMS), Marquardt's percent standard deviation (MPSD), hybrid error function (HYBRID), Chi-square error (X2) and a sum of absolute errors (EABS) equations, were also applied to test the isotherm models data. The PPAC experimental data were best suited by the HIM and FIM isotherm models. Elovich (EM), Pseudo-first-order (PFOM), Intraparticle diffusion (IPDM), Pseudo-second-order (PSOM), and Film diffusion (FDM) models were applied to study the kinetic adsorption results. The PSOM had a strong correlation coefficient (R2 > 0.99), and it was principally responsible for controlling the adsorption rate. Anions are typically absorbed during the adsorption mechanism of AY11 dye by PPAC owing to attractive electrostatic forces created with an increase in positively charged areas at acidic pH levels. The regenerated PPAC was used in six successive adsorption/desorption cycles. This study's outcomes show that PPAC successfully removes the AY11 dye from the aqueous solution; as a result, PPAC can be used repeatedly without experiencing considerable loss in effectiveness.

Adjusting pH Levels In Respect to Crustacean Hatching Rates

Currently, studies have been conducted focusing around aquatic species and how chemical properties within the water may impact their survival, such as the effect of pH levels on flounder eggs. In specific, the study discussed how acidic pH levels negatively affected their development and survival rate. However, there is limited research conducted pertaining to the connection between pH levels and crustaceans. This begs the question: how do differing pH levels in water affect the hatching rates of aquatic organisms, specifically crustaceans? Based on previous studies, if crustaceans are exposed to acidic pH levels, then the hatching rates will be negatively affected. In order to prove this, an experimental method was used with five samples with different pH levels and sea monkeys added to them. Sea monkeys, a hybrid breed of brine shrimp, were used in order to represent crustaceans in the experiment. The five samples were recorded hourly for times of initial hatching and the relative amount of eggs hatched. Concluding the experimental process the results showed that the basic pH levels had negative effects towards the hatching rates with no survival at 8.0 and very little survival at 7.5. Also, there was an increased rate of hatching for the acidic pH levels with the highest abundance of sea monkeys and the quickest to hatch at 6.0. Overall, the data concludes that the basic pH levels negatively affect the hatching rates of crustacean eggs, and the acidic pH levels had little effect on the hatching rates.

High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions

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

Effect of pH and Carbon Source on Phosphate Solubilization by Bacterial Strains in Pikovskaya Medium.

Phosphate-solubilizing bacteria (PSB) transform precipitated inorganic phosphorus into soluble orthophosphates. This study evaluated the efficiency of tricalcium and iron phosphate solubilization in Pikovskaya medium using five bacterial strains (A1, A2, A3, A5, and A6) cultured in acidic and alkaline pH levels. The bacterial strain that proved to be more efficient for P solubilization and was tolerant to pH variations was selected for assessing bacterial growth and P solubilization with glucose and sucrose in the culture medium. The bacterial strains were identified through 16S rRNA gene sequencing as Pseudomonas libanensis A1, Pseudomonas libanensis (A2), Bacillus pumilus (A3), Pseudomonas libanensis (A5), and Bacillus siamensis (A6). These five bacterial strains grew, tolerated pH changes, and solubilized inorganic phosphorus. The bacterial strain A3 solubilized FePO4 (4 mg L-1) and Ca3(PO4)2 (50 mg L-1). P solubilization was assayed with glucose and sucrose as carbon sources for A3 (Bacillus pumilus MN100586). After four culture days, Ca3(PO4)2 was solubilized, reaching 246 mg L-1 with sucrose in culture media. Using glucose as a carbon source, FePO4 was solubilized and reached 282 mg L-1 in six culture days. Our findings were: Pseudomonas libanensis, and Bacillus siamensis, as new bacteria, can be reported as P solubilizers with tolerance to acidic or alkaline pH levels. The bacterial strain B. pumilus grew using two sources of inorganic phosphorus and carbon, and it tolerated pH changes. For that reason, it is an ideal candidate for inorganic phosphorus solubilization and future production as a biofertilizer.

A novel and water-soluble material for coronavirus inactivation from oseltamivir in the cavity of methyl and sulfated-β-cyclodextrins through inclusion complexation

A potentially active water-soluble anti-viral with lesser toxic material from the Oseltamivir (OTV) has been produced by the sonication method. The formed material has been further characterized by UV–visible, FT-IR, powder XRD, SEM, TGA/DTA, ROESY, XPS, AFM and etc., The results of DFT calculation have proven that inclusion complexes (ICs) are theoretically and energetically more advantageous models and structures have also been proposed based on the results. Analysis of drug release has been carried out at three pH levels, and it is revealed the analysis is most helpful at acidic pH levels for the ICs with S-CD over H-CD. Over OTV without CDs, OTV:S-CD-ICs exhibited a very less cytotoxic ability on cancer cell lines than ICs with M-CD. ICs enhanced the coronavirus inactivation nature of OTV. This study provides for the first time a full characterization of ICs of OTV with CDs and highlights the impact of complexation on pharmacological activity.

Physico-Chemical Quality Of Drinking Water From Various Sources In Abia State, Nigeria

The majority of Nigerians lack access to a safe drinking water source, making sustainable and equitable access to safe drinking water a challenge. The current study was designed to evaluate the physicochemical quality of drinking water from various sources in 24 randomly selected communities throughout Abia State, Nigeria. These communities were selected from 8 Local Government Areas within the 3 senatorial zones of Abia State. Using sterile universal containers, water samples were collected from the major drinking water sources in the selected communities. On-site evaluation of the pH, electrical conductivity (EC), total dissolved solids (TDS) and temperature of the water samples was carried out using a HI9813-6 pH/EC/TDS/Temperature meter. The pH values of the water samples from all sampled communities ranged between 4.1 and 5.9, and the acidic pH levels of the water samples were not within the Nigerian Industrial Standard's (NIS) approved range of 6.5 - 8.5. Furthermore, the water sources in the selected communities were found to have ambient temperatures ranging from 25.8 - 31.8oC. The average electrical conductivity (0.04 µS/cm) and total dissolved solids (36.4 mg/L) of water samples from all senatorial zones studied were both within acceptable limits of 1000 µS/cm and 500 mg/L respectively. Although the other parameters (temperature, EC and TDS) evaluated in this study were within acceptable limits for drinking water physicochemical quality, this study emphasizes the importance of effective water treatment, safe distribution to households, and continuous monitoring and quality assessment of drinking water sources in Nigeria.

Digestibility of a Lignocellulose Supplemented Diet and Fecal Quality in Beagle Dogs.

Simple SummaryObesity is not only a serious health problem for humans, but is also recognized as an immense health threat in pets. The use of lignocellulose in extruded diet might be used in pet food companies as a strategy to reduce energy density. These findings suggest that including lignocellulose supplementation up to 4% in dogs’ diets was well accepted, with an allowable reduction of the apparent digestibility of the control diet. Moreover, the stool remains solid and well-formed , and it increases fecal dry matter, indicating that it should be considered as a potential source of dietary fiber in dog food.Lignocellulose (LC) might be used as a substitute fiber source for dogs as a strategy to decrease energy density and enhance gastrointestinal functionality. The objective of the present study was to compare the effects of including different levels of LC on apparent nutrient digestibility and fecal parameters (dry matter (DM), fecal score, and daily fecal output), as well as fecal fatty acid concentrations. Four diets were tested: control diet (no supplementation of LC; LC0), and three control diets diluted with increasing levels of LC: 1, 2, and 4% (LC1, LC2, and LC4). Six Beagle dogs (BW 17.1 kg ± 1.22) participated in a crossover experimental design. Before each experimental period, five days were used as a wash-out period. The fecal consistency was scored based on a 5-point scale (1 = very hard; 2 = solid, well-formed “optimum”; 3 = soft, still formed; 4 = pasty, slushy; and 5 = watery diarrhea). The results demonstrated that the organic matter apparent digestibility (p = 0.01) and nitrogen-free extract (NFE) (p < 0.01) was significantly lower for dogs fed LC4 compared to those fed LC0. Dogs fed LC2 and LC4 had a lower fecal consistency score (2.39 and 2.18, respectively; p < 0.05). The fecal DM was significantly the highest (p < 0.01), and the daily fecal output on fresh matter was lower (p < 0.05) when dogs were fed the LC4 diet compared with the LC0 diet. Including LC at 1% in the diet resulted in significantly higher fecal acidic pH levels. However, no differences among treatments were noted regarding fecal fatty acid concentrations.

Smart films of carbohydrate-based/sunflower wax/purple Chinese cabbage anthocyanins: A biomarker of chicken freshness

Innovative pH-colorimetric sensor film was fabricated from agar and methylcellulose matrix (AM) with various concentrations of sunflower wax (SFW) (6%, 9%, 12%, and 15% w/w) combined with purple Chinese cabbage (CPC) anthocyanins for tracking chicken breast freshness. A bio-composition film AM/CPC with (hydrophobic) SFW exhibited significant color variations in acidic pH level of (2–6) and a slight shift in alkaline pH levels ranging from (7–12), as well as marked color change due to ammonia vapor. Microstructure analyses revealed that SFW was fixed effectively into the AM-CPC matrices. The incorporation of varying SFW concentrations enhanced the mechanical, thermal, antioxidant activity, reduced anthocyanin release and physical properties (mainly water vapor permeability), with the best performance at AM/CPC/9% SFW. Interestingly, SFW films demonstrated perfect defense opposing UV–vis and visible light. Finally, it was proved that the efficiency of the pH-colorimetric film as an indicator for evaluating the freshness of chicken breast.

A pH-stable, mucin based nanoparticle system for the co-delivery of hydrophobic and hydrophilic drugs

Biopolymer-based drug carriers are commonly used for the development of safe delivery systems. However, biopolymer-based systems are often highly sensitive to the acidic pH levels in the stomach and release most of their cargo before they have reached their point of destination. Such premature drug release combined with the resulting high dose requirements is not cost-efficient and comes with the risk of unwanted side effects on non-target tissues/organs. This problem can be mitigated by the mucin-based drug carriers developed here, which exhibit good stability at acidic pH levels as proven by dynamic light scattering and enzymatic degradation tests with pepsin. In addition, the mucin-based particles can deliver hydrophobic and hydrophilic drugs simultaneously, which is demonstrated both with experiments performed under in vitro sink conditions and with drug transport tests involving eukaryotic cells as targets. As photo-induced cross-links covalently stabilize those particles, they can release their payload over time in a sustained manner. The drug carrier system introduced here combines good stability with high drug encapsulation efficiency and very good biocompatibility and thus may be valuable for a broad spectrum of applications in biological settings.

Simulated large joint fluid model for evaluating intra-articular antibiotic delivery systems: initial evaluation using antibiotic-loaded calcium sulfate beads.

Introduction: Local antimicrobial delivery via calcium sulfate (CaSO) beads is used as an adjunctive treatment for periprosthetic joint infection. There is limited clinical information describing the performance of antimicrobial-loaded CaSO (ALCS) in large-scale applications. We developed a simulated large joint model to study properties of eluting ALCS. Methods: The in vitro testing platform was an adapted standardized model for tribological testing of prosthetic total hips and total knees (ASTM F732). The model was 70 mL total fluid volume, 25 % bovine serum, and 75 % phosphate-buffered saline, using ISO standard 14242-1 for human synovial fluid simulation. Four brands of CaSO were evaluated. Each 10 mL of CaSO was loaded with 1.2 grams (g) of tobramycin and 1 g of vancomycin powders. A 35 mL bead volume, equaling 175 beads, of each product was placed in incubated flasks. The test period was 6 weeks with scheduled interval fluid exchanges. Fluid samples were tested for antibiotic and calcium concentrations and pH. Results: Antibiotic elution showed an initial burst on Day 1, followed by a logarithmic reduction over 1 week. Tobramycin fully eluted within 2.5 weeks. Vancomycin showed sustained release over 6 weeks. Calcium ion concentrations were high, with gradual decrease after 3 weeks. All four CaSO products were inherently acidic. Fluid became more acidic with the addition of antibiotics primarily driven by vancomycin. Discussion: Clinicians should be cognizant of tobramycin elution burst with ALCS in large loads. The main driver of acidic pH levels was vancomycin. We propose that joint complications may result from lowered fluid acidity, and we suggest clinical study of synovial pH.

Tumor microenvironment-responsive BSA nanocarriers for combined chemo/chemodynamic cancer therapy

Tumor microenvironment (TME), characterized by high glutathione (GSH), high hydrogen peroxide (H2O2) and acidic pH levels, is favorable for the growth, invasion and metastasis of cancer cells. Taking advantage of the specific characteristics of tumors, TME-responsive GCBD NPs are designed to deliver nanoscale coordination polymers (NCPs, GA-Cu) and chemotherapy drugs (doxorubicin, DOX) based on bovine serum albumin (BSA) nanocarriers into cancer cells for combined chemodynamic therapy (CDT) and chemotherapy. In an acidic environment, GCBD NPs could release approximately 90% copper ions, which can not only consume overexpressed GSH to modulate the TME but can also react with endogenous H2O2 in a Fenton-like reaction to achieve the CDT effect. Meanwhile, the released DOX could enter the nucleus of tumor cells and affect their proliferation to achieve efficient chemotherapy. Both in vitro and in vivo experiments showed that GCBD NPs had good biosafety and could effectively inhibit the growth of cancer cells. GCBD NPs are promising as a biocompatible nanoplatform to exploit TME characteristics for combined chemo and chemodynamic therapy, providing a novel strategy to eradicate tumors with high efficiency and specificity.Graphical

Vertical changes in the geochemical distributions of iron, manganese and heavy metals in wetland soil cores from cold temperate zones in northeastern China

Pedogenic processes influence the geochemical distributions of elements in soils. Such knowledge, however, is lacking on wetland soil in the cold temperate zone of northeastern China. Two wetland soil cores were collected, sliced at 5 cm intervals, and analyzed for pH, soil organic matter (SOM), Al, Fe, Ti, Mn, Co, Cr, Cu, Ni, and Pb. The results showed that the wetland soil cores were characterized by acidic pH levels, SOM accumulations in the A horizon, eluviation of Fe and Mn from the A and E horizons, and their illuviation in the B horizon. The heavy metals, Co and Pb, were leached from the A and E horizons and subsequently accumulated in the B horizon during pedogenic processes, while Cr, Cu, and Ni might not have migrated significantly. The average Co and Pb concentrations in the B horizon were 47.6 and 70.4 mg kg−1, respectively, which were several times higher than those in the A and E horizons. In the B horizon, five heavy metals, especially Co and Pb, preferentially partitioned in the Fe/Mn oxide phase (e.g., 45.4%, 27.5%, 9.4%, 8.3%, and 7.3% for Co, Pb, Ni, Cr, and Cu, respectively), following the residual phase. In the A and E horizons, however, these metals preferentially partitioned into different mineral phases (e.g., the Fe/Mn oxide phase for Co, organic matter phase for Cr and Cu, Fe/Mn oxide and organic matter phases for Ni, and carbonate and Fe/Mn oxide phases for Pb) following the residual phase. Therefore, pedogenic processes influenced the vertical distributions of both the heavy metal concentrations and their chemical forms in the wetland soil of cold temperate zones. This work provides insights into the behavior of major and trace metals in the soil depth profiles of seasonally waterlogged and freezing-thawing wetland soils.

Mitigating off-target distribution and enhancing cytotoxicity in breast cancer cells with alpha-ketoglutaric acid-modified Fe/Mg-CA nanoparticles

Abstract Purpose In this work, pH-sensitive alpha-ketoglutaric acid-modified Fe/Mg-carbonate apatite (α-KAM-Fe/Mg-CA) NPs were introduced and found to be capable of promoting the selective delivery of cancer-killing drug doxorubicin (DOX) in breast cancer cells, while simultaneously mitigating DOX toxicity on normal cells. Methods As part of the characterization and evaluation of α-KAM-Fe/Mg-CA NPs to target breast cancer cells, a series of assessments were performed, which included size measurements, morphological analysis, FTIR, cytotoxicity assessment, hemolysis, drug binding, cellular uptake, and pH-responsive drug release tests. Liquid chromatography-mass spectrometry was used to conduct the protein corona analysis of α-KAM-Fe/Mg-CA using 10% FBS (fetal bovine serum) and mice plasma. Furthermore, to investigate the distribution of DOX-loaded α-KAM-Fe/Mg-CA NPs in major tissues and the tumor, a biodistribution investigation was conducted in mammary tumor-induced Balb/c mouse models 24 h after the intravenous administration of DOX-loaded α-KAM-Fe/Mg-CA NPs. Results The in vitro pH-dependent release of DOX over time demonstrated that α-KAM-Fe/Mg-CA NPs were pH-responsive and degraded rapidly at acidic pH levels. When compared to free DOX, the DOX-loaded α-KAM-Fe/Mg-CA NPs demonstrated a potent antiproliferative effect on breast cancer cells. Confocal microscopy confirmed the effective internalization of DOX-loaded α-KAM-Fe/Mg-CA NPs in breast cancer cells. The protein corona analysis revealed an affinity for dysopsonins (serum albumin, apolipoproteins) and transport proteins that may assist in extending their blood circulation period. Furthermore, biodistribution data of DOX-loaded α-KAM-Fe/Mg-CA NPs in the mammary tumor-induced Balb/c mouse model indicated extended circulation in the bloodstream, reduced non-target distribution in major tissues, and increased drug accumulation in the tumor. Conclusion The results obtained suggest that α-KAM-Fe/Mg-CA NPs may emerge as a prospective candidate for delivering therapeutic cargos to treat malignant mammary tumors.

EP179: Expanding the phenotype of CLCN6-associated early-onset neurodegeneration

The de novo c.1658A>G (p.Tyr553Cys) missense variant in CLCN6, which encodes the late endosomal Cl-/H+-exchanger ClC-6, was recently identified as a novel pathogenic variant associated with severe, early-onset neurodegenerative disease in 3 unrelated European children. Global developmental delay, generalized hypotonia, respiratory insufficiency, and diffusion restriction on MRI brain were described as diagnostic features. On a cellular level, functional studies demonstrated a gain-of-function in ClC-6 especially prominent at acidic external pH levels, such as those in late endosomes and lysosomes.

Removal of Arsenate in drinking water sources by combined coagulation process

The objective of this study is to examine arsenate (As(V)) removal from drinking water sources with combined coagulation processes using Single-Walled Carbon Nanotubes (SWCNTs) and Multiwalled Carbon Nanotubes (MWCNTs). Ulutan Lake Water (ULW) in Zonguldak-Turkey, was used as drinking water source. Conventional coagulation experiments was conducted on using aluminum sulfate (Alum) and ferric chloride (FeCl3). Water samples were synthesized by spiking 300 µg/L As(V) into ULW samples and also all arsenic removal tests were performed with As(V). The maximum removal percentages of As(V) (97%) was observed with combined SWCNTs and FeCl3 in ULW. Similar to that of SWCNTs, the removal of As(V) (92%) during the coagulation processes occurred at MWCNT with the addition of FeCl3. Compared to SWCNTs, the removal percentage of As(V) was slightly lower when using only MWCNTs (76%). This result demonstrated that SWCNTs were generally more powerful than MWCNTs for removing the As(V). The presence of humic acid (HA) increased As(V) removal with related the solution pH. On the other hand, the changing of As(V) residual concentrations in ULW was observed as a function of pH and the removal of As(V) increases in the acidic pH levels whereas decreases alkaline pH levels. While As(V) removal efficiency was remained constant at acidic pH values, it decreased about 10% at pH 6, 7 and 8 as a result of the competitive adsorption between As(V) and HA. It was observed that the As(V) removal efficiency increased both low and high pH with monovalent electrolyte (NaCl) whereas di-valent ions (Ca+2 and Mg+2) improved As(V) removal only at pH 9 and 10 during the coagulation processes in ULW samples. The results of this study display that combined coagulation process is more effective than conventional coagulation alone for the As(V) removal.