Acid Function Research Articles

Exploring the formation mechanism of ferulic acid/hydroxypropyl-β-cyclodextrin inclusion complex: spectral analyses and computer simulation.

The biological functions of ferulic acid (FA) have garnered significant interest but its limited solubility and stability have led to low bioavailability. Hydroxypropyl-β-cyclodextrin (HP-β-CD), with its distinctive hollow structure, offers the potential for encapsulating hydrophobic molecules. The formation of an inclusion complex between FA and HP-β-CD may therefore be a viable approach to address the inherent limitations of FA. To investigate the underlying mechanism of the FA/HP-β-CD inclusion complex formation, a combination of spectral analyses and computer simulation was employed. The disappearance of the characteristic peaks of FA in Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the formation of an inclusion complex between FA and HP-β-CD. Thermogravimetry-derivative thermogravimetry (TG-DTG) studies demonstrated that the thermal stability of FA was enhanced due to the encapsulation of FA within HP-β-CD. Molecular dynamics simulation also provided evidence that FA successfully penetrated the HP-β-CD cavity, primarily driven by van der Waals interactions. The formation of the complex resulted in more compact HP-β-CD structures. The bioavailability of FA was also strengthened through the formation of inclusion complexes with HP-β-CD. The findings of this study have contributed to a deeper understanding of the interactions between FA and HP-β-CD, potentially advancing a delivery system for FA and enhancing the bioavailability of insoluble active components. © 2024 Society of Chemical Industry.

Nutritional Quality Implications: Exploring the Impact of a Fatty Acid-Rich Diet on Central Nervous System Development.

Given the comprehensive examination of the role of fatty acid-rich diets in central nervous system development in children, this study bridges significant gaps in the understanding of dietary effects on neurodevelopment. It delves into the essential functions of fatty acids in neurodevelopment, including their contributions to neuronal membrane formation, neuroinflammatory modulation, neurogenesis, and synaptic plasticity. Despite the acknowledged importance of these nutrients, this review reveals a lack of comprehensive synthesis in current research, particularly regarding the broader spectrum of fatty acids and their optimal levels throughout childhood. By consolidating the existing knowledge and highlighting critical research gaps, such as the effects of fatty acid metabolism on neurodevelopmental disorders and the need for age-specific dietary guidelines, this study sets a foundation for future studies. This underscores the potential of nutritional strategies to significantly influence neurodevelopmental trajectories, advocating an enriched academic and clinical understanding that can inform dietary recommendations and interventions aimed at optimizing neurological health from infancy.

Synthesis and Characterization of Enhanced Proton-Conducting Nafion<sup>® </sup>117- Silica Composite Membranes for Fuel Cell Applications

Nafion®/silica nanocomposite membranes were prepared by impregnation method from Nafion® 117 and sol-gel pre-synthesized n-octadecyl-trimethoxy silane (C18TMS) coated silica nanoparticles. The scanning electron microscope (SEM) of pristine silica particles displayed monodispersed nanospheres with diameters ranging from 150-350 nm; while Brunauer-Emmett-Teller (BET) analysis presented 760 m2/g BET surface area, a micropore-mesopore bimodal distribution of micropore systems with respective pore volume at 14.6 Å and 17.0 Å (2.01 x 10-3 cm3/g.Å), as well as the prolific mesopores centered at 29.5 Å (5.64 x 10-2 cm3/g.Å). Characterization of Nafion® 117 based membranes on SEM, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and x-ray diffraction (XRD), and tensile stress exhibited varying surface morphology with silica loadings, structural interaction between membrane support and the ion exchanger, thermal stabilities (up to 330 °C), crystalline nature, and reasonable mechanical stability of nanocomposite membranes. The maximum water uptake (44.8 %) and proton conductivity of (1.14 x10-2 S/cm) were obtained on low Nafion®/SiO2 (5%) loaded membrane. While both composite membranes displayed the improved reduction in methanol permeability, 2.43x10-07 cm2/s at 80 °C was obtained with high Nafion®/SiO2 (10%) loading. Improved water uptake and proton conductivity substantiate the high ion exchange capacity (IEC) of 1.81 meq.g-1 when compared to IEC of 0.93 meq.g-1 [pristine Nafion®] and 1.46 meq.g-1 [Nafion®/SiO2 (10%)]. The increase in IEC value may be due to the high acid functionalization of additional sulfonic acid groups surrounded by hydrophilic segments of nanosilica, which improves the properties of the membrane. The high proton conductivity coupled with great water retention capabilities indicated that the Nafion®/SiO2 nanocomposite membranes could be utilized as proton exchange membranes for medium temperature methanol fuel cells. Keywords: Fuel cells; nanocomposite membrane; SiO2 nanofillers; methanol permeability; ion exchange capacity

The Molecular Architecture and Mode of Action of Clostridium perfringens ε-Toxin

Clostridium perfringens ε-toxin has long been associated with a severe enterotoxaemia of livestock animals, and more recently, was proposed to play a role in the etiology of multiple sclerosis in humans. The remarkable potency of the toxin has intrigued researchers for many decades, who suggested that this indicated an enzymatic mode of action. Recently, there have been major breakthroughs by finding that it is a pore-forming toxin which shows exquisite specificity for cells bearing the myelin and lymphocyte protein (MAL) receptor. This review details the molecular structures of the toxin, the evidence which identifies MAL as the receptor and the possible roles of other cell membrane components in toxin binding. The information on structure and mode of action has allowed the functions of individual amino acids to be investigated and has led to the creation of mutants with reduced toxicity that could serve as vaccines. In spite of this progress, there are still a number of key questions around the mode of action of the toxin which need to be further investigated.

The changing metabolic landscape of bile acids - keys to metabolism and immune regulation.

Bile acids regulate nutrient absorption and mitochondrial function, they establish and maintain gut microbial community composition and mediate inflammation, and they serve as signalling molecules that regulate appetite and energy homeostasis. The observation that there are hundreds of bile acids, especially many amidated bile acids, necessitates a revision of many of the classical descriptions of bile acids and bile acid enzyme functions. For example, bile salt hydrolases also have transferase activity. There are now hundreds of known modifications to bile acids and thousands of bile acid-associated genes, especially when including the microbiome, distributed throughout the human body (for example, there are >2,400 bile salt hydrolases alone). The fact that so much of our genetic and small-molecule repertoire, inboth amount and diversity, is dedicated to bile acid function highlights the centrality of bile acids as key regulators of metabolism and immune homeostasis, which is, in large part, communicated via the gut microbiome.

β-Galactoside α 2-6 Sialyltransferase gene expression in Bombyx mori tissues

Bombyx mori is an important insect due to its genome, homology to humans, and ease of growth. Sialylation has been reported in some insects, but sialic acid biosynthesis cannot be observed in these insects. Sialic acids are negatively charged nine carbon sugars located terminally on glycoconjugates. Sialylation, which occurs after translation and is regulated by enzymes, has been studied in prokaryotes, dueterostomes, and protostomes. One of the enyzme that important for sialylation is sialyltransferases. This enyzme play role at linked sialic acid to glycoconjugates. In this study we investigated sialyltransferase (β-Galactoside α-2,6-Sialyltransferase I) gene expression in tissues of B. mori. B. mori larvae, which were fed with fresh mulberry leaves since hatching, were divided into two groups; the control group, which continued to be fed with fresh mulberry leaves in the 5th instar (last instar) and the treatment group, which was fed with mulberry leaves treated with sialic acid solution. Midgut, fat body, hemocyte, ovary and testicular tissues were dissected and gene expressions were examined with Real-Time PCR. The expression level observed in every tissue but increase seen in only fat body. Fat body is very important tissue for insect, plays a fundamental role in immunity, endocrine and detoxification processes. The reason for the highest gene expression in fat body can be attributed to the similarities in the functions of fat body and sialic acid and their roles in insects.

Non-enzymatic Detection of Uric Acid in Serum and Urine by Fluorescent and Visual Dual-Mode Sensor Based on 3-aminophenylboric Acid Functionalized Carbon Dots.

Herein, we developed a sophisticated dual-mode sensor that utilized 3-aminophenylboric acid functionalized carbon dots (APBA-CDs) to accurately detect uric acid (UA). Our innovative process involved synthesizing APBA-CDs that emitted at 369nm using a one-step hydrothermal method with 3-aminophenylboric acid and L-glutamine as precursors, ethanol and deionized water as solvents. Once UA was introduced to the APBA-CDs, the fluorescence of the system became visibly quenched. The results of Zeta potential, Fourier transformed infrared (FTIR) spectra, fluorescence lifetime, and other characteristics were analyzed to determine that the reaction mechanism was static quenching. This meant that after UA was mixed with APBA-CDs, it combined with the boric acid function on the surface to form complexes, resulting in a decrease in fluorescence intensity and a blue shift in the absorption peak at about 295nm in the Ultraviolet-visible (UV-vis) absorption spectra. We were pleased to report that we have successfully used the dual-reading platform to accurately detect UA in serum and human urine. It provided a superior quantitative and visual analysis of UA without the involvement of enzymes. We firmly believe that our innovative dual-mode sensor has immense potential in the fields of biosensing and health monitoring.

Cefotaxime Exposure-Caused Oxidative Stress, Intestinal Damage and Gut Microbial Disruption in Artemia sinica.

Cefotaxime (CTX) is an easily detectable antibiotic pollutant in the water environment, but little is known about its toxic effects on aquatic invertebrates, especially on the intestine. Here, we determined the oxidative stress conditions of A. sinica under CTX exposure with five concentrations (0, 0.001, 0.01, 0.1 and 1 mg/L) for 14 days. After that, we focused on changes in intestinal tissue morphology and gut microbiota in A. sinica caused by CTX exposure at 0.01 mg/L. We found malondialdehyde (MDA) was elevated in CTX treatment groups, suggesting the obvious antibiotic-induced oxidative stress. We also found CTX exposure at 0.01 mg/L decreased the villus height and muscularis thickness in gut tissue. The 16S rRNA gene analysis indicated that CTX exposure reshaped the gut microbiota diversity and community composition. Proteobacteria, Actinobacteriota and Bacteroidota were the most widely represented phyla in A. sinica gut. The exposure to CTX led to the absence of Verrucomicrobia in dominant phyla and an increase in Bacteroidota abundance. At the genus level, eleven genera with an abundance greater than 0.1% exhibited statistically significant differences among groups. Furthermore, changes in gut microbiota composition were accompanied by modifications in gut microbiota functions, with an up-regulation in amino acid and drug metabolism functions and a down-regulation in xenobiotic biodegradation and lipid metabolism-related functions under CTX exposure. Overall, our study enhances our understanding of the intestinal damage and microbiota disorder caused by the cefotaxime pollutant in aquatic invertebrates, which would provide guidance for healthy aquaculture.

Lactiplantibacillus plantarum strains KABP011, KABP012, and KABP013 modulate bile acids and cholesterol metabolism in humans.

Probiotics with high bile salt hydrolase (BSH) activity have shown to promote cardiovascular health. However, their mechanism(s) of action remain poorly understood. Here, we performed a pilot exploratory study to investigate effects of a 4-week intervention with escalating doses of a BSH-active formula containing Lactiplantibacillus plantarum strains KABP011, KABP012, and KABP013 on bile acid (BA), lipid profile, and lipoprotein function. Healthy overweight individuals were included in this study. The probiotic intake was associated with a progressive decrease of conjugated BAs in serum, due to the reduction of tauro- and glyco-conjugated forms. Plasma levels of fibroblast growth factor-19 were significantly reduced and correlated with BA changes. The probiotic induced significant changes in serum lipids, with reduction in non-HDL cholesterol (non-HDLc) and LDL cholesterol (LDLc) levels. The largest decrease was evidenced in the subgroup with higher baseline LDLc levels (LDLc > 130 mg/dL). Fasting levels of circulating apolipoprotein(Apo) B100 and ApoB48 were significantly reduced. Importantly, the decrease in non-HDLc levels was associated with a significant reduction in small LDL particles. Functional testing indicated that LDL particles had a significantly lower susceptibility to oxidation, while HDL particles gained antioxidant capacity after the probiotic intake. The microbiota profile in faeces collected at the end of the study was enriched with members of class Desulfovibrio, a taurine-consuming bacteria, likely because of the increase in free taurine in the gut due to the BSH activity of the probiotic. The intervention with L. plantarum strains induces beneficial effects on BA signature and lipoprotein profile. It reduces ApoB and small LDL levels and LDL susceptibility to oxidation and increases HDL antioxidant capacity. These metabolic profile changes suggest increased protection against atherosclerotic disease.

Modular Weaving DNAzyme in Skeleton of DNA Nanocages for Photoactivatable Catalytic Activity Regulation.

DNAzymes exhibit tremendous application potentials in the field of biosensing and gene regulation due to its unique catalytic function. However, spatiotemporally controlled regulation of DNAzyme activity remains a daunting challenge, which may cause nonspecific signal leakage or gene silencing of the catalytic systems. Here, we report a photochemical approach via modular weaving active DNAzyme into the skeleton of tetrahedral DNA nanocages (TDN) for light-triggered on-demand liberation of DNAzyme and thus conditional control of gene regulation activity. We demonstrate that the direct encoding of DNAzyme in TDN could improve the biostability of DNAzyme and ensure the delivery efficiency, comparing with the conventional surface anchoring strategy. Furthermore, the molecular weaving of the DNA nanostructures allows remote control of DNAzyme-mediated gene regulation with high spatiotemporal precision of light. In addition, we demonstrate that the approach is applicable for controlled regulation of the gene editing functions of other functional nucleic acids.

Modular Weaving DNAzyme in Skeleton of DNA Nanocages for Photoactivatable Catalytic Activity Regulation

AbstractDNAzymes exhibit tremendous application potentials in the field of biosensing and gene regulation due to its unique catalytic function. However, spatiotemporally controlled regulation of DNAzyme activity remains a daunting challenge, which may cause nonspecific signal leakage or gene silencing of the catalytic systems. Here, we report a photochemical approach via modular weaving active DNAzyme into the skeleton of tetrahedral DNA nanocages (TDN) for light‐triggered on‐demand liberation of DNAzyme and thus conditional control of gene regulation activity. We demonstrate that the direct encoding of DNAzyme in TDN could improve the biostability of DNAzyme and ensure the delivery efficiency, comparing with the conventional surface anchoring strategy. Furthermore, the molecular weaving of the DNA nanostructures allows remote control of DNAzyme‐mediated gene regulation with high spatiotemporal precision of light. In addition, we demonstrate that the approach is applicable for controlled regulation of the gene editing functions of other functional nucleic acids.

Abstract 7235: Exosome-mediated delivery of siRNA against NRF2 for treatment of lung cancer

Abstract Nuclear factor erythroid 2-related factor 2 (NRF2) activation is the third most common genetic event in lung adenocarcinomas (25%), primarily induced by loss of function mutations in its master regulator, KEAP1. NRF2 is a key modulator of tumor growth and metabolic reprogramming, resulting in resistance to traditional chemotherapeutics. Due to its role in modulating oxidative stress, sustained NRF2 overexpression promotes disease progression, particularly in lung cancer. This study demonstrates the effective knockdown of NRF2 expression by small interfering RNA (siRNA) delivered via a nanoplatform based on bovine colostrum exosomes to lung cancer cells, both in vitro and in vivo, resulting in inhibition of proliferation and disease progression. Bovine colostrum is an abundant source of exosomes. Here we present a novel exosome-polyethyleneimine matrix (EPM) to deliver therapeutic siRNA targeting NRF2 expression (siNRF2). Specific delivery of the EPM to tumors was further enhanced via folic acid (FA) functionalization, targeting folate receptors highly expressed on lung tumor cells. Exosomes were isolated from standardized colostrum powder through rehydration and differential centrifugation, and characterized by size, polydispersity index (pdi) and surface charge by Zetasizer, and the presence of surface protein markers by Western blot. siNRF2 was loaded onto the EPM, and the resultant EPM-siNRF2 complex was harvested by PEG precipitation. Entrapment efficiency was determined using 5’-32P-labeled siRNA as a tracer. The gene knockdown efficiency of EPM-siNRF2 was assessed in lung cancer (A549) cells by Western blot and the therapeutic effect of target knockdown in vitro was confirmed by analyzing the corresponding modulation in downstream targets of NRF2. The anti-tumor effect was then evaluated using both subcutaneous and orthotropic lung tumor models in immunocompromised mice. The EPM exhibited high entrapment efficiency (>90%) of siNRF2 (up to 20 μg) and protected entrapped siRNA from enzymatic degradation upon exposure to RNases. EPM-siNRF2 dose dependently decreased NRF2 expression in A549 lung cancer cells. When formulated with FA-functionalized exosomes, EPM-siNRF2 inhibited subcutaneous and orthotropic lung tumors in mice by over 57% (p<0.01) and 84% (p<0.001), respectively. Mice treated with FA-EPM-siNRF2 showed decreased levels of NRF2 in tumor tissue, but not in the adjacent lung, indicating FA-mediated targeted delivery. This bovine colostrum exosome based EPM technology showcases high efficiency in gene knockdown and lung tumor inhibition, providing a promising nanoplatform for delivering nucleic acid therapeutics to the tumor site. Funding: Supported from the NIH grant R44 CA-221487, 3P Biotechnology Contract and, in part, Agnes Brown Duggan Endowment. Keywords: Bovine colostrum, Exosomes, NRF2, siRNA, Lung cancer. Citation Format: Raghuram Kandimalla, Margaret Wallen, Jeyaprakash Jeyabalan, Disha N. Moholkar, Wendy Spencer, Ramesh C. Gupta, Farrukh Aqil. Exosome-mediated delivery of siRNA against NRF2 for treatment of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7235.

Abstract 7247: Exosome-mediated delivery of RNA and DNA: Enhanced efficiency with polycationic PEI-PEG

Abstract Emerging advances in gene therapy over the past few decades have revolutionized biomedical research. Our lab has pioneered bovine milk and colostrum-derived exosomes (Exo) and devised a nanoplatform for nucleic acid delivery achieving targetability with folic acid (FA) functionalization. We showed that bovine colostrum exosomes complexed with high MW polyethyleneimine (PEI-60K) can efficiently delivery siRNA and plasmid DNA (pDNA) in vitro and in vivo. We hypothesize that lower MW PEI may improve transfection efficiency and enhance oral uptake of EPM-siRNA, in addition to presumably higher degradability in a cellular system. We now report that exosomes and PEI of lower MW (25K)-PEG copolymer is as effective or more effective for delivery of siRNA and pDNA than PEI-60K. Incubation of exosomes, PEI-25K and siRNA in the presence of 5’-32P-labeled siRNA as a tracer showed high siRNA entrapment (>90%) based on the distribution of the radioactivity in EPM-siRNA precipitate compared with the supernatant. The efficacy of the EPM matrix is gene specific. As treatment of A549 lung cancer cells with EPM-(PEI-60K)-siKRAS showed 60% knockdown of target KRAS gene, which was enhanced to 70% by EPM-(PEI-25K)-siKRAS. Moreover, p53-pDNA delivered by EPM-25K resulted in nearly 2-fold higher expression of p53 in p53-null H1299 lung cancer cells compared with EPM-60K. However, still lower MW PEI (PEI-15K) diminished the transfection efficiency (36% KRAS knockdown). EPM formulated with PEI-60K and 25K had similar effect on cell viability of HEK293 cells. Upon in vivo testing, EPM-25K loaded with siKRAS and functionalized with folic acid (FA) showed time-dependent growth inhibition of A549-innoculated orthotopic lung tumors in NOD Scid mice eliciting 76% (p<0.01) tumor growth inhibition. The tumor inhibition was accompanied with 50% (p<0.05) knockdown of the target gene in the tumor tissue, while the adjacent lung tissue showed no modulation. The anti-tumor efficacy of siKRAS delivered by FA-functionalized EPM-25K is the same or somewhat higher than the efficacy reported previously with FA-functionalized EPM-60K.In conclusion, based on our in vitro and in vivo results, lower MW PEI (PEI-25K) is a suitable alternative for PEI-60K with boosted efficacy in terms of knockdown of KRAS. Our proposed technology offers a platform to advance and overcome the obstacles in the clinical translation of gene therapy. Funding: Work supported from funds provided by 3P Biotechnologies and in part Agnes Brown Duggan Funds. Disha Nagesh Moholkar is supported by IPIBS Fellowship, University of Louisville. Citation Format: Disha Nagesh Moholkar, Raghuram Kandimalla, Margaret Wallen, Jeyaprakash Jeyabalan, Wendy Spencer, Farrukh Aqil, Ramesh C. Gupta. Exosome-mediated delivery of RNA and DNA: Enhanced efficiency with polycationic PEI-PEG [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7247.

The Overlooked Potential of Sulfated Zirconia: Reexamining Solid Superacidity Toward the Controlled Depolymerization of Polyolefins.

Closed-loop recycling via an efficient chemical process can help alleviate the global plastic waste crisis. However, conventional depolymerization methods for polyolefins, which compose more than 50% of plastics, demand high temperatures and pressures, employ precious noble metals, and/or yield complex mixtures of products limited to single-use fuels or oils. Superacidic forms of sulfated zirconia (SZrO) with Hammet Acidity Functions (H0) ≤ - 12 (i.e., stronger than 100% H2SO4) are industrially deployed heterogeneous catalysts capable of activating hydrocarbons under mild conditions and are shown to decompose polyolefins at temperatures near 200 °C and ambient pressure. Additionally, confinement of active sites in porous supports is known to radically increase selectivity, coking and sintering resistance, and acid site activity, presenting a possible approach to low-energy polyolefin depolymerization. However, a critical examination of the literature on SZrO led us to a surprising conclusion: despite 40 years of catalytic study, engineering, and industrial use, the surface chemistry of SZrO is poorly understood. Ostensibly spurred by SZrO's impressive catalytic activity, the application-driven study of SZrO has resulted in deleterious ambiguity in requisite synthetic conditions for superacidity and insufficient characterization of acidity, porosity, and active site structure. This ambiguity has produced significant knowledge gaps surrounding the synthesis, structure, and mechanisms of hydrocarbon activation for optimized SZrO, stunting the potential of this catalyst in olefin cracking and other industrially relevant reactions, such as isomerization, esterification, and alkylation. Toward mitigating these long extant issues, we herein identify and highlight these current shortcomings and knowledge gaps, propose explicit guidelines for characterization of and reporting on characterization of solid acidity, and discuss the potential of pore-confined superacids in the efficient and selective depolymerization of polyolefins.

Use of Electrochemical Noise for the Study of Corrosion by Passivated CUSTOM 450 and AM 350 Stainless Steels

Precipitation-hardening stainless steels, like AM 350 and Custom 450, are extensively utilized in various aerospace applications. The latter steel is utilized for applications needing great strength and corrosion resistance. In contrast, the former steel has a good corrosion resistance and moderate strength. The purpose of this study was to analyze transient frequencies in the electrochemical noise of Custom 450 and AM 350 stainless steels that had been passivated for 60 and 90 min at 25 and 49 °C using baths of citric and nitric acid and then immersed in solutions containing 1% sulfuric acid (H2SO4) and 5% sodium chloride (NaCl). The potentiodynamic polychromatic curves employed electrochemical techniques and noise (EN) based on the ASTM-G5 and G199 standards. Two methods of data analysis were applied concerning EN: the domain of frequencies (power spectral density, PSD) and the time–frequency domain (Hilbert-Huang Transform). The PHSS passivated in citric acid indicated current densities in the H2SO4 solution between 10−2 and 10−3 mA/cm2, while those in the NaCl solution were recorded around 10−4 and 10−5 mA/cm2. The citric acid functions as a passivating agent. The results of the electrochemical noise analysis show that the PHSS passivated in nitric acid displayed a greater corrosion resistance. Moreover, there is a tendency for PHSS to be passivated in nitric acid to corrode locally.

The relationship between thiamin, folic acid and cognitive function in a rat model of uremia

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group (n = 12) and a sham-operated group (n = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2’-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases.

Sialic acids, commonly found as the terminal carbohydrate on the glycocalyx of mammalian cells, are pivotal checkpoint inhibitors of the innate immune system, particularly within the central nervous system (CNS). Sialic acid-binding immunoglobulin-like lectins (SIGLECs) expressed on microglia are key players in maintaining microglial homeostasis by recognizing intact sialylation. The finely balanced sialic acid-SIGLEC system ensures the prevention of excessive and detrimental immune responses in the CNS. However, loss of sialylation and SIGLEC receptor dysfunctions contribute to several chronic CNS diseases. Genetic variants of SIGLEC3/CD33, SIGLEC11, and SIGLEC14 have been associated with neurodegenerative diseases such as Alzheimer's disease, while sialyltransferase ST8SIA2 and SIGLEC4/MAG have been linked to psychiatric diseases such as schizophrenia, bipolar disorders, and autism spectrum disorders. Consequently, immune-modulatory functions of polysialic acids and SIGLEC binding antibodies have been exploited experimentally in animal models of Alzheimer's disease and inflammation-induced CNS tissue damage, including retinal damage. While the potential of these therapeutic approaches is evident, only a few therapies to target either sialylation or SIGLEC receptors have been tested in patient clinical trials. Here, we provide an overview of the critical role played by the sialic acid-SIGLEC axis in shaping microglial activation and function within the context of neurodegeneration and synaptopathies and discuss the current landscape of therapies that target sialylation or SIGLECs.

Microplastics affect membrane biofouling and microbial communities during gravity-driven membrane filtration of primary wastewater

Recently, gravity-driven membrane (GDM) filtration has been adopted as an alternative solution for decentralized wastewater treatment due to easy installation and maintenance, reduced energy and operation cost, and low global warming impact. This study investigated the influence of microplastic size (0.5–0.8 μm and 40–48 μm) and amount (0.1 and 0.2 g/L) on the membrane performance and microbial community in GDM systems for primary municipal wastewater treatment. The results showed that dosing microplastics in the GDM systems led to 9–54% lower permeate flux than that in the control. This was attributed to more cake formation (up to 6.4-fold) with more deposition of extracellular polymeric substances (EPS, up to 1.5-fold) and divalent cations (up to 2.1-fold) in the presence of microplastics, especially with increasing microplastic amount or size. However, the dosed microplastics promoted formation of heterogeneous cake layers with more porous nature, possibly because microplastics created void space in the cake and also tended to bind with divalent cations to reduce EPS-divalent cations interactions. In the biofilm of the GDM systems, the presence of microplastics could lower the number of total species, but it greatly enhanced the abundance of certain dominant prokaryotes (Phenylobacterium haematophilum, Planctomycetota bacterium, and Flavobacteriales bacterium), eukaryotes (Stylonychia lemnae, Halteria grandinella, and Paramicrosporidium saccamoebae), and virus (phylum Nucleocytoviricota), as well as amino acid and lipid metabolic functions. Especially, the small-size microplastics at a higher dosed amount led to more variations of microbial community structure and microbial metabolic functions.

A Review on the Role and Function of Cinnabarinic Acid, a "Forgotten" Metabolite of the Kynurenine Pathway.

In the human body, the majority of tryptophan is metabolized through the kynurenine pathway. This consists of several metabolites collectively called the kynurenines and includes, among others, kynurenic acid, L-kynurenine, or quinolinic acid. The wealth of metabolites, as well as the associated molecular targets and biological pathways, bring about a situation wherein even a slight imbalance in the kynurenine levels, both in the periphery and central nervous system, have broad consequences regarding general health. Cinnabarinic acid (CA) is the least known trace kynurenine, and its physiological and pathological roles are not widely understood. Some studies, however, indicate that it might be neuroprotective. Information on its hepatoprotective properties have also emerged, although these are pioneering studies and need to be replicated. Therefore, in this review, I aim to present and critically discuss the current knowledge on CA and its role in physiological and pathological settings to guide future studies.

Selective detection of nanomaterials: Gold nanorod imprinted matrices

Anisotropic nanostructures such as nanorods can be found in an increasing number of applications such as catalysis and imaging. Although their synthesis is well developed, their selective detection and separation are still in their infancy. Here, we demonstrate for the first time the selective recognition of gold nanorods (GNRs) by the nanoparticle-imprinted matrix (NAIM) approach. Specifically, GNRs stabilized by citrate (GNRs-cit) were adsorbed on an electrode surface modified with a positively charged polymer. The adsorption was followed by the electrochemical deposition of an aryldiazonium-based matrix around the GNRs-cit. Nanocavities having the shape of the imprinted GNRs were formed upon the removal of the nanoobject by electrochemical dissolution. We find that these nanocavities showed the ability to reuptake selectively GNRs similar to those initially imprinted. Furthermore, our findings clearly show that the recognition of the GNRs, namely, their reuptake by the nanocavities, depends on both the physical, i.e., structural fitness, and the chemical interactions between the imprinted GNRs and the matrix. For example, whereas a matrix bearing carboxylic acid functionalities repelled the GNRs stabilized by citric acid, a matrix formed by the electropolymerization of 4-acetylbenzenediazonium (ABD) exhibited good reuptake. A reuptake percentage, which is the ratio between the number of GNRs uptaken by the nanocavities divided by the number of the originally imprinted GNRs, of ca. 50% was obtained.