The mechanisms of pH regulation on promoting volatile fatty acids production from kitchen waste.

The anaerobic acid production experiments were conducted with the pretreated kitchen waste under pH adjustment. The results showed that pH 8 was considered to be the most suitable condition for acid production, especially for the formation of acetic acid and propionic acid. The average value of total volatile fatty acid at pH 8 was 8814 mg COD/L, 1.5 times of that under blank condition. The average yield of acetic acid and propionic acid was 3302 mg COD/L and 2891 mg COD/L, respectively. The activities of key functional enzymes such as phosphotransacetylase, acetokinase, oxaloacetate transcarboxylase and succinyl-coA transferase were all enhanced. To further explore the regulatory mechanisms within the system, the distribution of microorganisms at different levels in the fermentation system was obtained by microbial sequencing, results indicating that the relative abundances of Clostridiales, Bacteroidales, Chloroflexi, Clostridium, Bacteroidetes and Propionibacteriales, which were great contributors for the hydrolysis and acidification, increased rapidly at pH 8 compared with the blank group. Besides, the proportion of genes encoding key enzymes was generally increased, which further verified the mechanism of hydrolytic acidification and acetic acid production of organic matter under pH regulation.

Effects of subchronic and mild social defeat stress on the intestinal microbiota and fecal bile acid composition in mice.

The gut microbiota plays a crucial role in both the pathogenesis and alleviation of host depression by modulating the brain-gut axis. We have developed a murine model of human depression called the subchronic and mild social defeat stress (sCSDS) model, which impacts not only behavior but also the host gut microbiota and gut metabolites, including bile acids. In this study, we utilized liquid chromatography/mass spectrometry (LC/MS) to explore the effects of sCSDS on the mouse fecal bile acid profile. sCSDS mice exhibited significantly elevated levels of deoxycholic acid (DCA) and lithocholic acid (LCA) in fecal extracts, leading to a notable increase in total bile acids and 7α-dehydroxylated secondary bile acids. Consequently, a noteworthy negative correlation was identified between the abundances of DCA and LCA and the social interaction score, an indicator of susceptibility in stressed mice. Furthermore, analysis of the colonic microbiome unveiled a negative correlation between the abundance of CDCA and Turicibacter. Additionally, DCA and LCA exhibited positive correlations with Oscillospiraceae and Lachnospiraceae but negative correlations with the Eubacterium coprostanoligenes group. These findings suggest that sCSDS impacts the bidirectional interaction between the gut microbiota and bile acids and is associated with reduced social interaction, a behavioral indicator of susceptibility in stressed mice.

Structural analysis of type 3 resistant starch from Canna edulis during in vitro simulated digestion and its post-digested residue impact on human gut microbiota.

Introduction: Resistant starch (RS) has garnered attention for its health benefits, including modulating the gut microbiota and promoting the production of short-chain fatty acids (SCFAs). Methods: This study investigates structural changes of type 3 resistant starch from Canna edulis (CE) during in vitro simulated digestion and explores its health-relevant properties using healthy individuals' fecal microbiota. Results: CE, prepared with a RS content of 59.38%, underwent a comprehensive analysis employing X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During simulated digestion, XRD analysis demonstrated a significant rise in CE's relative crystallinity from 38.92 to 49.34%. SEM illustrated the transition of CE from a smooth to a rough surface, a notable morphological shift. Post-digestion, CE was introduced into microbial fermentation. Notably, propionic acid and valeric acid levels significantly increased compared to the control group. Furthere more, beneficial Bifidobacterium proliferated while pathogenic Escherichia-Shigella was suppressed. When comparing CE to the well-known functional food fructo-oligosaccharide (FOS), CE showed a specific ability to support the growth of Bifidobacterium and stimulate the production of short-chain fatty acids (SCFAs) without causing lactic acid accumulation. Discussion: CE demonstrates potential as a functional health food, with implications for gut health enhancement and SCFAs production.

Protein and amino acid digestibility: definitions and conventional oro-ileal determination in humans.

When assessing protein quality, a correction needs to be made to take into consideration the availability of the amino acids. This correction is based on the digestibility of the amino acids. It is recommended to use ileal (end of small intestine) digestibility as opposed to faecal digestibility. A correction needs to be made for endogenous (gut sourced as opposed to diet sourced) amino acids to give true digestibility as opposed to apparent digestibility. Also, this correction should be made by correcting the amino acid composition for individual amino acid digestibilities as opposed to correcting all amino acids for nitrogen digestibility. Determination of true ileal amino acid digestibility requires the collection of ileal digesta. In the human there are two methods that can be used; naso-ileal intubation and using the ileostomy model. Both are discussed in detail and it is concluded that both are appropriate methods to collect ileal digesta.

Elevated type-17 cytokines are present in axial spondyloarthritis stool.

Axial spondyloarthritis (axSpA) is characterized by type-17 immune-driven joint inflammation, and intestinal inflammation is present in around 70% of patients. In this study, we asked whether axSpA stool contained Th17-associated cytokines and whether this related to systemic Th17 activation. We measured stool cytokine and calprotectin levels by ELISA and found that patients with axSpA have increased stool IL-17A, IL-23, GM-CSF, and calprotectin. We further identified increased levels of circulating IL-17A+ and IL-17F+ T-helper cell lymphocytes in patients with axSpA compared to healthy donors. We finally assessed stool metabolites by unbiased nuclear magnetic resonance spectroscopy and found that multiple stool amino acids were negatively correlated with stool IL-23 concentrations. These data provide evidence of type-17 immunity in the intestinal lumen, and suggest its association with microbial metabolism in the intestine.

Theoretical insights into the reduction of Azurin metal site with unnatural amino acid substitutions.

Copper-containing proteins play crucial roles in biological systems. Azurin is a copper-containing protein which has a Type 1 copper site that facilitates electron transfer in the cytochrome chain. Previous research has highlighted the significant impact of mutations in the axial Met121 of the copper site on the reduction potential. However, the mechanism of this regulation has not been fully established. In this study, we employed theoretical modeling to investigate the reduction of the Type 1 copper site, focusing on how unnatural amino acid substitutions at Met121 influence its behavior. Our findings demonstrated a strong linear correlation between electrostatic interactions and the reduction potential of the copper site, which indicates that the perturbation of the reduction potential is primarily influenced by electrostatic interactions between the metal ion and the ligating atom. Furthermore, we found that CF/π and CF…H interactions could induce subtle changes in geometry and hence impact the electronic properties of the systems under study. In addition, our calculations suggest the coordination mode and ion-ligand distance could significantly impact the reduction potential of a copper site. Overall, this study offers valuable insights into the structural and electronic properties of the Type 1 copper site, which could potentially guide the design of future artificial catalysts.

Unsaturated fatty acids, omega-3 index and hospitalization in MISC.

The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids' levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I < 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization.

Utilization of diverse probiotics to create human health promoting fatty acids: A review.

Many probiotics produce functional lipids with health-promoting properties, such as short-chain fatty acids, linoleic acid and omega-3 fatty acids. They have been shown to maintain gut health, strengthen the intestinal barrier, and have anti-inflammatory and antioxidant effects. In this article, we provide an up-to-date review of the various functional lipids produced by probiotics. These probiotics can be incorporated into foods, supplements, or pharmaceuticals to produce these functional lipids in the human colon, or they can be used in industrial biotechnology processes to generate functional lipids, which are then isolated and used as ingredients. We then highlight the different physiological functions for which they may be beneficial to human health, in addition to discussing some of the challenges of incorporating probiotics into commercial products and some potential solutions to address these challenges. Finally, we highlight the importance of testing the efficacy and safety of the new generation of probiotic-enhanced products, as well as the great potential for the marketization of related products.

Effects of captan, mancozeb and azoxystrobin fungicides on motility, oxidative stress and fatty acid profiles in rainbow trout (Oncorhynchus mykiss) spermatozoa.

An in vitro study using rainbow trout spermatozoa was designed to evaluate the toxic effects of different concentrations of captan (CPT), mancozeb (MCZ), and azoxystrobin (AZX) fungicides on motility parameters, lipid peroxidation, SOD activity, total antioxidant capacity (TAC), and DPPH inhibition. Moreover, changes in fatty acids profiles caused by the fungicides were determined for the first time. The results revealed that motility parameters, SOD activities, TAC values, and DPPH inhibitions decreased significantly while lipid peroxidation increased after ≥2 µg/L of CPT, ≥1 µg/L of MCZ, and ≥5 µg/L of AZX incubations for 2 h at 4 °C. Additionally, 10 µg/L CPT, 5 µg/L MCZ, and 200 µg/L AZX reduced motility to the 50 % level. Our results clearly demonstrated significant changes in the fatty acids profiles of spermatozoa exposed to these concentrations of the fungicides. The highest lipid peroxidation and the lowest monounsaturated and polyunsaturated saturated fatty acids (MUFA and PUFA, respectively) were detected in AZX. Even though the susceptibility of spermatozoa to oxidative damage is generally attributed to PUFA contents, the results of this study have represented that MUFA content could play a part in this tendency. Moreover, the lower concentration of MCZ reduced motility to the % 50 level while it deteriorated the fatty acids profile less than did AZX. Overall, the present study demonstrated that the detrimental effects of the fungicides on mitochondrial respiration and related enzymes have more priority than oxidative stress in terms of their toxicities on spermatozoa. It has also been suggested that fish spermatozoa are a good model for determining changes in the fatty acid profiles by fungicides, probably, by other pesticides and environmental contaminants as well.

Whole transcriptome analysis identifies differentially expressed mRNA, miRNA and lncRNA associated with male sterility in the silkworm, Bombyx mori.

Insect sterility technology is gradually being applied to the control of lepidoptera pests, and the target gene for male sterility is the core of this technology. JMS is a mutant silkworm that exhibits male sterility, and to elucidate its formation mechanism, this study conducted a full transcriptome analysis of the testes of JMS and its wild-type silkworms 48 h after pupation, identifying 205 DElncRNAs, 913 mRNAs, and 92 DEmiRNAs. The KEGG pathway enrichment analysis of the DEmRNAs revealed that they were involved in the biosynthesis of amino acids and ECM-receptor interactions. Combined with ceRNA regulatory network KEGG analysis suggests that pathways from amino acid biosynthesis to hydrolytic processes of protein synthesis may play a crucial role in the formation of JMS mutant variants. Our study deepens our understanding of the regulatory network of male sterility genes in silkworms; it also provides a new perspective for insect sterility technology.

Gut-Derived Short-Chain Fatty Acids and Macrophage Modulation: Exploring Therapeutic Potentials in Pulmonary Fungal Infections.

Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, modulate immune cell functions, particularly macrophages. This review explores the potential therapeutic applications of SCFAs in pulmonary fungal infections, a critical concern due to their high mortality rates and antifungal resistance. SCFAs enhance macrophage functions by promoting phagosome-lysosome fusion, increasing reactive oxygen species production, and balancing cytokine responses. Pulmonary fungal infections, caused by pathogens like Aspergillus fumigatus, are prevalent in immunocompromised patients, including those with diabetes, chronic obstructive pulmonary disease, and those on high-dose corticosteroids. SCFAs have shown promise in improving macrophage function in these contexts. However, the application of SCFAs must be balanced against potential side effects, including gut microbiota disruption and metabolic disorders. Further research is needed to optimize SCFA therapy for managing pulmonary fungal infections.

Fatty acid preference for beta-oxidation in mitochondria of murine cultured astrocytes.

The brain utilizes glucose as a primary energy substrate but also fatty acids for the ß-oxidation in mitochondria. The ß-oxidation is reported to occur mainly in astrocytes, but its capacity and efficacy against different fatty acids remain unknown. Here, we show the fatty acid preference for the ß-oxidation in mitochondria of murine cultured astrocytes. Fatty acid oxidation assay using an extracellular flux analyzer showed that saturated or monosaturated fatty acids, palmitic acid and oleic acid, are preferred substrates over polyunsaturated fatty acids like arachidonic acid and docosahexaenoic acid. We also report that fatty acid binding proteins expressed in the astrocytes contribute less to fatty acid transport to mitochondria for ß-oxidation. Our results could give insight into understanding energy metabolism through fatty acid consumption in the brain.

Many locks to one key: N-acetylneuraminic acid binding to proteins.

Sialic acids play crucial roles in cell surface glycans of both eukaryotic and prokaryotic organisms, mediating various biological processes, including cell-cell interactions, development, immune response, oncogenesis and host-pathogen interactions. This review focuses on the ß-anomeric form of N-acetylneuraminic acid (Neu5Ac), particularly its binding affinity towards various proteins, as elucidated by solved protein structures. Specifically, we delve into the binding mechanisms of Neu5Ac to proteins involved in sequestering and transporting Neu5Ac in Gram-negative bacteria, with implications for drug design targeting these proteins as antimicrobial agents. Unlike the initial assumptions, structural analyses revealed significant variability in the Neu5Ac binding pockets among proteins, indicating diverse evolutionary origins and binding modes. By comparing these findings with existing structures from other systems, we can effectively highlight the intricate relationship between protein structure and Neu5Ac recognition, emphasizing the need for tailored drug design strategies to inhibit Neu5Ac-binding proteins across bacterial species.

Ribosome-Free Translation up to Pentapeptides via Template Walk on RNA Sequences.

The origin of translation is one of the most difficult problems of molecular evolution. Identifying molecular systems that translate an RNA sequence into a peptide sequence in the absence of ribosomes and enzymes is a challenge. Recently, single-nucleotide translation via coupling of 5' phosphoramidate-linked amino acids to 2'/3'-aminoacyl transfer-NMPs, as directed by the sequence of an RNA template, was demonstrated for three of the four canonical nucleotides. How single-nucleotide translation could be expanded to include all four bases and to produce longer peptides without translocation along the template strand remained unclear. Using transfer strands of increasing length containing any of the four bases that interrogate adjacent positions along the template, we now show that pentapeptides can be produced in coupling reactions and subsequent hydrolytic release in situ. With 2'/3'-aminoacylated mono-, di, tri- and tetranucleotides we thus show just how efficient translation can be without biomacromolecules.

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Acute kidney injury (AKI) remains a global public health problem with high incidence, high mortality rates, expensive medical costs, and limited treatment options. AKI can further progress to chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD). Previous studies have shown that trauma, adverse drug reactions, surgery, and other factors are closely associated with AKI. With further in-depth exploration, the role of gut microbiota in AKI is gradually revealed. After AKI occurs, there are changes in the composition of gut microbiota, leading to disruption of the intestinal barrier, intestinal immune response, and bacterial translocation. Meanwhile, metabolites of gut microbiota can exacerbate the progression of AKI. Therefore, elucidating the specific mechanisms by which gut microbiota is involved in the occurrence and development of AKI can provide new insights from the perspective of intestinal microbiota for the prevention and treatment of AKI.

Design, synthesis and evaluation of carbamate-bridged amino acid prodrugs of cycloicaritin with improved antitumor activity, aqueous solubility and phase II metabolic stability.

Cycloicaritin (CICT), a bioactive flavonoid derived from the genus Epimedium, exhibits a variety of beneficial biological activities, including promising anticancer effects. However, its poor oral bioavailability is attributed to its extremely low aqueous solubility and rapid elimination via phase II conjugative metabolism. To overcome these limitations, we designed and synthesized a series of carbamate-bridged prodrugs, protecting the hydroxyl group at the 3-position of cycloicaritin by binding with the N-terminus of a natural amino acid. The optimal prodrug 4b demonstrated a significant increase in aqueous solubility as compared to CICT, as well as improved stability in phase II metabolism, while allowing for a rapid release of CICT in the blood upon gastrointestinal absorption. The prodrug 4b also facilitated oral absorption through organic anion-transporting polypeptide 2B1-mediated transport and exhibited moderate cytotoxicity. Importantly, the prodrug enhanced the oral bioavailability of CICT and displayed dose-dependent antitumor activity with superior safety. In summary, the prodrug 4b is a novel potential antitumor drug candidate, and the carbamate-bridged amino acid prodrug approach is a promising strategy for the oral delivery of CICT.

Peptide Nucleic Acids: From Origami to Editing.

Peptide nucleic acids (PNAs) combine the programmability of native nucleic acids with the robustness and ease of synthesis of a peptide backbone. These designer biomolecules have demonstrated tremendous utility across a broad range of applications, from the formation of bespoke biosupramolecular architectures to biosensing and gene regulation. Herein, we explore some of the key developments in the application of PNA in chemical biology and biotechnology in the last 5 years and present anticipated key areas of future development.

Sterile Diet Causes Gut Microbiome Collapse of Cancer Patients Post Hematopoietic Cell Transplantation, But Normal Diet Recovers Them.

Though sterile diet, post-transplantation surgery is a clinical strategy for patient care to prevent the infiltration of gut pathogens, less is known about its effects on the gut microbiome. Here, the gut microbiome dynamics of leukemia patients following a 120-day "sterile-normal" diet strategy posthematopoietic cell transplantation are examined. In contrast to the traditional idea, a sterile diet leads to the lowest gut microbiota diversity (p < 0.05) and short-chain fatty acids, promoted the proliferation of potential pathogens such as Streptococcus (up by 16.93%) and Lactobacillus (up by 40.30%), and 43.32% reduction in nodes and an 85.33% reduction in edges within the microbial interaction's network. Interestingly, a normal diet allows the gut microbiome recovery and significantly promotes the abundance of beneficial bacteria. These results indicate that a sterile diet leads to a collapse of the patient's gut microbiome and promoted the proliferation of potential pathogens. This assay is a starting point for a more sophisticated assessment of the effects of a sterile diet. The work also suggests a basic principle for the re-establishment of microbial equilibrium that supplementation of microbial taxa may be the key to the restoration of the degraded ecosystem.

Short-chain fatty acids suppresses astrocyte activation by amplifying Trp-AhR-AQP4 signaling in experimental autoimmune encephalomyelitis mice.

The function of astrocytes in response to gut microbiota-derived signals has an important role in the pathophysiological processes of central nervous system (CNS) diseases. However, the specific effects of microbiota-derived metabolites on astrocyte activation have not been elucidated yet. Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice as a classical MS model. The alterations of gut microbiota and the levels of short-chain fatty acids (SCFAs) were assessed after EAE induction. We observed that EAE mice exhibit low levels of Allobaculum, Clostridium_IV, Clostridium_XlVb, Lactobacillus genera, and microbial-derived SCFAs metabolites. SCFAs supplementation suppressed astrocyte activation by increasing the level of tryptophan (Trp)-derived AhR ligands that activating the AhR. The beneficial effects of SCFAs supplementation on the clinical scores, histopathological alterations, and the blood brain barrier (BBB)-glymphatic function were abolished by intracisterna magna injection of AAV-GFAP-shAhR. Moreover, SCFAs supplementation suppressed the loss of AQP4 polarity within astrocytes in an AhR-dependent manner. Together, SCFAs potentially suppresses astrocyte activation by amplifying Trp-AhR-AQP4 signaling in EAE mice. Our study demonstrates that SCFAs supplementation may serve as a viable therapy for inflammatory disorders of the CNS.

Molecular self-assembled helix peptide nanotubes based on some amino acid molecules and their dipeptides: molecular modeling studies.

CONTEXT: The paper considers the features of the structure and dipole moments of several amino acids and their dipeptides which play an important role in the formation of the peptide nanotubes based on them. The influence of the features of their chirality (left L and right D) and the alpha-helix conformations of amino acids are taken into account. In particular, amino acids with aromatic rings, such as phenylalanine (Phe/F), and branched-chain amino acids (BCAAs)-leucine (Leu/L) and isoleucine (Ile/I)-as well as corresponding dipeptides (diphenylalanine (FF), dileucine (LL), and diisoleucine (II)) are considered. The main features and properties of these dipeptide structures and peptide nanotubes (PNTs), based on them, are investigated using computational molecular modeling and quantum-chemical semi-empirical calculations. Their polar, piezoelectric, and photoelectronic properties and features are studied in detail. The results of calculations of dipole moments and polarization, as well as piezoelectric coefficients and band gap width, for different types of helical peptide nanotubes are presented. The calculated values of the chirality indices of various nanotubes are given, depending on the chirality of the initial dipeptides-the results obtained are consistent with the law of changes in the type of chirality as the hierarchy of molecular structures becomes more complex. The influence of water molecules in the internal cavity of nanotubes on their physical properties is estimated. A comparison of the results of these calculations by various computational methods with the available experimental data is presented and discussed. METHOD: The main tool for molecular modeling of all studied nanostructures in this work was the HyperChem 8.01 software package. The main approach used here is the Hartree-Fock (HF) self-consistent field (SCF) with various quantum-chemical semi-empirical methods (AM1, PM3, RM1) in the restricted Hartree-Fock (RHF) and in the unrestricted Hartree-Fock (UHF) approximations. Optimization of molecular systems and the search for their optimal geometry is carried out in this work using the Polak-Ribeire algorithm (conjugate gradient method), which determines the optimized geometry at the point of their minimum total energy. For such optimized structures, dipole moments D and electronic energy levels (such as EHOMO and ELUMO), as well as the band gap Eg = ELUMO - EHOMO, were then calculated. For each optimized molecular structure, the volume was calculated using the QSAR program implemented also in the HyperChem software package.