The felting of wool directly on the sheep largely affects its value as a raw material for the textile industry. In this regard, the aim of this study was to investigate the amino acid and mineral composition of wool affected by this defect in sheep of the Ukrainian Carpathian Mountain breed. Experimental wool samples were divided into guard and down fibers. The amino acid composition was determined using an AAA-400 amino acid analyzer, the mineral composition was determined using an atomic absorption spectrophotometer (Thermo Scientific iCE 3500), and sulfur was determined by the nephelometric method based on the turbidity of a barium sulfate suspension stabilized with glycerin. It has been shown that the process of wool felting is accompanied by partial degradation of fibers resulting from the destruction of disulfide, ionic, and hydrogen bonds, as indicated by a significant decrease in the total amino acid content, due to reductions in aspartic (P < 0.01) and glutamic (P < 0.01) acids, arginine (P < 0.05), as well as cystine (P < 0.01) and histidine (P < 0.05) in down fibers, and lysine (P < 0.01) in guard fibers. The observed decrease in calcium and copper content in felted wool indicates a disruption of ionic interactions with the functional groups of amino acids, which play a key role in stabilizing the structural organization of wool fibers, while the decrease in sulfur content in down fibers confirms the destruction of disulfide bonds. Therefore, the results of the study indicate that wool felting is the result of biochemical processes leading to disruption of the keratin structure of the fiber. In the future, the obtained data may be used to develop comprehensive approaches aimed at preventing and eliminating this wool defect.
The PhI(OAc)2-oxidation of the triterpene lupeol by manganese porphyrin was achieved, leading to 94% of lupeol conversion. Conditions aligned with principles of green chemistry, including the use of ethyl acetate as a solvent and iodobenzene diacetate as an oxidant, were studied. This approach led to the production of eight products from lupeol, notably achieving transformations at the C20 olefin moiety; six lupeol's products were isolated whereas the other two had their structures proposed supported on basic chemical tests (e.g., Fehling's test) and well‑established reactivity patterns in organic chemistry. These modifications were performed without the typical preceding protection of the C3 hydroxyl of lupeol, simplifying the synthetic route. Besides, the isopropenyl group of lupeol was converted to carboxylic acids through one-pot oxidation. This study reinforces the promising use of manganese porphyrins as catalysts for the oxidative transformation of other natural products of biological interest.
Previous studies have shown that alterations in the gut microbiota and its derived metabolites, branched-chain amino acids (BCAAs), are correlated with T-cell-associated immune imbalance and Parkinson's disease (PD). However, the associations among BCAAs, gastrointestinal dysfunction and T-cell-related gut inflammation remain unclear. This study showed that the constipation symptoms in the PD mice persisted after chronic MPTP treatment. An imbalance in the CD4+ T-cell subtypes was observed in the colonic lamina propria (cLP), mesenteric lymph nodes (mLNs), and spleen. Metagenomic and metabolomic analyses showed that microbial dysbiosis promoted BCAA degradation rather than biosynthesis, and reduced BCAA levels were confirmed in the serum. BCAA supplementation alleviated constipation symptoms and increased Th1 and Th17 cell infiltration in the cLP, mLNs and spleen were significantly attenuated after BCAA treatment. This study highlights the therapeutic value of BCAAs in mitigating gut immune inflammation-associated constipation symptoms in PD.
Multiple sclerosis (MS) is an immune-mediated chronic neuroinflammatory and neurodegenerative disorder. Inflammation in MS disrupts the barriers between blood and central nervous system and affects transport and diffusion of metabolites between blood and cerebrospinal fluid (CSF). In this exploratory retrospective case-control study, we used targeted metabolomics to evaluate differences in serum and CSF amino acid and neurotransmitter levels between patients with MS (n = 73) and non-neuroinflammatory controls (n = 78). The influence of patient characteristics, including sex, age, disease duration, severity and treatment status, was also analzyed. Although no significant differences in serum and CSF metabolite levels were found between MS and control patients, a stratification by sex uncovered significantly reduced metabolites in male MS patients compared to male controls in CSF but not in serum. While in male MS patients CSF histidine levels were decreased, female MS patients showed increased levels. Further, sex-specific associations of amino acids and neurotransmitters with disease duration and disability were observed. MS patients exhibited enhanced positive correlations between CSF and serum analyte levels. In serum, only a few amino acids, along with serotonin and glutathione, were associated with MS disease duration. Overall, this study suggests that targeted metabolomics of selected analytes in matched CSF and serum samples is a valuable approach for assessing alterations in CSF-serum metabolite associations in MS, as well as sex-specific imbalances between excitatory and inhibitory neurotransmitters across disease duration. Our findings further highlight the importance of considering sex as a key biological factor in MS.
The bioconversion of agricultural crop straw using black soldier fly larvae (BSFL, Hermetia illucens) offers a promising strategy for recycling residual nutrients into high-value insect biomass. However, rearing BSFL on crop straw alone typically results in delayed development and poor substrate conversion efficiency. Here, we compared BSFL performance across three common agricultural residues-corn stover, rice straw, and wheat straw-and found that larvae reared on corn stover achieved significantly greater body weight and crude fat content. Ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC/ESI-MS) revealed higher levels of branched-chain amino acids (BCAAs) in corn stover than in the other substrates. Supplementation experiments confirmed that BCAAs significantly enhanced larval biomass and lipid accumulation. Gas chromatography (GC) analysis showed marked increases in lauric and oleic acid content in BSFL fed BCAA-supplemented rice straw. RNA interference (RNAi)-mediated knockdown of key BCAA catabolic genes including branched-chain amino acid aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKDH) impaired BCAA catabolism, resulting in reduced growth and fat storage. These findings demonstrate that enrichment of BCAAs in corn stover are efficiently assimilated by BSFL under low-nitrogen conditions to promote lipid accumulation, which offering a practical strategy to enhance bioconversion efficiency in waste valorization and insect-based protein production.
The activation by Lewis acids (LAs) and visible-light excitation are two appealing strategies for generating highly oxidizing metal oxo species for catalytic oxidation reactions. Herein, we report the first systematic study on the activation of both the ground and excited states of a luminescent osmium(VI) dioxo dicyano complex (OsO2). Strong interactions of OsO2 with a variety of LAs were found via binding to the cyano ligands: LA-NC-Os-CN-LA, which allow the isolation and structural determination of the first examples of M=O/LA adducts. OsO2/2LA interactions also cause a large increase in the reduction potentials/oxidizing power of the adducts in both ground and excited states. Notably, the reduction potential (Epc) of OsO2 is shifted from -0.04 V (vs. NHE) to 1.21 V in the presence of Sc(OTf)3, which enables it to oxidize a variety of organic substrates. More significantly, the Epc for the excited state of OsO2 (OsO2*) is shifted from 2.21 to 3.50 V upon binding to Sc(OTf)3, which to our knowledge is the strongest metal oxo oxidant ever generated in solution. OsO2*/2Sc(OTf)3 readily catalyzes the oxidation of benzene and its derivatives by H2O2 at ambient conditions, with a TON up to 8660 and gram-scale production of phenol from benzene.
Understanding the subcellular localization of RNA and proteins is critical to dissecting gene regulation in eukaryotic organisms. However, this task is elusive as existing fractionation methods often rely on protoplast isolation or commercial kits, that are labor-intensive, costly, and can introduce stress-induced transcriptomic and proteomic changes. Here, we present a simple, rapid, and cost-effective protocol for the fractionation of nuclear and cytoplasmic components directly from diverse plant tissues, that does not require protoplastization. This Subcellular-fractionation protocol in 3 steps (a.k.a. "bueno, bonito y barato" -spanish for "good, nice and cheap"-), referred to as "SuB3", yields nuclear- and cytoplasmic- enriched subcellular fractions suitable for downstream applications such as RT-PCR, RNA/cDNA sequencing, and Western blotting. The procedure is based on sequential detergent-assisted extraction and centrifugation and enables the simultaneous isolation of RNA and protein from the same biological material. Due to its simplicity, speed, and broad compatibility, this protocol is a valuable tool for plant molecular biology laboratories investigating subcellular dynamics of gene expression.
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Diaryl ureas and thioureas have long been known to uncouple oxidative phosphorylation in isolated mitochondria and cells. However, the mechanism of this action remains poorly understood. The prevailing current view is that substituted diaryl ureas can increase the proton conductance of lipid membranes by forming complexes with fatty acids. For 1,3-bis[4-(trifluoromethyl)phenyl]urea (TFMP-urea), we showed that this substituted diphenylurea, in the absence of fatty acids at neutral pH, accelerated proton transport and H+/Cl- symport on planar bilayer lipid membranes (BLMs) and liposomes loaded with the fluorescent pH-sensitive probe 8-hydroxypyrene-1,3,6-trisulfonic acid. The protonophoric action of TFMP-urea proceeded via translocation of neutral protonated form and anionic deprotonated form through the membrane. The presence of palmitic acid in the lipid mixture led to a several-fold increase in the BLM current mediated by TFMP-urea and an improvement in its proton selectivity. We also showed that bovine serum albumin reduced the BLM current mediated by TFMP-urea due to its ability to bind this compound.
Palladium-catalyzed β and γ-C-H arylation of free carboxylic acids with both aryl boron reagents and aryl iodides has been extensively developed in recent years. Replacing these aryl coupling partners with simple arenes remains a significant challenge. By developing pyridone-morpholine ligands, we disclosed the β-methylene C-H (hetero)arylation of acyclic aliphatic acids and the γ-(hetero)arylation of cycloalkane carboxylic acids using benzene, furan, thiophene, and C-2 substituted pyridine as coupling partners. Preliminary mechanistic studies suggest that the reaction proceeds via ligand-promoted dehydrogenation of aliphatic carboxylic acids, C(sp2)-H activation of (hetero)arenes, and subsequent hydroarylation. Building on the mechanistic insights, we developed a dual-ligand catalysis system with one ligand promoting dehydrogenation and the other enhancing subsequent steps to enable coupling of C(sp3)-H bonds with indoles and pyrroles as reaction partners.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its inflammatory-fibrotic phenotype (MASH) exhibit pronounced immunometabolic coupling. This review synthesizes evidence along the gut-liver axis, from epithelial tight-junction and gut vascular barrier (GVB) failure to TLR4-MyD88/TRIF-NF-κB amplification and NLRP3 inflammasome activation and outlines the logic of the gut-derived exposure spectrum-lipopolysaccharide (LPS), endogenous ethanol, bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). We position BA-FXR/TGR5, SCFAs-GPR41/43, and AMPK/Nrf2 as upstream/downstream modulators that reset inflammatory thresholds and confer stage-dependent druggability. Based on node-to-pathway mapping, we summarize mechanisms and translational signals for berberine (BBR), Qushihuayu (QSHY), Da-Chai-Hu Decoction (DCHD), and polysaccharides (e.g., Astragalus, Ganoderma), emphasizing pharmacokinetic and site-of-exposure constraints that support "gut-first" actions. We propose a minimal companion biomarker set-LBP/sCD14, BA profiles with FGF19-C4 dynamics, and IL-1β/GSDMD-N-paired with hierarchical imaging gates (≥30% relative MRI-PDFF decline; MRE/ELF) to underpin response typing and go/no-go decisions. Finally, we highlight critical gaps (direct human GVB readouts; longitudinal multi-omics bridged to clinical outcomes) and outline a biomarker-driven multi-arm multi-stage (MAMS) pathway for adaptive, stratified development of multi-target traditional medicine interventions in MASLD/MASH.
The functional efficacy of dietary Jamun leaf meal (JLM) on growth performance, physiological status, immune competence, and disease resistance was evaluated in Pangasianodon hypophthalmus. Comprehensive phytochemical profiling revealed the presence of flavonoids, phenolic acids, terpenoids, vitamins, amino acids, and minerals in the JLM extract. Five isonitrogenous and isocalorific experimental diets containing 0, 0.5, 1.0, 1.5, 2% JLM were prepared and fed to the respective treatment groups for 60 days. The group fed with 1% JLM diet exhibited improved weight gain (16.46 ± 0.12 g), specific growth rate (1.41 ± 0.02% day⁻1), protein efficiency ratio (2.47 ± 0.06), and feed conversion ratio (1.34 ± 0.03) (P < 0.05). Pre-challenge, the haematological, biochemical, immune, and antioxidant parameters improved significantly in 1% JLM-fed group (P < 0.05). Post-challenge, the stress biomarkers, namely glucose, cholesterol, and triglycerides, and hepatic enzymes were significantly elevated (P < 0.05) in the control group compared to the JLM-fed groups. Furthermore, the cumulative survival was significantly higher in the 1% JLM-fed group (87.67 ± 5.7%) than in the control group (P < 0.05). In conclusion, dietary administration of JLM at 1% inclusion level enhances growth and health performance in P. hypophthalmus and is a potential feed supplement.
To determine the impact of a commercially available docosahexaeonic acid (DHA) supplement (DHA, methylslfonylmethane, and mushroom blend) on equine alveolar macrophage metabolism and lipid and protein profiles in bronchoalveolar lavage (BAL) supernatant. This was a prospective, sequential, placebo-controlled study using 10 healthy adult horses. Bronchoalveolar lavage fluid was collected at baseline, following 45 days of oral placebo administration, and following 45 days of oral commercially available DHA supplement, with a 14-day washout. Whole blood was collected following placebo and DHA supplementation. Bronchoalveolar lavage samples were collected for airway cytology. Adherent cells were isolated from BAL cell pellets and used to measure alveolar macrophage oxygen consumption rate and extracellular acidification rate. Protein and lipid profiles were measured in BAL supernatant. 7 horses completed the study. The DHA supplementation significantly decreased the whole-blood ratio of omega-6 to omega-3 fatty acids and significantly increased the ratio of DHA to arachidonic acid. Following DHA supplementation, mean alveolar macrophage basal and maximal respiratory capacity increased, and protein and lipid profiles in BAL supernatant were altered. There was no significant change in BAL cytology during any study period. Oral administration of a DHA supplement increased alveolar macrophage oxygen consumption rate and altered lipid and protein profiles in BAL supernatant. Changes in alveolar macrophage metabolism may indicate a greater population of M2 (anti-inflammatory) alveolar macrophages. These findings suggest that oral DHA supplementation may promote an anti-inflammatory profile in the lower airway, which could be beneficial for horses with subclinical airway inflammation and horses routinely exposed to airway-triggering environments.
Polyethylene is one of the most extensively used plastics worldwide. It is highly resistant to biodegradation, and its accumulation in the environment has become a major global concern. The aim of this study was to isolate an low-density polyethylene (LDPE)-degrading strain and investigate its putative degradation mechanism. The Gram-positive strain, Paenrthrobacter nicotinovorans JPEA-9, which was isolated from plastic waste in a landfill site, degraded LDPE powder and film, causing weight losses of 14.4 ± 0.1% after 20 days and 7.0 ± 0.8% after 120 days, respectively. Among the reported LDPE-degrading strains within the genus Paenarthrobacter, JPEA-9 showed the highest degradation activity. The degradation of LDPE film was characterized using water contact angle measurement, scanning electron microscopy, and Fourier transform infrared spectroscopy, while the degradation products were analyzed using liquid chromatography-tandem mass spectrometry. During the 120-day incubation, the LDPE film showed increased surface roughness, enhanced absorption bands associated with oxygen-containing functional groups and reduced surface hydrophobicity. C35 and C37 fatty acids were identified as degradation products. Genome analysis further revealed four candidate genes encoding cytochrome P450, alcohol dehydrogenase, aldehyde dehydrogenase, and esterase that may be associated with LDPE biodegradation. Based on the combined results of biodegradation characterization and whole-genome analysis, a putative multi-enzyme degradation mechanism was proposed. This study provides the first genome-level insight into LDPE biodegradation by Paenarthrobacter nicotinovorans and broadens the known diversity of LDPE-degrading bacteria, thereby laying a foundation for future studies on microbial bioremediation of plastics.
Hepatocellular carcinoma (HCC) remains a major global cause of cancer-related deaths. HCC development, immune evasion, and treatment resistance are significantly influenced by the aberrant activation of the NF-κB and JAK/STAT signaling pathways. The review provides a thorough and critical analysis of recent developments in nanocarrier-mediated targeting of NF-κB and JAK/STAT pathways in HCC. It demonstrates the molecular interactions between various pathways and their implications for inflammation, angiogenesis, hepatocarcinogenesis, and resistance to both immunotherapy and chemotherapy. A variety of nanoplatforms, such as polymeric nanoparticles, lipid-based systems, inorganic nanomaterials, and biomimetic carriers, are designed to enhance the delivery of small-molecule inhibitors, nucleic acids, and combination therapies, improving pharmacokinetic and pharmacodynamic profiles. The review highlights ligand-functionalized and stimulus-responsive nanocarriers designed for controlled drug release and targeted therapy in the liver environment. Co-modulation of NF-κB and JAK/STAT signaling via nanotechnology enhances antitumor efficacy and decreases systemic toxicity, as supported by preclinical and recent translational data. Lastly, important issues such as scalability, biosafety, and regulatory concerns are discussed. Future directions for integrating precision cancer techniques with nanomedicine are proposed. This analysis emphasizes the therapeutic potential of targeting the NF-κB and JAK/STAT pathways with nanotechnology to enhance outcomes in HCC.
Some areas of the world have high natural background levels of naturally occurring radionuclides (NOR) and/or rare earth elements (REE). With high background radiation risk, knowledge about, for example, uptake by crops is required in the process of assessing radiation doses to humans. In the Fen complex, in Norway, underlying bedrock has elevated levels of both NOR and REE. In Mining hill where these bedrocks surface and there are also legacy mines, soils also have high background levels. Most of Fen complex is, however, covered by thick Holocene deposits but some of its agricultural soils are situated near the areas of surfacing carbonatite bedrock and legacy mines. We assess whether there has been any influence on the levels in the agricultural soils within the Fen complex from the areas with high NOR and REE soil background. We also determine uptake from soils by cereals into grain or grain with hull, and present concentration ratios (CR) for NOR and REE in this high background area. In particular, the REE CRs are an important augmentation to existing sparse datasets. We furthermore assess whether uptake can be biased by any soil particles adhering to cereal grain or grain with hull. We investigate whether washing (or not washing) and use of different acids for dissolution may affect ICP-MS results on common elements. We also address soil mass in cereal samples using Scandium and Titanium as tracers for soil particles and assess the potential magnitude of bias CR.
Fuping goat milk powder is a kind of geographical indication protected food in China. To realize a rapid and accurate identification of Fuping goat milk, in this paper, an identification method was proposed based on nuclear magnetic resonance and machine learning to accurately distinguish Fuping goat milk on small scale geographical authenticity. Deuterated chloroform was selected as extraction solvent, partial least squares discriminant analysis (PLSDA), random forest (RF) and support vector machine (SVM) models were constructed using seven different geographical origin goat milk samples in Shaanxi Province. The identification based on PLS-DA model was unsatisfactory, the RF model performed better, and the SVM model showed best performance with accuracy rate reached 100% based on selected 17 features, and the 5-fold cross-validation accuracy was 94.7% ± 7.2%. It is disclosed that different geographic samples have different chemical compositions, particularly unsaturated fatty acids, such as conjugated linoleic acid.
ADP-ribosylation is an essential post-translational modification that contributes to key cellular processes, such as DNA damage repair, cell-cycle progression, chromatin remodeling, mitochondrial function, and immune responses in mammalian cells. This modification derives from NAD+ and is regulated by dedicated writer, eraser, and reader proteins that govern its installation, removal, and recognition. Traditionally viewed as a protein-centered modification, ADP-ribosylation has recently been extended to nucleic acids, with ADP-ribosylated DNA and RNA now identified in both mammalian and bacterial systems. These discoveries reveal previously underappreciated layers of nucleic acid-based regulation and suggest that NAD+-dependent chemistry integrates genome maintenance, RNA metabolism, and cellular stress responses. In this review, we first outline the major mammalian ADP-ribosylation machineries, including the families of writer, eraser, and reader proteins, and discuss how their activities are coordinated. We then examine emerging roles of ADP-ribosylation in mitochondria, with a focus on mitochondrial DNA repair and metabolic control. Finally, we highlight recent advances in understanding NAD+-dependent modifications of DNA and RNA in mammalian and bacterial cells, including terminal and nucleobase-linked ADP-ribosylation and NAD capping, and discuss outstanding questions regarding their physiological functions and interplay with protein post-translational modification and other nucleic acid modifications.
Environmental exposure to complex chemical mixtures threatens metabolic health by disrupting the liver-gut microbiota axis. This study assesses a multi-pollutant cocktail (PC) comprising As, Cd, Hg, diclofenac and flumequine, on bile acid (BA) homeostasis in mice and evaluates the protective potential of dietary selenium. PC exposure induced mortality and body-weight loss despite sublethal individual doses, suggesting synergistic toxicity. Selenium supplementation, however, attenuated weight loss and partially reduced mortality. Hepatic profiling showed that antibiotic-induced microbiota depletion sharply reduced taurocholic acid, whereas PC exposure increased total hepatic BAs. However, selenium normalized total BAs and partially restored secondary species. Cholic acid remained stable, while PC exposure nearly depleted glycocholic and deoxycholic acids and increased taurodeoxycholic acid, a shift associated with colorectal and lung pathologies. These findings suggest xenobiotic-mediated disruption of BA conjugation and dysregulation of nuclear receptors, potentially predisposing to hepatic steatosis. Collectively, these findings support selenium as a nutritional strategy to mitigate antibiotic-induced dysbiosis and PC-induced hepatotoxicity, preserving metabolic integrity under chemical stress.
Glaciers cover a substantial portion of the world and are home to various biological populations. The Himalayas constitute the largest glaciated region outside the poles; hence, they are regarded as "The Third Pole" of the World. There are around 84 glaciers in the Teesta basin (Sikkim Himalaya). There is substantially less data available on the microbial diversity embedded in the glacial ice core samples of the Sikkim Himalaya, as well as their physico-chemistry and potential geomorphological hazards related to their retreat or decrease in snow-line cover. The present study aims to evaluate the microbial diversity in the glacier ice core region and the study area; therefore, two glaciers in the Sikkim Himalaya were chosen: Frey-Peak and Rathong Glacier. The bacterial diversity analysis reveals the prevalence of various phyla, including Pseudomonadota, Actinomycetota, Bacillota, and Bacteroidota. The random forest model reveals the significant contributions of various elements, including Na, Mg, K, Ca, and Zn, to the alpha diversity of the studied glaciers. Among physicochemical parameters, pH was found to contribute the most in shaping bacterial diversity. Cluster of Orthologous Groups (COG) analysis underscored a predominance of genes associated with amino acids (23.5%), carbohydrates (18.93%), lipids (10.88%), energy (17.26%), coenzymes (9.38%), and ion transport/metabolism (14.71%). KEGG (Kyoto Encyclopedia of Genes and Genomes) Orthology (KO) analysis revealed the presence of 4,915 to 96,954 genes. Interestingly, the metagenomic analysis revealed the presence of specific species of Bradyrhizobium, Beijerinckia, Burkholderia, and Corynebacterium, which are associated with nitrogen metabolism, suggesting their potential involvement in biogeochemical processes. Additionally, a total of 59 to 419 bacterial genes related to sulphur metabolism were deduced through the KEGG functional analysis. The study detected the presence of various antibiotic resistance genes corresponding to different classes of antibiotics, including aminoglycoside, tetracycline, fluoroquinolone, macrolide, and erythromycin. Network analysis reveals that antibiotic resistance genes primarily interact with the phyla Pseudomonadota, Bacillota, and Actinomycetota. The melting of glaciers, a significant effect of climate change, may release contaminants, antibiotic resistance genes, and pathogenic bacteria into free-flowing rivers, potentially impacting human health.