Carbimazole has disadvantages on different body organs, especially the thyroid gland and, rarely, the adrenal glands. Most studies have not suggested any solution or medication for ameliorating the noxious effects of drugs on the glands. Our study focused on the production of xylooligosaccharide (XOS), which, when coadministered with carbimazole, relieves the toxic effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity. This XOS produced by Aspergillus terreus xylanase was covalently immobilized using microbial Scleroglucan gel beads, which improved the immobilization yield, efficiency, and operational stability. Over a wide pH range (6-7.5), the covalent immobilization of xylanase on scleroglucan increased xylanase activity compared to that of its free form. Additionally, the reaction temperature was increased to 65 °C. However, the immobilized enzyme demonstrated superior thermal stability, sustaining 80.22% of its original activity at 60 °C for 120 min. Additionally, the full activity of the immobilized enzyme was sustained after 12 consecutive cycles, and the activity reached 78.33% after 18 cycles. After 41 days of storage at 4 °C, the immobilized enzyme was still active at approximately 98%. The immobilized enzyme has the capability to produce xylo-oligosaccharides (XOSs). Subsequently, these XOSs can be coadministered alongside carbimazole to mitigate the adverse effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity.

We propose a closed-loop pretreatment process, wherein volatiles produced during steam explosion pretreatment were recovered and reintroduced as acid catalysts into the pretreatment system. The volatiles were separated through a drastic decompression process followed by a steam explosion process and recovered as a liquified catalyst (LFC) through a heat exchanger. The LFC effectively served as an acid catalyst for hemicellulose hydrolysis, significantly decreasing residence time from 90 min to 30 min to achieve 80 % conversion yield at 170 °C. Hydrolysates with high content of lower molecular weight oligomeric sugars were obtained using LFC, and were considered advantageous for application as prebiotics. These results are attributed to the complementary features of acetic acid and furfural contained within the LFC. Computational simulation using Aspen Plus was used to investigate the effects of recycling on LFC, and it demonstrated the feasibility of the catalyst-recirculating system. A validation study was conducted based on simulation results to predict the actual performance of the proposed pretreatment system. Based on these results, the recirculating system was predicted to improve the conversion yield and low-molecular weight oligomers yield by 1.5-fold and 1.6-fold, respectively.

PANoptosis is manifested with simultaneous activation of biomarkers for both pyroptotic, apoptotic and necroptotic signaling via the molecular platform PANoptosome and it is involved in pathologies of various inflammatory diseases including hemophagocytic lymphohistiocytosis (HLH). Scutellarin is a flavonoid isolated from herbal Erigeron breviscapus (Vant.) Hand.-Mazz. and has been shown to possess multiple pharmacological effects, but it is unknown whether scutellarin has any effects on PANoptosis and related inflammatory diseases. In this study, we found that scutellarin inhibited cell death in bone marrow-derived macrophages (BMDMs) and J774A.1 cells treated with TGF-β-activated kinase 1 (TAK1) inhibitor 5Z-7-oxozeaenol (OXO) plus lipopolysaccharide (LPS), which has been commonly used to induce PANoptosis. Western blotting showed that scutellarin dose-dependently inhibited the activation biomarkers for pyroptotic (Caspase-1p10 and GSDMD-NT), apoptotic (cleaved Casp3/8/9 and GSDME-NT), and necroptotic (phosphorylated MLKL) signaling. The inhibitory effect of scutellarin was unaffected by NLRP3 or Caspase-1 deletion. Interestingly, scutellarin blocked the assembly of PANoptosome that encompasses ASC, RIPK3, Caspase-8 and ZBP1, suggesting its action on upstream signaling. Consistent with this, scutellarin inhibited mitochondrial damage and mitochondrial reactive oxygen species (mtROS) generation in cells treated with OXO+LPS. Further, mito-TEMPO that can scavenge mtROS significantly inhibited OXO+LPS-induced PANoptotic cell death. In line with the in vitro results, scutellarin markedly alleviated systemic inflammation, multiple organ injury, and activation of PANoptotic biomarkers in mice with HLH. Collectively, our data suggest that scutellarin can inhibit PANoptosis by suppressing mitochondrial damage and mtROS generation and thereby mitigating multiple organ injury in mice with inflammatory disorders.

The high prevalence of cancer and detrimental side effects associated with many cancer treatments necessitate the search for effective alternative therapies. Natural products are increasingly being recognized and investigated for their potential therapeutic benefits. Scutellaria barbata D. Don (SBD), a plant with potent antitumor properties, has attracted significant interest from oncology researchers. Its primary flavonoid components-scutellarin and luteolin-which have limited oral bioavailability due to poor absorption. This hinders its application for cancer treatment. The gut microbiota, which is considered a metabolic organ, can modulate the biotransformation of compounds, thereby altering their bioavailability and efficacy. In this study, we employed liquid chromatography tandem mass spectrometry (LC-MS/MS 8060) and ion trap-time of flight (LC-MSn-IT-TOF) analysis to investigate the ex vivo metabolism of scutellarin and luteolin by the gut microbiota. Five metabolites and one potential metabolite were identified. We summarized previous studies on their antitumor effects and performed in vitro tumor cell line studies to prove their antitumor activities. The possible key pathway of gut microbiota metabolism in vitro was validated using molecular docking and pure enzyme metabolic experiments. In addition, we explored the antitumor mechanisms of the two components of SBD through network pharmacology, providing a basis for subsequent target identification. These findings expand our understanding of the antitumor mechanisms of SBD. Notably, this study contributes to the existing body of knowledge regarding flavonoid biotransformation by the gut microbiota, highlighting the therapeutic potential of SBD in cancer treatment. Moreover, our results provide a theoretical basis for future in vivo pharmacokinetic studies, aiming to optimize the clinical efficacy of SBD in oncological applications.

Renal ischemia-reperfusion injury (IRI) is an integral process in renal transplantation, which results in compromised graft survival. Macrophages play an important role in both the early inflammatory period and late fibrotic period in response to IRI. In this study, we investigated whether scutellarin (SCU) could protect against renal IRI by regulating macrophage polarization. Mice were given SCU (5-50 mg/kg) by gavage 1 h earlier, followed by a unilateral renal IRI. Renal function and pathological injury were assessed 24 h after reperfusion. The results showed that administration of 50 mg/kg SCU significantly improved renal function and renal pathology in IRI mice. In addition, SCU alleviated IRI-induced apoptosis. Meanwhile, it reduced macrophage infiltration and inhibited pro-inflammatory macrophage polarization. Moreover, in RAW 264.7 cells and primary bone marrow-derived macrophages (BMDMs) exposed to SCU, we found that 150 μM SCU inhibited these cells to polarize to an inflammatory phenotype induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). However, SCU has no influence on anti-inflammatory macrophage polarization in vivo and in vitro induced by in interleukin-4 (IL-4). Finally, we explored the effect of SCU on the activation of the mitogen-activated protein kinase (MAPK) pathway both in vivo and in vitro. We found that SCU suppressed the activation of the MAPK pathway, including the extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and p38. Our results demonstrated that SCU protects the kidney against IRI by inhibiting macrophage infiltration and polarization toward pro-inflammatory phenotype via the MAPK pathway, suggesting that SCU may be therapeutically important in treatment of IRI.

BACKGROUND: Nails accumulate the alcohol metabolite, ethyl glucuronide (ETG), and the cannabis metabolite, carboxy- delta-9-THC over 3-6 months. Few studies have examined nail toxicology testing\'s sensitivity and specificity and the agreement between nail testing and self-reported alcohol and marijuana use.
METHODS: In an ongoing clinical trial, 1101 veterans completed initial telephone questionnaires and were then asked to mail nail clippings for substance use analysis. We examined sensitivity and specificity of ETG and carboxy- delta-9-THC in nails compared to self-report of alcohol use patterns (the AUDIT-C) and substance-related harms (alcohol and THC subscales of the ASSIST). We then examined factors associated with discordance between nails and self-report.
RESULTS: Almost two-thirds (707/1101) of respondents mailed in nail clippings. Those with returned nails were disproportionately married, white race, older, and less depressed. At a threshold of 8pg/mg, sensitivity was only.50 to detect risky alcohol use and.49 to detect alcohol-related issues. Sensitivity for marijuana issues was only.61. Specificity was greater than.77 for all measures. Factors associated with positive nails/negative self-report (i.e. false positives) for risky alcohol use on the Audit-C included more pain and being unmarried; false positive nails for alcohol-related issues on the ASSIST were associated with being unmarried and non-Hispanic ethnicity. False positive nails for THC-related issues on the ASSIST were associated with being African American, Hispanic, and having had legal issues.
CONCLUSIONS: At standard cut-offs, nail measures had low sensitivity and higher specificity. The groups who disproportionately submit positive nails/negative self-report could have substance use patterns not adequately captured by self-report, inaccurate self-report due to social pressures, or distinct drug metabolism.

Lignocellulose is an abundant renewable bio-macromolecular complex, which can be used to produce biomethane and other high-value products. The lignin, presents in lignocellulose is typically regarded as an inhibitor of anaerobic digestion. Therefore, it is crucial to develop a novel selective separation strategy to achieve efficient biomethane production and all-component utilization of biomass. Hence, a combination of two-step pretreatment and solid-state anaerobic digestion was employed to enhance the production of biomethane and to generate valuable chemicals from poplar waste. Optimal conditions (4 % acetic acid, 170 °C, and 40 min) resulted in 70.85 % xylan removal, yielding 50.28 % xylo-oligosaccharides. The effect of a strong acid 4-CSA-based novel three-constituent DES on delignification was investigated from 80 °C to 100 °C; the cellulose content of DES pretreated poplar increased from 64.11 % to 80.92 %, and the delignification rate increased from 49.0 % to 90.4 %. However, high delignification of the pretreated poplar (DES-100 and DES-110) led to a rapid accumulation of volatile organic acids during the hydrolysis and acidogenesis stages, resulting in methanogenesis inhibition. The highest biomethane yield of 208 L/kg VS was achieved with DES-80 (49.0 % delignification), representing a 148 % improvement compared over untreated poplar. This approach demonstrates the potential for comprehensive utilization of all components of biomass waste.

OBJECTIVE: New characterized carbohydrate-active enzymes are needed for use as tools to discriminate complex carbohydrate structural features. Fungal glycoside hydrolase family 3 (GH3) β-xylosidases have been shown to be useful for the structural elucidation of glucuronic acid (GlcA) and arabinofuranose (Araf) substituted oligoxylosides. A homolog of these GH3 fungal enzymes from the bacterium Segatella baroniae (basonym Prevotella bryantii), Xyl3C, has been previously characterized, but those studies did not address important functional specificity features. In an interest to utilize this enzyme for laboratory methods intended to discriminate the structure of the non-reducing terminus of substituted xylooligosaccharides, we have further characterized this GH3 xylosidase.
RESULTS: In addition to verification of basic functional characteristics of this xylosidase we have determined its mode of action as it relates to non-reducing end xylose release from GlcA and Araf substituted oligoxylosides. Xyl3C cleaves xylose from the non-reducing terminus of β-1,4-xylan until occurrence of a penultimate substituted xylose. If this substitution is O2 linked, then Xyl3C removes the non-reducing xylose to leave the substituted xylose as the new non-reducing terminus. However, if the substitution is O3 linked, Xyl3C does not hydrolyze, thus leaving the substitution one-xylose (penultimate) from the non-reducing terminus. Hence, Xyl3C enables discrimination between O2 and O3 linked substitutions on the xylose penultimate to the non-reducing end. These findings are contrasted using a homologous enzyme also from S. baroniae, Xyl3B, which is found to yield a penultimate substituted nonreducing terminus regardless of which GlcA or Araf substitution exists.

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

Xylooligosaccharides (XOs) have shown high potential as prebiotics with nutritional and health benefits. In this work, XOs were obtained from highly purified, carboxy-reduced glucuronoarabinoxylans by treatment with Driselase®. The mixtures were fractionated, and the structures were elucidated by methylation analysis and NMR spectroscopy. Antioxidant activity was determined by the methods of DPPH and β-carotene/linoleic acid. It was found that the most active oligosaccharides (P3 and G3) comprised 4 or 5 xylose units, plus two arabinoses and one 4-O-methylglucose as side chains, their sequence of units was determined. The optimal concentration for their use as antioxidants was 2 mg/mL. The synthetic antioxidant butylated hydroxytoluene (BHT, 0.2 mg/mL) showed a percentage of inhibition 15% higher than P3. Although its concentration was ∼10 times higher, P3 is non-toxic, and could have great advantages as food additive. These results show that pure XOs exert significant antioxidant activity, only due to their carbohydrate nature.