A Recyclable Inorganic Lanthanide Cluster Catalyst for Chemoselective Aerobic Oxidation of Thiols.

Optimizing lanthanide catalyst performance with organic ligands often encounters significant challenges, including susceptibility to water or oxygen and complex synthesis pathways. To address these issues, our research focuses on developing inorganic lanthanide clusters with enhanced stability and functionality. In this study, we introduce the [Sm6O(OH)8(H2O)24]I8(H2O)8 cluster (Sm-OC) as a sustainable and efficient catalyst for the aerobic oxidation of thiols under heating conditions. The Sm-OC catalyst demonstrated remarkable stability, outstanding recyclability, and excellent chemoselectivity across a diverse range of functional groups in 38 different tests. Notably, it enables efficient unsymmetrical disulfide synthesis and prevents the formation of over-oxidized by-products, highlighting its superior performance. This Sm-OC catalyst provides a practical and robust tool for the precise construction of versatile disulfides, thus establishing a template for the broader use of lanthanide clusters in organic synthesis.

Atypical Plant miRNA cal-miR2911: Robust Stability against Food Digestion and Specific Promoting Effect on Bifidobacterium in Mice.

Previous studies showed that cal-miR2911, featuring an atypical biogenesis, could target genes of virus and in turn inhibit virus replication. Given its especial sequence motif and cross-kingdom potential, the stability of miR2911 under digestive environment and its impact on intestinal microbes in mice were examined. The results showed that miR2911 was of considerable stability during oral, gastric, and intestinal digestion. The coingested food matrix enhanced its stability in the gastric phase, contributing to the existence of miR2911 in mouse intestines. The survival miR2911 promoted the growth of Bifidobacterium in mice and maintained the overall composition and diversity of the gut microbiota. miR2911 specifically entered the cells of Bifidobacterium adolescentis and potentially modulated the gene expression as evidenced by the dual-luciferase assay. The current study provided evidence on the cross-kingdom communication between dietary miRNAs and gut microbes, suggesting that modulating target bacteria using miRNAs for nutritional and therapeutic ends is promising.

Application of Iodine as a Catalyst in Aerobic Oxidations: A Sustainable Approach for Thiol Oxidations.

Iodine is a well-known oxidant that is widely used in organic syntheses. Thiol oxidation by stoichiometric iodine is one of the most commonly employed strategies for the synthesis of valuable disulfides. While recent advancements in catalytic aerobic oxidation conditions have eliminated the need for stoichiometric oxidants, concerns persist regarding the use of toxic or expensive catalysts. In this study, we discovered that iodine can be used as a cheap, low-toxicity catalyst in the aerobic oxidation of thiols. In the catalytic cycle, iodine can be regenerated via HI oxidation by O2 at 70 °C in EtOAc. This protocol harnesses sustainable oxygen as the terminal oxidant, enabling the conversion of primary and secondary thiols with remarkable efficiency. Notably, all 26 tested thiols, encompassing various sensitive functional groups, were successfully converted into their corresponding disulfides with yields ranging from >66% to 98% at a catalyst loading of 5 mol%.

Plant miRNA bol-miR159 Regulates Gut Microbiota Composition in Mice: In Vivo Evidence of the Crosstalk between Plant miRNAs and Intestinal Microbes.

New evidence reveals that bol-miR159, an miRNA rich in fruits and vegetables, cross-kingdomly functions in mammalian bodies. However, whether the miRNA could regulate gut microbiota remains unclear. Here, the effect of miR159 on mouse intestinal microbes was comprehensively examined. The results showed that supplementation of miR159 to the chow diet significantly enhanced the diversity of mouse gut microbiota without causing pathological lesions or inflammatory responses on the intestines. At the phylum level, miR159 increased the abundance of Proteobacteria and decreased the Firmicute-to-Bacteroidetes (F/B) ratio. miR159 had prebiotic-like effects on mouse gut microbiota, as it promoted the growth of the bacteria that is beneficial for maintaining gut health. The miRNA can target bacteria genes and get into the bacteria cells. The data provide direct in vivo evidence on the crosstalk between plant miRNAs and intestinal microbes, highlighting the potential for miRNA-based strategies that modulate gut microbes to improve host health.

Lycium ruthenicum Murr. anthocyanins inhibit hyperproliferation of synovial fibroblasts from rheumatoid patients and the mechanism study powered by network pharmacology.

BACKGROUND: Rheumatoid arthritis (RA), is a typical autoimmune disease affecting nearly 1% of the world's population. The dysfunctional hyperproliferation of synovial fibroblast (SF) in articular cartilage of RA patients is considered as the essential etiology. Traditional chemotherapeutic agents for RA treatment are imperfect for their high cost and unpredictable side-effects. L. ruthenicum anthocyanins (LRAC) is a natural product that of potential for therapeutic application against RA. METHODS: LRAC was characterized by UPLC-MS/MS. Bioinformatics analyses based on network pharmacology were applied to predict the potential targets of LRAC, and to select DEGs (differentially expressed genes) caused by RA pathogenesis from GSE77298. Interactions between LRAC and the predicted targets were evaluated by molecular docking. Effects of LRAC on SFs from RA patients were examined by in vitro assays, which were analyzed by flow cytometry and western blotting (WB). RESULTS: LRAC was able to inhibit the abnormal proliferation and aggressive invasion of SFs from RA patients. LRAC was mainly constituted by petunidin (82.7%), with small amount of delphinidin (12.9%) and malvidin (4.4%) in terms of anthocyanidin. Bioinformatics analyses showed that in 3738 RA-related DEGs, 58 of them were collectively targeted by delphinidin, malvidin and delphinidin. AR, CDK2, CHEK1, HIF1A, CXCR4, MMP2 and MMP9, the seven hub genes constructed a central network mediating the signal transduction. Molecular docking confirmed the high affinities between the LRAC ligands and the protein receptors encoded by the hub genes. The in vitro assays validated that LRAC repressed the growth of RASF by cell cycle arresting and cell invasion paralyzing (c-Myc/p21/CDK2), initiating cell apoptosis (HIF-1α/CXCR4/Bax/Bcl-2), and inducing pyroptosis via ROS-dependent pathway (NOX4/ROS/NLRP3/IL-1ß/Caspase-1). CONCLUSION: LRAC can selectively inhibit the proliferation of RASFs, without side-effecting immunosuppression that usually occurred for RA treatment using MTX (methotrexate). These findings demonstrate the potential application of LRAC as a phytomedicine for RA treatment, and provide a valid approach for exploring natural remedies against autoimmune diseases.

Fu Brick Tea Alleviates Constipation via Regulating the Aquaporins-Mediated Water Transport System in Association with Gut Microbiota.

This study aimed to investigate the amendatory effects of Fu brick tea aqueous extract (FTE) on constipation and its underlying molecular mechanism. The administration of FTE by oral gavage (100 and 400 mg/kg·bw) for 5 weeks significantly increased fecal water content, improved difficult defecation, and enhanced intestinal propulsion in loperamide (LOP)-induced constipated mice. FTE also reduced colonic inflammatory factors, maintained the intestinal tight junction structure, and inhibited colonic Aquaporins (AQPs) expression, thus normalizing the intestinal barrier and colonic water transport system of constipated mice. 16S rRNA gene sequence analysis results indicated that two doses of FTE increased the Firmicutes/Bacteroidota (F/B) ratio at the phylum level and increased the relative abundance of Lactobacillus from 5.6 ± 1.3 to 21.5 ± 3.4% and 28.5 ± 4.3% at the genus level, subsequently resulting in a significant elevation of colonic contents short-chain fatty acids levels. The metabolomic analysis demonstrated that FTE improved levels of 25 metabolites associated with constipation. These findings suggest that Fu brick tea has the potential to alleviate constipation by regulating gut microbiota and its metabolites, thereby improving the intestinal barrier and AQPs-mediated water transport system in mice.

Quantitative analysis of miRNAs using SplintR ligase-mediated ligation of complementary-pairing probes enhanced by RNase H (SPLICER)-qPCR.

Here, a method using SplintR ligase-mediated ligation of complementary-pairing probes enhanced by RNase H (SPLICER) for miRNAs quantification was established. The strategy has two steps: (1) ligation of two DNA probes specifically hybridize to target miRNA and (2) qPCR amplifying the ligated probe. The miRNA-binding regions of the probes are stem-looped, a motif significantly reduces nonspecific ligation at high ligation temperature (65°C). The ends of the probes are designed complementary to form a paired probe, facilitating the recognition of target miRNAs with low concentrations. RNase H proved to be able to stabilize the heteroduplex formed by the probe and target miRNA, contributing to enhanced sensitivity (limit of detection = 60 copies). High specificity (discriminating homology miRNAs differing only one nucleotide), wide dynamic range (seven orders of magnitude) and ability to accurately detect plant miRNAs (immune to hindrance of 2'-O-methyl moiety) enable SPLICER comparable with the commercially available TaqMan and miRCURY assays. SYBR green I, rather than expensive hydrolysis or locked nucleic acid probes indispensable to TaqMan and miRCURY assays, is adequate for SPLICER. The method was efficient (<1 h), economical ($7 per sample), and robust (able to detect xeno-miRNAs in mammalian bodies), making it a powerful tool for molecular diagnosis and corresponding therapy.

Synergistic antitumor effects of polysaccharides and anthocyanins from Lycium ruthenicum Murr. on human colorectal carcinoma LoVo cells and the molecular mechanism.

The antitumor effects of Lycium ruthenicum Murr. polysaccharides (LRPS) and Lycium ruthenicum Murr. anthocyanins (LRAC) were comprehensively investigated in this study. LPRS was obtained by water extraction and alcohol precipitation and further purified using diethylaminoethyl cellulose (DEAE-Cellulose) and Sephadex G-75 columns. High-performance liquid chromatography (HPLC) and Fourier transform-infrared (FT-IR) spectroscopy were used to characterize the purified LRPS. The results showed that the purified LRPS contained heteropolysaccharides, mainly composed of arabinose, galactose, and glucose with weight percentage of 41.2%, 33.6%, and 10.8%, respectively. More importantly, LRPS (500 µg/ml) and LRAC (80 µg/ml) failed to impede the proliferation of tumor cells when applied solely (48 h incubation), yet remarkable antineoplastic effects were found once they were applied altogether, since the LoVo cells, a typical human colorectal carcinoma cell line, were significantly inhibited by the mixture of LRPS (150 µg/ml) and LRAC (20 µg/ml) (LRPS&AC) in 24 h. The antineoplastic activity resulted from the combination of both LRPS and LRAC (LRPS&AC), by means of blocking the cell cycle at the G0-G1 phase and inducing LoVo cell apoptosis via reactive oxygen species (ROS)-dependent pathway. The inhibitory effects of LRPS&AC were specific to the tumor cells, without imposing on the proliferation of normal cells. Western blotting revealed that the antitumor effect was related to the mitochondria-mediated apoptosis launched by the cross-action of PI3K/Akt (phosphatidylinositol 3-kinase/protein kinase B) and JAK2/STAT3 (janus kinase 2/signal transduction and activator of transcription 3) signaling pathways. These findings for the first time reveal the synergistic antitumor effects of LRPS&AC and the related mechanisms, which enable Lycium ruthenicum Murr. to serve as a natural source to develop therapeutic reagents and functional foods with antineoplastic properties.

Digestion of Plant Dietary miRNAs Starts in the Mouth under the Protection of Coingested Food Components and Plant-Derived Exosome-like Nanoparticles.

The regulatory functions of plant miRNAs on mammalian bodies are controversial, mainly because stability of the miRNAs in the digestive tract, as the prerequisite for their cross-kingdom effects, has somehow been overlooked. Hence, as the first stage of food ingestion, stability of plant miRNAs in human saliva has been investigated. The results show that plant miRNAs are of considerable resistance against salivary digestion, as surviving miRNAs more than 20 fM are detected. The stability varies dramatically, which can be explained by the difference in tertiary structure, governing their affinities to RNase. Surprisingly, miRNAs of low initial concentrations can end up with high survival rates after digestion. Plant miRNAs can be loaded into exosome-like nanoparticles (ELNs) and microcapsules formed by food components, both of which protect the miRNAs from being degraded in human saliva. Overall, plant miRNAs can apply certain strategies to maintain constant concentrations, paving the way for their potential cross-kingdom effects.