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Conductive polymers, integral to advancements in wearable devices, energy storage, healthcare and more, are crafted by integrating polymers with conductive elements like carbon substances, metals, and their particles. Drawing inspiration from natural water movement, this study introduces a method for crafting high-performance conductive composite films. This technique involves regulating the microstructure space of GaIn-based polymers under the mechanical pressure, where the fluid metal improves the internal microstructure gaps of the material. The presence of hydroxyl/carboxyl groups within the polymer enables the bonding with Ga3+ ions from the liquid metal (LM), securing them in place. This innovative process significantly boosts the material's electrical and thermal conductivity, as well as its mechanical integrity. This methodology has been successfully applied to enhance the attributes of GaIn-based composite films, utilizing nanocellulose fibers, chitosan nanofibers, and Kevlar-29 fibers as foundational materials. To demonstrate the method's effectiveness, a durable, highly thermally and electrically conductive GaIn-based MXene/nanocellulose composite film was developed and investigated in detail. This film showcased remarkable electromagnetic shielding with a high SSE/t value of 7718.91 dB cm2 g−1, and its performance mechanism was detailed through finite element analysis. Notably, the inclusion of GaIn endowed the film with excellent opto-electro-thermal conversion and heat-responsive deformation capabilities, highlighting its suitability for smart applications. Therefore, this research establishes a versatile approach for designing conductive films by merging liquid metal with polymers, potentially setting the stage for the creation of highly conductive composites in future. [Display omitted] [ABSTRACT FROM AUTHOR]

Using phosphogypsum (mainly composed of dihydrate gypsum) as raw material to prepare α-hemihydrate gypsum (α-HH) is an effective way for high-value utilization of phosphogypsum solid waste. Sodium ions can effectively promote the transformation of dihydrate gypsum to α-HH and enhance the driving force of crystal transformation. However, during this process, sodium impurities may be doped into the α-HH crystals, resulting in an efflorescence phenomenon when α-HH products are used, which affects the use of the products. In this paper, the formation of sodium impurities in the process of preparing α-HH in NaCl solution was studied by the laboratory test, XRD, XPS, SEM and XRF. Possible forms and diffusion paths of sodium impurities in hemihydrate gypsum crystals are studied by density functional based tight binding methods. The results show that sodium impurities tend to exist in hemihydrate gypsum crystals by doping at interstitial sites. Moreover, there are a large number of interstitial sites in hemihydrate gypsum, which are critical for the diffusion of sodium impurities. [Display omitted] • Possible forms and diffusion paths of Na impurities in hemihydrate gypsum crystals are studied. • The interstitial site in hemihydrate gypsum crystals is critical for Na impurity doping and diffusion. • The crystal transformation of DH to α-HH in solution is the key condition for the formation of Na impurity. [ABSTRACT FROM AUTHOR]

[Display omitted] • The CMG composite membranes could achieve a tensile strength of 36.12 MPa with good flexibility. • The CMG composite membranes could achieve a maximum thermal conductivity of approximately 9.11 W/m·K. • The maximum SSE/t value of CMG composite membranes was 6444.1 dB·cm2·g−1. • The CMG composite membranes showed excellent electrothermal conversion behavior and photothermal effects. With the rapid development of science and technology, information security and multiscenario applications of electronic equipment have received increasing attention in recent years. Therefore, the design and development of multifunctional electromagnetic interference shielding materials are key to solving the current development needs of electronic equipment. Based on the above topics, multifunctional liquid metal gallium (Ga)-doped transition metal carbides/nitrides (MXenes)/cellulose nanofiber (CNF/MXene@Ga, CMG) composite membranes with a nacre-like "brick–mortar" layered structure were synthesized using an ultrasonic probe and vacuum-assisted filtration. By optimizing the design, the CMG composite membranes could achieve a tensile strength of 36.12 MPa with good flexibility and could achieve a maximum thermal conductivity of approximately 9.11 W/m·K. The heterogeneous interface between MXenes and Ga nanoparticles and the intercalation of Ga nanoparticles significantly influenced the composite membranes for the absorption of electromagnetic waves, which yielded a specific shielding effectiveness per unit volume (SSE/t) of 6444.1 dB·cm2·g−1; this value is over the vast majority reported in the current literature. Further studies confirmed that the CMG composite membranes possessed excellent electrothermal and photothermal conversion functions. The electrothermal conversion agreed with Joule's law. Moreover, the phase transition behavior of Ga also imparts the membranes with the ability to store heat. The photothermal conversion ability was attributed to the surface plasmon resonance effect of Ga. Therefore, this work provides material support for the information security and multi-scenario applications of electronic equipment. [ABSTRACT FROM AUTHOR]

Retinoic acid (RA) and bile acids share common roles in regulating lipid homeostasis and insulin sensitivity. In addition, the receptor for RA (retinoid x receptor) is a permissive partner of the receptor for bile acids, farnesoid x receptor (FXR/NR1H4). Thus, RA can activate the FXR-mediated pathway as well. The current study was designed to understand the effect of all-trans RA on bile acid homeostasis. Mice were fed an all-trans RA-supplemented diet and the expression of 46 genes that participate in regulating bile acid homeostasis was studied. The data showed that all-trans RA has a profound effect in regulating genes involved in synthesis and transport of bile acids. All-trans RA treatment reduced the gene expression levels of Cyp7a1 , Cyp8b1 , and Akr1d1 , which are involved in bile acid synthesis. All-trans RA also decreased the hepatic mRNA levels of Lrh-1 (Nr5a2) and Hnf4α (Nr2a1), which positively regulate the gene expression of Cyp7a1 and Cyp8b1 . Moreover, all-trans RA induced the gene expression levels of negative regulators of bile acid synthesis including hepatic Fgfr4 , Fxr , and Shp (Nr0b2) as well as ileal Fgf15 . All-trans RA also decreased the expression of Abcb11 and Slc51b , which have a role in bile acid transport. Consistently, all-trans RA reduced hepatic bile acid levels and the ratio of CA/CDCA, as demonstrated by liquid chromatography-mass spectrometry. The data suggest that all-trans RA-induced SHP may contribute to the inhibition of CYP7A1 and CYP8B1, which in turn reduces bile acid synthesis and affects lipid absorption in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

• The mixed solutions of glycerol and Na 2 SO 4 was proposed to prepare α-HH from PG. • The conversion of PG into α-HH followed the dissolution-crystallization theory. • The morphology of α-HH could be regulated by citric acid. • Citric acid could adsorb on the α-HH surface by chelating with the calcium atoms. Preparation of α-hemihydrate gypsum (α-HH) from phosphogypsum (PG) by atmospheric hydrothermal method has a good application prospect due to the mild reaction conditions, the solution medium and modifier are important factors to control the formation and growth of α-HH crystals. In this study, the mixed solutions of glycerol and Na 2 SO 4 was proposed to transform PG into α-HH and the conversion mechanism was revealed, the morphology of α-HH was regulated by citric acid and its adsorption mechanism was clarified. The results show that the increase of glycerol and Na 2 SO 4 concentrations could accelerate the conversion of PG to α-HH, but this caused a decrease in the particles size of α-HH. The conversion of PG to α-HH in the mixed solutions will successively pass through dissolution, dissolution-crystallization and equilibrium three stages. With the increase of citric acid concentration, the α-HH crystals are enlarged in width and decreased in aspect ratio, which is attributed to citric acid could overcome the electrostatic repulsion by the carboxyl group chelating with the calcium atoms to adsorb on the surface of α-HH. [ABSTRACT FROM AUTHOR]

The ability to ensure nutritional and food security is seriously threatened by the ever-growing global population. Overreliance on a few staple food crops such as wheat, rice and maize will no longer be able to satisfy the rising demand for future food. Even with increasing agricultural production, over 820 million people are still facing food insecurity and at least 2 billion are facing nutrition insecurity. Therefore, it is imperative to focus on finding simple and sustainable solution to the present threat of global food insecurity. Besides staple food crops, harnessing nutrient-dense, climate-resilient, and locally available crops for production, marketing and consumption as " Smart Foods " for the future is needed. Buckwheat is a potential smart food because of its stress resistance and nutritional properties as well as strong antioxidant activity due to presence of flavonoids. This paper comprises a comprehensive review of the scientific literature on the valorization of buckwheat crops in terms of germplasm resources, breeding and genetic improvements for yield, bioactive compounds, biological activities and its potential application in food and pharmaceutical industries. Identification of elite cultivars and exploitation of buckwheat derived gluten-free bakery and non-bakery food stuffs and beverages such as tea, beer and wine should be explored for human consumption. Abundance of bioactive compounds results in high anti-oxidant, anti-microbial, anti-glycemic, anti-cancer properties and other health-promoting activities highlighting buckwheat's potential application as nutraceuticals and pharmaceuticals. • With a burgeoning world population, pressure on the production of adequate food. • Homogenization of human diets has a significant bearing on health and nutritional security of the masses. • Buckwheat is a potential smart food because of its balanced amino acid composition and rich bioactive compounds. • Buckwheat-fractions are used to develop several health promoting food stuffs. [ABSTRACT FROM AUTHOR]

Neuronal nitric oxide synthase (nNOS) plays a pivotal role in the pathological process of neuronal injury in the development of epilepsy. Our previous study has demonstrated that nitric oxide (NO) derived from nNOS in the epileptic brain is neurotoxic due to its reaction with the superoxide radical with the formation of peroxynitrite. Neuropeptide Y (NPY) is widely expressed in the mammalian brain, which has been implicated in energy homeostasis and neuroprotection. Recent studies suggest that nNOS may act as a mediator of NPY signaling. Here in this study, we sought to determine whether NPY expression is regulated by nNOS, and if so, whether the regulation of NPY by nNOS is associated with the neuronal injuries in the hippocampus of epileptic brain. Our results showed that pilocarpine-induced temporal lobe epilepsy (TLE) mice exhibited an increased level of nNOS expression and a decreased level of NPY expression along with hippocampal neuronal injuries and cognition deficit. Genetic deletion of nNOS gene, however, significantly upregulated hippocampal NPY expression and reduced TLE-induced hippocampal neuronal injuries and cognition decline. Knockdown of NPY abolished nNOS depletion-induced neuroprotection and cognitive improvement in the TLE mice, suggesting that inhibition of nNOS protects against hippocampal neuronal injuries by increasing neuropeptide Y expression in TLE mice. Targeting nNOS-NPY signaling pathway in the epileptic brain might provide clinical benefit by attenuating neuronal injuries and preventing cognitive deficits in epilepsy patients. [Display omitted] • NOS enzymatic activity is increased in the hippocampus of TLE mice. • Inhibition of nNOS suppresses TLE-induced cognitive impairment. • Inhibition of nNOS suppresses TLE-induced neuroinflammation and neuronal injuries. • nNOS negatively regulates NPY expression in the hippocampus of TLE mice. • Inhibition of nNOS suppresses TLE-induced neural injuries in a NPY-dependent manner. [ABSTRACT FROM AUTHOR]

Gynostemma pentaphyllum (Thunb.) Makino has traditional applications in Chinese medicine to treat lipid abnormalities. Gypenosides (GPs), the main bioactive components of Gynostemma pentaphyllum , have been reported to exert hypolipidemic effects through multiple mechanisms. The lipid-lowering effects of GPs may be attributed to the aglycone portion resulting from hydrolysis of GPs by the gut microbiota. However, to date, there have been no reports on whether gypenoside aglycones (Agl), the primary bioactive constituents, can ameliorate hyperlipidemia by modulating the gut microbiota. This study explored the potential therapeutic effects of gypenoside aglycone (Agl) in a rat model of high-fat diet (HFD)-induced hyperlipidemia. A hyperlipidemic rat model was established by feeding rats with a high-fat diet. Agl was administered orally, and serum lipid levels were analyzed. Molecular techniques, including RT-polymerase chain reaction (PCR) and fecal microbiota sequencing, were used to investigate the effects of Agl on lipid metabolism and gut microbiota composition. Agl administration significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and mitigated hepatic damage induced by HFD. Molecular investigations have revealed the modulation of key lipid metabolism genes and proteins by Agl. Notably, Agl treatment enriched the gut microbiota with beneficial genera, including Lactobacillus , Akkermansia , and Blautia and promoted specific shifts in Lactobacillus murinus , Firmicutes bacterium CAG:424 , and Allobaculum stercoricanis. This comprehensive study established Agl as a promising candidate for the treatment of hyperlipidemia. It also exhibits remarkable hypolipidemic and hepatoprotective properties. The modulation of lipid metabolism-related genes, along with the restoration of gut microbiota balance, provides mechanistic insights. Thus, Agl has great potential for clinical applications in hyperlipidemia management. [Display omitted] • Gypenosides can be absorbed into the bloodstream by conversion to gypenoside aglycones. • Gypenoside aglycones alter the structure and abundance of intestinal flora in hyperlipidaemic rats. • Gypenoside aglycones can alter the expression of genes related to lipid metabolism and serum lipid levels. • Agl intervention increased the enrichment of carbohydrate enzymes. [ABSTRACT FROM AUTHOR]

With significant advancements in high-resolution mass spectrometry, there has been a substantial increase in the amount of chemical component data acquired from natural products. Therefore, the rapid and efficient extraction of valuable mass spectral information from large volumes of high-resolution mass spectrometry data holds crucial significance. This study illustrates a targeted annotation of the metabolic products of alkaloid and sesquiterpene components from Dendrobium nobile (D. nobile) aqueous extract in mice serum through the integration of an in-houses database, R programming, a virtual metabolic product library, polygonal mass defect filtering, and Kendrick mass defect strategies. The research process involved initially establishing a library of alkaloids and sesquiterpenes components and simulating 71 potential metabolic reactions within the organism using R programming, thus creating a virtual metabolic product database. Subsequently, employing the virtual metabolic product library allowed for polygonal mass defect filtering, rapidly screening 1705 potential metabolites of alkaloids and 3044 potential metabolites of sesquiterpenes in the serum. Furthermore, based on the chemical composition database of D. nobile and online mass spectrometry databases, 95 compounds, including alkaloids, sesquiterpenes, and endogenous components, were characterized. Finally, utilizing Kendrick mass defect analysis in conjunction with known alkaloids and sesquiterpenes targeted screening of 209 demethylation, methylation, and oxidation products in phase I metabolism, and 146 glucuronidation and glutathione conjugation products in phase II metabolism. This study provides valuable insights for the rapid and accurate annotation of chemical components and their metabolites in vivo within natural products. [Display omitted] • PMDF and virtual metabolic products library were used to screening of potential metabolites in serum. • Targeted characterization metabolites in vivo were conducted using Kendrick mass defect strategies. • Totally 95 exogenous and endogenous components were annotated from mice serum by LC-MS/MS. [ABSTRACT FROM AUTHOR]

• Prognostic signature of m6A-associated lncRNAs constructed in thyroid cancer. • Prognostic signature correlate with immune infiltration. • Prognostic signature correlates with response to immunotherapy. • LINC02471 and DOCK9-DT as new biomarkers in thyroid cancer. Thyroid cancer (THCA) is the most common endocrine malignancy worldwide and has been rising at the fastest rate in recent years. Long-stranded non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) have been associated with immunotherapy efficacy and cancer prognosis. However, how m6A-associated lncRNAs (mrlncRNAs) affect the prognosis of patients with thyroid cancer is unclear. Therefore, this study utilized The Cancer Genome Atlas (TCGA) database to provide thyroid cancer-related transcriptomic data and related clinical data. The R program was used to identify m6A-related lncRNAs, and a risk model consisting of two lncRNAs (LINC02471 and DOCK9-DT) was obtained using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Kaplan-Meier survival analysis and transient subject operating characteristics (ROC) were used for analysis. The results showed a substantial association between immune cell infiltration and risk scores. Independent analyses confirmed that the expression of LINC02471 and DOCK9-DT was significantly higher in thyroid cancer tissues than in normal tissues, suggesting that they may be useful biomarkers for thyroid cancer. [ABSTRACT FROM AUTHOR]

Ordered microscale titanium (Ti) surface topography with homogeneous cell-sized microholes (20 µm in diameter) was fabricated using simple electrochemical etching. The as-prepared surface imposed with uniform titania nanotubes (TNTs, 70 nm in diameter) through electrochemical anodization showed no considerable change in the initial microscale morphology. Bone marrow mesenchymal stem cells (BMSCs) were used in evaluating the bioactivity. Compared with polished Ti and unordered microtextured Ti, the ordered microtextured Ti formed by electrochemical etching remarkably promoted cell attachment, alkaline phosphatase activity, collagen secretion, extracellular matrix mineralization, and osteogenesis-related gene expr essi on but considerably inhibited cell proliferation. After TNTs were introduced to the ordered microtextured Ti, cell attachment and osteogenic differentiation indexes were further enhanced, and cell proliferation recovered over time. The ordered micro-/nanotextured Ti surface was more conducive to the cell attachment, proliferation, and osteogenesis of BMSCs than polished Ti with and without TNTs, unordered microtextured Ti with and without TNTs, and unitary ordered microtextured Ti. Thus, the novel ordered bio-inspired micro-/nanotextured structure composed of cell-sized microholes and TNTs on the Ti surface possessed a favorable interfacial environment that improved osseointegration, potentially optimizing Ti implant surface topography. [Display omitted] • A novel ordered micro-/nanotextured titanium structure was fabricated. • The structure composed of cell-sized microholes and titania nanotubes. • Bone marrow mesenchymal stem cells were used in evaluating the bioactivity. • Cell attachment and osteogenesis-inducing ability were enhanced. • Cell proliferation could recover over time. [ABSTRACT FROM AUTHOR]

Dendrobium nobile Lindl. (DNL) is a traditional Chinese ethnobotanical herb. Dendrobine (DNE) has been designated as a quality indicator for DNL in the Chinese Pharmacopoeia. DNE exhibits various pharmacological activities, including the reduction of blood lipids, regulation of blood sugar levels, as well as anti-inflammatory and antioxidant properties. The objective of this study is to explore the impact of DNE on lipid degeneration in nonalcoholic fatty liver disease (NAFLD) liver cells and elucidate its specific mechanism. The findings aim to offer theoretical support for the development of drugs related to DNL. We utilized male C57BL/6J mice, aged 6 weeks old, to establish a NAFLD model. This model allowed us to assess the impact of DNE on liver pathology and lipid levels in NAFLD mice. We investigated the mechanism of DNE's regulation of lipid metabolism through RNA-seq analysis. Furthermore, a NAFLD model was established using HepG2 cells to further evaluate the impact of DNE on the pathological changes of NAFLD liver cells. The potential mechanism of DNE's improvement was rapidly elucidated using HT-qPCR technology. These results were subsequently validated using mouse liver samples. Following the in vitro activation or inhibition of PPARα function, we observed changes in DNE's ability to ameliorate pathological changes in NAFLD hepatocytes. This mechanism was further verified through RT-qPCR and Western blot analysis. DNE demonstrated a capacity to enhance serum TC, TG, and liver TG levels in mice, concurrently mitigating liver lipid degeneration. RNA-seq analysis unveiled that DNE primarily modulates the expression of genes related to metabolic pathways in mouse liver. Utilizing HT-qPCR technology, it was observed that DNE markedly regulates the expression of genes associated with the PPAR signaling pathway in liver cells. Consistency was observed in the in vivo data, where DNE significantly up-regulated the expression of PPARα mRNA and its protein level in mouse liver. Additionally, the expression of fatty acid metabolism-related genes (ACOX1, CPT2, HMGCS2, LPL), regulated by PPARα, was significantly elevated following DNE treatment. In vitro experiments further demonstrated that DNE notably ameliorated lipid deposition, peroxidation, and inflammation levels in NAFLD hepatocytes, particularly when administered in conjunction with fenofibrate. Notably, the PPARα inhibitor GW6471 attenuated these effects of DNE. In summary, DNE exerts its influence on the expression of genes associated with downstream fat metabolism by regulating PPARα. This regulatory mechanism enhances liver lipid metabolism, mitigates lipid degeneration in hepatocytes, and ultimately ameliorates the pathological changes in NAFLD hepatocytes. [Display omitted] • Dendrobine has capable of improving hepatic pathological changes in mice with NAFLD. • Dendrobine ameliorates hepatocellular steatosis, lipid peroxidation and inflammation in NAFLD. • Dendrobine ameliorates hepatic steatosis by modulating PPARα-related signaling in NAFLD. [ABSTRACT FROM AUTHOR]

Abstract: Fenretinide is significantly more effective in inducing apoptosis in cancer cells than all-trans retinoic acid (ATRA). The current study uses a genome-wide approach to understand the differential role fenretinide and ATRA have in inducing apoptosis in Huh7 cells. Fenretinide and ATRA-induced gene expressions and DNA bindings were profiled using microarray and chromatin immunoprecipitation with anti-RXRα antibody. The data showed that fenretinide was not a strong transcription regulator. Fenretinide only changed the expressions of 1 093 genes, approximately three times less than the number of genes regulated by ATRA (2 811). Biological function annotation demonstrated that both fenretinide and ATRA participated in pathways that determine cell fate and metabolic processes. However, fenretinide specifically induced Fas/TNFα-mediated apoptosis by increasing the expression of pro-apoptotic genes i.e., DEDD2, CASP8, CASP4, and HSPA1A/B; whereas, ATRA induced the expression of BIRC3 and TNFAIP3, which inhibit apoptosis by interacting with TRAF2. In addition, fenretinide inhibited the expression of the genes involved in RAS/RAF/ERK-mediated survival pathway. In contrast, ATRA increased the expression of SOSC2, BRAF, MEK, and ERK genes. Most genes regulated by fenretinide and ATRA were bound by RXRα, suggesting a direct effect. This study revealed that by regulating fewer genes, the effects of fenretinide become more specific and thus has fewer side effects than ATRA. The data also suggested that fenretinide induces apoptosis via death receptor effector and by inhibiting the RAS/RAF/ERK pathway. It provides insight on how retinoid efficacy can be improved and how side effects in cancer therapy can be reduced. [Copyright &y& Elsevier]

The Chinese medicine Daji (the aerial part of Cirsium japonicum DC.) and its charred product (Cirsii Japonici Herba Carbonisata) have been widely used as hemostatic agents or diuretic agents to prepare a variety of Chinese herbal formula. Pectolinarigenin (PEC), one of the most abundant constituents in both Daji and its charred product, has been considered as the key effective substance responsible for the major pharmacological activities of Daji, including hemostasis, hepatoprotective, anti-tumor and anti-osteoporosis effects. However, the major metabolic pathways of PEC in humans and the influence of PEC metabolism on its biological activities are poorly understood. To characterize the main metabolic pathway(s) and key enzymes of PEC in human biological systems, as well as to reveal the influence of PEC metabolism on its biological activities. The metabolic stability assays of PEC were investigated in human liver microsomes (HLM). The O -glucuronide of PEC was biosynthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy. The key enzymes responsible for O- glucuronidation of PEC in humans were assigned by performing UGT reaction phenotyping, chemical inhibition and enzymatic kinetic assays. The agonist effects of PEC and its O -glucuronide on nuclear factor erythroid2-related factor 2 (Nrf2), Peroxisome proliferator activated receptors (PPARα and PPARβ) were tested at the cellular level. PEC could be readily metabolized to form a mono- O -glucuronide in both human liver microsome (HLM) and human intestinal microsome (HIM). The mono- O -glucuronide was bio-synthesized by mouse liver S9 and its structure was fully characterized as PEC-7- O -β-D-glucuronide (PEC- O -7-G). UGT1A1, UGT1A3 and UGT1A9 are key enzymes responsible for PEC-7- O -glucuronidation in HLM, while UGT1A1, UGT1A9 and 1A10 may play key roles in this reaction in HIM. Biological tests revealed that PEC displayed strong agonist effects on Nrf2, PPARα and PPARβ, whereas PEC-7- O -glucuronide showed relatively weak Nrf2 agonist effect and very weak PPAR agonist effects, indicating that PEC-7- O -glucuronidation strongly weaken its agonist effects on Nrf2 and PPAR. Our results demonstrate that 7- O -glucuronidation is the major metabolic pathway of PEC in human tissues, while UGT1A1, 1A3 and 1A9 are key contributing enzymes responsible for PEC-7- O -glucuronidation in human liver. It is also found that PEC 7- O -glucuronidation significantly weakens the Nrf2 and PPAR agonist effects. All these findings are very helpful for the pharmacologists to deep understand the metabolic rates of PEC in humans. [Display omitted] • PEC- O -glucuronidation is a major metabolic pathway of PEC in humans. • The glucuronide was biosynthesized and fully characterized as PEC-7- O -β-D-glucuronide. • UGT1A1, UGT1A3 and UGT1A7-10 catalyzed PEC-7- O -glucuronidation. • PEC-7- O -glucuronidation strongly reduced the Nrf2 and PPAR agonist effects of PEC. [ABSTRACT FROM AUTHOR]

Human umbilical cord mesenchymal stem cells (HUMSCs) have been documented to be effective for several immune disorders including inflammatory bowel diseases (IBD). However, it remains unclear how HUMSCs function in regulating immune responses and intestinal flora in the trinitrobenzene sulfonic acid (TNBS)-induced IBD model. We assessed the regulatory effects of HUMSCs on the gut microbiota, T lymphocyte subpopulations and related immune cytokines in the TNBS-induced IBD model. The mice were divided into the normal, TNBS, and HUMSC-treated groups. The effect of HUMSCs was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Metagenomics Illumina sequencing was conducted for fecal samples. We demonstrated that the disease symptoms and pathological changes in the colon tissues of TNBS-induced colitis mice were dramatically ameliorated by HUMSCs, which improved the gut microbiota and rebalanced the immune system, increasing the abundance of healthy bacteria (such as Lactobacillus murinus and Lactobacillus johnsonii), the Firmicutes/Bacteroidetes ratio, and the proportion of Tregs; the Th1/Th17 ratio was decreased. Consistently, the expression levels of IFN-γ and IL-17 were significantly decreased, and transforming growth factor-β1 (TGF-β1) levels were significantly increased in the plasma of colitis mice HUMSC injection. Our experiment revealed that HUMSCs mitigate acute colitis by regulating the rebalance of Th1/Th17/Treg cells and related cytokines and remodeling the gut microbiota, providing potential future therapeutic targets in IBD. • HUMSCs effectively alleviate TNBS-induced colitis symptoms in mice and improve TNBS-induced colon damage. • Injection of HUMSCs inhibits Th1/Th17 and promotes Treg to restore immune balance. • Gut bacteria, play an important role in regulating the balance of Th1/Th17 and Treg. [ABSTRACT FROM AUTHOR]

Dendrobium, which belongs to the family of Orchidaceae, is a highly valuable traditional Chinese medicine commonly used in China. It exerts pharmacological activities such as antitumor and hypoglycemia effects, and its main components are alkaloids, polysaccharides, and terpenoids, among others. In recent years, research on the clinical application of Dendrobium in antitumor therapy has gained increasing attention. Accumulating evidence suggests that the active components of Dendrobium possess significant inhibitory effects on the viability of cancer cells as evident from in vivo and in vitro experiments, which indicates that Dendrobium exerts significant anticancer effect in treating and preventing cancer development, inhibiting the underlying potential molecular mechanisms, including suppression of cancer cell growth and proliferation, epithelial-mesenchymal transition (EMT), apoptosis induction, tumor angiogenesis, and reinforcement of cisplatin (DDP) -induced apoptosis. We herein present a review that summarizes the research progress of the application of Dendrobium in cancer therapy and its molecular mechanisms. This review describes the positive aspects of the active ingredients of Dendrobium in the treatment of cancers in various systems of the human body, their inhibitory effects on tumor survival and tumor microenvironment, and their potential mechanisms. Additionally, this review proposes future application prospects of Dendrobium in cancer therapy to promote further research and future extensive clinical applications of Dendrobium in cancer therapy. [ABSTRACT FROM AUTHOR]

Although a growing body of research has recently shown how crucial inflammation and infection are to all major diseases, several of the medications currently available on the market have various unfavourable side effects, necessitating the development of alternative therapeutic choices. Researchers are increasingly interested in alternative medications or active components derived from natural sources. Naringenin is a commonly consumed flavonoid found in many plants, and since it was discovered to have nutritional benefits, it has been utilized to treat inflammation and infections caused by particular bacteria or viruses. However, the absence of adequate clinical data and naringenin's poor solubility and stability severely restrict its usage as a medicinal agent. In this article, we discuss naringenin's effects and mechanisms of action on autoimmune-induced inflammation, bacterial infections, and viral infections based on recent research. We also present a few suggestions for enhancing naringenin's solubility, stability, and bioavailability. This paper emphasizes the potential use of naringenin as an anti-inflammatory and anti-infective agent and the next prophylactic substance for the treatment of various inflammatory and infectious diseases, even though some mechanisms of action are still unclear, and offers some theoretical support for its clinical application. [Display omitted] • Naringenin posses anti-inflammatory effect in autoimmune illnesses. • Naringenin is a natural product with anti-infective and antiviral effect. • The absorption of naringenin can be improved by nano-coated, Pectin, cocrystals, etc. [ABSTRACT FROM AUTHOR]

• The Poly(ionic liquids)/MXene organogels are firstly fabricated via radiation method. • The fabrication strategy is radiation-induced in situ polymerization and crosslinking. • The PILs/MXene gels possess a double cross-linked structure. • The gels exhibited rapidly self-healing ability, excellent anti-freezing properties. • The well-designed gels showing considerable potential in flexible wearable devices. As a new type of flexible electronic materials, conductive gels have attracted considerable interest because of their distinctive physical and chemical properties. In this work, the ILs with -C=C- double bond function as monomer and crosslinker, respectively; while the two-dimensional (2D) transition metal carbides/nitrides (Ti 3 C 2 T x MXene) functioned simultaneously as a "crosslinker" and nanofiller, then a series of new poly(ionic liquid)/MXene (C n -PIL/MXene) gels with stable covalent and non-covalent cross-linking structures based on n-alkyl-imidazolium (n = 2, 8) ionic liquid and MXene are fabricated by a one-step radiation method. The results reveal that the gel containing shorter alkyl (C 2 -PIL/MXene) is more suitable for flexible materials. Additionally, the C 2 -PIL/MXene gel exhibits remarkable stretchability (nearly 600%), good conductivity (4.9 mS cm−1), rapidly self-healing ability (within 8 min), excellent adhesion (266.9 kPa), and a fast response time (within 100 ms) due to the stable covalent bonding and abundant hydrogen bonding in the gel network. Notably, the C 2 -PIL/MXene gel also shows an excellent anti-freezing property (−60 °C), excellent durability (90 days at room temperature), and outstanding antibacterial activity against E. coli (99.82%) and S. aureus (99.98%). In addition, the multi-functional sensor based on the C 2 -PIL/MXene gel exhibits a real-time and rapid response to detect various human activities, recognize writing strokes, and realize the encrypted transmission of information, thus showing considerable potential in flexible smart wearable devices. [ABSTRACT FROM AUTHOR]

Magnetic composites Fe 3 O 4 /Cu-BTC and Fe 3 O 4 /Cu-BTC/GO were one-step synthesized and characterized. It was found that GO can help Fe 3 O 4 encapsulated more homogeneously. Fe 3 O 4 /Cu-BTC particles were “sea-island” structure, while Fe 3 O 4 /Cu-BTC/GO particles were uniform spherical structure with a bigger size. It can be explained by the excellent hydrophilicity of GO. IBU loading and IBU release of different particles were compared. Fe 3 O 4 /Cu-BTC/GO was found to have larger IBU loading and better IBU release. It was concluded that addition of GO changed the adsorption mechanic for IBU, which strengthened the IBU loading and led to the lower IBU release. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths worldwide. Sporadic CRC develops from normal mucosa via adenoma to adenocarcinoma, which provides a long screening window for clinical detection. However, early diagnosis of sporadic colorectal adenoma (CRA) and CRC using serum metabolic screening remains unclear. The purpose of this study was to identify some promising signatures for distinguishing the different pathological metabolites of colorectal mucosal malignant transformation. A total of 238 endogenous metabolites were elected. We found that CRA and CRC patients had 72 and 73 different metabolites compared with healthy controls, respectively. There were 20 different metabolites between CRA and CRC patients. The potential metabolites of tumor growth (including patients with CRA and CRC) were found, such as A- d -glucose, D-mannose, N -acetyl-D-glucosamine, L-cystine, Sarcosine, TXB 2, 12-Hete, and chenodeoxycholic acid. Compared with CRA, 3,4,5-trimethoxybenzoic acid was significantly higher in CRC patients. There results prompt us to use the potential serum signatures to screen CRC as the novel strategy. Serum metabolite screening is useful for early detection of mucosal intestinal malignancy. We will further investigate the roles of these promising biomarkers during intestinal tumorigenesis in future. CRC is one of the main causes of cancer-related deaths worldwide. Sporadic CRC develops from normal mucosa via adenomas to adenocarcinoma, which provides a long screening window for about 5–10 years. We adopt the metabolic analysis of extensive targeted metabolic technology. The main purpose of the metabolic group analysis is to detect and screen the different metabolites, thereby performing related functional prediction and analysis of the differential metabolites. In our study, 30 samples are selected, divided into 3 groups for metabolic analysis, and 238 metabolites are elected. In 238 metabolites, we find that CRA patients have 72 different metabolites compared with health control. Compared with health control, CRC have 73 different metabolites. Compared with CRA and CRC patients, there are 20 different metabolites. The annotation results of the significantly different metabolites are classified according to the KEGG pathway type. The potential metabolites of tumor growth stage (including patients with CRA and CRC) are found, such as A- d -glucose, D-mannose, N -acetyl-D-glucosamine, L-cystine, sarcosine, TXB 2, 12-Hete and chenodeoxycholic acid. Compared with CRA patients, CRC patients had significantly higher 3,4,5-trimethoxybenzoic acid level. It is prompted to use serum different metabolites to screen CRC to provide new possibilities. • In this study, 30 samples were selected, divided into 3 groups (including CRA, CRC, and healthy control group) for metabolic studies, and 238 metabolites were elected. • We used the combination of UPLC-MS/MS detection platform, metwell databases and multiple statistical analysis to integrate and explore the potential different metabolites. • The method of combining fold change and VIP values of OPLS-DA model were used to screen the differential metabolites. • The annotation results of the significantly different metabolites were classified according to the KEGG pathway type. The potential metabolites of tumor growth stage (including patients with CRA and CRC) were found, such as A- d -glucose, D-mannose, N -acetyl-D-glucosamine, L-cystine, sarcosine, TXB 2, 12-Hete and chenodeoxycholic acid. • Compared with CRA patients, CRC patients had significantly higher 3,4,5-trimethoxybenzoic acid level. [ABSTRACT FROM AUTHOR]

• A a novel covalent organic polymers (AB-COP) is firstly prepared. • AB-COP is firstly used to purify biflavonoids from Selaginella doederleinii. • Properties, performance and mechanism are investigated comprehensively. • 4.Compared with commonly used materials, AB-COP has excellent enrichment effect. • New purification method is developed for biflavonoids from natural products. Herein, a novel covalent organic polymers (COP) material based on acylhydrazone bond (AB-COP) was prepared as an efficient extraction material for enriching natural medicine biflavonoids from Selaginella doederleinii Hieron. The obtained AB-COP structure was characterized in detail. And it was the first time to investigate the effect of AB-COP on the adsorption of biflavonoids. The effects of initial concentration of solution, adsorption temperature, solid-liquid ratio, adsorption time on the adsorption of biflavonoids were studied. In addition, adsorption kinetic model, adsorption thermodynamic model and density functional theory (DFT) were also investigated to evaluate the adsorption mechanism. At the same time, the static desorption and reusability of AB-COP were investigated. Finally, the dynamic enrichment effect of AB-COP for biflavonoids was investigated. The results showed that AB-COP was successfully synthesized by Fourier transform infrared spectroscopy (FT-IR), solid state nuclear magnetism (NMR), X-ray diffraction (XRD), thermogravimetric analysis (TG), scanning electron microscopy (SEM), laser particle size analysis and Brunner Emmet Teller (BET) specific surface area test. The optimized adsorption parameters of AB-COP were initial concentration of 0.5 mg/mL, temperature of 45 °C, solid-liquid ratio of 10:10 (mg/mL), adsorption time of 60 min. The Langmuir adsorption isotherm could effectively describe the adsorption process, the pseudo-secondary adsorption model could accurately explain the adsorption mechanism, and the DFT calculations revealed that the interaction forces of AB-COP and biflavonoids were π-π stacking and hydrogen bonding. In addition, AB-COP successfully resolved biflavonoids through urea-methanol (1.3 mol/L), and the material can be reused at least four times. Finally, the solid phase extraction (SPE) chromatographic column prepared by AB-COP was successfully applied to the enrichment of biflavonoids from S. doederleinii , and the effect was significantly better than traditional chromatography materials, andthis method was also successfully applied to the enrichment of flavonoids in other plant extracts including Flos sophorae, Pericarpium viride, Lophatheri herba, Herba cuscutae. These results provide references for further purification of bioactive ingredients from plant extracts by using AB-COP. [ABSTRACT FROM AUTHOR]

Strychnine is one of the main bioactive and toxic constituents of Semen Strychni. In the present study, the neurotoxic effects of strychnine, and the role of individual differences in metabolism on susceptibility to neurotoxicity of strychnine were investigated. The acute toxicity was observed by a single dose of strychnine (2.92 mg/kg, i.g.) in rats, the epileptic stages of rats were scored according to Racine's scale. The neurotoxicity of strychnine was evaluated by the levels of ROS, MDA, SOD and GSH in hippocampus, striatum, and cortex tissues measurements and histopathological analysis. The concentrations of strychnine in the plasma, hippocampus, striatum, and cortex tissues were determined using high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). The expressions of the cytochrome P450, which is the most critical protein family involved in drugs metabolism, were detected by proteomics. The mechanism of susceptibility to neurotoxicity of strychnine was elucidated by correlation analysis among above indicators. The results indicated that striatum and cortex were the main toxic targets of strychnine, and the CYP3A1 might be a susceptible biomarker to neurotoxicity of strychnine. These results provide valuable insights into the neurotoxic susceptibility of strychnine that will aid in the rational clinical use of strychnine (possibly including Semen Strychni). [ABSTRACT FROM AUTHOR]

Abstract: A rapid, selective and sensitive ultra-performance liquid chromatography–electrospray ionization mass spectrometry (UPLC–ESIMS) method was firstly developed and validated for the simultaneous determination of two hepatotoxic pyrrolizidine alkaloids (HPAs), senecionine (SEN), adonifoline (ADO), and their N-oxides (SENNOX and ADONOX), the main metabolites in rat serum. The whole analysis was achieved within 4.5min by gradient elution on an ACQUITY UPLC BEH C18 column (50mm×2.1mm, i.d. 1.7μm) following a solid phase extraction for serum samples. Good linearity was achieved using weighted (1/x 2) least squares linear regression over a 1600-fold dynamic range for SEN and ADO (LLOQ was about 0.006μg/ml) and 800-fold dynamic range for SENNOX and ADONOX (LLOQ was about 0.012μg/ml). The R.S.D. of intra- and inter-day precision was below 4.91% and 11.15% respectively, while the R.E. of accuracy was within 4.52%, 6.81%, 2.69%, and 7.12% for SEN, SENNOX, ADO, and ADONOX, respectively. The developed method was successfully applied to the in vivo pharmacokinetic study in rats after intravenous administration of SEN and ADO. [Copyright &y& Elsevier]

Accumulation of hepatic lipid promotes systemic metabolic dysfunction and results in fatty liver. Our previous studies have shown that the alkaloids of Dendrobium nobile Lindl. (DNLA) could regulate the lipid metabolism gene expression in livers of mice. However, the protective effects on hepatic lipid homeostasis and the underlying mechanisms are still unclear. The C57BL/6 male mice were randomly divided into four groups, including control group, model group, DNLA treatment group, and simvastatin positive control group. Mice in the control group and the other three groups were fed with control diet and high fat diet during the full course of this study, respectively. Hepatic lipid accumulation was induced by HFD in mice after 18 weeks of feeding. DNLA (15 mg/kg) and simvastatin (20 mg/kg) were administrated intragastrically in the DNLA treatment group and simvastatin positive control group for another 18 weeks, respectively. HE staining and Oil-Red-O staining of liver tissues were observed. TC and TG levels in liver were assayed. The amount of major bile acids in mice livers were quantified by UPLC-MS. Expression levels of genes were tested by the real-time PCR. The results of HE staining and Oil-Red-O staining showed that DNLA could improve hepatic lipid homeostasis. DNLA significantly decreased liver TC and TG levels in the DNLA group. Moreover, the UPLC-MS analysis showed that DNLA did not only influence the hepatic bile acid quantity but did raise the hydrophilicity. Compared with the model group, DNLA decreased the hepatic levels of several free bile acids, including LCA, DCA, CA, and CDCA, and increased most important taurine-conjugated bile acids levels in liver, including TMCAs, TCDCA, TUDCA, and THDCA. In addition, DNLA also decreased the CA/CDCA ratio. The gene expression levels of Cyp27a1 , Cyp3a11 , Fxr , and Shp were up-regulated in DNLA treatment group. DNLA may improve the hepatic abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the taurine-conjugated bile acids which are highly hydrophilic and contribute to the excretion of cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption. Image 1 [ABSTRACT FROM AUTHOR]