Chemical fuel-driven transient 2D supramolecular organic frameworks (SOFs): catalysis for green synthesis.

Mimicking the dissipative assemblies found in living systems fueled by bioenergy, we present a novel chemical fuel-driven transient 2D SOF, formed via the redox reaction-driven transient self-assembly of tetraphenylene-based structural units and cucurbit[8]uril (CB[8]). The system was initiated by adding sodium dithionite (SDT) as the fuel, leading to the formation of 2D SOFs through 2 : 1 host-guest complexation between the viologen cation radical and CB[8]. These 2D SOFs then spontaneously disassemble over time as the radicals are oxidized by air. The temporal assembly and lifetimes of these transient SOFs can be controlled by adjusting the concentrations of the fuel. Moreover, the resulting transient 2D SOFs exhibited remarkable potential as catalysts for the green synthesis of benzyl sulfones in water.

Cyclic adenosine 3', 5'-monophosphate (cAMP) signaling is a crucial therapeutic target for ulcerative colitis.

The pathogenesis of ulcerative colitis (UC), a chronic intestine inflammatory disease primarily affecting adolescents, remains uncertain. Contemporary studies suggest that a confluence of elements, including genetic predispositions, environmental catalysts, dysregulated immune responses, and disturbances in the gut microbiome, are instrumental in the initiation and advancement of UC. Among them, inflammatory activation and mucosal barrier damage caused by abnormal immune regulation are essential links in the development of UC. The impairment of the mucosal barrier is intricately linked to the interplay of various cellular mechanisms, including oxidative stress, autophagy, and programmed cell death. An extensive corpus of research has elucidated that level of cyclic adenosine 3',5'-monophosphate (cAMP) undergo modifications in the midst of inflammation and participate in a diverse array of cellular operations that mitigate inflammation and the impairment of the mucosal barrier. Consequently, a plethora of pharmacological agents are currently under development, with some advancing through clinical trials, and are anticipated to garner approval as novel therapeutics. In summary, cAMP exerts a crucial influence on the onset and progression of UC, with fluctuations in its activity being intimately associated with the severity of the disease's manifestation. Significantly, this review unveils the paramount role of cAMP in the advancement of UC, offering a tactical approach for the clinical management of individuals afflicted with UC.

Anti-inflammatory discovery of sesquiterpenoids and a jasmonic acid derivative from Artemisia stolonifera.

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.

Influence of Gut Microbiota-Mediated Immune Regulation on Response to Chemotherapy.

The involvement of the gut microbiota in anti-cancer treatment has gained increasing attention. Alterations to the structure and function of the gut bacteria are important factors in the development of cancer as well as the efficacy of chemotherapy. Recent studies have confirmed that the gut microbiota and related metabolites influence the pharmacological activity of chemotherapeutic agents through interactions with the immune system. This review aims to summarize the current knowledge of how malignant tumor and chemotherapy affect the gut microbiota, how the gut microbiota regulates host immune response, and how interactions between the gut microbiota and host immune response influence the efficacy of chemotherapy. Recent advances in strategies for increasing the efficiency of chemotherapy based on the gut microbiota are also described. Deciphering the complex homeostasis maintained by the gut microbiota and host immunity provides a solid scientific basis for bacterial intervention in chemotherapy.

Chemical composition of Artemisia argyi essential oil and its antifungal activity against dermatophytes by inhibiting oxidative phosphorylation and causing oxidative damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Dermatophytes are notorious pathogens capable of infecting various mammals skin, posing serious threats to human health and overall life quality worldwide. Artemisia argyi has been recorded and applied for over a thousand years to treat skin itching. Although it has the potential to be developed as a plant-based antifungal agent, it's antifungal activity and action mechanism of active ingredients are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the chemical composition, antifungal activity against skin fungi, and potential mechanisms of Artemisia argyi essential oil (AEO). MATERIALS AND METHODS: The chemical composition of AEO was analyzed by gas chromatography-mass spectrometry (GC-MS) firstly. Flat growth restraint and double half dilution tests was performed to evaluate AEO antifungal activity against Microsporum gypseum, Trichophyton mentagrophytes, and Trichophyton rubrum. And then, the physiological mechanism of AEO inhibiting dermatophytes was systematically explored through scanning electron microscopy, relative conductivity, membrane leakage, ROS content, and antioxidant enzyme activity. Finally, the main pathways were screened through transcriptome sequencing, while the related genes expression levels and enzyme activity were validated. RESULTS: Monoterpenes and sesquiterpenoids were the most highly representative class of AEO. AEO had powerful antifungal activity against M. gypseum, T. mentagrophytes, and T. rubrum, with minimum inhibitory concentration (MIC) values of 0.6, 1.2, and 1.2 µL/mL, respectively. Moreover, AEO can also damage the cell membrane integrity of T. mentagrophytes, resulting in cellular extravasation of intracellular substances. Transcriptome analysis revealed that the main target of AEO is to inhibit electron transfer and oxidative phosphorylation during respiration, ultimately leading to obstruction of normal ATP synthesis and energy metabolism in mitochondria. And a large amount of ROS will generate due to the incompletely catalysis of oxygen under mitochondrial complexes. Coupled with the decrease of antioxidant enzyme (SOD, POD) activity, excessive accumulation of ROS will cause serious oxidative damage to cells and eventually exhibiting antifungal activity against dermatophytes. CONCLUSIONS: The present study demonstrated that Artemisia argyi was a valuable source of active compounds with antifungal activity. These findings support AEO as a potential agent to inhibit dermatophytes and prevent related dermatophytoses.

Highly sensitive and simultaneous detection of ascorbic acid, dopamine, and uric acid using Pt@g-C3N4/N-CNTs nanocomposites.

The detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) is crucial for understanding and managing various illnesses. In this research, Pt@g-C3N4 nanoparticles were synthesized via hydrothermal method and combined with N-doped carbon nanotubes (N-CNTs). The Pt@g-C3N4/N-CNTs-modified glassy carbon (GC) electrode was fabricated as an electrochemical sensor for the determination of AA, DA, and UA. The linear response range of AA, DA, and UA in the optimal condition was 100-3,000 µM, 1-100 µM, and 2-215 µM boasting a low detection limit (S/N = 3) of 29.44 µM (AA), 0.21 µM (UA), and 2.99 µM (DA), respectively. Additionally, the recoveries of AA, DA, and UA in serum sample were 100.4%-106.7%. These results corroborate the feasibility of the proposed method for the simultaneous, sensitive, and reliable detection of AA, DA, and UA. Our Pt@g-C3N4/N-CNTs/GC electrode can provide a potential strategy for disease diagnosis and health monitoring in clinical settings.

The water-soluble subfraction from Artemisia argyi alleviates LPS-induced inflammatory responses via multiple pathways and targets in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Artemisia argyi has been used medicinally and eaten for more than 2000 years in China. It is widely reported in treating inflammatory diseases such as eczema, dermatitis, arthritis, allergic asthma and colitis. Although several studies claim that its volatile oil and organic reagent extracts have certain anti-inflammatory effects, the water-soluble fractions and molecular mechanisms have not been studied. AIM OF THE STUDY: To evaluate the therapeutic effect of A. argyi water extract (AAWE) on lipopolysaccharide (LPS)-induced inflammatory responses and to identify the most effective water-soluble subfractions. Moreover, the relevant pharmacological and molecular mechanisms by which the active subfraction mitigates inflammation were further investigated. MATERIALS AND METHODS: Firstly, RAW 264.7 cells stimulated with LPS were treated with AAWE (50, 100, and 200 µg/mL) or the water-soluble subfractions separated by D101 macroporous resin (AAWE1-AAWE4, 100 µg/mL), and NO production and mRNA levels of inflammatory genes were evaluated to determine the most effective water-soluble subfractions. Secondly, the chemical components of the active subfraction (AAWE4) were analyzed by UPLC-QTOF-MS. Thirdly, transcriptome and network pharmacology analysis, RT-qPCR and Western blotting assays were conducted to explore the underlying anti-inflammatory mechanism and active compounds of AAWE4. Subsequently, the binding ability of the potential active components in AAWE4 to the core targets was further determined by molecular docking. Eventually, the in vivo anti-inflammatory activity of AAWE4 (1.17, 2.34 and 4.68 g/kg, administered per day for 7 d) was evaluated in mice with LPS-induced systemic inflammation. RESULTS: In this study, AAWE showed excellent anti-inflammatory effects, and its water-soluble subfraction AAWE4 exhibited the strongest inhibitory effect on NO concentration and inflammatory gene mRNA expression after LPS stimulation, indicating that it was the most effective subfraction. Thereafter, four main compounds in AAWE4 were confirmed or tentatively identified by UPLC-QTOF-MS, including three flavonoid glycosides and one phenolic acid. Furthermore, the transcriptome and network pharmacology analysis showed that AAWE4 inhibited inflammation via multiple pathways and multiple targets. Based on the RT-qPCR and Western blotting results, AAWE4 downregulated not only the p38, PI3K, CCL5, MMP9, AP-1, and BCL3 mRNA expression levels activated by LPS but also their upstream and downstream protein expression levels and protein phosphorylation (p-AKT/AKT, p-p38/p38, p-ERK/ERK, p-JNK/JNK). Moreover, four identified compounds (isochlorogenic acid A, vicenin-2, schaftoside and isoschaftoside) could significantly inhibit NO content and the overexpression of inflammatory factors TNF-α, IL-1ß, iNOS and COX-2 mRNA induced by LPS, and the molecular docking confirmed the high binding activity of four active compounds with selected core targets (p38, AKT1, MMP9, and CCL5). In addition, the mRNA expression and immunohistochemical analysis showed that AAWE44 could inhibit lung inflammation via multiple pathways and multiple targets in vivo. CONCLUSIONS: The findings of this study suggest that the water-soluble subfraction AAWE4 from A. argyi ameliorated the inflammation caused by LPS through multiple pathways and multiple targets in vitro and in vivo, providing scientific support for the medicinal use of A. argyi. Importantly, it shows that the A. argyi subfraction AAWE4 can be developed as an anti-inflammatory drug.

Two novel freshwater hyphomycetes, in Acrogenospora (Minutisphaerales, Dothideomycetes) and Conioscypha (Conioscyphales, Sordariomycetes) from Southwestern China.

Freshwater fungi are highly diverse in China and frequently reported from submerged wood, freshwater insects, herbaceous substrates, sediments, leaves, foams, and living plants. In this study, we investigated two freshwater species that were collected from Yunnan and Guizhou provinces in China. Detailed morphological analysis complemented by multi-gene phylogenetic analyses based on LSU, SSU, ITS, RPB2 and TEF1-α sequences data revealed them to be two new saprobic species, namely Acrogenosporaalangiisp. nov. and Conioscyphayunnanensissp. nov. in their asexual morphs. Additionally, Acrogenosporaalangiisp. nov. is reported for the first time as a freshwater ascomycete associated with the medicinal plant Alangiumchinense (Alangiaceae). Detailed morphological descriptions, illustrations and updated phylogenetic relationships of the new taxa are provided herein.

Artemisia argyi extract subfraction exerts an antifungal effect against dermatophytes by disrupting mitochondrial morphology and function.

Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 µg·mL-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g-1) and jaceosidin (4.17 ± 0.18 mg·g-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).

[Prediction analysis of quality markers and resource evaluation of Artemisiae Argyi Folium based on chemical composition and network pharmacology].

This study is based on ultra-high-performance liquid chromatography(UPLC), gas chromatography-mass spectrometry(GC-MS), and network pharmacology methods to analyze and predict potential quality markers(Q-markers) of Artemisiae Argyi Folium. First, UPLC and GC-MS techniques were used to analyze the content of 12 non-volatile components and 8 volatile components in the leaves of 33 Artemisia argyi germplasm resources as candidate Q-markers. Subsequently, network pharmacology was employed to construct a "component-target-pathway-efficacy" network to screen out core Q-markers, and the biological activity of the markers was validated using molecular docking. Finally, cluster analysis and principal component analysis were performed on the content of Q-markers in the 33 A. argyi germplasm resources. The results showed that 18 candidate components, 60 targets, and 185 relationships were identified, which were associated with 72 pathways related to the treatment of 11 diseases and exhibited 5 other effects. Based on the combination of freedom and component specificity, six components, including eupatilin, cineole, ß-caryophyllene, dinatin, jaceosidin, and caryophyllene oxide were selected as potential Q-markers for Artemisiae Argyi Folium. According to the content of these six markers, cluster analysis divided the 33 A. argyi germplasm resources into three groups, and principal component analysis identified S14 as having the highest overall quality. This study provides a reference for exploring Q-markers of Artemisiae Argyi Folium, establishing a quality evaluation system, further studying its pharmacological mechanisms, and breeding new varieties.

Morpho-Phylogenetic Evidence Reveals Novel Species and New Records of Botryosphaeriaceae in China and Thailand.

Species in the Botryosphaeriaceae are common plant pathogens, endophytes, and saprobes found on a variety of mainly woody hosts. Botryosphaeriaceae is a high-profile fungal family whose genera have been subjected to continuous revisions in recent years. Surveys conducted during 2019 and 2020 on several decaying woody hosts (from dead arial twigs, branches, stems, bark, and seed pods) in China and Thailand revealed a high diversity of Botryosphaeriaceae fungi. Identification of 16 Botryosphaeriaceae isolates was carried out based on both morphological characteristics and phylogenetic analyses of combined ITS, LSU, tef1-α, and tub2 sequence data. Four novel species (Dothiorella ovata, Do. rosacearum, Do. septata, and Lasiodiplodia delonicis) and seven previously known species (Botryosphaeria fujianensis, Diplodia mutila, Di. seriata, L. crassispora, L. mahajangana, Macrophomina euphorbiicola and Sphaeropsis eucalypticola) were identified while new hosts and geographical records were reported. This study indicates that the fungal family Botryosphaeriaceae seems to be common and widespread on a broad range of hosts in China and Thailand.

[Anti-inflammatory material basis and mechanism of Artemisia stolonifera based on UPLC-Q-TOF-MS combined with network pharmacology and molecular docking].

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.

[Comparison of growth and quality of wild and cultivated Artemisia stolonifera].

This paper aims to compare the difference of growth and quality between wild and cultivated Artemisia stolonifera, thereby providing references for further development and utilization of A. stolonifera. The wild and cultivated A. stolonifera from different altitudes were collected, and the agronomic characters, moxa yield, volatile components, flavonoids, and phenolic acids were determined. The results showed that the cultivated species were taller and stronger, with more leaves and branches, than the wild species. The moxa yield and combustion quality of wild products were higher than those of cultivated products. The content of main volatile components in cultivated products was higher than that in wild products. The content of flavonoids and phenolic acids in wild products was higher than that in cultivated products. At high altitude, the ignition performance, combustion persistence, comprehensive combustion performance, and heat release during combustion of the wild and cultivated A. stolonifera. were optimal. At middle altitude, the content of main characteristic volatile components and flavone phenolic acids in the leaves of the cultivated and wild A. stolonifera were the highest. At low altitude, the combustion quality and the content of the above components of the cultivated A. stolonifera decrease significantly. Considering the combustion quality and the content of the internal components of the leaf lint, the middle and high altitude areas are suitable for the artificial cultivation of A. stolonifera.

Electrochemical H2O2 sensor based on a Au nanoflower-graphene composite for anticancer drug evaluation.

Reliable H2O2 sensors for in situ cellular monitoring under drug stimulation can be developed as a powerful and versatile tool for drug evaluation. Herein, a novel electrochemical biosensor capable of detecting and quantifying H2O2 was fabricated by graphene and shape-controlled gold nanostructures. With the help of polyelectrolytes, gold exhibited hierarchical flower-like nanostructures. This kind of nanozyme material exhibited a prominent electrochemical response for H2O2. Electrocatalytic activity for H2O2 reduction with high sensitivity (5.07◊10-4 mA µmol L-1 cm-2) and good detection capability (the lowest detection limit is 4.5 µmol L-1 (S/N = 3)) were achieved. This electrochemical biosensor was successfully used to measure the concentration of H2O2 released from HepG2 hepatoma cells. Ascorbic acid (AA) and Camellia nitidissima Chi saponins (CNCS) were selected as model drugs, and their anticancer activities were compared by in situ monitoring of H2O2. Interestingly, the electrochemical sensor showed remarkable sensitivity, accuracy, and rapidity compared with the traditional enzymatic detection kit. In brief, the as-synthesized nanostructured H2O2 sensors can be applied to assess the antitumor properties of candidate drugs and inspire developments for personalized health care monitoring and cancer treatment.

Complexation of Apigenin and Oxymatrine Leading to Enhanced Anti-inflammatory Activity.

Apigenin (APG) is a well-known dietary flavonoid with multiple bioactivities, but its poor aqueous solubility may result in low oral bioavailability and thus compromised therapeutic effects. In the present study, APG was complexed with oxymatrine (OMT), a natural quinolizidine alkaloid, for enhanced anti-inflammatory activity, and the related mechanisms in the interaction of APG with OMT were investigated. Fourier transform-infrared spectroscopy, fluorescence spectroscopy, Raman spectroscopy, and proton nuclear magnetic resonance spectroscopy characterizations demonstrated the occurrence of an APG-OMT complex formed at a molar ratio of 1:2. Then, molecular dynamics simulations and quantum chemical calculations were utilized to elucidate that hydrogen bonding, van der Waals forces, and hydrophobic effects were the main forces acting in the formation of the APG-OMT complex. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of APG in the APG-OMT complex was significantly higher than that of APG alone. Finally, bioactivity evaluation in the lipopolysaccharide-induced acute inflammatory injury mouse models showed that the APG-OMT complex exhibited more potent anti-inflammatory effects than APG alone. This study confirmed that APG and OMT exerted enhanced anti-inflammatory effects through self-complexation, which may provide a novel strategy for improving the bioavailability and bioactivity of natural product mixtures.

[Effect of apigenin in combination with oxymatrine on non-small cell lung cancer and mechanism].

This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 µmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.

Gut microbiota mediated the individualized efficacy of Temozolomide via immunomodulation in glioma.

BACKGROUND: Temozolomide (TMZ) is the preferred chemotherapy strategy for glioma therapy. As a second-generation alkylating agent, TMZ provides superior oral bio-availability. However, limited response rate (less than 50%) and high incidence of drug resistance seriously restricts TMZ's application, there still lack of strategies to increase the chemotherapy sensitivity. METHODS: Luci-GL261 glioma orthotopic xenograft model combined bioluminescence imaging was utilized to evaluate the anti-tumor effect of TMZ and differentiate TMZ sensitive (S)/non-sensitive (NS) individuals. Integrated microbiomics and metabolomics analysis was applied to disentangle the involvement of gut bacteria in TMZ sensitivity. Spearman's correlation analysis was applied to test the association between fecal bacteria levels and pharmacodynamics indices. Antibiotics treatment combined TMZ treatment was used to confirm the involvement of gut microbiota in TMZ response. Flow cytometry analysis, ELISA and histopathology were used to explore the potential role of immunoregulation in gut microbiota mediated TMZ response. RESULTS: Firstly, gut bacteria composition was significantly altered during glioma development and TMZ treatment. Meanwhile, in vivo anti-cancer evaluation suggested a remarkable difference in chemotherapy efficacy after TMZ administration. Moreover, 16s rRNA gene sequencing and non-targeted metabolomics analysis revealed distinct different gut microbiota and immune infiltrating state between TMZ sensitive and non-sensitive mice, while abundance of differential gut bacteria and related metabolites was significantly correlated with TMZ pharmacodynamics indices. Further verification suggested that gut microbiota deletion by antibiotics treatment could accelerate glioma development, attenuate TMZ efficacy and inhibit immune cells (macrophage and CD8α+ T cell) recruitment. CONCLUSIONS: The current study confirmed the involvement of gut microbiota in glioma development and individualized TMZ efficacy via immunomodulation, hence gut bacteria may serve as a predictive biomarker as well as a therapeutic target for clinical TMZ application.

Intraspecific variation in genome size in Artemisia argyi determined using flow cytometry and a genome survey.

Different collections and accessions of Artemisia argyi (Chinese mugwort) harbour considerable diversity in morphology and bioactive compounds, but no mechanisms have been reported that explain these variations. We studied genome size in A. argyi accessions from different regions of China by flow cytometry. Genome size was significantly distinct among origins of these 42 Chinese mugwort accessions, ranging from 8.428 to 11.717 pg. There were no significant intraspecific differences among the 42 accessions from the five regions of China. The clustering analysis showed that these 42 A. argyi accessions could be divided into three groups, which had no significant relationship with geographical location. In a genome survey, the total genome size of A. argyi (A15) was estimated to be 7.852 Gb (or 8.029 pg) by K-mer analysis. This indicated that the results from the two independent methods are consistent, and that the genome survey can be used as an adjunct to flow cytometry to compensate for its deficiencies. In addition, genome survey can provide the information about heterozygosity, repeat sequences, GC content and ploidy of A. argyi genome. The nuclear DNA contents determined here provide a new reference for intraspecific variation in genome size in A. argyi, and may also be a potential resource for the study of genetic diversity and for breeding new cultivar.

Active fractions of golden-flowered tea (Camellia nitidissima Chi) inhibit epidermal growth factor receptor mutated non-small cell lung cancer via multiple pathways and targets in vitro and in vivo.

As a medicine-food homology (MFH) plant, golden-flowered tea (Camellia nitidissima Chi, CNC) has many different pharmacologic activities and is known as "the queen of the tea family" and "the Panda of the Plant world". Several studies have revealed the pharmacologic effects of CNC crude extract, including anti-tumor, anti-oxidative and hepatoprotective activity. However, there are few studies on the anti-tumor active fractions and components of CNC, yet the underlying mechanism has not been investigated. Thus, we sought to verify the anti-non-small cell lung cancer (NSCLC) effects of four active fractions of CNC. Firstly, we determined the pharmacodynamic material basis of the four active fractions of CNC (Camellia. leave. saponins, Camellia. leave. polyphenols, Camellia. flower. saponins, Camellia. flower. polyphenols) by UPLC-Q-TOF-MS/MS and confirmed the differences in their specific compound contents. Then, MTT, colony formation assay and EdU incorporation assay confirmed that all fractions of CNC exhibit significant inhibitory on NSCLC, especially the Camellia. leave. saponins (CLS) fraction on EGFR mutated NSCLC cell lines. Moreover, transcriptome analysis revealed that the inhibition of NSCLC cell growth by CLS may be via three pathways, including "Cytokine-cytokine receptor interaction," "PI3K-Akt signaling pathway" and "MAPK signaling pathway." Subsequently, quantitative real-time PCR (RT-qPCR) and Western blot (WB) revealed TGFB2, INHBB, PIK3R3, ITGB8, TrkB and CACNA1D as the critical targets for the anti-tumor effects of CLS in vitro. Finally, the xenograft models confirmed that CLS treatment effectively suppressed tumor growth, and the key targets were also verified in vivo. These observations suggest that golden-flowered tea could be developed as a functional tea drink with anti-cancer ability, providing an essential molecular mechanism foundation for MFH medicine treating NSCLC.