Anti-inflammatory probiotics HF05 and HF06 synergistically alleviate ulcerative colitis and secondary liver injury.

Given the limited efficacy and adverse effects associated with conventional drugs, probiotics are emerging as a promising therapeutic strategy for mitigating the chronic nature of ulcerative colitis (UC) and its consequential secondary liver injury (SLI). Limosilactobacillus fermentum HF06 and Lactiplatibacillus plantarum HF05 are strains we screened with excellent anti-inflammatory and probiotic properties in vitro. In this study, the intervention of HF06 and HF05 in combination (MIXL) was found to be more effective in alleviating intestinal inflammation and secondary liver injury in UC mice compared to supplementing with the two strains individually. Results demonstrated that MIXL effectively attenuated colon shortening and weight loss, downregulated the expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 mRNA in the intestines, mitigated SLI, and augmented the enzymatic activities of SOD, CAT, and GSH-Px in the liver. MIXL enhances the intestinal barrier in UC mice, regulates the structure and composition of the gut microbiota, promotes the abundance of Lactobacillus, and suppresses the abundance of bacteria associated with inflammation and liver injury, including Clostridium_Sensu_Stricto_1, Escherichia, Shigella, Enterococcus, Corynebacterium, Desulfovibrio, and norank_f__Oscillospiraceae. This study demonstrated the synergistic effect of HF06 and HF05, providing a reliable foundation for the alleviation of UC.

Appropriate Nitrogen form Ratio and UV-A Supplementation Increased Quality and Production in Purple Lettuce (Lactuca sativa L.).

Purple lettuce (Lactuca sativa L. cv. Zhongshu Purple Lettuce) was chosen as the trial material, and LED intelligent light control consoles were used as the light sources. The purpose was to increase the yield and quality of purple lettuce while lowering its nitrate level. By adding various ratios of NO3--N and NH4+-N to the nutrient solution and 20 µmol m-2 s-1 UV-A based on white, red, and blue light (130, 120, 30 µmol m-2 s-1), the effects of different NO3--N/NH4+-N ratios (NO3--N, NO3--N/NH4+-N = 3/1, NH4+-N) and UV-A interaction on yield, quality, photosynthetic characteristics, anthocyanins, and nitrogen assimilation of purple lettuce were studied. In order to produce purple lettuce hydroponically under controlled environmental conditions, a theoretical foundation and technological specifications were developed, taking into account an appropriate UV-A dose and NO3--N/NH4+-N ratio. Results demonstrate that adding a 20 µmol m-2 s-1 UV-A, and a NO3--N/NH4+-N treatment of 3/1, significantly reduced the nitrate level while increasing the growth, photosynthetic rate, chlorophyll, carotenoid, and anthocyanin content of purple lettuce. The purple leaf lettuce leaves have an enhanced capacity to absorb nitrogen. Furthermore, plants have an acceleration of nitrogen metabolism, which raises the concentration of free amino acids and soluble proteins and promotes biomass synthesis. Thus, based on the NO3--N/NH4+-N (3/1) treatment, adding 20 µmol m-2 s-1 UV-A will be helpful in boosting purple lettuce production and decreasing its nitrate content.

High-Proportion Blue Light Irradiation at the End-of-Production Stage Promotes the Biosynthesis and Recycling of Ascorbate in Lettuce.

Ascorbate (AsA), an essential antioxidant for both plants and the human body, plays a vital role in maintaining proper functionality. Light plays an important role in metabolism of AsA in horticultural plants. Our previous research has revealed that subjecting lettuce to high light irradiation (HLI) (500 µmol·m-2·s-1) at the end-of-production (EOP) stage effectively enhances AsA levels, while the optimal light quality for AsA accumulation is still unknown. In this study, four combinations of red (R) and blue (B) light spectra with the ratio of 1:1 (1R1B), 2:1 (2R1B), 3:1 (3R1B), and 4:1 (4R1B) were applied to investigate the biosynthesis and recycling of AsA in lettuce. The results demonstrated that the AsA/total-AsA content in lettuce leaves was notably augmented upon exposure to 1R1B and 2R1B. Interestingly, AsA levels across all treatments increased rapidly at the early stage (2-8 h) of irradiation, while they increased slowly at the late stage (8-16 h). The activity of L-galactono-1,4-lactone dehydrogenase was augmented under 1R1B treatment, which is pivotal to AsA production. Additionally, the activities of enzymes key to AsA cycling were enhanced by 1R1B and 2R1B treatments, including ascorbate peroxidase, dehydroascorbate reductase, and monodehydroascorbate reductase. Notably, hydrogen peroxide and malondialdehyde accumulation increased dramatically following 16 h of 1R1B and 2R1B treatments. In addition, although soluble sugar and starch contents were enhanced by EOP-HLI, this effect was comparatively subdued under the 1R1B treatment. Overall, these results indicated that AsA accumulation was improved by irradiation with a blue light proportion of over 50% in lettuce, aligning with the heightened activities of key enzymes responsible for AsA synthesis, as well as the accrual of hydrogen peroxide. The effective strategy holds the potential to enhance the nutritional quality of lettuce while bolstering its antioxidant defenses.

Research on the Impact of Deep Eutectic Solvent and Hot-Water Extraction Methods on the Structure of Polygonatum sibiricum Polysaccharides.

Deep eutectic solvent (DES) and hot-water extraction (HWE) methods were utilized to extract polysaccharides from Polygonatum sibiricum, referred to as DPsP and WPsP, respectively. The extracted polysaccharides were purified using the Superdex-200 dextran gel purification system, resulting in three components for each type of polysaccharide. The structures of these components were characterized. The molecular weight analysis revealed that DPsP components had slightly larger molecular weights compared with WPsP, with DPsP-A showing a slightly higher dispersity index and broader molecular weight distribution. The main monosaccharide components of both DPsP and WPsP were mannose and glucose, while DPsP exhibited a slightly greater variety of sugar components compared with WPsP. FTIR analysis demonstrated characteristic polysaccharide absorption peaks in all six PSP components, with a predominance of acidic pyranose sugars. NMR analysis revealed the presence of pyranose sugars, including rhamnose and sugar aldehyde acids, in both DPsP-B and WPsP-A. DPsP-B primarily exhibited ß-type glycosidic linkages, while WPsP-A predominantly displayed α-type glycosidic linkages, with a smaller fraction being ß-type. These findings indicated differences in monosaccharide composition and structure between PSPs extracted using different methods. Overall, this study provided experimental evidence for future research on the structure-function relationship of PSPs.

Chiral-Flux-Phase-Based Topological Superconductivity in Kagome Systems with Mixed Edge Chiralities.

Recent studies have attracted intense attention on the quasi-2D kagome superconductors AV_{3}Sb_{5} (A=K, Rb, and Cs) where the unexpected chiral flux phase (CFP) associates with the spontaneous time-reversal symmetry breaking in charge density wave states. Here, commencing from the 2-by-2 charge density wave phases, we bridge the gap between topological superconductivity and time-reversal asymmetric CFP in kagome systems. Several chiral topological superconductor (TSC) states featuring distinct Chern numbers emerge for an s-wave or a d-wave superconducting pairing symmetry. Importantly, these CFP-based TSC phases possess unique gapless edge modes with mixed chiralities (i.e., both positive and negative chiralities), but with the net chiralities consistent with the Bogoliubov-de Gennes Chern numbers. We further study the transport properties of a two-terminal junction, using Chern insulator or normal metal leads via atomic Green's function method with Landauer-Büttiker formalism. In both cases, the normal electron tunneling and the crossed Andreev reflection oscillate as the chemical potential changes, but together contribute to plateau transmissions (1 and 3/2, respectively) that exhibit robustness against disorder. These behaviors can be regarded as the signature of a TSC hosting edge states with mixed chiralities.

A combined proteomics and metabolomics analysis reveals the invisible regulation of plant root responses to oxybenzone (benzophenone-3) stress.

Oxybenzone, an environmental pollutant affecting both agriculture and aquatic ecological integrity, has been demonstrated to act as a physiological and metabolic inhibitor on plants, animals, and microorganisms. Research on oxybenzone in higher plants has focused on the above-ground anatomy (leaves), while research on the under-ground parts (roots) has been neglected. In this study, the changes in plant root protein expression and metabolic pathways under oxybenzone treatment were explored through a combined proteomics and metabolomics analysis. A total of 506 differential proteins and 96 differential metabolites were identified, which were mainly distributed in critical pathways such as those for carbon (C) and nitrogen (N) metabolism, lipid metabolism, and antioxidation. Bioinformatics analysis shows that oxybenzone toxicity is predominantly reflected in alterations to root respiratory homeostasis and the manifestation of damaging reactive oxygen species (ROS) and membrane lipid peroxidation, changes to disease resistance-associated proteins, changes to normal C-flow distribution, and the inhibition of cell absorption and utilization of N sources. Plants respond to oxybenzone stress mainly by reconfiguring the mitochondrial electron-transport-chain to bypass oxidative-damage components; improving the efficiency of the antioxidant system to remove excessively accumulated ROS; promoting the detoxification of harmful membrane lipid peroxides; increasing osmotic adjustment substance (such as proline and raffinose) accumulation; adjusting C flow distribution to produce more nicotinamide adenine dinucleotide phosphate (NADPH) for the glutathione cycle; and accumulating free amino acids to increase plant stress tolerant. Our results are the first to map the changes in the physiological and metabolic regulatory network of higher plant roots under oxybenzone stress.

Proteomics and Lysine Acetylation Modification Reveal the Responses of Pakchoi (Brassica rapa L. ssp. chinensis) to Oxybenzone Stress.

The broad-spectrum UV filter oxybenzone is toxic to plants at environmentally relevant concentrations. Lysine acetylation (LysAc) is one of the essential post-translational modifications (PTMs) in plant signaling responses. The goal of this study was to uncover the LysAc regulatory mechanism in response to toxic exposures to oxybenzone as a first step in elucidating xenobiotic acclimatory reactions by using the model Brassica rapa L. ssp. chinensis. A total of 6124 sites on 2497 proteins were acetylated, 63 proteins were differentially abundant, and 162 proteins were differentially acetylated under oxybenzone treatment. Bioinformatics analysis showed that a large number of antioxidant proteins were significantly acetylated under oxybenzone treatment, implying that LysAc alleviated the adverse effects of reactive oxygen species (ROS) by inducing antioxidant systems and stress-related proteins; the significant changes in acetylation modification of enzymes involved in different branches of carbon metabolism in plants under oxybenzone treatment mean that plants can change the direction of carbon flow allocation by regulating the activities of carbon metabolism-related enzymes. Our results profile the protein LysAc under oxybenzone treatment and propose an adaptive mechanism at the post-translational level of vascular plants in response to pollutants, providing a dataset reference for future related research.

Deuterated [18F]fluoroethyl tropane analogs as dopamine transporter probes: Synthesis and biological evaluation.

INTRODUCTION: The dopamine transporter (DAT) is vitally correlated with Parkinson's disease (PD) and other neurodegenerative diseases. Non-invasive imaging of DAT contributes to early diagnosis and monitoring of related diseases. Recently, we reported a deuterated [18F]fluoroethyl tropane analogue [18F]FECNT-d4 as a potential DAT PET imaging agent. The objective of this work was to extend the investigation by comparing four deuterated [18F]fluoroethyl tropane derivatives ([18F]2a-d) to develop metabolically stable DAT radioligands. METHODS: Four fluoroethyl substituted phenyl-tropane compounds 1a-d and deuterated compounds 2a-d were synthesized and their IC50 values to DAT were evaluated. The [18F]fluoroethyl ligands [18F]1a-d and [18F]2a-d were obtained from corresponding labeling precursors by one-step radio-labeling reactions and investigated in terms of lipophilicity and in vitro binding affinity studies. [18F]1d and [18F]2d were then selected for further evaluations by in vivo metabolism study, biodistribution, ex vivo autoradiography, and microPET imaging studies. RESULTS: [18F]1a-d and [18F]2a-d were obtained in radiochemical yield of 11-32 % with molar activities of 28-54 GBq/µmol. The 1d and 2d exhibited relatively high affinity to DAT (IC50: 1.9-2.1 nM). Ex vivo autoradiography and microPET studies showed that [18F]2d selectively localized on DAT-rich striatal regions and the specific signal could be blocked by DAT inhibitor. Biodistribution results showed that [18F]2d consistently exhibited a higher ratio of the target to non-target (striatum/cerebellum) than [18F]1d. Furthermore, metabolism study indicated that the in vivo metabolic stability of [18F]2d was superior to that of [18F]1d. CONCLUSION: Our findings suggested that the deuterated compound [18F]2d might be a potential probe for DAT PET imaging in the brain.

Exosomal circFBLIM1 Promotes Hepatocellular Carcinoma Progression and Glycolysis by Regulating the miR-338/LRP6 Axis.

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Circular RNAs (circRNAs) play a vital role in cancer development and progression. This study investigated the role and potential mechanism of circRNA filamin binding LIM protein 1 (circFBLIM1) in HCC. Methods: Exosomes were identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot assay. The levels of circFBLIM1, miR-338, and low-density lipoprotein receptor-related protein 6 (LRP6) were measured by quantitative real-time polymerase chain reaction or Western blot. Glycolysis was analyzed by detecting glucose consumption, lactate production, ATP level, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis was detected by flow cytometry. Xenograft assay was performed to analyze tumor growth in vivo. The interaction among circFBLIM1, miR-338, and LRP6 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. This study was approved by the Institutional Review Board of the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. Results: CircFBLIM1 was highly expressed in HCC serum exosomes and HCC cells. Inhibition of circFBLIM1 confined HCC glycolysis and progression. CircFBLIM1 knockdown blocked tumorigenesis in vivo. CircFBLIM1 was a sponge of miR-338 and promoted HCC progression and glycolysis by regulating miR-338. Moreover, miR-338 suppressed HCC progression and glycolysis via targeting LRP6. Mechanistically, circFBLIM1 functioned as an miR-338 sponge to upregulate LRP6. Conclusion: CircFBLIM1 facilitated HCC progression and glycolysis via modulating the miR-338/LRP6 axis, which may provide promising therapeutic targets for HCC.

The analysis of lysine succinylation modification reveals the mechanism of oxybenzone damaging of pakchoi (Brassica rapa L. ssp. chinensis).

Oxybenzone (OBZ), one of a broad spectrum of ultraviolet (UV) absorbents, has been proven to be harmful to both plants and animals, while omics analysis of big data at the molecular level is still lacking. Lysine succinylation (Ksuc) is an important posttranslational modification of proteins that plays a crucial role in regulating the metabolic network in organisms under stress. Here, we report the changes in intracellular Ksuc modification in plants under OBZ stress. A total of 1276 succinylated sites on 507 proteins were identified. Among these sites, 181 modified proteins were hypersulfinylated/succinylated in OBZ-stressed pakchoi leaves. Differentially succinylated proteins (DSPs) are distributed mainly in the chloroplast, cytoplasm, and mitochondria and are distributed mainly in primary metabolic pathways, such as reactive oxygen species (ROS) scavenging, stress resistance, energy generation and transfer, photosynthetic carbon fixation, glycolysis, and the tricarboxylic acid (TCA) cycle. Comprehensive analysis shows that Ksuc mainly changes the carbon flow distribution, enhances the activity of the antioxidant system, affects the biosynthesis of amino acids, and increases the modification of histones. The results of this study first showed the profiling of the Kusc map under OBZ treatment and proposed the adaptive mechanism of pakchoi in response to pollutants and other abiotic stresses at the posttranslational level, which revealed the importance of Ksuc in the regulation of various life activities and provides a reference dataset for future research on molecular function.

Mechanism of [CO2] Enrichment Alleviated Drought Stress in the Roots of Cucumber Seedlings Revealed via Proteomic and Biochemical Analysis.

Cucumber is one of the most widely cultivated greenhouse vegetables, and its quality and yield are threatened by drought stress. Studies have shown that carbon dioxide concentration ([CO2]) enrichment can alleviate drought stress in cucumber seedlings; however the mechanism of this [CO2] enrichment effect on root drought stress is not clear. In this study, the effects of different drought stresses (simulated with 0, 5% and 10% PEG 6000, i.e., no, moderate, and severe drought stress) and [CO2] (400 µmol·mol-1 and 800 ± 40 µmol·mol-1) on the cucumber seedling root proteome were analyzed using the tandem mass tag (TMT) quantitative proteomics method. The results showed that after [CO2] enrichment, 346 differentially accumulating proteins (DAPs) were found only under moderate drought stress, 27 DAPs only under severe drought stress, and 34 DAPs under both moderate and severe drought stress. [CO2] enrichment promoted energy metabolism, amino acid metabolism, and secondary metabolism, induced the expression of proteins related to root cell wall and cytoskeleton metabolism, effectively maintained the balance of protein processing and degradation, and enhanced the cell wall regulation ability. However, the extent to which [CO2] enrichment alleviated drought stress in cucumber seedling roots was limited under severe drought stress, which may be due to excessive damage to the seedlings.

Glycine assists in efficient synthesis of herbal carbon dots with enhanced yield and performance.

As a special type of biomass, herbal medicine often contains a variety of biologically active substances, and taking it as a carbon source, it is expected to produce various types of biologically functional carbon dots (CDs). However, there are few reports in this field, especially in achieving enhanced performance of CDs by improving the utilization efficiency of active substances in medicinal materials. In this work, by adding glycine as an auxiliary agent in the preparation of CDs from herbal medicine (Exocarpium Citri Grandis), the carboxyl and amino groups of the adjuvant provided more reactive sites, which greatly improved the yield of CDs (about 6 times). More importantly, the antioxidant and biological activities of herbal CDs were also improved. By controlling the functional groups of adjuvants, the effects of carboxyl and amino groups in adjuvants on the synthesis of herbal CDs were compared. The results reveal that both carboxyl and amino groups can react with the substances in the carbon source, and the influence of amino groups was greater. After adding glycine, the size of the CDs became larger, resulting from the more abundant functional groups on the carbon skeleton, which was the main reason for the improved performance of the CDs. Finally, the biological activity experiment demonstrated that CDs derived from Exocarpium Citri Grandis and glycine could greatly enhance the vitality of cells and activate immune cells, which are expected to be applied in the field of cell reproduction and biological immunity. The method proposed in this work provides a potential strategy for high-yield preparation of CDs from biomass.

Structure and Processing Properties of Nine Yam (Dioscorea opposita Thunb) Starches from South China: A Comparison Study.

In order to explore the processing and application potential of Chinese yam starch, nine kinds of Chinese yam starch (GY11, GY5, GY2, GXPY, LCY, SFY, MPY, SYPY, ASY) from South China were collected and characterized. The chemical composition, rheological properties, thermal properties, and in vitro starch digestion were compared, and the correlation between the structure and processing properties of these yam starches was analyzed using Pearson correlation. The results show that GY2 had the highest amylose content of 28.70%. All the yam starches were similarly elliptical, and all the yam starch gels showed pseudoplastic behavior. Yam starches showed similar pasting temperatures and resistant starch content, but SYPY showed the largest particle size (28.4 µm), SFY showed the highest setback (2712.33 cp), and LCY showed the highest peak viscosity (6145.67 cp) and breakdown (2672.33 cp). In addition, these yam starches also showed different crystal types (A-type, B-type, C-type), relative crystallinity (26.54-31.48%), the ratios of 1045/1022 cm-1 (0.836-1.213), pasting properties, and rheological properties, so the yam starches have different application potentials. The rheological and pasting properties were related to the structural properties of starch, such as DI, Mw, and particle size, and were also closely related to the thermodynamic properties. The appropriate processing methods and purposes of the processed products of these yam starches can be selected according to their characteristics.

Synthesis and biological evaluation of 18F-labelled dopamine D3 receptor selective ligands.

The dopamine D3 receptor (D3R) is highly expressed in the limbic regions of the brain and closely related to a variety of neurological disorders including Parkinson's disease, schizophrenia and drug-seeking behavior. In vivo imaging of D3R with radio-labelled tracers and positron emission tomography (PET) has become a powerful technique in related disorders. In this study, we synthesized three novel aromatically 18F-labelled phenylpiperazine-like D3R selective radioactive ligands ([18F]5b, [18F]8b and [18F]11b) and developed a simple, rapid and efficient 18F-labelling method by condition optimization. Radiosynthesis of [18F]5b, [18F]8b and [18F]11b was achieved by 18F-fluorination from nitroarene precursors. Final radiochemical purities of [18F]5b, [18F]8b and [18F]11b solution were > 99% and remained good stability (> 98% for up to 6 h) in PBS and FBS. PET imaging and cellular binding studies revealed that [18F]8b had a higher D3R affinity than [18F]5b and [18F]11b. Autoradiography and biodistribution studies of the brain showed that [18F]8b had medium intensity specific accumulation in the striatum and cortex. Meanwhile, the low skeletal uptake of [18F]8b revealed a good in vivo stability with negligible defluorination. These results indicated that [18F]8b might be a potential 18F-labelled D3R PET imaging agent.

Image-Based vs. Parametric Modelling of Concrete Meso-Structures.

Damage initiation and crack propagation in concrete are associated with localisation of energy dissipation by the concrete meso-structure. Meso-scale models are, therefore, required for realistic analysis of concrete non-linear behaviour. Such models are constructed either from X-ray Computed Tomography images (image-based modelling) or by in silico meso-structure generation (parametric modelling), while both approaches are widely used and their advantages and disadvantages are recognised, little work is done on comparing their performance in predicting measured macroscopic behaviour with equivalent constitutive relations for meso-structural features. This work uses microstructure characterisation and mechanical behaviour data to construct, validate and compare the two modelling approaches. The macroscopic behaviour obtained with both meso-structural models is found to be in good agreement with experimental data. Differences are observed only between the predicted distributions of damage within specimens. These outcomes suggest that the computationally simpler parametric meso-structures are sufficient to derive stress-strain behaviour for engineering-scale models in the absence of other environmental factors. The observed differences in damage distribution could be important for analysis of coupled behaviour, e.g., mass transport and chemical reactions affecting local mechanical properties and being affected by local damage. Establishing the importance of damage distribution is such cases requires further research.

Physiological and Transcriptomic Analyses Revealed the Implications of Abscisic Acid in Mediating the Rate-Limiting Step for Photosynthetic Carbon Dioxide Utilisation in Response to Vapour Pressure Deficit in Solanum Lycopersicum (Tomato).

The atmospheric vapour pressure deficit (VPD) has been demonstrated to be a significant environmental factor inducing plant water stress and affecting plant photosynthetic productivity. Despite this, the rate-limiting step for photosynthesis under varying VPD is still unclear. In the present study, tomato plants were cultivated under two contrasting VPD levels: high VPD (3-5 kPa) and low VPD (0.5-1.5 kPa). The effect of long-term acclimation on the short-term rapid VPD response was examined across VPD ranging from 0.5 to 4.5 kPa. Quantitative photosynthetic limitation analysis across the VPD range was performed by combining gas exchange and chlorophyll fluorescence. The potential role of abscisic acid (ABA) in mediating photosynthetic carbon dioxide (CO2) uptake across a series of VPD was evaluated by physiological and transcriptomic analyses. The rate-limiting step for photosynthetic CO2 utilisation varied with VPD elevation in tomato plants. Under low VPD conditions, stomatal and mesophyll conductance was sufficiently high for CO2 transport. With VPD elevation, plant water stress was gradually pronounced and triggered rapid ABA biosynthesis. The contribution of stomatal and mesophyll limitation to photosynthesis gradually increased with an increase in the VPD. Consequently, the low CO2 availability inside chloroplasts substantially constrained photosynthesis under high VPD conditions. The foliar ABA content was negatively correlated with stomatal and mesophyll conductance for CO2 diffusion. Transcriptomic and physiological analyses revealed that ABA was potentially involved in mediating water transport and photosynthetic CO2 uptake in response to VPD variation. The present study provided new insights into the underlying mechanism of photosynthetic depression under high VPD stress.

Structure Characterization of Polysaccharide from Chinese Yam (Dioscorea opposite Thunb.) and Its Growth-Promoting Effects on Streptococcus thermophilus.

To clarify the mechanisms underlying the growth-promoting effects of yam polysaccharide on Streptococcus thermophilus (S. thermophilus), the yam polysaccharide was extracted using a deep eutectic solvents (DESs) method and separated into four fractions by DEAE-cellulose 52. These fractions were used as the alternative carbon source to substitute lactose to compare their growth-promoting effects on S. thermophilus. Furthermore, their molecular weight, monosaccharide and functional groups' composition, microscopic forms and other basic structure characterizations were analyzed. The results showed that all the fractions could significantly promote S. thermophilus growth, and fractions exhibited significantly different growth-promoting effects, whose viable count increased by 6.14, 6.03, 11.48 and 11.29%, respectively, relative to those in the M17 broth medium. Structure-activity relationship analysis revealed that the high growth-promoting activity of yam polysaccharide might be more dependent on the higher molecular weight, the higher galacturonic acid content and its complex spatial configuration, and the existence of ß-glycosides would make the yam polysaccharide have a better growth-promoting effect on S. thermophilus.

Inhibitory effects of everolimus in combination with paclitaxel on adriamycin-resistant breast cancer cell line MDA-MB-231.

OBJECTIVE: We aimed to evaluate the therapeutic effects of paclitaxel in combination with mTOR inhibitor everolimus on adriamycin-resistant breast cancer cell line MDA-MB-231 (MDA-MB-231/ADR). MATERIALS AND METHODS: MDA-MB-231/ADR cells were treated with different concentrations of paclitaxel and everolimus. The IC50 values after 48 h of treatment were measured by the MTT assay. The apoptosis rate and cell cycle were detected by flow cytometry. The protein expressions of Akt, PI3K, mTOR, p-pI3K, p-AKT and p-mTOR were detected by Western blot. RESULTS: When paclitaxel at ≥1.56 µg/ml was used, the growth of MDA-MB-231/ADR cells was inhibited more significantly than that of control group (P < 0.05). After treatment with ≥6.25 µg/ml everolimus, the cell growth was also suppressed more significantly (P < 0.05). The IC50 values of everolimus and paclitaxel were 32.50 µg/ml and 7.80 µg/ml, respectively. The inhibition rate of paclitaxel plus everolimus was significantly enhanced with increasing paclitaxel concentration (P < 0.001). After treatment with 7.80 µg/ml paclitaxel, the two drugs had best synergistic inhibitory effects on proliferation. Compared with drugs alone, the combination significantly promoted apoptosis (P < 0.001). The paclitaxel + everolimus group had significantly more cells in the G0-G1 phase than those of control and individual drug groups (P < 0.001). Everolimus significantly decreased mTOR and p-mTOR expressions compared with those of control group (P < 0.001). Compared with everolimus alone, the combination reduced the expressions more significantly (P < 0.05). Paclitaxel decreased the expression levels of PI3K, p-PI3K and p-AKT. Compared with paclitaxel alone, the combination significantly promoted the reduction of PI3K, p-PI3K and p-AKT expressions (P < 0.05). CONCLUSION: Everolimus can enhance the effect of paclitaxel on MDA-MB-231/ADR cells, inhibit cell proliferation, induce apoptosis and arrest cell cycle in the G1 phase mainly by down-regulating the expressions of key proteins in the mTOR signaling pathway.