Semisynthesis and antitumor activity of endertiin B and related triterpenoids from Ganoderma lucidum.

Ganoderma lucidum, a fungus used in traditional Chinese medicine, is known for its medicinal value attributed to its active components called Ganoderma triterpenoids (GTs). However, the limited isolation rate of these GTs has hindered their potential as promising drug candidates. Therefore, it is imperative to achieve large-scale preparation of GTs. In this study, four GTs were effectively synthesised from lanosterol. The antitumor activity of these GTs was evaluated in vivo. Endertiin B exhibited potent inhibitory activity against breast cancer cells (9.85 ± 0.91 µM and 12.12 ± 0.95 µM). Further investigations demonstrated that endertiin B significantly upregulated p21 and p27 and downregulated cyclinD1 expression, arresting the cell cycle at the G0/G1 phase and inducing apoptosis by decreasing BCL-2 and increasing BAX and BAK levels. Additionally, endertiin B was found to reduce the expression of proteins associated with the PI3K-AKT signaling pathway. To summarize, endertiin B effectively inhibited cell proliferation by blocking the cell cycle and inducing apoptosis through the PI3K-AKT pathway.

Preparation and Reactivity of Core-Shell Al@CL-20 Composites Embedded with Graphene-Based Complexes as Catalysts.

Incomplete combustion of Al in solid propellants can be effectively resolved by coating of an oxidizer at the microscale. In this paper, Al@CL-20 composites with polydopamine as the interfacial layer were prepared using this strategy. The structure, heat of reaction, thermal decomposition properties, and combustion performances of these composites under the effects of graphene oxide (GO) and graphene-based carbohydrazide complexes (GO-CHZ-M, M = Co2+, Ni2+) have been comprehensively investigated. The experimental results show that the heat of reaction of Al@CL-20 is 6482 J g-1, which is 561 J g-1 higher than that of the corresponding mechanical mixture. The presence of GO-CHZ-Co can further increase the heat of reaction of Al@CL-20 to 6729 J g-1 with a decreased activation energy by about 54.8%. Under the synergistic effect of interfacial control and GO-CHZ-M, the ignition delay time of Al@CL-20-Co decreases from 5.1 to 4.2 ms. Besides, the D50 of the combustion condensed products (CCPs) decreased from 5.62 to 4.33 µm, indicating the combustion efficiency of Al is greatly improved.

Enhancing the Ignition and Combustion Performances of Solid Propellants Incorporating Al Particles Inside Oxidizers.

The combustion efficiency of Al plays a critical role in the combustion of high-energy aluminum-based solid propellants. For traditional formulations, the Al powders are dispersed in the binder matrix, leading to limited contact with the oxidizers and hence usually insufficient combustion and higher values of the pressure exponent. In this paper, various core-shell structural Al/oxidizer composites such as Al@HMX, Al@AP, and AP@Al have been prepared by a spray-drying technique based on which solid propellants with precise interfacial control between Al particles and oxidizers were realized. Compared to the control sample, the modified propellants have a greater heat of explosion of 5890 J g-1 (15% higher) and a reduced ignition delay time of 58 ms (65% decrease). Without changing the content of components, the burn rates of propellants can be easily modulated by tuning the interfacial contact of Al and oxidizers, where it varies in a wide range of 4.56-5.79 mm s-1 at the same pressure of 1 MPa. After introducing Al/oxidizer composites, the lowest pressure exponent of 0.19 within 1-15 MPa could be achieved by using Al@HMX and AP@Al composites. The agglomeration of Al was also inhibited by using Al/oxidizer composites, and the mechanism can be interpreted by using a classical "pocket" model. Moreover, the improved combustion efficiency of the solid propellants was verified by a noticeable reduction in the unreacted Al content.

High-Energy Composite Fuels with Improved Combustion Efficiency by Using AlH3 Embedded with Al Particles.

Aluminum hydride (AlH3) has attracted much attention due to its potential to replace aluminum (Al) as a novel energetic material in solid propellants. In this research, ammonium perchlorate (AP) and perfluoropolyether (PFPE) as functionalized coatings and a combination of acoustic resonance and spray drying technology have been employed to prepare AlH3@Al@AP (AHAPs) and AlH3@Al@AP@PFPE (AHAPs-F) energetic composite particles. The formulations of composite propellants and modified AlH3 particles were designed and fabricated. Their thermal reactivity, reaction heat, density, vacuum stability, combustion performance, and condensed combustion products (CCPs) have been systematically investigated. The results show that the solid propellants containing AHAPs (SP13) and AHAPs-F (SP14) composites can significantly enhance the reactivity and energy output compared to conventional solid propellants with the mechanical mixture Al/AlH3 (SP12). In particular, the total heat releases of SP13 and SP14 are almost 1.2 and 1.7 times higher than those of conventional ones (SP12, 1442 J g-1), respectively. Among the AlH3-based propellants, SP14 propellants exhibit the highest reaction heat of 5887 J g-1, the most intensive flame radiation of 31.4 × 103, and the highest combustion wave temperature of 2495 °C. Moreover, the particle size distribution of CCPs from SP14 propellants is much narrower and smaller than that of SP12, resulting in higher combustion efficiency.

Climate, not grazing, influences soil microbial diversity through changes in vegetation and abiotic factors on geographical patterns in the Eurasian steppe.

Livestock grazing has a significant impact on the biodiversity of nature grassland ecosystems, which is mainly regulated by climate factors. Soil microbes are essential components of biogeochemical cycles. However, the coupling effects of grazing with MAT (mean annual temperature) and MAP (mean annual precipitation) on soil microbial communities remain inconsistent. Our study considered the various climates in four grasslands as natural temperature and precipitation gradients combined with grazing intensity (GI). We collected and analyzed vegetation and soil physiochemical properties from four grasslands. Our results showed that climate factors (CF) changed ß diversity of soil bacteria and fungi while grazing intensity and their interaction merely affected fungi ß diversity. Furthermore, climate factors and grazing intensity impacted changes in vegetation and soil physiochemical properties, with their interaction leading to changes in EC and MBC. Our analysis revealed that climate factors contributed 13.1% to bacteria community variation while grazing intensity contributed 3.01% to fungi community variation. Piecewise SEM analysis demonstrated that MAT and MAP were essential predictors of bacteria ß diversity, which was significantly affected by vegetation and soil carbon and nitrogen. At the same time, MAP was an essential factor of fungi ß diversity and was mainly affected by soil nitrogen. Our study indicated that bacteria and fungi ß diversity was affected by different environmental processes and can adapt to specific grazing intensities over time.

Mechanism of Interaction between Ammonium Perchlorate and Aluminum.

There is an interactive effect between ammonium perchlorate (AP) and aluminum (Al) powder during the combustion process of composite solid propellants, but the mechanism of this effect is still lacking. Using quantum chemical methods, we investigated this mechanism from a molecular perspective. The interaction process between Al and AP was analyzed by comparing the chemical bond changes between the atoms during the reaction process of the Al/AP system and the AP unimolecular thermal decomposition system. The results show that Al atoms alter the reaction mechanism of AP thermal decomposition, significantly decreasing the activation energy of AP decomposition at high temperature but increasing that at low temperature. Meanwhile, the temperature-dependent rate constant of each basic reaction was calculated by transition state theory. The rate constants increase with temperature. Under high temperature and pressure, Al can increase the high-temperature decomposition rate of AP by up to 1-3 orders of magnitude.

Short-Term Clinical Response and Changes in the Fecal Microbiota and Metabolite Levels in Patients with Crohn's Disease After Stem Cell Infusions.

Recent studies have shown a close relationship between the gut microbiota and Crohn's disease (CD). This study aimed to determine whether mesenchymal stem cell (MSC) treatment alters the gut microbiota and fecal metabolite pathways and to establish the relationship between the gut microbiota and fecal metabolites. Patients with refractory CD were enrolled and received 8 intravenous infusions of MSCs at a dose of 1.0 × 106 cells/kg. The MSC efficacy and safety were evaluated. Fecal samples were collected, and their microbiomes were analyzed by 16S rDNA sequencing. The fecal metabolites at baseline and after 4 and 8 MSC infusions were identified by liquid chromatography-mass spectrometry (LC--MS). A bioinformatics analysis was conducted using the sequencing data. No serious adverse effects were observed. The clinical symptoms and signs of patients with CD were substantially relieved after 8 MSC infusions, as revealed by changes in weight, the CD activity index (CDAI) score, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). Endoscopic improvement was observed in 2 patients. A comparison of the gut microbiome after 8 MSC treatments with that at baseline showed that the genus Cetobacterium was significantly enriched. Linoleic acid was depleted after 8 MSC treatments. A possible link between the altered Cetobacterium abundance and linoleic acid metabolite levels was observed in patients with CD who received MSCs. This study enabled an understanding of both the gut microbiota response and bacterial metabolites to obtain more information about host-gut microbiota metabolic interactions in the short-term response to MSC treatment.

γ-Aminobutyric acid plays a key role in alleviating Glomerella leaf spot in apples.

The fungal disease Glomerella leaf spot (GLS) seriously impacts apple production. As a nonprotein amino acid, γ-aminobutyric acid (GABA) is widely involved in biotic and abiotic stresses. However, it is not clear whether GABA is involved in a plant's response to GLS, nor is its molecular mechanism understood. Here, we found that exogenous GABA could significantly alleviate GLS, reduce lesion lengths, and increase antioxidant capacity. MdGAD1 was identified as a possible key gene for GABA synthesis in apple. Further analysis indicated that MdGAD1 promoted antioxidant capacity to improve apple GLS resistance in transgenic apple calli and leaves. Yeast one-hybrid analysis identified the transcription factor MdWRKY33 upstream of MdGAD1. Electrophoretic mobility shift assay, ß-glucuronidase activity, and luciferase activity further supported that MdWRKY33 bound directly to the promoter of MdGAD1. The content of GABA and the transcription level of MdGAD1 in the MdWRKY33 transgenic calli were higher than that of the wild type. When MdWRKY33 transgenic calli and leaves were inoculated with GLS, MdWKRY33 positively regulated resistance to GLS. These results explained the positive regulatory effects of GABA on apple GLS and provided insight into the metabolic regulatory network of GABA.

Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalizing the gut microbiota.

BACKGROUND: Crohn's disease (CD) is a chronic non-specific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD. Therefore, it is of great significance to find new treatment strategies for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach. However, the mechanism by which MSCs alleviate CD and how MSCs affect gut microbes are still unclear and need further elucidation. METHODS: We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in mice and analysed the microbiota in faecal samples from the control group, the TNBS group and the TNBS + MSC group with faecal 16S rDNA sequencing. Subsequent analyses of alpha and beta diversity were all performed based on the rarified data. PICRUStII analysis was performed on the 16S rRNA gene sequences to infer the gut microbiome functions. RESULTS: MSC Treatment improved TNBS-induced colitis by increasing survival rates and relieving symptoms. A distinct bacterial signature was found in the TNBS group that differed from the TNBS + MSC group and controls. MSCs prevented gut microbiota dysbiosis, including increasing α-diversity and the amount of Bacteroidetes Firmicutes and Tenericutes at the phylum level and decreasing the amount of Proteobacteria at the phylum level. MSCs alleviated the increased activities of sulphur and riboflavin metabolism. Meanwhile some metabolic pathways such as biosynthesis of amino acids lysine biosynthesis sphingolipid metabolism and secondary bile acid biosynthesis were decreased in the TNBS group compared with the control group and the TNBS + MSC group CONCLUSIONS: Overall, our findings preliminarily confirmed that colitis in mice is closely related to microbial and metabolic dysbiosis. MSC treatment could modulate the dysregulated metabolism pathways in mice with colitis, restoring the abnormal microbiota function to that of the normal control group. This study provides insight into specific intestinal microbiota and metabolism pathways linked with MSC treatment, suggesting a new approach to the treatment of CD.

CCR2-overexpressing mesenchymal stem cells targeting damaged liver enhance recovery of acute liver failure.

BACKGROUND: Mesenchymal stem cell (MSC) transplantation is emerging as a promising cell therapeutic strategy in acute liver failure (ALF) clinical research. The potency of MSCs to migrate and engraft into targeted lesions could largely determine their clinical efficacy, in which chemokine/receptor axes play a crucial role. Unfortunately, the downregulation of chemokine receptors expression after in vitro expansion results in a poor homing capacity of MSCs. METHODS: By evaluating the chemokine expression profile in the liver of ALF patients and ALF mice, we found that CCL2 expression was highly upregulated in damaged livers, while the corresponding receptor, CCR2, was lacking in cultured MSCs. Thus, we genetically modified MSCs to overexpress CCR2 and investigated the targeted homing capacity and treatment efficacy of MSCCCR2 compared to those of the MSCvector control. RESULTS: In vivo and ex vivo near-infrared fluorescence imaging showed that MSCCCR2 rapidly migrated and localized to injured livers in remarkably greater numbers following systemic infusion, and these cells were retained in liver lesions for a longer time than MSCvector. Furthermore, MSCCCR2 exhibited significantly enhanced efficacy in the treatment of ALF in mice, which was indicated by a dramatically improved survival rate, the alleviation of liver injury with reduced inflammatory infiltration and hepatic apoptosis, and the promotion of liver regeneration. CONCLUSIONS: Altogether, these results indicate that CCR2 overexpression enhances the targeted migration of MSCs to damaged livers, improves their treatment effect, and may provide a novel strategy for improving the efficacy of cell therapy for ALF.

Preparation of multi-scale FOX-7 particles and investigation of sensitivity and thermal stability.

Multi-scale ultrafine 1,1-diamino-2,2-dinitroethene (FOX-7) samples with different particle size were fabricated and specifically, nano-FOX-7 was successfully prepared by a green mechanophysical milling method. All samples were characterized by field emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD). Impact and friction sensitivities of the samples were tested and thermal analysis was performed by differential scanning calorimetry (DSC) and thermogravimetry (TG). Ultrafine particles with a mean size of 40 nm, 0.9 µm and 3.4 µm respectively showed less sensitivity than raw FOX-7, whose particles size was about 20 µm. The critical drop height H 50 of ultrafine FOX-7 increased from 129 cm to 172 cm, 142 cm and 136 cm, respectively and the friction sensitivity reduced from 32% to 8%, 16% and 20%, respectively. Furthermore, the apparent activation energy of ultrafine particles increased compared with raw materials, which suggested the thermal stability of the ultrafine particles was improved.

Effects of non-uniform root zone salinity on growth, ion regulation, and antioxidant defense system in two alfalfa cultivars.

A split-root system was established to investigate the effects of uniform (0/0, 50/50, and 200/200 mM salt [NaCl]) and non-uniform (0/200 and 50/200 mM NaCl) salt stress on growth, ion regulation, and the antioxidant defense system of alfalfa (Medicago sativa) by comparing a salt-tolerant (Zhongmu No.1) and salt-sensitive (Algonquin) cultivar. We found that non-uniform salinity was associated with greater plant growth rate and shoot dry weight, lower leaf Na+ concentration, higher leaf potassium cation (K+) concentration, lower lipid peroxidation, and greater superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), and peroxidase (EC 1.11.1.7) activities, compared to uniform salt stress in both alfalfa cultivars. Under non-uniform salinity, a significant increase in Na+ concentration and Na+ efflux and a decline in K+ efflux in the no-saline or low-saline part of the roots alleviated salt damage. Our results also demonstrated that proline and antioxidant enzymes accumulated in both the no- or low-saline and high-saline roots, revealing that osmotic adjustment and antioxidant defense had systemic rather than localized effects in alfalfa plants, and there was a functional equilibrium within the root system under non-uniform salt stress. The salt-tolerant cultivar Zhongmu No.1 exhibited greater levels of growth compared to Algonquin under both uniform and non-uniform salt stress, with Na+ tolerance and efflux abilities more effective and greater antioxidant defense capacity evident for cultivar Zhongmu No.1.

Association Mapping for Fiber-Related Traits and Digestibility in Alfalfa (Medicago sativa).

Association mapping is a powerful approach for exploring the molecular genetic basis of complex quantitative traits. An alfalfa (Medicago sativa) association panel comprised of 336 genotypes from 75 alfalfa accessions represented by four to eight genotypes for each accession. Each genotype was genotyped using 85 simple sequence repeat (SSR) markers and phenotyped for five fiber-related traits in four different environments. A model-based structure analysis was used to group all genotypes into two groups. Most of the genotypes have a low relative kinship (<0.3), suggesting population stratification not be an issue for association analysis. Generally, the Q + K model exhibited the best performance to eliminate the false associated positives. In total, 124 marker-trait associations were predicted (p < 0.005). Among these, eight associations were predicted in two environments repeatedly and 20 markers were predicted to be associated with multiple traits. These trait-associated markers will greatly help marker-assisted breeding programs to improve fiber-related quality traits in alfalfa.

Evaluation of Leymus chinensis quality using near-infrared reflectance spectroscopy with three different statistical analyses.

Due to a boom in the dairy industry in Northeast China, the hay industry has been developing rapidly. Thus, it is very important to evaluate the hay quality with a rapid and accurate method. In this research, a novel technique that combines near infrared spectroscopy (NIRs) with three different statistical analyses (MLR, PCR and PLS) was used to predict the chemical quality of sheepgrass (Leymus chinensis) in Heilongjiang Province, China including the concentrations of crude protein (CP), acid detergent fiber (ADF), and neutral detergent fiber (NDF). Firstly, the linear partial least squares regression (PLS) was performed on the spectra and the predictions were compared to those with laboratory-based recorded spectra. Then, the MLR evaluation method for CP has a potential to be used for industry requirements, as it needs less sophisticated and cheaper instrumentation using only a few wavelengths. Results show that in terms of CP, ADF and NDF, (i) the prediction accuracy in terms of CP, ADF and NDF using PLS was obviously improved compared to the PCR algorithm, and comparable or even better than results generated using the MLR algorithm; (ii) the predictions were worse compared to laboratory-based spectra with the MLR algorithmin, and poor predictions were obtained (R2, 0.62, RPD, 0.9) using MLR in terms of NDF; (iii) a satisfactory accuracy with R2 and RPD by PLS method of 0.91, 3.2 for CP, 0.89, 3.1 for ADF and 0.88, 3.0 for NDF, respectively, was obtained. Our results highlight the use of the combined NIRs-PLS method could be applied as a valuable technique to rapidly and accurately evaluate the quality of sheepgrass hay.

[Alfalfa quality evaluation in the field by near-infrared reflectance spectroscopy].

To explore the feasibility of using near-infrared reflectance spectroscopy (NIRS) to evaluate alfalfa quality rapidly in the field and try to find the appropriate machine and sample preparation method, the representative population of 170 fresh alfalfa samples collected from different regions with different stages and different cuts were scanned by a portable NIRS spectrometer (1 100 - 1 800 nm). This is the first time to build models of fresh alfalfa to rapidly estimate quality in the field for harvesting in time. The calibrations of dry matter (DM), crude protein (CP), neutral detergent fiber (NDF) and acid detergent fiber (ADF) were developed through the partial least squares regression (PLS). The determination coefficients of cross-validation (R2((CV)) were 0.831 4, 0.597 9, 0.803 6, 0.786 1 for DM, CP, NDF, ADF, respectively; the root mean standard error of cross-validation (RMSECV) were 1.241 1, 0.261 4, 0.990 3, 0.830 6; The determination coefficients of validation (R2(V)) were 0.815 0, 0.401 1, 0.784 9, 0.752 1 and the root mean standard errors of validation(RMSEP)were 1.06, 0.31, 0.95, 0.80 for DM, CP, NDF, ADF, respectively. For fresh alfalfa ,the calibration of DM, NDF, ADF can do rough quantitative analysis but the CP's calibration is failed. however, as CP in alfalfa hay is enough for animal and the DM, NDF and ADF is the crucial indicator for evaluating havest time, the model of DM, NDF and ADF can be used for evaluating the alfalfa quality rapidly in the field.