Phase Engineering of W-Doped MoS2 by Magneto-Hydrothermal Synthesis for Hydrogen Evolution Reaction.

Molybdenum disulfide (MoS2 ) has been proved as an excellent potential hydrogen evolution reaction (HER) catalyst. Compared with thermodynamically stable 2H-MoS2 , 1T-MoS2 exhibits higher conductivity and catalytic activity, whereas it is usually difficult to prepare since of thermodynamically metastable. Herein, a feasible method is reported to fabricate ambient-stable MoS2 with high concentration 1T phase through magnetic free energy synergistic microstrain induced by W doping under low magnetic field. The 1T phase proportion in MoS2 can be as high as 80% and is ambient-stable for more than one year. The catalyst prepared under a magnetic field of 3 T delivers an overpotential of 195 mV at a current density of 10 mA cm-2 and has a long-term stability over 50 h. This work provides a novel strategy for preparation of MoS2 with high 1T concentration and high stability.

Regulation of Sulfur Atoms in MoSx by Magneto-Electrodeposition for Hydrogen Evolution Reaction.

Compared with crystalline molybdenum sulfide (MoS2 ) employed as an efficient hydrogen evolution reaction (HER) catalyst, amorphous MoSx exhibits better activity. To synthesize amorphous MoSx , electrodeposition serving as a convenient and time-saving method is successfully applied. However, the loading mass is hindered by limited mass transfer efficiency and the available active sites require further improvement. Herein, magneto-electrodeposition is developed to synthesize MoSx with magnetic fields up to 9 T to investigate the effects of a magnetic field in the electrodeposition processing, as well as the induced electrochemical performance. Owing to the magneto-hydrodynamic effect, the loading mass of MoSx is obviously increased, and the terminal S2- serving as the active site is enhanced. The optimized MoSx catalyst delivers outstanding HER performance, achieving an overpotential of 50 mV at a current density of 10 mA cm-2 and the corresponding Tafel slope of 59 mV dec-1 . The introduction of a magnetic field during the electrodeposition process will provide a novel route to prepare amorphous MoSx with improved electrochemical performance.

Mechanical stretch promotes apoptosis and impedes ciliogenesis of primary human airway basal stem cells.

BACKGROUND: Airway basal stem cells (ABSCs) have self-renewal and differentiation abilities. Although an abnormal mechanical environment related to chronic airway disease (CAD) can cause ABSC dysfunction, it remains unclear how mechanical stretch regulates the behavior and structure of ABSCs. Here, we explored the effect of mechanical stretch on primary human ABSCs. METHODS: Primary human ABSCs were isolated from healthy volunteers. A Flexcell FX-5000 Tension system was used to mimic the pathological airway mechanical stretch conditions of patients with CAD. ABSCs were stretched for 12, 24, or 48 h with 20% elongation. We first performed bulk RNA sequencing to identify the most predominantly changed genes and pathways. Next, apoptosis of stretched ABSCs was detected with Annexin V-FITC/PI staining and a caspase 3 activity assay. Proliferation of stretched ABSCs was assessed by measuring MKI67 mRNA expression and cell cycle dynamics. Immunofluorescence and hematoxylin-eosin staining were used to demonstrate the differentiation state of ABSCs at the air-liquid interface. RESULTS: Compared with unstretched control cells, apoptosis and caspase 3 activation of ABSCs stretched for 48 h were significantly increased (p < 0.0001; p < 0.0001, respectively), and MKI67 mRNA levels were decreased (p < 0.0001). In addition, a significant increase in the G0/G1 population (20.2%, p < 0.001) and a significant decrease in S-phase cells (21.1%, p < 0.0001) were observed. The ratio of Krt5+ ABSCs was significantly higher (32.38% vs. 48.71%, p = 0.0037) following stretching, while the ratio of Ac-tub+ cells was significantly lower (37.64% vs. 21.29%, p < 0.001). Moreover, compared with the control, the expression of NKX2-1 was upregulated significantly after stretching (14.06% vs. 39.51%, p < 0.0001). RNA sequencing showed 285 differentially expressed genes, among which 140 were upregulated and 145 were downregulated, revealing that DDIAS, BIRC5, TGFBI, and NKX2-1 may be involved in the function of primary human ABSCs during mechanical stretch. There was no apparent difference between stretching ABSCs for 24 and 48 h compared with the control. CONCLUSIONS: Pathological stretching induces apoptosis of ABSCs, inhibits their proliferation, and disrupts cilia cell differentiation. These features may be related to abnormal regeneration and repair observed after airway epithelium injury in patients with CAD.

Postintubation Tracheal Stenosis Evaluated by Endobronchial Optical Coherence Tomography: A Canine Model Study.

BACKGROUND: The predictors and airway morphological changes during the development of postintubation tracheal stenosis (PITS) have not been well elucidated. OBJECTIVES: To elucidate the validation of endobronchial optical coherence tomography (EB-OCT) in assessing the airway morphological changes in PITS. METHODS: We performed oral endotracheal intubation in 12 beagles to establish the PITS model. EB-OCT was performed respectively before modeling and on the 1st, 7th, and 12th day after extubation in 9 canines, and was conducted consecutively in 3 canines during the development of PITS. Histological findings and the thickness and gray-scale value of the tracheal wall assessed by EB-OCT measurements were analyzed and compared. RESULTS: The tracheal wall edema, granulation tissue proliferation, cartilage destruction in PITS, and airway wall thickening detected by EB-OCT were in concordance with the histopathological measurements. The consecutive EB-OCT observation of the airway structure demonstrated the tracheal wall thickness significantly increased from 344.41 ± 44.19 µm before modeling to 796.67 ± 49.75 µm on the 9th day after modeling (p < 0.05). The airway wall gray-scale values assessed by EB-OCT decreased from 111.19 ± 14.71 before modeling to 74.96 ± 4.08 on the 9th day after modeling (p < 0.05). The gray-scale value was negatively correlated with the airway wall thickness (r = -0.945, p = 0.001). CONCLUSION: The EB-OCT imaging, in concordance with the histopathological finding, was validated for assessing the airway morphological changes during the development of PITS. The EB-OCT evaluation of cartilage damage and gray-scale value measurement might help predict the development and prognosis of PITS.

Salidroside protects cortical neurons against glutamate-induced cytotoxicity by inhibiting autophagy.

Recent evidence suggests that glutamate-induced cytotoxicity contributes to autophagic neuron death and is partially mediated by increased oxidative stress. Salidroside has been demonstrated to have neuroprotective effects in glutamate-induced neuronal damage. The precise mechanism of its regulatory role in neuronal autophagy is, however, poorly understood. This study aimed to probe the effects and mechanisms of salidroside in glutamate-induced autophagy activation in cultured rat cortical neurons. Cell viability assay, Western blotting, coimmunoprecipitation, and small interfering RNA were performed to analyze autophagy activities during glutamate-evoked oxidative injury. We found that salidroside protected neonatal neurons from glutamate-induced apoptotic cell death. Salidroside significantly attenuated the LC3-II/LC3-I ratio and expression of Beclin-1, but increased (SQSTM1)/p62 expression under glutamate exposure. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, decreased LC3-II/LC3-I ratio, attenuated glutamate-induced cell injury, and mimicked some of the protective effects of salidroside against glutamate-induced cell injury. Molecular analysis demonstrated that salidroside inhibited cortical neuron autophagy in response to glutamate exposure through p53 signaling by increasing the accumulation of cytoplasmic p53. Salidroside inhibited the glutamate-induced dissociation of the Bcl-2-Beclin-1 complex with minor affects on the PI3K/Akt/mTOR signaling pathways. These data demonstrate that the inhibition of autophagy could be responsible for the neuroprotective effects of salidroside on glutamate-induced neuronal injury.

Determination of rivaroxaban, apixaban and edoxaban in rat plasma by UPLC-MS/MS method.

To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of rivaroxaban, apixaban and edoxaban in rat plasma. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm × 50 mm, 1.7 µm) using gradient elution with a mobile phase of acetonitrile and 0.1 % formic acid in water at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 436.1 â†’ 145.1 for rivaroxaban, m/z 460.0 â†’ 443.1 for apixaban, m/z 548.2 â†’ 366.1 for edoxaban and m/z 285.2 â†’ 193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 1.0-200 ng/mL for rivaroxaban, 1.0-100 ng/mL for apixaban and 1.0-500 ng/mL for edoxaban. Total time for each chromatograph was 3.5 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations <10.5 % and the accuracy values ranged from -9.9 to 11.3 %. The method was successfully applied to a pharmacokinetic study of rivaroxaban, apixaban and edoxaban in rats.

[Estimation of Fraction of Absorbed Photosynthetically Active Radiation for Winter Wheat Based on Hyperspectral Characteristic Parameters].

Estimating fraction of absorbed photosynthetically active radiation (FPAR) precisely has great importance for detecting vegetation water content, energy and carbon cycle balance. Based on this, ASD FieldSpec 3 and SunScan canopy analyzer were applied to measure the canopy spectral reflectance and photosynthetically active radiation over whole growth stage of winter wheat. Canopy reflectance spectral data was used to build up 24 hyperspectral characteristic parameters and the correlation between FPAR and different spectral characteristic parameters were analyzed to establish the estimation model of FPAR for winter wheat. The results indicated that there were extremely significant correlations (p<0.01) between FPAR and hyperspectral characteristic parameters except the slope of blue edge (Db). The correlation coefficient between FPAR and the ratio of red edge area to blue edge area (VI4) was the highest, reaching at 0.836. Seven spectral parameters with higher correlation coefficient were selected to establish optimal linear and nonlinear estimation models of FPAR, and the best estimating models of FPAR were obtained by accuracy analysis. For the linear model, the inversin model between green edge and FPAR was the best, with R2, RMSE and RRMSE of predicted model reaching 0.679, 0.111 and 20.82% respectively. For the nonlinear model, the inversion model between VI2 (normalized ratio of green peak to red valley of reflectivity) and FPAR was the best, with R2, RMSE and RRMSE of predicted model reaching 0.724, 0.088 and 21.84% for. In order to further improve the precision of the model, the multiple linear regression and BP neural network methods were used to establish models with multiple high spectral parameters BP neural network model (R2=0.906, RMSE=0.08, RRMSE=16.57%) could significantly improve the inversion precision compared with the single variable model. The results show that using hyperspectral characteristic parameters to estimate FPAR of winter wheat is feasible. It provides a new method and theoretical basis for monitoring the dynamic change of FPAR in real time, effectively and accurately during the growth stage of winter wheat.

Based on CiteSpace Insights into Illicium verum Hook. f. Current Hotspots and Emerging Trends and China Resources Distribution.

Illicium verum Hook. f. is a globally significant spice, which is recognized in China as a food-medicine homolog and extensively utilized across the pharmaceutical, food, and spice industries. China boasts the world's leading resources of I. verum, yet its comprehensive utilization remains relatively underexplored. Through a resource survey of I. verum and the application of bibliometric visualization using CiteSpace, this study analyzed 324 papers published in the Web of Science Core Collection (WOSCC) from 1962 to 2023 and 353 core documents from China's three major databases (CNKI, Wanfang Database, and VIP Database). I. verum from Guangxi province towards various southern provinces in China, with autumn fruits exhibited superior quality and market value over their spring fruits. Literature in WOSCC emerged earlier, with a research emphasis on food science technology and pharmacology pharmacy domains. WOSCC research on I. verum could be divided into two phases: an embryonic period (1962-2001) and a growth period (2002-2023), showing an overall upward trend in publication. The three major Chinese databases contain a larger number of publications, with a focus on the food sector, which could be categorized into three stages: an embryonic period (1990-1999), a growth period (2000-2010), and a stable period (2011-2023), with an overall downward trend in publication. Both Chinese and international research hotspots converge on the medical applications of I. verum, with antioxidant bioactivity research emerging as a prevailing trend. This study delineated the resource distribution of I. verum across China and identified the research hotspots and trends both in China and internationally. The findings are beneficial for guiding researchers in swiftly establishing their research focus and furnishing decision-makers with a comprehensive reference for industry information.

Estimation of complete mutual information exploiting nonlinear magnitude-phase dependence: Application to spatial FNC for complex-valued fMRI data.

BACKGROUND: Real-valued mutual information (MI) has been used in spatial functional network connectivity (FNC) to measure high-order and nonlinear dependence between spatial maps extracted from magnitude-only functional magnetic resonance imaging (fMRI). However, real-valued MI cannot fully capture the group differences in spatial FNC from complex-valued fMRI data with magnitude and phase dependence. METHODS: We propose a complete complex-valued MI method according to the chain rule of MI. We fully exploit the dependence among magnitudes and phases of two complex-valued signals using second and fourth-order joint entropies, and propose to use a Gaussian copula transformation with a lower bound property to avoid inaccurate estimation of joint probability density function when computing the joint entropies. RESULTS: The proposed method achieves more accurate MI estimates than the two histogram-based (normal and symbolic approaches) and kernel density estimation methods for simulated signals, and enhances group differences in spatial functional network connectivity for experimental complex-valued fMRI data. COMPARISON WITH EXISTING METHODS: Compared with the simplified complex-valued MI and real-valued MI, the proposed method yields higher MI estimation accuracy, leading to 17.4 % and 145.5 % wider MI ranges, and more significant connectivity differences between healthy controls and schizophrenia patients. A unique connection between executive control network (EC) and right frontal parietal areas, and three additional connections mainly related to EC are detected than the simplified complex-valued MI. CONCLUSIONS: With capability in quantifying MI fully and accurately, the proposed complex-valued MI is promising in providing qualified FNC biomarkers for identifying mental disorders such as schizophrenia.

An injectable collagen peptide-based hydrogel with desirable antibacterial, self-healing and wound-healing properties based on multiple-dynamic crosslinking.

Conventional collagen-based hydrogels as wound dressing materials are usually lack of antibacterial activity and easily broken when encountering external forces. In this work, we developed a collagen peptide-based hydrogel as a wound dressing, which was composed of adipic acid dihydrazide functionalized collagen peptide (Col-ADH), oxidized dextran (ODex), polyvinyl alcohol (PVA) and borax via multiple-dynamic reversible bonds (acylhydrazone, amine, borate ester and hydrogen bonds). The injectable hydrogel exhibited satisfactory self-healing ability, antibacterial activity, mechanical strength, as well as good biocompatibility and biodegradability. In vivo experiments demonstrated the rapid hemostasis, accelerated cell migration, and promoted wound healing capacities of the hydrogel. These results indicate that the multifunctional collagen peptide-based hydrogel has great potentials in the field of wound dressings.

Systematic pharmacology and experimental validation to elucidate the inflammation-associated mechanism of Huanglian Wendan (HLWD) decoction in the treatment of MAFLD associated with atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic-associated fatty liver disease (MAFLD) and atherosclerosis are very common disorders that frequently coexist. The therapeutic efficacy of Huanglian Wendan (HLWD) decoction, a traditional Chinese medicine (TCM) prescription, is satisfactory in treating MAFLD associated with atherosclerosis. However, the underlying mechanisms through which HLWD exerts its effects need to be elucidated. Given the complex composition of HLWD and its multiple therapeutic targets, pharmacological investigation is challenging. AIM OF THIS STUDY: This study aimed to identify the effective compounds in HLWD and elucidate the mechanisms involved in its therapeutic effect on MAFLD associated with atherosclerosis. MATERIALS AND METHODS: We used a systematic pharmacology method to identify effective compounds present in HLWD and determine the mechanism by which it affects MAFLD associated with atherosclerosis. The effective components of HLWD were identified through ultrahigh-performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Next, a comprehensive in silico method was used to predict potential related targets and disease targets for these compounds to establish corresponding pathways. The accuracy of our assumed systemic pharmacology results was determined by conducting follow-up experiments. RESULTS: By conducting UHPLC-Q-Orbitrap HRMS combined with network analysis, we identified 18 potentially active components of HLWD and assessed the inflammatory regulatory mechanism by which it affects MAFLD associated with atherosclerosis on the basis of 52 key targets. We used a high-fat, high-cholesterol (HFHC)-induced mice model of MAFLD associated with atherosclerosis to confirm our results. We found that administering HLWD significantly improved the appearance of their liver and reduced their body weight, liver weight, blood lipids, hepatic damage, and hepatic pathology. HLWD also decreased atherosclerotic lesion areas, foam cells, and inflammatory cells in the aorta. HLWD showed anti-inflammatory effects, suppressed M1 polarization, and promoted M2 polarization in the liver and aorta. HLWD might also regulate peroxisome proliferator-activated receptor-γ (PPARγ)/nuclear factor kappa-B (NF-κB) signaling to influence macrophage polarization and inflammation. CONCLUSIONS: Our results showed that HLWD protected against HFHC diet-induced MAFLD associated with atherosclerosis by regulating PPARγ/NF-κB signaling, thus adjusting macrophage polarization and inflammation. Additionally, pharmacochemistry research, network pharmacology analysis, and experimental verification can be combined to form a comprehensive model used in studies on TCM.

[A new triterpenoid from Pittosporum glabratum Lindl].

The roots of Pittosporum glabratum Lindl. (Pittosporaceae) have been used as a folk medicine for the treatment of rheumatic arthritis, insomnia and hypertension. Only a few chemical or biological studies on P. glabratum have been reported. As part of our ongoing phytochemical research on this plant, four compounds were isolated. Their structures were identified as 3beta, 6beta, 19alpha, 21alpha, 24-pentahydroxy-12-en-28-oleanolic acid (1), 3-O-beta-D-glucuronopyranosyl-28-O-beta-D-glucopyranosyl siaresinolic acid (2), 3, 4, 5-trimethoxyphenyl-1-O-beta-D-(5-O-syringoyl)-apiofuranosyl-(1 --> 6)-beta-D-glucopyranoside (3) and 3, 4, 5-trimethoxyphenol-1-O-beta-D-apiofuranosyl-(1 --> 6)-beta-D-glucopyranoside (4) on the basis of physical evidence and spectroscopic analysis. Among them, compound 1 is a new triterpenoid, and compounds 2-4 are isolated from the genus Pittosporum for the first time.

Galactosylated Core-Shell Nanoparticles with pH/GSH Dual Sensitivity for Targeting Hepatocellular Carcinoma.

Galactosylated core-shell nanoparticles (NPs) with diameters of sub-50 nm were fabricated in one pot by reversible addition-fragmentation chain transfer (RAFT) soap-free emulsion polymerization. Their galactosylated shells and acidic cores endow them with high targeting and drug loading efficiencies, respectively. Morever, the physical shrinkage and cleavage of the disulfide cross-linked NPs can realize the rapid release of loaded doxorubicin (DOX) under pH 5.0 and reduced glutathione (GSH) conditions. The combination of these excellent properties resulted in an even lower IC50 of DOX-loaded NPs than free DOX, demonstrating that this platform would be promising in targeting the therapy of hepatocellular carcinoma.

Sub-50 nm core-shell nanoparticles with the pH-responsive squeezing release effect for targeting therapy of hepatocellular carcinoma.

The development of drug delivery systems with high drug loading capacity, low leakage at physiological pH, and rapid release at the lesion sites remains an ongoing challenge. In this work, core-shell poly(6-O-methacryloyl-D-galactose)@poly(tert-butyl methacrylate) (PMADGal@PtBMA) nanoparticles (NPs) of sub-50 nm are facilely synthesized by reversible addition-fragmentation chain transfer (RAFT) soap-free emulsion polymerization with the assistance of 12-crown-4. A hydrophilic poly(methacrylic acid) (PMAA) core can then be revealed after deprotection of the tert-butyl groups, which is negatively charged and can adsorb nearly 100% of incubated doxorubicin (DOX) from a solution at pH 7.4. The physical shrinkage of PMAA chains below pH 6.0 endows the core with the squeezing effect, therefore realizing rapid drug release. It is demonstrated that the DOX release rate of PMADGal@PMAA NPs at pH 5 was 4 times that at pH 7.4. Cellular uptake experiments confirm the high targeting ability of the galactose modified PMADGal shell to human hepatocellular carcinoma (HepG2) cells. The fluorescence intensity of DOX in HepG2 cells is 4.86 times that of HeLa cells after 3 h incubation. Moreover, 20% cross-linked NPs show the highest uptake efficiency by HepG2 cells due to their moderate surface charge, size and hardness. In summary, both the core and the shell of PMADGal@PMAA NPs promise the rapid site-specific release of DOX in HepG2 cells. This work provides a facile and an effective strategy to synthesize core-shell NPs for hepatocellular carcinoma targeting therapy.

Autologous Airway Basal Cell Transplantation Alleviates Airway Epithelium Defect in Recurrent Benign Tracheal Stenosis.

BACKGROUND: Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis. METHODS: An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks. RESULTS: Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells. CONCLUSIONS: Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis.

Deleted in lymphocytic leukemia 2 (DLEU2): a possible biomarker that holds promise for future diagnosis and treatment of cancer.

The mechanism of deleted in lymphocytic leukemia 2 (DLEU2)-long non-coding RNA in tumors has become a major point of interest in recent research related to the occurrence and development of a variety of tumors. Recent studies have shown that the long non-coding RNA DLEU2 (lncRNA-DLEU2) can cause abnormal gene or protein expression by acting on downstream targets in cancers. At present, most lncRNA-DLEU2 play the role of oncogenes in different tumors, which are mostly associated with tumor characteristics, such as proliferation, migration, invasion, and apoptosis. The data thus far show that because lncRNA-DLEU2 plays an important role in most tumors, targeting abnormal lncRNA-DLEU2 may be an effective treatment strategy for early diagnosis and improving the prognosis of patients. In this review, we integrated lncRNA-DLEU2 expression in tumors, its biological functions, molecular mechanisms, and the utility of DLEU2 as an effective diagnostic and prognostic marker of tumors. This study aimed to provide a potential direction for the diagnosis, prognosis, and treatment of tumors using lncRNA-DLEU2 as a biomarker and therapeutic target.

Effects of human umbilical cord blood mononuclear cells on ovalbumin-induced asthma in mice.

Background: Umbilical cord blood mononuclear cells (UCMNCs) show broad immune-modulation effects, which may be helpful for treating asthma. Effects of UCMNCs on asthma were investigated with mouse model in present study. Methods: Asthma was induced in BALB/c mice by ovalbumin (OVA) immunization and challenge. Asthmatic mice were then treated on days 7 and 20 with intravenous injections of UCMNCs in doses of 4×105, 2×106, and 107 cells per mouse for the low-dose UCMNC (UCMNCL), medium-dose UCMNC (UCMNCM), and high-dose UCMNC (UCMNCH) groups, respectively. Fetal mouse blood mononuclear cells (FMMNCs) were administered to FMMNC group at a dose of 2×106 cells per mouse as approximate allograft control. Airway hyperresponsiveness (AHR), airway inflammation indexes, and CD4/CD8 T cell subsets were measured at day 25. Results: Compared with the model group, AHR in the UCMNCL group, inflammation score of lung tissue in the UCMNCM group, interleukin (IL)-5 in bronchoalveolar lavage fluid (BALF) in UCMNCL group, IL-5 and IL-13 in BALF in UCMNCM group, and IL-17 in serum in UCMNCH group were significantly inhibited. Compared with the model group, CD4+CD8+ T cells were reduced in the UCMNCL group, while decrease of CD4-CD8- T cells and increase of CD4+CD8- T cells were further strengthened in UCMNCM group. FMMNC treatment significantly reduced the IL-13 and IL-17 in serum, decreased CD4-CD8- and CD4+CD8- T cells, and increased the CD4+CD8+ and CD4-CD8+ T cells in BALF. Conclusions: UCMNCs can modulate AHR, T-helper (Th)2 inflammation, and airway injury in experimental asthma at appropriate dose.

Metabolic rewiring in keratinocytes by miR-31-5p identifies therapeutic intervention for psoriasis.

Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes of psoriatic skin, and we show that expression in keratinocytes is induced by limited glucose availability and enables increased survival under limiting glucose conditions by increasing glutamine metabolism. In addition, miR-31 expression results in not only secretion of specific metabolites (aspartate and glutamate) but also secretion of immunomodulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibitors of miR31-induced metabolic rewiring and metabolic crosstalk with immune cells alleviate psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.

A new triterpenoid saponin from Sanguisorba officinalis.

A new 19-oxo-18,19-seco-ursane-type triterpenoid saponin, named sanguisoside A (1), along with nine known triterpenoid saponins (2-10), was isolated from the roots of Sanguisorba officinalis. Their structures were determined on the basis of spectroscopic analysis and chemical method. Compounds 2 and 3 showed cytotoxic activity against SGC-7901, SMMC-7721, A549, and DU145 cell lines.