Diterpenoids with an unusual tricyclo[10.3.0.02,9]pentadecane skeleton from Pedilanthus tithymaloides as multidrug resistance modulators.

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.

Prone positioning improves ventilation-perfusion matching assessed by electrical impedance tomography in patients with ARDS: a prospective physiological study.

BACKGROUND: The physiological effects of prone ventilation in ARDS patients have been discussed for a long time but have not been fully elucidated. Electrical impedance tomography (EIT) has emerged as a tool for bedside monitoring of pulmonary ventilation and perfusion, allowing the opportunity to obtain data. This study aimed to investigate the effect of prone positioning (PP) on ventilation-perfusion matching by contrast-enhanced EIT in patients with ARDS. DESIGN: Monocenter prospective physiologic study. SETTING: University medical ICU. PATIENTS: Ten mechanically ventilated ARDS patients who underwent PP. INTERVENTIONS: We performed EIT evaluation at the initiation of PP, 3 h after PP initiation and the end of PP during the first PP session. MEASUREMENTS AND MAIN RESULTS: The regional distribution of ventilation and perfusion was analyzed based on EIT images and compared to the clinical variables regarding respiratory and hemodynamic status. Prolonged prone ventilation improved oxygenation in the ARDS patients. Based on EIT measurements, the distribution of ventilation was homogenized and dorsal lung ventilation was significantly improved by PP administration, while the effect of PP on lung perfusion was relatively mild, with increased dorsal lung perfusion observed. The ventilation-perfusion matched region was found to increase and correlate with the increased PaO2/FiO2 by PP, which was attributed mainly to reduced shunt in the lung. CONCLUSIONS: Prolonged prone ventilation increased dorsal ventilation and perfusion, which resulted in improved ventilation-perfusion matching and oxygenation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04725227. Registered on 25 January 2021.

A cross-sectional survey on the lung ultrasound training and practice of respiratory therapists in mainland China.

PURPOSE: This national study aimed to investigate the lung ultrasound (LUS) training and practice of respiratory therapists (RTs) in mainland China. METHODS: A cross-sectional multicenter survey was conducted from May 22, 2021 to August 12, 2021, through online platforms. This survey included RTs in mainland China. The survey was divided into four sections: (1) demographic characteristics and basic information; (2) basic information about LUS training and practice; (3) LUS practice details; and (4) Other ultrasound training and practice. RESULTS: A total of 514 responses were received, and 494 valid responses were included in the analysis. 81.2% (401/494) participants' highest degree of education was a bachelor's degree, and 43.1% (213/494) participants were at level II in terms of job ranking. 99.2%(490/494) participants agreed that the RTs needed to learn lung ultrasound, but only 12.3% (61/494) participants had received a LUS training course. Further, 66.2% (327/494) experienced participants responded to Sect. 3. Most of RTs used LUS when the patient had hypoxia (265/327, 81%) or dyspnea (260/317, 79.5%); they also used it during spontaneous breathing trial(SBT) (191/327, 58.4%) or in prone position (177/327, 54.1%). The A-line (302/327, 92.4%), B-line (299/327, 91.4%), lung slide (263/327, 80.4%), and bat sign (259/327, 79.2%) were well known as LUS signs. Also, 30.6% (100/327) participants did not use the LUS protocol in their clinical practice, and only 25.4%(83/327) participants said they had used LUS scores. Moreover, 55.7% (182/327) participants frequently changed the respiratory therapy strategy according to LUS results. CONCLUSIONS: We should improve the number and workplace of RTs in mainland China in the future. We should also standardize the application of LUS practice and training for RTs in mainland China and establish corresponding certification pathways.

Two New Eremophilane-Type Sesquiterpenoids from Ligularia sagitta.

Two new eremophilane-type sesquiterpenoids, sagittacins F and G (1 and 2), together with one known isomer of sagittacin F (3) were isolated from the leaves and stems of Ligularia sagitta. Their structures were elucidated by interpretation of spectroscopic data and the absolute configurations of 1 and 3 were determined by X-ray spectroscopy. Compound 1 belongs to a rare class of eremophilane-type sesquiterpenoid featuring an α-oriented hydroxy group at C-1. A nitric oxide (NO) production inhibitory assay was applied to evaluate their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 2 and 3 exhibited modest NO production inhibitions with IC50 values of 45.15±2.72 and 49.83±2.34 µM, respectively.

Osteoporosis risk assessment using multilayered gold-nanoparticle thin film via SALDI-MS measurement.

A powerful technique to detect bone biomarkers has been developed for assessment of osteoporosis at the early stage. Two-dimensional multilayered gold-nanoparticle thin film (MTF-AuNPs) was demonstrated as a promising test platform for detection of bone biomarker, hydroxyproline (HYP), measured by surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). With strong surface plasmon resonance and excellent homogeneity, facilely prepared, highly ordered, and large-scale MTF-AuNPs revealed high sensitivity of HYP in the SALDI-MS measurement without additional matrixes, such as α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB). Furthermore, the mass spectrum of HYP with MTF-AuNPs was significantly improved in signal intensity enhancement, background noise reduction, and signal-to-noise ratio amplification. The excellent reproducibility of HYP spectra with only 9.3% relative signal variation could be attributed to MTF-AuNPs' high absorbance at a wavelength of 337 nm, low heat capacity, superior thermal conductivity, and outstanding homogeneity. The calibration curve showed high linear correlation between mass spectrum intensity and HYP concentration in the range of 1 to 100 µM, covering the whole level in healthy people and osteoporosis patients. In particular, the serum sample was directly deposited onto the MTF-AuNP sample substrate without any pretreatment and its HYP concentration was then successfully determined. We believe that the combination of SALDI-MS and MTF-AuNP sample substrates would be a potential approach for bone biomarker detection in the osteoporosis risk assessment. Graphical abstract.

Corrigendum to "Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF-κB Pathway in Type 2 Diabetic db/db Mice".

[This corrects the article DOI: 10.1155/2016/1405924.].

Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF-κB Pathway in Type 2 Diabetic db/db Mice.

The receptor activator of NF-κB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-κB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-κB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-κB pathway.

[Identification of original species of Mantidis Oötheca (Sangpiaoxiao) based on DNA barcoding].

Both market research and literature reports both found that the ootheca of mantodea was all used as medicine. However, Chinese Pharmacopoeia only records the ootheca of three mantis species. The clinical use of ootheca unrecorded in Chinese Pharmacopoeia, will pose potential risks to drug safety. It's urgent to identify the origin of Mantidis Oötheca. The current researches about original animal in Mantidis Oötheca are based on morphology and unanimous. DNA barcoding fill gaps of the traditional morphological identification, which is widely used in animal classification studies. This study first use DNA barcoding to analyze genetic distance among different Mantidis Oötheca types, align COI sequences between mantis and Mantidis Oötheca and construct the phylogeny tree. The result confirmed that Tenodera sinensis and Hierodula patellifera were the origin insects of Tuanpiaoxiao and Heipiaoxiao, respectively, and Statilia maculate and Mantis religiosa were the origin insects of Changpiaoxiao.

The study on designed gamified mobile learning model to assess students' learning outcome of accounting education.

This study constructs an innovative course for accounting teaching based on a student-centered strategy. The curriculum is designed through the effective teaching module (BOPPPS) to assist students to understand accounting knowledge. A game-based mobile learning environment is created by developing an accounting mobile game and combining it with a mobile learning system (TronClass). The private technology university students had been selected by purposive sampling. A total of 81 accounting majored students, among them, 41 students are in the experimental group, and the rest were in the control group. The quasi-experimental design was to be applied in curriculum development. Meanwhile, quantitative data were collected by questionnaires and the qualitative data were collected through interviews. The result shows that game-based mobile learning can be beneficial to teaching effectiveness. And the regression model supports that information quality and service quality have positive predictive power on use intention. In addition, use intention and user satisfaction impacted learning engagement positively. Further, user satisfaction has a mediating effect. Finally, some suggestions are put forward to provide references for accounting educators and researchers.

[Differentiation of rat bone marrow mesenchymal stem cells into adipocytes and blockage of the differentiation].

OBJECTIVE: To explore the pathogenesis of tumors by blocking the normal differentiation process of stem cells. METHODS: Bone marrow mesenchymal stem cells (BMSCs) from rats were isolated, cultured and purified by whole bone marrow adherence method. The rat BMSCs were induced to differentiate into adipocytes with dexamethasone, insulin and indomethacin. Blockage of the differentiation process was induced by 3-methylcholanthrene (3-MC). RESULTS: The differentiation experiment showed that at 30 days after the induction, oil red O staining-positive cells occurred with increased intracytolasmic lipid droplets, characteristic for adipocytes. The differentiation blockage experiment showed that at 30 days after induction, the deposits of oil red O staining-cytoplasmic lipid droplets was significantly reduced, indicating that the blocked cells were adipocytes, but not fully differentiated. Morphological identification showed that cell contact inhibition disappeared, abnormal cell nuclei, increased number of micronucleus aberration and karyotype abnormalities, indicating that malignant transformation of the stem cells occurred after the differentiation blockage. CONCLUSIONS: The results of this study show a blockage of the differentiation of that stem cells at the intermediate phase, and a tendency of malignant transformation of the stem cells. The results of our study provide new evidence that cancer stem cells may be originated by suppression of stem cell differentiation.

Preparation and evaluation of Pd-Sn modified Ru-Ir electrode for denitrification of high chlorine ammonia-nitrogen wastewater.

In this paper, Pd-Sn modified Ru-Ir electrode was prepared by thermal oxidation method, and the effects of doping amount of Pd-Sn and synthesis conditions on Pd-Sn modified Ru-Ir electrode performance were studied. Linear sweep voltammetry(LSV), cyclic voltammetry(CV), and the Tafel curve were used to study the electrochemical performance of the Pd-Sn modified Ru-Ir electrode materials. The effects of the doping amount of Pd-Sn on the microstructure and valence states of Pd-Sn modified Ru-Ir electrode materials were investigated by SEM, TEM, XRD, and XPS. When the mass of Pd-Sn accounted for 1.5% of the total mass of the elements, the molar ratio of Ru-Ir was 2:1, and the molar ratio of Pd-Sn was 3:1; the LSV, CV, and the Tafel curves indicated that Pd-Sn modified Ru-Ir electrode had the lowest chlorine evolution potential (1.0640 V vs. SCE), the best CV curve coincidence, and the smallest corrosion current density (6.5 × 10-4 A/cm2), showing the best chlorine evolution performance, the best durability, and corrosion resistance; the characterization of SEM, TEM, XRD, and XPS showed that Pd-Sn was successfully doped into Ru-Ir electrode materials; the crystallinity of Pd-Sn modified Ru-Ir electrode was the highest, and the binding energy was the lowest, but the crystal form of Ru-Ir solid solution did not have changed. The optimal synthesis conditions of Pd-Sn modified Ru-Ir electrode material were as follows: Pd-Sn molar ratio was 3:1, calcination temperature was 500 ℃, calcination time was 4 h, and water was used as solvent. Pd-Sn modified Ru-Ir electrode can efficiently treat high chlorine ammonia-nitrogen wastewater, when the reaction volume was 200 mL, the initial concentration of NH3-N was 100 mg/L, the concentration of chloride ion was 5000 mg/L, the current was 0.75 A, and the reaction time was 40 min; the removal rate of ammonia nitrogen can reach 100%.Responsible editor: Weiming Zhang.

Jatrophane diterpenoids with cytotoxic activity from the whole plant of Euphorbia heliosocpia L.

Eight undescribed jatrophane diterpenoids, euphohelinoids A-H, along with 11 known analogues were isolated from the whole plant of Euphorbia heliosocpia L. Among them, euphohelinoids A and B contain a rare type of jatrophane diterpenoid skeleton with a 7,8-seco scaffold. To the best of our knowledge, only two such jatrophane diterpenoids have been reported. In addition, euphohelinoids G and H belong to a rare class of jatrophane diterpene possessing a ß-hydroxy group at C-11. Structure elucidation of these undescribed diterpenoids was performed by spectroscopic analysis, including NMR, HRESIMS, IR, electronic circular dichroism (ECD) and DP4+ analysis. The cytotoxicity of 17 abundant jatrophane diterpenes was evaluated against HepG2, HeLa, HL-60, and SMMC-7721 cell lines. Seven compounds presented potent cytotoxicity against the four tested cell lines with IC50 values from 8.1 to 29.7 µM. Moreover, preliminary structure-activity relationships for these jatrophane diterpenoids were discussed.

A sensitive colorimetric probe for detection of the phosphate ion.

In the present article, we report a novel colorimetric probe (TNT@MB) for the detection of the phosphate ion, which is based on the strong binding affinity between the phosphate ion and titanium dioxide nanotubes (TNTs). TNTs were synthesized from TiO2 nanoparticles by hydrothermal treatment. The obtained TNTs had an average length of 200 ± 50 nm and an average width of 12 ± 5 nm. TNT@MB was prepared by adsorbing methyl blue onto TNTs in acidic condition. The optimal synthesis conditions for TNT@MB consisted in having 0.05 g of TNTs react with 1 µmole of methyl blue at pH 2 for 90 min. TNTs and TNT@MB were characterized by UV-vis diffuse reflection spectroscopy, TEM, FTIR, and XPS. The phosphate-ion sensing behavior of TNT@MB was investigated by UV-visible spectroscopy. The phosphate-ion concentration linear range and detection limit of this method based on TNT@MB were 1-40 µM and 0.59 µM, respectively. A sample of lake water was used as a real sample, and analyte recovery rates were measured in the 102.5-103.6% range, with relative standard deviations below 5.6% (n = 3). We also found that this probe could be reused after regeneration in alkaline solution. These results indicate that as a colorimetric probe, TNT@MB has the advantages of being environmentally friendly, inexpensive, and simple to use, as well as giving rise to an easily observable color change.

Overexpression of ribonucleotide reductase small subunit, RNRM, increases cordycepin biosynthesis in transformed Cordyceps militaris.

Cordycepin was the first adenosine analogue used as an anticancer and antiviral agent, which is extracted from Cordyceps militaris and hasn't been biosynthesized until now. This study was first conducted to verify the role of ribonucleotide reductases (RNRs, the two RNR subunits, RNRL and RNRM) in the biosynthesis of cordycepin by over expressing RNRs genes in transformed C. militaris. Quantitative real-time PCR (qRT-PCR) and western blotting results showed that the mRNA and protein levels of RNR subunit genes were significantly upregulated in transformant C. militaris strains compared to the control strain. The results of the HPLC assay indicated that the cordycepin was significantly higher in the C. militaris transformants carrying RNRM than in the wild-type strain, whereas the RNRML was preferentially downregulated. For the C. militaris transformant carrying RNRL, the content of cordycepin wasn't remarkably changed. Furthermore, we revealed that inhibiting RNRs with Triapine (3-AP) almost abrogated the upregulation of cordycepin. Therefore, our results suggested that RNRM can probably directly participate in cordycepin biosynthesis by hydrolyzing adenosine, which is useful for improving cordycepin synthesis and helps to satisfy the commercial demand of cordycepin in the field of medicine.

Cyclopropanyldehydrocostunolide LJ attenuates high glucose-induced podocyte injury by suppressing RANKL/RANK-mediated NF-κB and MAPK signaling pathways.

AIMS: The aim of this research was to investigate the effects of cyclopropanyldehydrocostunolide (also named LJ), a derivative of sesquiterpene lactones (SLs), on high glucose (HG)-induced podocyte injury and the associated molecular mechanisms. METHODS: Differentiated mouse podocytes were incubated in different treatments. The migration and albumin filtration of podocytes were examined by Transwell filters. The protein and mRNA levels of MCP-1 were measured using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (q-PCR). Protein expression and phosphorylation were detected by western blot, and the nuclear translocation of NF-κB was performed with a confocal microscope. The gene expression of the receptor activator for NF-κB (RANK) was silenced by small interfering RNA (siRNA). RESULTS: Our results showed that HG enhanced migration, albumin filtration and MCP-1 expression in podocytes. At the molecular level, HG promoted the phosphorylation of NF-κB/p65, IKKß, IκBα, mitogen-activated protein kinase (MAPK) and the nuclear translocation of p65. LJ reversed the effects of HG in a dose-dependent manner. Furthermore, our data provided the first demonstration that the receptor activator for NF-κB ligand (RANKL) and its cognate receptor RANK were overexpressed in HG-induced podocytes and were downregulated by LJ. RANK siRNA also attenuated HG-induced podocyte injury and markedly inhibited the activation of NF-κB and MAPK signaling pathways. CONCLUSIONS: LJ attenuates HG-induced podocyte injury by suppressing RANKL/RANK-mediated NF-κB and MAPK signaling pathways.