Comparative transcriptomic analysis of genes involved in stem lignin biosynthesis in woody and herbaceous Paeonia species.

Paeonia is recognized globally due to its ornamental value. However, the mechanisms behind the formation of distinct levels of lignification in Paeonia stems remain largely unknown. In this study, we selected three representative Paeonia species, namely P. ostii (shrub), P. lactiflora (herb), and P. × 'Hexie' (semi-shrub), to evaluate and contrast their respective anatomical structure, phytochemical composition and transcriptomic profile. Our results showed that the degree of lignin deposition on the cell wall, along with the total amount of lignin and its monomers (especially G-lignin) were higher in P. ostii stems compared to the other two species at almost all development stages except 80 days after flowering. Furthermore, we estimated a total number of unigenes of 60,238 in P. ostii, 43,563 in P. × 'Hexie', and 40,212 in P. lactiflora from stem transcriptome. We then built a co-expression network of 25 transcription factors and 21 enzyme genes involved in lignin biosynthesis and identified nine key candidate genes. The expression patterns of these genes were positively correlated with the transcription levels of PAL, C4H, 4CL2, CCR, and COMT, as well as lignin content. Moreover, the highest relative expression levels of CCR, 4CL2, and C4H were found in P. ostii. This study provides an explanation for the observed differences in lignification between woody and herbaceous Paeonia stems, and constitutes a novel reference for molecular studies of stem-specific lignification process and lignin biosynthesis that can impact the ornamental industry.

Clinical features and risk factors associated with severe COVID-19 patients in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS: The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.

A comprehensive study of three species of Paeonia stem and leaf phytochemicals, and their antioxidant activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia plants have been widely used as traditional Chinese medicinal materials for more than 2,000 years in the treatment of cardiovascular, extravasated blood and female genital diseases; paeoniflorin and paeonol have been implicated as the plants' primary active ingredients. AIM OF THE STUDY: Previous studies have been singularly focused on the chemical constituents and content variation of the Paeonia roots in the advancement of traditional Chinese medicine, with the plants' stems and leaves considered useless. This study aims to explore the chemical constituents, content variation, and antioxidant capacity in Paeonia stems and leaves for the future utilization of traditional Chinese medicine, given that current practices of digging and trade endanger Paeonia in the wild. MATERIALS AND METHODS: Herein, secondary metabolites from the stems and leaves from six developmental stages of the annual growth cycle of Paeonia ostii T. Hong & J. X. Zhang, P. 'Hexie', and P. lactiflora Pall. were qualitatively and quantitatively analyzed via high-performance liquid chromatography with a diode array detector (HPLC-DAD) and high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Antioxidant capacity at each stage was also evaluated by various free radical scavenging assays. RESULTS: A total of 24 metabolites were detected and identified, including 5 monoterpene glycosides, 4 tannins, 5 phenols, 9 flavonoids, and paeonol. Excepting paeonol and the phenols, the levels of each metabolite category were significantly higher in the leaves than the stems during all developmental stages. The paeoniflorin content in the P. ostii leaves was the highest during the first developmental stage and higher than the standards of the Chinese Pharmacopoeia, suggesting it to be the optimal harvesting stage for medicinal uses. Notably, the antioxidant capacity of the leaves was significantly greater than in the stems, particularly for the leaves of P. 'Hexie'. CONCLUSION: Our study indicates that the leaves of P. 'Hexie' have the potential to be a worthy medicinal substitute to Paeonia roots due to their high monoterpene glycosides, phenols, and flavonoids as well as their strong antioxidant capacity. Further, this study provides a theoretical basis for the development and utilization of non-root Paeonia plant sections as medicinal plant resources.

Ecotopic over-expression of PoCHS from Paeonia ostii altered the fatty acids composition and content in Arabidopsis thaliana.

Chalcone synthase (CHS) is the key enzyme in the flavonoid biosynthetic pathway and has been studied in many plants, but the function of the CHS gene has not been well characterized in Paeonia ostii. In this study, we obtained a CHS homolog gene from P. ostii, which possessed the putative conserved amino acids of chalcone synthase by multiple alignment analysis and demonstrated the highest expression in developing seeds. In vitro assays of the recombinant PoCHS protein confirmed enzymatic activity using malonyl-CoA and 4-coumaroyl-CoA as substrates, and the optimal pH and reaction temperature were 7.5 and 40 °C, respectively. Furthermore, ectopic over-expression of PoCHS in Arabidopsis up-regulated the expression levels of genes involved in seed development (ABI), glycolysis (PKp2, PDH-E1a, and SUS2/3), and especially fatty acid biosynthesis (BCCP2, CAC2, CDS2, FatA, and FAD3). This resulted in an increased unsaturated fatty acid content, especially α-linolenic acid, in transgenic Arabidopsis seeds. In this study, we examined the functions of CHS homolog of P. ostii and demonstrated its new function in seed fatty acid biosynthesis.

Predictive factors of cough after uniportal video-assisted thoracoscopic pulmonary resection.

BACKGROUND: Cough is one of the shared complications after lung surgery. In this study, a prospective analysis was conducted for exploring the risk factors of persistent cough after uniportal video-assisted thoracoscopic pulmonary resection. METHODS: One hundred thirty-five patients with pulmonary nodules who underwent surgical treatment in the same surgical group from November 2019 to January 2020 were enrolled in this prospective study. The severity of cough and its impact on patients' quality of life before and after surgery were assessed by the Mandarin Chinese version of the Leicester cough questionnaire (LCQ-MC), and postoperative cough was tested by the cough visual analog scale (VAS) and cough symptom score (CSS). Risk factors of cough after pulmonary resection (CAP) were determined by univariate and multivariate logistic regression analysis. RESULTS: The incidence of postoperative cough was 24.4% (33 of 135 patients). Univariate analysis showed that gender (female), the surgical site (upper right), the resection (lobectomy), subcarinal lymph node dissection, postoperative acid reflux, length of hospitalization contributed to the development of CAP resection. Multivariate logistic regression analysis showed that the resection (lobectomy) (OR 3.590, 95% CI: 0.637-20.300, P=0.017), subcarinal lymph node dissection (OR 4.420, 95% CI: 1.342-14.554, P=0.001), postoperative acid reflux (OR 13.55, 95% CI: 3.186-57.633, P<0.001) and duration of anesthesia (over 153 minutes, OR 0.987, 95% CI: 0.978-0.997, P=0.011) were independent risk factors for postoperative cough. CONCLUSIONS: The application of uniportal video-assisted thoracoscopic techniques to several types of lung surgery are conducive to enhanced recovery after surgery (ERAS). Postoperative cough is related to an ocean of factors, the resection (lobectomy), subcarinal lymph node dissection, postoperative acid reflux, and duration of anesthesia (over 153 minutes) are independent high-risk factors for CAP resection. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04204148).

Outstanding antioxidant pickering high internal phase emulsions by co-assembled polyphenol-soy ß-conglycinin nanoparticles.

This work reports a kind of novel antioxidant Pickering high internal phase emulsions (HIPEs; with an oil fraction, ϕ > 0.74) stabilized by soy ß-conglycinin (ß-CG) and polyphenol complex nanoparticles, as outstanding protective containers for lipophilic nutraceuticals. The nanoparticles with a representative polyphenol ((-)-epigallocatechin-3-gallate; EGCG) encapsulated were fabricated through an ethanol-mediated dissociation and re-assembly process of ß-CG, with greater particle size and higher surface hydrophilicity observed at higher initial EGCG concentrations. Using these co-assembled nanoparticles as sole stabilizers, a kind of HIPE gels with similar gel stiffness and microstructure, could be easily fabricated at ϕ = 0.8 and a protein concentration in the aqueous phase of 1.0 wt% using polyunsatuated fatty acid-rich flaxseed oil as the dispersed phase. These HIPE gels were extraordinarily stable against heating or long-term storage, but susceptible to freeze-thawing. The as-fabricated HIPEs showed an excellent protection to ß-carotene (encapsulated in oil phase) against heating, as well as an inhibition of lipid oxidation. The oxidation protection was in an EGCG concentration dependent manner. The results would be of interest for providing a novel strategy to fabricate functionalized Pickering HIPEs as potential containers or delivery systems for lipophilic nutraceuticals.

A Novel Laboratory-Based Model to Predict the Presence of Obstructive Coronary Artery Disease.

Commonly used tools to assess the probability of obstructive-coronary artery disease (CAD) were derived based on Caucasian cohorts, with their performance in China is still unknown. Furthermore, most were established based on non-laboratory variables, contributing to the limited predictive ability to some extent. Thus, we developed and internally validated a laboratory-based model with data from a Chinese cohort of 8963 inpatients, with suspected stable chest pain, referred to catheter-based coronary angiography (CAG) from September 2007 to April 2019, and then compared the present model's performance with the four most commonly used prediction tools, Coronary Artery Disease Consortium 1/2 Score (CAD1/2), Duke clinical score (DCS), and Diamond-Forrester score (DF). The final model was developed by random forest method, including 8 predictors derived from 70 variables. Five-fold cross-validation was performed to evaluate the model's prediction accuracy. In the external validation set, the present model showed a superior area under the receiver-operating curve (0.816), followed by DCS (0.66), CAD2 (0.61), CAD1 (0.59) and at last DF (0.58), respectively. Furthermore, the present model correctly classified 74.4% of obstructive-CAD patients as high-risk, and correctly classified more than one third of non-obstructive-CAD patients as low-risk. The present model's net reclassification improvement (NRI) showed a significant positive reclassification over CAD1 (NRI = 0.60, P < 0.001), DF (NRI = 0.59, P < 0.001), CAD2 (NRI = 0.57, P < 0.001), and DCS (NRI = 0.43, P < 0.001). Decision curve analysis demonstrated that the present model provided a larger net benefit compared with CAD1/2, DCS, and DF. In conclusion, the novel model, using 8 laboratory and non-laboratory variables, performed well in risk stratifying patients with suspected chest pain regarding the presence of obstructive-CAD in the present Chinese cohort.

Efficacy and safety of intravenous lidocaine in propofol-based sedation for ERCP procedures: a prospective, randomized, double-blinded, controlled trial.

BACKGROUND AND AIMS: Propofol-based sedation is widely used in ERCP procedures, but adverse respiratory or cardiovascular events commonly occur. Intravenous injection of lidocaine has an analgesic effect and can reduce the requirements of fentanyl and propofol during abdominal surgery. The objective of this study was to assess the efficacy and safety of intravenous lidocaine on propofol requirements during ERCP procedures. METHODS: Forty-eight patients scheduled for ERCP were randomly divided into 2 groups, the lidocaine group and the control group. All patients received .02 mg/kg midazolam and .1 µg/kg sufentanil intravenously as premedication. A bolus of propofol was applied for induction of sedation, and perfusion of propofol was applied for maintenance. Patients in the lidocaine group received a bolus of 1.5 mg/kg lidocaine intravenously followed by continuous infusion of 2 mg/kg/h, whereas the control group received the same volumes of saline solution. The primary outcome was the propofol requirement during ERCP. RESULTS: Compared with the control group, propofol requirements were reduced by 33.8% in the lidocaine group (212.0 ± 118.2 mg vs 320.0 ± 189.6 mg, P = .023). Involuntary movement was less common in the lidocaine group than in the control group (12.5% vs 41.7%, P = .049). In the lidocaine group, postprocedure pain and fatigue, as measured by the visual analog scale, were significantly reduced (0 [range, 0-4] vs 3 [range, 0-5], P = .005; 2 [range, 0-4] vs 5 [range, 2-8], P < .001).The incidence of oxygen desaturation, hypotension, and bradycardia tended to be lower in the lidocaine group. CONCLUSIONS: Intravenous lidocaine can significantly decrease propofol requirements during ERCP, with higher sedation quality and endoscopist satisfaction. (Clinical trial registration number: NCT03996577.).

Late Pleistocene speciation of three closely related tree peonies endemic to the Qinling-Daba Mountains, a major glacial refugium in Central China.

Determining the factors promoting speciation is a major task in ecological and evolutionary research and can be aided by phylogeographic analysis. The Qinling-Daba Mountains (QDM) located in central China form an important geographic barrier between southern subtropical and northern temperate regions, and exhibit complex topography, climatic, and ecological diversity. Surprisingly, few phylogeographic analyses and studies of plant speciation in this region have been conducted. To address this issue, we investigated the genetic divergence and evolutionary histories of three closely related tree peony species (Paeonia qiui, P. jishanensis, and P. rockii) endemic to the QDM. Forty populations of the three tree peony species were genotyped using 22 nuclear simple sequence repeat markers (nSSRs) and three chloroplast DNA sequences to assess genetic structure and phylogenetic relationships, supplemented by morphological characterization and ecological niche modeling (ENM). Morphological and molecular genetic analyses showed the three species to be clearly differentiated from each other. In addition, coalescent analyses using DIYABC conducted on nSSR variation indicated that the species diverged from each other in the late Pleistocene, while ecological niche modeling (ENM) suggested they occupied a larger area during the Last Glacial Maximum (LGM) than at present. The combined genetic evidence from nuclear and chloroplast DNA and the results of ENM indicate that each species persisted through the late Pleistocene in multiple refugia in the Qinling, Daba, and Taihang Mountains with divergence favored by restricted gene flow caused by geographic isolation, ecological divergence, and limited pollen and seed dispersal. Our study contributes to a growing understanding of the origin and population structure of tree peonies and provides insights into the high level of plant endemism present in the Qinling-Daba Mountains of Central China.

Modelling environmentally suitable areas for the potential introduction and cultivation of the emerging oil crop Paeonia ostii in China.

Paeonia ostii is a traditional ornamental and medicinal species that has attracted considerable interest for its high oil value. To facilitate the effective and rational cultivation and application of P. ostii in China, it is necessary to determine its potential spatial habitat distribution and environmental requirements. Using high-resolution environmental data for current and future climate scenarios, the potential suitable area and climatic requirements of P. ostii were modelled. Among the 11 environmental variables investigated, growing degree days, precipitation of the wettest month, mean temperature of the coldest quarter, global UV-B radiation, annual precipitation, and soil pH played major roles in determining the suitability of a habitat for the cultivation of P. ostii. Under the current environmental conditions in China, a total area of 20.31 × 105 km2 is suitable for growing P. ostii, accounting for 21.16% of the country's total land area. Under the two future climate scenario/year combinations (i.e., representative concentration pathways [RCPs], RCP2.6 and RCP8.5 in 2050), this species would increase its suitable area at high latitudes while decrease at low latitudes. These results present valuable information and a theoretical reference point for identifying the suitable cultivation areas of P. ostii.

Fatty Acid Composition, Phytochemistry, Antioxidant Activity on Seed Coat and Kernel of Paeonia ostii from Main Geographic Production Areas.

Paeonia ostii is an important woody oil plant cultivated in China on a large scale. Its seed oil is enriched with unsaturated fatty acids and a high content of alpha-linolenic acid (ALA), which are beneficial to human health. The aim of this research is to determine the qualitative traits characteristic of P. ostii seed from various production areas in China. In this study, seed quality traits were evaluated on the basis of proximate composition, content of fatty acids, tocopherol, secondary metabolites, and the antioxidant activity of seed coat (PSC) and kernel (PSK). A high content of total fatty acids (298.89-399.34 mg g-1), crude protein (16.91%-22.73%), and total tocopherols (167.83-276.70 µg g-1) were obtained from PSK. Significant differences were found in the content of palmitic acids (11.31-14.27 mg g-1), stearic acids (2.42-4.24 mg g-1), oleic acids (111.25-157.63 mg g-1), linoleic acids (54.39-83.59 mg g-1), and ALA (99.85-144.71 mg g-1) in the 11 main production areas. Eight and seventeen compounds were detected in PSC and PSK, respectively. A significantly higher content of total phenols was observed in PSC (139.49 mg g-1) compared with PSK (3.04 mg g-1), which was positively related to antioxidant activity. This study indicates that seeds of P. ostii would be a good source of valuable oil and provides a basis for seed quality evaluation for the production of edible oil and potential ALA supplements from the promising woody oil plant.

Memory T cells delay the progression of atherosclerosis via AMPK signaling pathway.

BACKGROUND: Memory T cells play a key role in the development of atherosclerosis (AS). This study aimed to investigate the role of AMPK signaling pathway of spleen memory T cells in the pathogenesis of AS in high-fat diet (HFD) fed mice. METHODS: Mice were divided into 5 groups: normal group, AS group, AS + solvent group, AS + Compound C (AMPK inhibitor) group and AS + A-769662 (AMPK agonist) group. HFD animals were intraperitoneally treated with Compound C at 20 mg/kg thrice weekly or A-769662 at 30 mg/kg once daily for 15 weeks. Then, the degree of AS was assessed, and the proportion of memory T cell was determined by flow cytometry. RESULTS: AS was evident in the aorta of HFD mice. The areas of plaque formation in both AS + Compound C group and AS + A-769662 group reduced as compared to the AS group and AS + solvent group. After intervention of AMPK activity, the proportion of memory T cells in the spleen reduced as compared to the AS group and AS + solvent group; the pro proportion of memory T cells in HFD groups was markedly higher than in the normal group and this increase was more evident in the AS + Compound C than in the AS + A-769662 group. CONCLUSIONS: The decreased memory T cells can improve AS, which may be related to the AMPK signaling pathway. Thus, AMPK in the memory T cells may serve as a target in the prevention and treatment of AS.

Effects of arterial blood on the venous blood vessel wall and differences in percentages of lymphocytes and neutrophils between arterial and venous blood.

Vascular sclerosis mostly occurs in arteries and is mainly related to anatomic structure and hemodynamics of artery. This study aimed to investigate effects of arterial blood on vein wall and explore differences of composition between arterial and venous blood.Ultrasound was used to examine the distal venous structure of arteriovenous fistula in uremia patients. Immunohistochemistry was used to study the pathology of the distal vein. Twelve patients were divided into control group and trial group. Patients received an arteriovenous fistula within 1 month in control group. Patients had undergone this surgery ≥2 years before in the trial group. Blood samples were collected from the aortic, arterial, and venous vessels of 51 patients who had taken coronary angiography and analyzed with blood routine rest, biochemical, and immunological measures to compare the differences of blood composition between artery and vein. This study was registered with the China Clinical Trial Center website under registration number ChiCTR-OOC-16008085.In the trial group, the vascular wall of distal veins of fistula were thickened and hardened. No significant differences of blood composition were found between the aortic and radial arterial blood. However, the differences in the percentages of lymphocytes and neutrophils between arterial and venous blood were significant (Pa = .0095, Pb = .01).Under smooth hemodynamic conditions, arterial blood caused hardening of the venous wall. Arterial and venous blood differed in the percentage of lymphocyte and neutrophils. This may contribute to the vascular sclerosis that is observed in arteries more often than veins.

Influence of Air Pollution on Hospital Admissions in Adult Asthma in Northeast China.

BACKGROUND: Asthma is a common chronic respiratory disease and is related to air pollution exposure. However, only a few studies have concentrated on the association between air pollution and adult asthma. Moreover, the results of these studies are controversial. Therefore, the present study aimed to analyze the influence of various pollutants on hospitalization due to asthma in adults. METHODS: A total of 1019 unrelated hospitalized adult asthma patients from Northeast China were recruited from 2014 to 2016. Daily average concentrations of air pollutants (particulate matter <2.5 µm [PM2.5], particulate matter <10 µm [PM10], sulfur dioxide [SO2], nitrogen dioxide [NO2], and carbon monoxide [CO]) were obtained from the China National Environmental Monitoring Centre website from 2014 to 2016. Cox logistic regression analysis was used to analyze the relationship between air pollutants and hospital admissions in adult asthma. RESULTS: The maximum odds ratio (OR) value for most air pollutants occurred on lag day 1. Lag day 1 was chosen as the exposure period, and 8 days before onset was chosen as the control period. Three pollutants (PM2.5, CO, and SO2) were entered into the regression equation, and the corresponding OR (95% confidence interval) was 0.995 (0.991-0.999), 3.107 (1.607-6.010), and 0.979 (0.968-0.990), respectively. CONCLUSIONS: A positive association between hospital admissions and the daily average concentration of CO was observed. CO is likely to be a risk factor for hospital admissions in adults with asthma.

Organ preservation: from the past to the future.

Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservation. However, preservation time with SCS is limited as prolonged cold storage increases the risk of early graft dysfunction that contributes to chronic complications. Furthermore, the growing demand for the use of marginal donor organs requires methods for organ assessment and repair. Machine perfusion has resurfaced and dominates current research on organ preservation. It is credited to its dynamic nature and physiological-like environment. The development of more sophisticated machine perfusion techniques and better perfusates may lead to organ repair/reconditioning. This review describes the history of organ preservation, summarizes the progresses that has been made to date, and discusses future directions for organ preservation.

Inhibition of MicroRNA-21-5p Promotes the Radiation Sensitivity of Non-Small Cell Lung Cancer Through HMSH2.

BACKGROUND: This study aimed to explore the effects of microRNA-21-5p (miR-21-5p) on the radiation sensitivity of non-small cell lung cancer (NSCLC) and the involvement of human MutS homolog 2 (hMSH2) One hundred fourteen NSCLC patients at stage II or III who received surgery and postoperative radiotherapy were enrolled in this study. METHODS: The patients were assigned into radiation-sensitive and -insensitive groups. NSCLC A549 cells were transfected to generate control, Negative control (NC), miR-21-5p inhibitor, miR-21-5p mimic, small interfering hMSH2 (sihMSH2), miR-21-5p inhibitor + sihMSH2 and hMSH2 overexpression groups. Immunohistochemistry was performed to detect the hMSH2 expression in transfected and irradiated cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to evaluate A549 miR-21-5p and hMSH2 expression in transfected and irradiated cells. A colony formation assay was adopted for cell survival analysis. The relationship between miR-21-5p and hMSH2 was verified by a luciferase reporter assay. Cell viability was measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and apoptosis was assessed by flow cytometry. NSCLC nude mouse models were established, and tumor volumes and tumor weights were recorded. RESULTS: The radiation-sensitive group of patients exhibited lower miR-21-5p but higher hMSH2 expression than the insensitive group. For irradiated A549 cells, lower cell survival, higher apoptosis, increased miR-21-5p expression and decreased hMSH2 expression were observed at 6 and 8 Gy than at 0, 2 and 4 Gy; compared to 6 Gy, cell survival and hMSH2 expression were decreased and apoptosis and miR-21-5p expression were increased at 8 Gy. Additionally, miR-21-5p was found to target hMSH2. Compared with the control group, the cell survival rate was lower and the apoptosis rate higher in the miR-21-5p inhibitor group, whereas the opposite was observed for the miR-21-5p mimic and sihMSH2 groups. For the mouse model, decreased tumor volume and tumor weight and higher hMSH2 expression were found in the miR-21-5p inhibitor, radiation, hMSH2 overexpression, miR-21-5p inhibitor + radiation and hMSH2 overexpression + radiation groups compared with the control group. In addition, tumor volume and tumor weight were decreased and hMSH2 expression increased in the miR-21-5p inhibitor + radiation and hMSH2 overexpression + radiation groups compared with the radiation alone group. CONCLUSION: These findings indicate that inhibition of miR-21 can promote the radiation sensitivity of NSCLC by targeting hMSH2.

A self-assembled polyjuglanin nanoparticle loaded with doxorubicin and anti-Kras siRNA for attenuating multidrug resistance in human lung cancer.

Lung cancer is a leading cause of cancer-associated mortality worldwide, which has a low survival rate. Multidrug resistance (MDR) is a major obstacle that hinders the treatment of lung cancer. Doxorubicin (DOX) is an anthracycline glycoside antibiotic, having a broad spectrum of anticancer activity against various solid tumors. Juglanin is a natural production, mainly extracted from green walnut husks of Juglans mandshurica, exhibiting various bioactivities. Here, we demonstrated that the combination of drug, gene and nanoparticle overcame MDR, inhibiting lung cancer progression. A novel nanoparticular pre-chemosensitizer was applied to develop a self-assembled nanoparticle formula of amphiphilic poly(juglanin (Jug) dithiodipropionic acid (DA))-b-poly(ethylene glycol) (PEG)-siRNA Kras with DOX in the core (DOX/PJAD-PEG-siRNA). The formed nanoparticles, appeared spherical shape, had mean particle size of 81.8 nm, and the zeta potential was -18.62 mV. The in vitro drug release results suggested that a sustained release was observed in DOX/PJAD-PEG-siRNA nanoparticles compared to the free DOX. Jug could improve the cytotoxicity of DOX to cancer cells with MDR. Oncogene, Kras, was dose-dependently reduced by treatment of DOX/PJAD-PEG-siRNA nanoparticles. Additionally, P-glycoprotein (MDR1) and c-Myc, contributing to tumor progression, were suppressed by the nanoparticles, while p53 was improved in drug-resistant cells. Colony formation analysis suggested that DOX/PJAD-PEG-siRNA nanoparticles showed the most effective role in reducing cancer cell proliferation. In vivo, DOX/PJAD-PEG-siRNA nanoparticles reduced tumor growth compared to the free DOX, accompanied with reduced KI-67 and enhanced TUNEL positive levels in drug-resistant xenografted nude mice. Thus, the findings above indicated that juglanin, as a chemosensitizer, potentiate the anti-cancer role of DOX in drug-resistant cancer cells. And the nanoparticles exhibited stronger antitumor efficiency, suggesting potential value in the treatment of lung cancer.

Genetic analyses reveal independent domestication origins of the emerging oil crop Paeonia ostii, a tree peony with a long-term cultivation history.

Paeonia ostii, a member of tree peony, is an emerging oil crop with important medical and oil uses and widely cultivated in China. Dissolving the genetic diversity and domestication history of this species is important for further genetic improvements and deployments. We firstly selected 29 simple sequence repeats (SSRs) via transcriptome mining, segregation analyses and polymorphism characterizations; then, 901 individuals from the range-wide samples were genotyped using well-characterized SSR markers. We observed moderate genetic diversity among individuals, and Shaanxi Province was identified as the center of genetic diversity for our cultivated plants. Five well-separated gene pools were detected by STRUCTURE analyses, and the results suggested that multiple independent domestication origins occurred in Shaanxi Province and Tongling City (Anhui Province). Taken together, the genetic evidence and the historical records suggest multiple long-distance introductions after the plant was domesticated in Shandong, Henan and Hunan provinces. The present study provides the first genetic evaluation of the domestication history of P. ostii, and our results provide an important reference for further genetic improvements and deployments of this important crop.

MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway.

OBJECTIVE: To investigate the effects of microRNA-7 (miR-7) on the proliferation, migration and invasion of non-small cell lung cancer NSCLC) cells by targeting FAK through ERK/MAPK signaling pathway. METHODS: NSCLC tissues and adjacent normal tissues were obtained from 160 NSCLC patients after operation. NSCLC cell lines (A549, H1299 and H1355) and a normal human fetal lung fibroblast cell line (MRC-5) were obtained. NSCLC cells were assigned into miR-7 inhibitors, miR-7 mimics, blank, miR-7 mimics control, miR-7 inhibitors control, FAK siRNA and miR-7 inhibitors + FAK siRNA groups. The expressions of miR-7 and FAK mRNA in tissues and cell lines were detected by qRT-PCR and Western-Blotting. Cell proliferation, migration and invasion were detected by MTT assay, wound scratch assay and Transwell assay. RESULTS: Compared with adjacent normal tissues, miR-7 expression was down-regulated, but the mRNA and protein expressions of FAK, ERK and MAPK were up-regulated. Compared with the blank and mimics control groups, miR-7 significantly increased but FAK, ERK and MAPK expressions decreased in miR-7 mimics and FAK siRNA groups. Cell proliferation, migration and invasion were inhibited in the miR-7 mimics and FAK siRNA groups, while opposite regarding miR-7 inhibitors group. CONCLUSION: The miR-7 can inhibit the activation of ERK/MAPK signaling pathway by down-regulating FAK expression, thereby suppressing the proliferation, migration and invasion of NSCLC cells. The miR-7 and its target gene FAK may be novel targets for the diagnosis and treatment of NSCLC.