Transcription factor PbNAC71 regulates xylem and vessel development to control plant height.

Dwarfism is an important agronomic trait in fruit breeding programs. However, the germplasm resources required to generate dwarf pear (Pyrus spp.) varieties are limited. Moreover, the mechanisms underlying dwarfism remain unclear. In this study, "Yunnan" quince (Cydonia oblonga Mill.) had a dwarfing effect on "Zaosu" pear. Additionally, the dwarfism-related NAC transcription factor gene PbNAC71 was isolated from pear trees comprising "Zaosu" (scion) grafted onto "Yunnan" quince (rootstock). Transgenic Nicotiana benthamiana and pear OHF-333 (Pyrus communis) plants overexpressing PbNAC71 exhibited dwarfism, with a substantially smaller xylem and vessel area relative to the wild-type controls. Yeast one-hybrid, dual-luciferase, chromatin immunoprecipitation-qPCR, and electrophoretic mobility shift assays indicated that PbNAC71 downregulates PbWalls are thin 1 expression by binding to NAC-binding elements in its promoter. Yeast two-hybrid assays showed that PbNAC71 interacts with the E3 ubiquitin ligase PbRING finger protein 217 (PbRNF217). Furthermore, PbRNF217 promotes the ubiquitin-mediated degradation of PbNAC71 by the 26S proteasome, thereby regulating plant height as well as xylem and vessel development. Our findings reveal a mechanism underlying pear dwarfism and expand our understanding of the molecular basis of dwarfism in woody plants.

[Post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation. METHODS: Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group. Besides the treatment as the control group, in the observation group, the four-step acupuncture therapy for opening orifices and benefiting throat was supplemented. Step 1: the three areas of scalp acupuncture on the affected side were stimulated. Step 2: pricking method was operated on the posterior pharyngeal wall. Step 3: bleeding technique was operated at Jinjin (EX-HN 12) and Yuye (EX-HN 13). Step 4: deep insertion of needle was operated at three-pharynx points. The needles were retained for 30 min at the three areas of scalp acupuncture and the three-pharynx points. The intervention of each group was delivered once daily, 6 times a week, at the interval of 1 day. One course of treatment was 1 week and 4 successive courses were required. The rating of Kubota water swallow test, the score of standardized swallowing assessment (SSA) and the rating of Rosenbek penetration- aspiration scale (PAS) were observed before and after treatment in patients of the two groups. The incidence of clinical complications and clinical efficacy were compared between the two groups. RESULTS: Compared with those before treatment, the rating of Kubota water swallow test, the scores of SSA and the rating of PAS of patients in the two groups were decreased after treatment (P<0.01), and the values of the observation group were lower than those of the control group after treatment (P<0.05). The incidence of clinical complications in the observation group was 13.3% (4/30), lower than 36.7% (11/30) in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was better than 70.0% (21/30) in the control group (P<0.05). CONCLUSION: The four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation can improve the swallowing function of patients with post-stroke dysphagia and reduce the incidence of clinical complications.

Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases.

Metformin (MTF) and berberine (BBR) share several therapeutic benefits in treating metabolic-related disorders. However, as the two agents have very different chemical structure and bioavailability in oral route, the goal of this study is to learn their characteristics in treating metabolic disorders. The therapeutic efficacy of BBR and MTF was systemically investigated in the high fat diet feeding hamsters and/or ApoE(-/-) mice; in parallel, gut microbiota related mechanisms were studied for both agents. We discovered that, although both two drugs had almost identical effects on reducing fatty liver, inflammation and atherosclerosis, BBR appeared to be superior over MTF in alleviating hyperlipidemia and obesity, but MTF was more effective than BBR for the control of blood glucose. Association analysis revealed that the modulation of intestinal microenvironment played a crucial role in the pharmacodynamics of both drugs, in which their respective superiority on the regulation of gut microbiota composition and intestinal bile acids might contribute to their own merits on lowering glucose or lipids. This study shows that BBR may be a good alternative for MTF in treating diabetic patients, especially for those complicated with dyslipidemia and obesity.

Antioxidant Activity and the Potential Mechanism of the Fruit From Ailanthus altissima Swingle.

The fruits of Ailanthus altissima Swingle (AS) possess a variety of pharmacological activities. Its antioxidant activity and the potential mode of action have not yet been investigated. In in vitro studies, AS revealed the strong reducing power and DPPH scavenging effect, but hydroxyl radical scavenging activity and ferrous ions-chelating ability were not strong. Meanwhile, the oxidative stress RAW264.7 cell injury model was established, the low and medium-doses of AS showed significant protective effects on the viability of H2O2-treated cells by CCK-8 method. Besides, three doses of AS all increased the activities of SOD, CAT, and GSH-Px and decreased the MDA level compared with the H2O2 group, suggesting it significantly relieved oxidative stress of cells. The active ingredients and related targets of AS were collected by HERB and Swiss Target Prediction database, the common targets of drugs and diseases database were conducted by GeneCards database platform and the Venny platform. We screened the core targets of AS like threonine kinase1 (AKT1), mitogen-activated protein kinase 1 (MAPK1), sirtuin-1 (SIRT1), mechanistic target of rapamycin kinase (MTOR) by STRING database, and the key pathways involved PI3K-AKT and FoxO signaling pathway by KEGG pathway enrichment analysis. Besides, qRT-PCR revealed AS preconditioning significantly up-regulated the expression level of AKT1, SIRT1, MAPK1, and MTOR in model cells, and the effect was related to the regulation of FoxO and PI3K/AKT signaling pathway. In summary, AS showed significant antioxidant activity and its potential mechanism was regulating FoxO and PI3K/AKT signaling pathway.

[Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis].

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (n=1 184), tracheal intubation (n=166), and extensive cardiopulmonary resuscitation (ECPR; n=116). The three groups were compared in terms of general information and clinical outcomes. RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (P < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased (P < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased (P < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications (P < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group (P < 0.05). CONCLUSIONS: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.

Clinical characteristics of coronavirus disease 2019 (COVID-19) in patients out of Wuhan from China: a case control study.

BACKGROUND: A large-scale global outbreak of coronavirus disease-19 (COVID-19) out of Wuhan, from China, occurred in January 2020. To examine the clinical characteristics of COVID-19 in infected patients out of Wuhan, from China. METHODS: Thirteen patients were confirmed to be infected with novel coronavirus-2019 (2019-nCoV) between January 27 and February 8, 2020, in Baoji city, Shannxi, northwestern China. Epidemiological and clinical information, and computed to morphology imaging data from all COVID-19 patients were collected; cases were divided into two groups according to the severity of infection (mild or severe). RESULTS: Nine (9/13) COVID-19 patients exhibited mild disease severity, and defined as second-generation human-to-human transmission cases. Most patients (11/13) had a history of travel to or from Wuhan. There were no differences in sex and age between the mild and severe cases (all P > 0.05). A moderate degree of fever (11/13), cough (13/13), and fatigue (8/13) were common symptoms; however, there was no statistical difference between mild and severe cases in this regard (all P > 0.05). Oxyhemoglobin saturation and oxygenation index decreased, and C-reactive protein (CRP) and serum amyloid A (SAA) levels were elevated in all patients with COVID-19 infection, with statistically significant differences between those with severe disease and mild infection (all P < 0.05). Twelve of 13 COVID-19 patients exhibited changes in chest CT imaging features, and time course changes were different between mild and severe cases (all P < 0.05). CONCLUSION: Most cases of COVID-19 infection were second-generation human-to-human transmissions from Wuhan and were mild in severity. The clinical characteristics of COVID-19 varied. Oxyhemoglobin saturation, oxygenation index, CRP and SAA levels, and CT features were reliable parameters to evaluate the severity of COVID-19 infection. However, a few patients with mild COVID-19 disease lacked typical characteristics such as fever and changes in CT imaging features.

[Reconstruction of the March-April average maximum air temperature over 165 years based on Pinus tabuliformis tree-rings of Zhen'an County, Shaanxi Province, China]. / åŸºäºŽæ²¹æ¾æ ‘è½®é‡å»ºé™•è¥¿çœé•‡å®‰åŽ¿165年以来3­4月平均最高气温.

We used tree rings of Pinus tabuliformis sampled in the Muwang National Forest Park to establish a standardized chronology (STD) and calculated the correlation coefficients between the standardized chronology and climatic factors of Zhen'an meteorological station. With linear regression analysis, we reconstructed the March-April mean maximum temperature of Zhen'an over 165 years from 1853 to 2017. The highest correlation coefficient was observed between the standardized chronology and the March-April mean maximum temperature (r=0.596, n=60, P＜0.01). The variance interpretation of the March-April mean maximum temperature reconstruction function was 33.2%, and the reconstruction function and results were credible and reliable. Warm years occurred 25 times and cold years occurred 29 times in the reconstruction sequence. The warm years were more accompanied by flood events, while the cold years were accompanied by more drought events. Temperature fluctuated obviously in the reconstruction sequence, with two cold periods (1902-1917 and 1953-2000) and four warm periods (1868-1892, 1917-1937, 1941-1953 and 2001-2012). The obvious periodic variations of 2-7, 8-15, 18-28, 75-96, and 100-125 years were found in the reconstruction sequence, in which the quasi-113, 88 and 22 years were the first, second and third main periods, respectively. These variations might potentially be the fingerprints of some climate change forces such as solar activity, monsoon and EI Niño-Southern Oscillation (ENSO) activity.

DUSP26 regulates podocyte oxidative stress and fibrosis in a mouse model with diabetic nephropathy through the mediation of ROS.

Diabetic nephropathy (DN) is a leading cause of renal failure worldwide. Unfortunately, the pathogenetic mechanism of DN is far from to be understood. Dual-specificity phosphatase 26 (DUSP26) is a member of the Dusp protein family, and is suggested to be involved in divers biological and pathological processes, such as cell growth, differentiation, inflammation and apoptosis. However, its role in the development of DN is still vague. In this study, we found that DUSP26 expression was increased in kidney of DN patients. Then, the wild type (DUSP26+/+) and gene knockout (DUSP26-/-) mice were used to further explore the effects of DUSP26 on DN development induced by streptozotocin (STZ). DUSP26 deficiency accelerated renal injury and dysfunction, as evidenced by the elevated glomerulosclerosis, reduced expression of Nephrin and promoted glomerular basement membrane thickness. In addition, STZ treatment resulted in reactive oxygen species (ROS) accumulation, H2O2 overproduction and superoxide dismutase (SOD) reduction in renal cortex or glomeruli of mice. The ROS production caused the activation of mitogen-activated protein kinase (MAPKs) signaling in kidney glomeruli of STZ-induced mice. These in vivo pathological processes were further confirmed in the differentiated podocytes stimulated by glucose (GLU). Intriguingly, we found that STZ-induced DN as mentioned above was further accelerated by DUSP26-/- in mice following STZ injection. Moreover, STZ-induced fibrosis in kidney glomeruli of DN mice was markedly prolonged in DUSP26-knockout mice through potentiating transforming growth factor-ß1 (TGF-ß1) expression. More importantly, reducing ROS generation could significantly abolish DUSP26 knockdown-exacerbated TGF-ß1 expression and MAPKs activation, thereby protecting podocytes from GLU-induced podocyte injury. Thus, DUSP26-regulated DN development was largely dependent on ROS generation. Taken together, we concluded that DUSP26 might be a promising therapeutic target for developing effective treatments against DN progression.

Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases.

Cardiovascular and metabolic disease (CMD) remains a main cause of premature death worldwide. Berberine (BBR), a lipid-lowering botanic compound with diversified potency against metabolic disorders, is a promising candidate for ameliorating CMD. The liver is the target of BBR so that liver-site accumulation could be important for fulfilling its therapeutic effect. In this study a rational designed micelle (CTA-Mic) consisting of α-tocopheryl hydrophobic core and on-site detachable polyethylene glycol-thiol shell is developed for effective liver deposition of BBR. The bio-distribution analysis proves that the accumulation of BBR in liver is increased by 248.8% assisted by micelles. Up-regulation of a range of energy-related genes is detectable in the HepG2 cells and in vivo. In the high fat diet-fed mice, BBR-CTA-Mic intervention remarkably improves metabolic profiles and reduces the formation of aortic arch plaque. Our results provide proof-of-concept for a liver-targeting strategy to ameliorate CMD using natural medicines facilitated by Nano-technology.

Radiomics signature: A potential biomarker for the prediction of MGMT promoter methylation in glioblastoma.

BACKGROUND: In glioblastoma (GBM), promoter methylation of the DNA repair gene O-methylguanine-DNA methyltransferase (MGMT) is associated with beneficial chemotherapy. PURPOSE/HYPOTHESIS: To analyze radiomics features for utilizing the full potential of medical imaging as biomarkers of MGMT promoter methylation. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: In all, 98 GBM patients with known MGMT (48 methylated and 50 unmethylated tumors). FIELD STRENGTH/SEQUENCE: 3.0T magnetic resonance (MR) images, containing T1 -weighted image (T1 WI), T2 -weighted image (T2 WI), and enhanced T1 WI. ASSESSMENT: A region of interest (ROI) of the tumor was delineated. A total of 1665 radiomics features were extracted and quantized, and were reduced using least absolute shrinkage and selection operator (LASSO) regularization. STATISTICAL TESTING: After the support vector machine construction, accuracy, sensitivity, and specificity were computed for different sequences. An independent validation cohort containing 20 GBM patients was utilized to further evaluate the radiomics model performance. RESULTS: Radiomics features of T1 WI reached an accuracy of 67.54%. Enhanced T1 WI features reached an accuracy of 82.01%, while T2 WI reached an accuracy of 69.25%. The best classification system for predicting MGMT promoter methylation status originated from the combination of 36 T1 WI, T2 WI, and enhanced T1 WI images features, with an accuracy of 86.59%. Further validation on the independent cohort of 20 patients produced similar results, with an accuracy of 80%. DATA CONCLUSION: Our results provide further evidence that radiomics MR features could predict MGMT methylation status in preoperative GBM. Multiple imaging modalities together can yield putative noninvasive biomarkers for the identification of MGMT. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1380-1387.

Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma.

Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine protein kinase and belongs to the extracellular signal-regulated kinases/microtubule-associated protein kinase families (Erks/MAPKs). Previous studies have indicated that abnormal expressions of NLK played critical roles in various types of human cancers. Recent studies suggested that NLK expression was significantly upregulated in the hepatocellular carcinoma (HCC) specimens. However, the clinical significance of NLK expression in HCC remains largely unknown. In this study, we focused on the clinical significance of NLK in HCC and found that high expression of NLK was significantly associated with Edmondson-Steiner grade (P = 0.002), tumor size (P = 0.022), and no. of tumor nodules (P < 0.001), and NLK was positively correlated with proliferation marker Ki-67 (P < 0.01). Univariate analysis suggested that NLK expression was associated with poor prognosis (P < 0.001). Multivariate analysis indicated that NLK expression was an independent prognostic indicator for HCC (P = 0.0370). In conclusion, NLK overexpression is associated with poor overall survival in patients with HCC, it might be an independent poor prognostic marker for HCC.

Efficacy of mannatide combined with sodium cantharidate vitamin B6 in the treatment of malignant pleural effusions.

OBJECTIVE: To evaluate the efficacy of mannatide combined with sodium cantharidate vitamin B6 in the treatment of malignant pleural effusions. MATERIALS AND METHODS: Data for 69 patients with malignant pleural effusions who did not receive systemic chemotherapy were collected. Injection into the thorax using mannatide combined with sodium cantharidate vitamin B6 was performed for 37 patients in the experimental group and mannatide combined with cisplatin for 32 patients in the control group. Objective responses, KPS (Karnofsky Scoring) and incidences of side effects between the two groups were compared. RESULTS: 13 patients reached CR (complete response) and 11 PR (partial response) in the experimental group, while 12 patients reached CR and 9 PR in the control group, the difference in overall objective responses between the two groups not being significant (66.7% vs 63.6%, p=0.806). However, improvement of KPS in the experimental group was greater than in the control group; total side-effect incidences during the period of treatment were 22.2% (8/36) and 54.5% (18/33), respectively (p=0.006). CONCLUSIONS: Regimen of mannatide combined with sodium cantharidate vitamin B6 had better improvement in quality-of-life and symptom relief, with a lower side-effect incidence in treatment of malignant pleural effusions.

A preclinical in vivo investigation of high-intensity focused ultrasound combined with radiotherapy.

This study aims to perform an in vivo investigation evaluating the injury to the pancreas and adjacent tissue of swine resulting with high-intensity focused ultrasound (HIFU) combined with radiotherapy (RT). The protocol was approved by the animal ethics committee at the Peking University First Hospital. A total of 12 domestic swine were divided into four groups: control, HIFU only, RT only and HIFU + RT. The injury to the pancreas, adjacent tissue and tissue within the acoustic path of the HIFU beam was assessed based on gross and histologic findings. For the targeted region of the pancreas, the score of the combined group was higher than that of the HIFU group and there was significant difference. For the acoustic path tissue, there was no significant difference except between the control group and the other groups. HIFU combined with RT increased the injury to the targeted pancreas, without increased injury to tissue outside of the targeted region.

Synthesis, biological evaluation and molecular docking studies of amide-coupled benzoic nitrogen mustard derivatives as potential antitumor agents.

A series of amide-coupled benzoic nitrogen mustard derivatives as potential EGFR and HER-2 kinase inhibitors were synthesized and reported for the first time. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Of all the studied compounds, compounds 5b and 5t exhibited the most potent inhibitory activity, which was comparable to the positive control erlotinib. Docking simulation was performed to position compounds 5b and 5t into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicated that some of the benzoic nitrogen mustard derivatives possessed high antiproliferative activity against MCF-7. In particular, compounds 5b and 5t with potent inhibitory activity in tumor growth inhibition may function as potential antitumor agents.

Mutation analysis of p63 gene in the first Chinese family with ADULT syndrome.

BACKGROUND: ADULT syndrome (acro-dermato-ungual-lacrimal-tooth syndrome) is a rare ectodermal dysplasia disorder known as autosomal dominant inheritance. Recent studies have linked p63 gene mutation to the development of this disease. However, the genetic characteristics of ADULT syndrome were still not well understood. METHODS: Mutation analysis of p63 gene in the first Chinese ADULT syndrome family was performed using direct DNA sequencing. RESULTS: The sequence analysis of exon 8 of p63 gene disclosed a heterozygous G>A substitution at nucleotide 893 (R298Q) in the proband. In addition, a single nucleotide polymorphism (SNP) rs16864880 in the downstream flanking region (DFR) of p63 exon 8 was also identified in this family. The proband and the paternal side including her father exhibited the C/G genotype at this position. The C/G variant frequency in the paternal was significantly higher as compared with the maternal (6/10 vs 0/6, P = 0.034). CONCLUSIONS: ADULT syndrome may be caused by the p63 gene mutation, and it might have closer genetic association with the paternal side in this family.

[Study of huchang qingfei pellets on immune function in rats infected with Mycoplasma pneumoniae].

OBJECTIVE: To study the effects and mechanism of Huchang Qingfei pellets on immune function in rats infected with mycoplasma pneumoniae. METHOD: A rat model of mycoplasmal pneumonia (MP) was developed in repeated intranasal infectious routes and then the humoral and cellular immunocompetences were detected by radioimmunoassay, immune-turbidimetry and flow cytometry. RESULT: The levels of serum IgG,IgM and IL-2, IL-6 were enhinced obviously, the complement C3 and TNF-alpha were decreased and the ratio of CD4+ /CD8+ was improved significantly in the Huchang groups as compared with MP model group. CONCLUSION: Huchang Qingfei pellets can reinforce immune function via preventing both cellular and humoral immunity from depression in the rats with MP.

[Effect of Huchang Qingfei concentrated pellets on E-cadherin expression in lung tissue of mice infected with Mycoplasma pneumoniae].

OBJECTIVE: To investigate the effects of Huchang Qingfei concentrated pellets on the expression of E-cadherin (E-cd) in the lung tissue from mice infected with Mycoplasma pneumoniae (MP). METHOD: A mice model of Mycoplasmal pneumonia (MPP) was developed by repeatedly intranasal infectious route. Transmission electronic microscope (TEM) and immunohistochemistry stain were performed to observe the pathological changes and expression of E-cd in lung tissues. RESULT: Under TEM it was found that the cellular membrane was ruptured, mitochondria was denatured, crista was broken in the pulmonary cells of the model group; the all above parameters in Huchang medicated group were improved obviously. The immunohistochemistry test showed that strong positive brown stain of E-cd expression was found in the pulmonary epithelial cell membrane and bronchial periphery in the model group, however, in the medicated group, the E-cd expression level in the cellular membrane was decreased and the expression ratio was dropped significantly as compared with the model controls. CONCLUSION: Huchang Qingfei concentrated pellets can inhibit the overexpression of E-cd in the lung tissue of mice with MP-infection, which may be helpful for prevention and treatment of pulmonary injury caused by MPP.