ABSTRACT Purpose: This study aimed to develop a minimally invasive surgical procedure for laminar lift and posterior cervical laminoplasty via the intermuscular approach using a canine model. Methods: Six Alaskan dogs were used for developing the surgical approach. The bilateral laminae of C3-7 were cut with an ultrasonic osteotome and fixed with bilateral plates to maintain the lamina lifting and reshape a wider spinal canal. The important structures, such as ligaments, supraspinous ligaments, interspinous ligaments, and ligamentum flavum were preserved. The therapeutic effect was evaluated by preoperative and postoperative imaging results and neck mobility. Results: The surgical procedures were all successfully performed in the 6 animals. All the dogs survived well within 1 year of postoperative follow-up. The postoperative neck mobility was as good as the preoperative one. Computed tomography results showed that the anteroposterior diameter of the spinal canal was successfully enlarged and maintained well. Conclusions: The minimally invasive surgical procedure for laminar lift and posterior cervical laminoplasty via the intermuscular approach was feasible in a canine model, which might be applied in clinical practice.

Abstract Objective This study aimed to explore the precise temporospatial distributions of bone morphogenetic protein (BMP) and Wnt signaling pathways during postnatal development of mammalian tooth roots after the termination of crown morphogenesis. Methodology A total of two transgenic mouse lines, BRE-LacZ mice and BAT-gal mice, were undertaken. The mice were sacrificed on every postnatal (PN) day from PN 3d up to PN 21d. Then, the first lower molars were extracted, and the dissected mandibles were stained with 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) and fixed. Serial sections at 10 µm were prepared after decalcification, dehydration, and embedding in paraffin. Results We observed BMP/Smads and Wnt/β-catenin signaling activities in the dental sac, dental pulp, and apical papilla with a certain degree of variation. The position of activation of the BMP/Smad signaling pathway was located more coronally in the early stage, which then gradually expanded as root elongation proceeded and was associated with blood vessels in the pulp and developing complex apical tissues in the later stage. However, Wnt/β-catenin signaling was highly concentrated in the mesenchyme below the cusps in the early stage, gradually expanded to regions around the root in the transition/root stage, and then disappeared entirely in the later stage. Conclusions These results further confirmed the participation of both BMP and Wnt canonical signaling pathways in tooth root development, as well as formed the basis for future studies on how precisely integrated signaling pathways regulate root morphogenesis and regeneration.

Abstract Background: Atherosclerosis (AS) is the most common type in cardiovascular disease. Due to its complex pathogenesis, the exact etiology of AS is unclear. circRNA has been shown to play an essential role in most diseases. However, the underlying mechanism of circRNA in AS has been not understood clearly. Methods: Quantitative Real-Time PCR assay was used to detect the expression of circRSF1, miR-135b-5p and histone deacetylase 1 (HDAC1). Western blot was applied to the measure of protein expression of HDAC1, B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), cleaved-caspase-3, vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM1) and E-selectin. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Dual luciferase reporter assay and RIP assay was used to determine the relationship among circRSF1, miR-135b-5p and HDAC1. Besides, an ELISA assay was performed to measure the levels of IL-1β, IL-6, TNF-α and IL-8. Results: In this study, ox-LDL inhibited circRSF1 and HDAC1 expression while upregulated miR-135b-5p expression in Human umbilical vein endothelial cells (HUVECs). Importantly, ox-LDL could inhibit HUVECs growth. Moreover, promotion of circRSF1 or inhibition of miR-135b-5p induced cell proliferation while inhibited apoptosis and inflammation of ox-LDL-treated HUVECs, which was reversed by upregulating miR-135b-5p or downregulating HDCA1 in oxLDL-treated HUVECs. More than that, we verified that circRSF1 directly targeted miR-135b-5p and HDAC1 was a target mRNA of miR-135b-5p in HUVECs. Conclusion: CircRSF1 regulated ox-LDL-induced vascular endothelial cell proliferation, apoptosis and inflammation through modulating miR-135b-5p/HDAC1 axis in AS, providing new perspectives and methods for the treatment and diagnosis of AS.

Abstract Objectives: To investigate the diagnostic performance of single-source dual-energy computed tomography (DECT) based on gemstone spectral imaging technology (including Discovery CT750HD and Revolution CT) in patients with suspected feet/ankles gouty arthritis, and evaluate the urate deposition with a novel semi-quantitative DECT scoring system. Methods: A total of 196 patients were consecutively included. Feet and ankles were evaluated in all patients by single-source DECT scan. The 2015 EULAR/ACR criteria were used as the reference for the diagnosis of gout. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of DECT for the diagnosis of gout in the early (≤1 year), middle (1-3 years), and late (> 3 years) disease durations were calculated. Besides, a novel semi-quantitative DECT scoring system was assessed for the measurement of urate deposition, and the correlation between the scores and the clinical and serological data were also evaluated. Moreover, the influences of artifacts on the diagnostic performance of DECT were also determined. Results: The sensitivity, specificity, and AUC of DECT in 196 patients were 38.10, 96.43%, and 0.673 in the early-stage group; 62.96, 100.00%, and 0.815 in the middle-stage group; and 77.55, 87.50%, and 0.825 in the late-stage group, respectively. The overall diagnostic accuracies in the AUC of DECT (Discovery CT750HD and Revolution CT) in the middle and late stages of gout were higher than that in the early stage of gout. Besides, the monosodium urate crystals were deposited on the first metatarsophalangeal joints and ankles/midfeet. Age, the presence of tophus, bone erosion, and disease duration considerably affected the total urate score. No statistical difference in the positive detection of nail artifact, skin artifact, vascular calcification, and noise artifact was found between the case and control groups. Conclusion: DECT (Discovery CT750HD and Revolution CT) showed promising diagnostic accuracy for the detection of urate crystal deposition in gout but had limited diagnostic sensitivity for short-stage gout. Longer disease duration, the presence of tophus, and bone erosion were associated with the urate crystal score system. The artifacts do not remarkably affect the diagnostic performance of DECT in gout.

RESUMEN La distribución generalizada de roca blanda y suelo blando en el entorno de humedales hidrológicos es un problema común de ingeniería geotécnica en las zonas costeras de construcción. Para resolver este problema se propone un método de estudio para las características de consolidación y deformación de rocas blandas y cimientos de suelos blandos en ambientes de humedales hidrológicos. Como área de estudio se definió la sección K9+280-K11+120 a lo largo de la sección Fu-Nehe de la Carretera Nacional 111. Se analizaron las características de consolidación y deformación y las condiciones de carga de los cimientos del suelo blando bajo la carga de relleno del terraplén, los métodos de tratamiento de los cimientos de rocas blandas, las condiciones del estrato, los cambios de temperatura y los efectos del tiempo. Los resultados muestran que aunque la capa de suelo y roca blanda del humedal no es gruesa, el asentamiento de roca blanda y suelo representa más del 80 % del asentamiento total. La temperatura negativa tiene cierta influencia en el asentamiento de consolidación de los cimientos de rocas blandas, que se manifiesta principalmente en la diferencia entre el proceso de asentamiento de la zona de separación central y los cimientos de suelos blandos de la calzada; la presión de poro del agua de la base de roca blanda se disipa en diversos grados. De acuerdo con los resultados de monitoreo del asentamiento y la presión del agua de los poros, los sacos de arena son más adecuados para el tratamiento de ingeniería de cimientos de rocas blandas en humedales hidrológicos. Los resultados de la investigación pueden proporcionar una referencia para el estudio, el cálculo y el diseño de la consolidación y la deformación de los cimientos de rocas blandas en humedales hidrológicos.

ABSTRACT The widespread distribution of soft rock and soft soil in a hydrological wetland environment is a common geotechnical engineering problem encountered in coastal engineering construction. A study method for consolidation and deformation characteristics of soft rock and soft soil foundation in a hydrological wetland environment is proposed to solve this problem. The study area was limited to the K9+280-K11+120 section along the Fu-Nehe section of National Highway 111. The consolidation and deformation characteristics and loading conditions of soft soil foundation under embankment filling load, treatment methods of the soft rock foundation, stratum conditions, temperature changes, and time effects are analyzed. The results show that although the wetland soft rock and soil layer is not thick, the settlement of soft rock and soil accounts for more than 80% of the total settlement. The negative temperature has a certain influence on the consolidation settlement of soft rock foundation, which is mainly manifested in the difference between the settlement process of the central separation zone and the roadbed soft soil foundation. The pore water pressure of soft rock foundation dissipates to varying degrees. According to the monitoring results of settlement and pore water pressure, bagged sand wells are more suitable for soft rock foundation engineering treatment in a hydrological wetland. The research results can provide a reference for the study, calculation, and design of the consolidation and deformation of soft rock foundation in a hydrological wetland.

We aimed to investigate the association of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) with acute ischemic stroke (AIS), and its association with disease severity, inflammation, and recurrence-free survival (RFS) in AIS patients. One hundred and twenty AIS patients and 120 controls were recruited. Venous blood samples from AIS patients (within 24 h after symptoms onset) and controls (at entry to study) were collected to detect plasma lnc-MALAT1 expression by real-time quantitative polymerase chain reaction. AIS severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Plasma concentrations of inflammation factors (including C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8, IL-10, IL-17, and IL-22) were measured and RFS was calculated. lnc-MALAT1 expression was decreased in AIS patients compared to controls, and it had a close correlation with AIS (AUC=0.791, 95% CI: 0.735-0.846). For disease condition, lnc-MALAT1 expression negatively correlated with NIHSS score and pro-inflammatory factor expression (including CRP, TNF-α, IL-6, IL-8, and IL-22), while it positively correlated with anti-inflammatory factor IL-10 expression. Furthermore, lnc-MALAT1 expression was elevated in AIS patients with diabetes. For prognosis, no statistical correlation of lnc-MALAT1 expression with RFS was found, while a trend for longer RFS was observed in patients with lnc-MALAT1 high expression compared to those with lnc-MALAT1 low expression.

Abstract Purpose: To investigate the mechanisms by which PD98059 and LY294002 interfere with the abnormal deposition of extracellular matrix regulated by connective tissue growth factor (CTGF) of rat pulmonary artery smooth muscle cells (PASMCs). Methods: Rat PASMCs were cultured and separated into a control group. Real-time fluorescence quantitative PCR was performed to detect the expression of collagen III and fibronectin mRNA. Immunohistochemistry and western blot analyses were performed to detect the expression of collagen III protein. Results: The expression of collagen III and fibronectin mRNA was greater in PASMCs stimulated with CTGF for 48 h, than in the control group. After 72h of stimulation, the expression of collagen III protein in the PASMCs was greater than in the control. The equivalent gene and protein expression of the CPL group were much more significant. Conclusions: CTGF can stimulate the gene expression of collagen III and fibronectin in PASMCs, which may be one of the factors that promote pulmonary vascular remodeling (PVR) under the conditions of pulmonary arterial hypertension (PAH). PD98059 and LY294002 can inhibit the ERK1/2 and PI3K/PKB signaling pathways, respectively, thus interfering with the biological effects of CTGF. This may be a new way to reduce PAH-PVR.

BACKGROUND: α-Farnesene is a volatile sesquiterpene synthesized by the plant mevalonate (MVA) pathway through the action of α-farnesene synthase. The α-farnesene synthase 1 (MdAFS1) gene was isolated from apple peel (var. white winterpearmain), and transformed into tobacco (Nicotiana tabacum NC89). The transgenic plants had faster stem elongation during vegetative growth and earlier flowering than wild type (WT). Our studies focused on the transgenic tobacco phenotype. RESULTS: The levels of chlorophyll and soluble protein decreased and a lower seed biomass and reduced net photosynthetic rate (Pn) in transgenic plants. Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and superoxide radicals (O2._) had higher levels in transgenics compared to controls. Transgenic plants also had enhanced sensitivity to oxidative stress. The transcriptome of 8-week-old plants was studied to detect molecular changes. Differentially expressed unigene analysis showed that ubiquitin-mediated proteolysis, cell growth, and death unigenes were upregulated. Unigenes related to photosynthesis, antioxidant activity, and nitrogen metabolism were downregulated. Combined with the expression analysis of senescence marker genes, these results indicate that senescence started in the leaves of the transgenic plants at the vegetative growth stage. CONCLUSIONS: The antioxidative defense system was compromised and the accumulation of reactive oxygen species (ROS) played an important role in the premature aging of transgenic plants.

The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficileinfection, especially to investigate which agent was superior for treating either mild or severe C. difficileinfection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficileinfection in terms of both initial clinical cure rates (risk ratio, RR = 0.91, 95% confidence interval, CI = 0.84-0.98, p= 0.02) and sustained cure rates (RR = 0.88, 95% CI = 0.82-0.96, p= 0.003). For mild C. difficileinfection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR = 0.94, 95% CI = 0.84-1.04, p= 0.21) and sustained cure rates (RR = 0.93, 95% CI = 0.83-1.05, p= 0.26). For severe C. difficileinfection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR = 0.81, 95% CI = 0.69-0.95, p= 0.009), whereas sustained cure rates were similar (RR = 0.86, 95% CI = 0.72-1.02, p= 0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR = 0.88, 95% CI = 0.64-1.21, p= 0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficileinfection (RR = 0.95, 95% CI = 0.56-1.60, p= 0.85) and severe C. difficileinfection (RR = 1.27, 95% CI = 0.85-1.91, p= 0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR = 0.87, 95% CI = 0.56-1.35, p= 0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficileinfection compared with metronidazole, especially in patients with severe C. difficileinfection. In view of these data, vancomycin may be considered first line therapy for severe C. difficileinfection.

ResumoIntrodução:O stent coronário intravascular tem sido utilizado no tratamento de doença arterial coronária, com uma maior limitação de restenose intra-stent (RIS). O aço inoxidável 316 tem sido amplamente utilizado para stents. Neste estudo, foi desenvolvido um novo método de revestimento para reduzir a RIS para revestir simultaneamente o fator de crescimento endotelial vascular (VEGF) e anti-CD34 em aço inoxidável 316L.Métodos:Placas de aço inoxidável 316L redondas no grupo DH foram polimerizadas com compostos gerados a partir da reacção de condensação de dopamina e heparina utilizando N- (3-dimetilaminopropil) -N'-etilcarbodiimida (EDC) e N-hidroxissuccinimida (NHS). Dezesseis folhas a partir do grupo DH foram ainda imersas em 1 ug/ml de VEGF 165 e 3 mg/ml de heparina sódica, um após outro por 10 vezes, sendo denominado como o grupo D-(HV)10. Oito folhas de D-(HV)10 foram revestidas com anticorpo anti-CD34 e denominado como grupo D-(HV)10-A. Testes de imunofluorescência e ELISA foram usados para avaliar se os discos de aço inoxidável 316L foram revestidos com sucesso com VEGF e anticorpo anti-CD34.Resultados:Os resultados dos testes de imunofluorescência e ELISA mostraram que o VEGF pôde ser detectado nos grupos D-(HV)10 e D-(HV)10-A, evidenciando que as chapas de aço foram cobertas com VEGF com sucesso. O anticorpo anti-CD34 podia apenas ser observado no grupo D-(HV)10-A, o único grupo revestido com anticorpo CD34. Ambos os resultados sugerem que as chapas de aço inoxidável 316L foram revestidas com sucesso com VEGF e anticorpo anti-CD34.Conclusão:Nosso estudo desenvolveu um método para revestir simultaneamente VEGF e anti-CD34 de aço inoxidável. Esta pesquisa tem um papel fundamental para a nova estratégia de revestimento.

AbstractIntroduction:Intravascular coronary stenting has been used in the treatment of coronary artery disease (CAD), with a major limitation of in-stent restenosis (ISR). The 316 stainless steel has been widely used for coronary stents. In this study, we developed a novel coating method to reduce ISR by simultaneously coating vascular endothelial growth factor (VEGF) and anti-CD34 antibody on 316L stainless steel.Methods:Round 316L stainless steel sheets in the D-H group were polymerized with compounds generated from condensation reaction of dopamine and heparin using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). Sixteen sheets from the D-H group were further immersed into 1ug/ml VEGF165 and 3mg/ml heparin sodium one after another for 10 times, and named as the D-(H-V)10 group. Eight sheets from the D-(H-V)10 group were coated with anti-CD34 antibody and termed as the D-(H-V)10-A group. Immunofluorescence assay and ELISA were used to evaluate whether the 316L stainless steel disks were successfully coated with VEGF and anti-CD34 antibody.Results:The results of immunofluorescence assay and ELISA showed that VEGF could be detected in the D-(H-V)10 and D-(H-V)10-A group, suggesting the steel sheets were successfully covered with VEGF. Anti-CD34 antibody could only be observed in the D-(H-V)10-A group, which was the only group coated with CD34 antibody. Both results suggested that the 316L stainless steel sheets were successfully coated with VEGF and anti-CD34 antibody.Conclusion:Our study developed a method to simultaneously coat VEGF and anti-CD34 antibody to stainless metal steel. This research serves as a fundamental role for a novel coating strategy.

Introduction Acinetobacter baumannii has attained an alarming level of resistance to antibacterial drugs. Clinicians are now considering the use of older agents or unorthodox combinations of licensed drugs against multidrug-resistant strains to bridge the current treatment gap. We investigated the in vitro activities of combination treatments that included colistin with vancomycin, norvancomycin or linezolid against multidrug-resistant Acinetobacter baumannii. Methods The fractional inhibitory concentration index and time-kill assays were used to explore the combined effects of colistin with vancomycin, norvancomycin or linezolid against 40 clinical isolates of multidrug-resistant Acinetobacter baumannii. Transmission electron microscopy was performed to evaluate the interactions in response to the combination of colistin and vancomycin. Results The minimum inhibitory concentrations (MICs) of vancomycin and norvancomycin for half of the isolates decreased below the susceptibility break point, and the MIC of linezolid for one isolate was decreased to the blood and epithelial lining fluid concentration using the current dosing regimen. When vancomycin or norvancomycin was combined with subinhibitory doses of colistin, the multidrug-resistant Acinetobacter baumannii test samples were eradicated. Transmission electron microscopy revealed that subinhibitory doses of colistin were able to disrupt the outer membrane, facilitating a disruption of the cell wall and leading to cell lysis. Conclusions Subinhibitory doses of colistin significantly enhanced the antibacterial activity of vancomycin, norvancomycin, and linezolid against multidrug-resistant Acinetobacter baumannii.

The changes of cell ultra structure as well as Ca2+ homeostasis involved in the drought-induced maize leaf senescence was investigated. Meanwhile, many indicatives of leaf senescence including thiobarbituric acid reactive substance (MDA), electrolyte leakage (EL), and chlorophyll along with soluble proteins were also detected during the process. The Polyethylene glycol6000(PEG6000)-incubated detached leaves showed a slight increase in the MDA content and electrolyte leakage during the first 30 min of our detection, which was corresponded to an unobvious alteration of the cell ultrastructure. Other typical senescence parameters measured in whole leaf exhibited a moderate elevation as well. Thereafter, however, the EL and MDA rose to a large extent, which was correlated with a dramatic damage to the cell ultrastructure with concomitant sharp decrease in the chlorophyll and soluble proteins content. The deposits of calcium antimonite, being an indicator for Ca2+ localization, were observed in the vacuoles as well as intercellular spaces in the leaves grown under normal condition. Nevertheless, after PEG treatment, it was revealed a distinct increment of Ca2+ in the cytoplasm as well as chloroplasts and nuclei. Moreover, with long-lasting treatment of PEG to the detached leaves, the concentration of Ca2+ as described above showed a continuous increment which was consist with the remarked alteration of physiological parameters and severe damage to the ultrastructure of cells, all of which indicated the leaf senescence. Such drought-induced leaf senescence might result from a loss of the cell's capability to extrude Ca2+. All above findings give us a good insight into the important role of Ca2+ homeostasis in the process of leaf senescence accelerated by the drought stress.

Este é o primeiro relato mostrando que 3-(diclorofenil)isocumarinas e (±)-3,4-(dihidroisocumarinas) são inibidores do crescimento de plantas e fungos. 3-Diclorofenilisocumarinas foram sintetizadas pela condensação de ácido homoftálico com cloretos de diclorobenzoíla. A hidrólise alcalina destas isocumarinas formou ceto ácidos. 3-(Diclorofenil)-3,4-dihidroisocumarinas racêmicas foram obtidas pela redução de ceto ácidos a hidróxi-ácidos racêmicos, seguida pela ciclodehidratação, usando anidrido acético. As atividades herbicida, fungicida e inseticida dos compostos sintetizados foram avaliadas. Alguns dos compostos sintetizados mostraram excelentes atividades fungicida e herbicida, mas nenhum deles apresentou efeito inseticida nos insetos usados nos testes. Este estudo sugere que isocumarinas e compostos relacionados podem ser usados como guias para o planejamento de herbicidas e fungicidas bioativos.

This is the first report showing that 3-(dichlorophenyl)isocoumarins and (±)-3,4-dihydroisocoumarins are plant and plant fungus growth inhibitors. 3-Dichlorophenylisocoumarins were synthesized by condensation of homophthalic acid with dichlorobenzoyl chlorides. The alkaline hydrolysis of these isocoumarins afforded keto acids. Racemic 3-(Dichlorophenyl)-3,4-dihydroisocoumarins were obtained by reduction of keto acids to racemic hydroxy acids, followed by cyclodehydration using acetic anhydride. The herbicidal, fungicidal and insecticidal activities of the synthesized compounds have been evaluated. Some of the synthesized compounds show excellent herbicidal and fungicidal activities but none of the synthesized compounds presented any insecticidal effects on the test insects. The findings of this study suggest that isocoumarins and related compounds may serve as lead compounds towards the design of bioactive herbicides and fungicides.