Electrochemical Trifluoromethylation and Sulfonylation of N-Allylamides: Synthesis of Oxazoline Derivatives.

We report a new method for the synthesis of trifluoromethylated and sulfonylated oxazolines by electrochemical radical cascade cyclizations of N-allylamides with sodium trifluoromethanesulfinate or sulfonylhydrazines. This protocol provides a green and useful strategy to synthesize trifluoromethylated and sulfonylated oxazolines with a broad substrate scope under ambient conditions.

Decreased syntaxin17 expression contributes to the pathogenesis of acute pancreatitis in murine models by impairing autophagic degradation.

Acute pancreatitis (AP) is an inflammatory disease of the exocrine pancreas. Disruptions in organelle homeostasis, including macroautophagy/autophagy dysfunction and endoplasmic reticulum (ER) stress, have been implicated in human and rodent pancreatitis. Syntaxin 17 (STX17) belongs to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) subfamily. The Qa-SNARE STX17 is an autophagosomal SNARE protein that interacts with SNAP29 (Qbc-SNARE) and the lysosomal SNARE VAMP8 (R-SNARE) to drive autophagosome-lysosome fusion. In this study, we investigated the role of STX17 in the pathogenesis of AP in male mice or rats induced by repeated intraperitoneal injections of cerulein. We showed that cerulein hyperstimulation induced AP in mouse and rat models, which was characterized by increased serum amylase and lipase activities, pancreatic edema, necrotic cell death and the infiltration of inflammatory cells, as well as markedly decreased pancreatic STX17 expression. A similar reduction in STX17 levels was observed in primary and AR42J pancreatic acinar cells treated with CCK (100 nM) in vitro. By analyzing autophagic flux, we found that the decrease in STX17 blocked autophagosome-lysosome fusion and autophagic degradation, as well as the activation of ER stress. Pancreas-specific STX17 knockdown using adenovirus-shSTX17 further exacerbated pancreatic edema, inflammatory cell infiltration and necrotic cell death after cerulein injection. These data demonstrate a critical role of STX17 in maintaining pancreatic homeostasis and provide new evidence that autophagy serves as a protective mechanism against AP.

Endovascular thrombectomy in acute ischemic stroke patients with prestroke disability (mRS ≥2): A systematic review and meta-analysis.

Objective: The effect of endovascular thrombectomy (EVT) in acute ischemic stroke patients with prestroke disability (modified Rankin Scale score, mRS) ≥2) has not been well-studied. This study aimed to assess the safety and benefit of EVT in patients with prestroke disability. Methods: According to PRISMA guidelines, literature searching was performed using PubMed, Embase, and Cochrane databases, for a series of acute ischemic stroke patients with prestroke mRS ≥2 treated by EVT. Random-effects meta-analysis was used to pool the rate of return to prestroke mRS and mortality at 3-month follow-up. Results: In total, 13 observational studies, with 2,625 patients, were analyzed. The rates of return to prestroke mRS in patients with prestroke mRS of 2-4 were 20% (120/588), 27% (218/827), and 31% (34/108), respectively. Patients with prestroke disability treated by EVT had a higher likelihood of return to prestroke mRS (relative risk, RR, 1.86; 95% CI 1.28-2.70) and a lower likelihood of mortality (RR 0.75; 95%CI 0.58-0.97) compared with patients with standard medical treatment. Successful recanalization (Thrombolysis in Cerebral Infarction grade 2b-3) after EVT gave a higher likelihood of return to prestroke mRS (RR 2.04; 95% CI 1.17-3.55) and lower mortality (RR 0.72; 95% CI 0.62-0.84) compared with unsuccessful reperfusion. Conclusions: Acute ischemic stroke patients with prestroke disability may benefit from EVT. Withholding EVT on the sole ground of prestroke disabilities may not be justified.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/.

Electrosynthesis of (hetero)aryl nitriles from α-imino-oxy acids via oxidative decarboxylation/N-O cleavage.

A new method for the synthesis of (hetero)aryl nitriles via iminyl radicals has been developed through the electrochemical oxidative decarboxylation of α-imino-oxy acids. This protocol provides an efficient approach to nitriles with a broad range of functional-group tolerance under ambient conditions and can be applied for one-pot gram-scale synthesis.

Distribution Characteristics of Soil Viruses Under Different Precipitation Gradients on the Qinghai-Tibet Plateau.

Viruses are extremely abundant in the soil environment and have potential roles in impacting on microbial population, evolution, and nutrient biogeochemical cycles. However, how environment and climate changes affect soil viruses is still poorly understood. Here, a metagenomic approach was used to investigate the distribution, diversity, and potential biogeochemical impacts of DNA viruses in 12 grassland soils under three precipitation gradients on the Qinghai-Tibet Plateau, which is one of the most sensitive areas to climate change. A total of 557 viral operational taxonomic units were obtained, spanning 152 viral families from the 30 metagenomes. Both virus-like particles (VLPs) and microbial abundance increased with average annual precipitation. A significant positive correlation of VLP counts was observed with soil water content, total carbon, total nitrogen, soil organic matter, and total phosphorus. Among these biological and abiotic factors, SWC mainly contributed to the variability in VLP abundance. The order Caudovirales (70.1% of the identified viral order) was the predominant viral type in soils from the Qinghai-Tibet Plateau, with the Siphoviridae family being the most abundant. Remarkably, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes represented by glycoside hydrolases were identified, indicating that soil viruses may play a potential role in the carbon cycle on the Qinghai-Tibet Plateau. There were more diverse hosts and abundant CAZyme genes in soil with moderate precipitation. Our study provides a strong evidence that changes in precipitation impact not only viral abundance and virus-host interactions in soil but also the viral functional potential, especially carbon cycling.

Current research progress of isoflurane in cerebral ischemia/reperfusion injury: a narrative review.

Cerebral ischemia/reperfusion injury is an important factor leading to poor prognosis in ischemic stroke patients. Therefore, it is particularly important to find effective remedial measures to promote the health of patients to return to society. Isoflurane is a safe and reliable anesthetic gas with a long history of clinical application. In recent years, its protection function to human body has been widely recognized, and nowadays isoflurane for cerebral protection has been widely studied, and the stable effect of isoflurane has satisfied many researchers. Basic studies have shown that isoflurane's protection of brain tissue after ischemia/reperfusion involves a variety of signaling pathways and effector molecules. Even though many signaling pathways have been described, more and more studies focus on exploring their mechanisms of action, in order to provide strong evidence for clinical application. This could prompt the introduction of isoflurane therapy to clinical patients as soon as possible. In this paper, several confirmed signaling pathways will be reviewed to find possible strategies for clinical treatment.

[In vivo and in vitro Experiment of E74-Like Factor 5 Overexpression Inhibiting the Biological Behavior of Colon Cancer Cells].

OBJECTIVE: To investigate the effect of E74-like factor 5 (ELF5) overexpression on the growth and invasion ability of colorectal cancer cells and its effect on tumor formation in nude mice. METHODS: Human colorectal cancer SW480 and HT-29 cells were divided into 5 groups: the lentivirus (LV)- GFP group transfected with empty vector LV- GFP, the LV- ELF5 group transfected with recombinant LV- ELF5, the shRNA-NC group transfected with empty vector shRNA-NC, the shRNA- ELF5 group transfected with recombinant shRNA- ELF5, and the control group, not transfected with any vector. Seventy-two h after transfection, the cell supernatant containing lentivirus was collected. The mRNA expression level of ELF5 in each group was examined by real-time fluorescent quantitative PCR (RT-qPCR). The protein expression levels of ELF5, apoptosis-related cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9, and invasion-related E-cadherin and N-cadherin were checked with Western blot. CCK-8 was used to check cell viability. Colony formation experiment was done to evaluate colony formation rate. Flow cytometry was used to assess cell apoptosis. Transwell migration assay was used to examine cell invasion. TUNEL assay was used to examine the apoptosis of tissues cells. Immunohistochemistry test was done to determine the expression of E-cadherin and N-cadherin in tissues. 20 BALB/c nude mice were put into 4 groups (5 in each group): LV- GFP group, shRNA-NC group, LV- ELF5 group, and shRNA- ELF5 group. Recombinant lentiviral SW480 cell supernatants were subcutaneously injected into nude mice to construct nude mice tumorigenesis models and the volume changes of transplanted tumors were monitored. On the 30th day, transplanted tumor tissues from the nude mice were extracted and the tumor mass was measured. Western blot was done to measure the expression of ELF4 protein in the transplanted tumors. TUNEL staining was used to check cell apoptosis in the tissues, and the positive expression of N-cadherin in the transplanted tumor was measured by immunohistochemical tests. RESULTS: Compared with the control group, there was no statistically significant difference in the indicators of the two cell lines in the LV- GFP group and shRNA-NC group. The results of Western blot and RT-qPCR showed that the ELF5 protein and mRNA of the LV- ELF5 group of the two cell lines were up-regulated ( P<0.05, compared with those of the LV- GFP group), and the ELF5 protein and mRNA of the shRNA- ELF5 group were down-regulated ( P<0.05). The ELF5 overexpression system and interference system were successfully constructed. Compared with the LV- GFP group, data from the LV- ELF5 group showed that cell viability and colony formation rate ( P<0.05) were reduced, SW480 and HT-29 cell apoptosis was promoted, cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9 protein expression was up-regulated ( P<0.05), cell invasion was inhibited, and the expression of E-cadherin protein was up-regulated while the expression of N-cadherin protein was down-regulated ( P<0.05). After ELF5 interference, the above-mentioned expression of cells demonstrated an opposite trend ( P<0.05, comparing shRNA- ELF5 group with shRNA-NC group). In vivo experimental results indicated that ELF5 overexpression reduced tumor volume and tumor mass ( P<0.05), promoted cell apoptosis in tissues ( P<0.05), and inhibited N-cadherin protein expression ( P<0.05). When ELF5 expression was inhibited, the above mentioned experimental results showed the opposite trend. CONCLUSION: In vivo and in vitro experiments showed that ELF5 overexpression could promote the apoptosis of colorectal cancer cells and inhibit the growth and invasion of colorectal cancer cells.

Negative Pressure Wound Therapy in Necrotizing Fasciitis of the Head and Neck.

PURPOSE: Necrotizing fasciitis is a severe soft tissue infection that is uncommon in the head and neck region. Despite the advancement of care over the past few decades, the mortality rate remains high. Negative pressure wound therapy (NPWT), an advanced wound-healing technique, has become increasingly popular for a wide variety of complicated wounds. Since December 2015, we have used this technique in the management of necrotizing fasciitis of the head and neck. We report a consecutive case series treated with NPWT as the initial surgical procedure. MATERIALS AND METHODS: Seven patients who received a surgical diagnosis of necrotizing fasciitis of the head and neck underwent surgery under general anesthesia. After complete debridement, an NPWT device was applied for positive drainage of the involved areas. The drainage tube was connected to a central negative pressure system. The device was not replaced or removed until the infection was controlled. Then, a conventional drainage approach was used. RESULTS: Of the 7 patients, 6 underwent the surgical procedure and NPWT once; the remaining patient underwent these procedures twice. The infectious cavities showed a clean wound covered with healthy granulation formation during the removal of the NPWT device. The following course was uneventful. The mean time for wound healing was 17.3 ± 6.1 days. CONCLUSIONS: NPWT provides various advantages compared with conventional debridement and drainage, resulting in excellent clinical outcomes. This method could be recommended as an alternative approach in the management of necrotizing fasciitis in the head and neck region.

Identification and characterization of a series of novel HCN channel inhibitors.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in controlling pacemaker activity in both heart and nervous system. Developing HCN channel inhibitors has been proposed to be an important strategy for the treatment of pain, heart failure, arrhythmias, and epilepsy. One HCN channel inhibitor, ivabradine, has been clinically approved for the treatment of angina pectoris and heart failure. In this study, we designed and synthesized eight alkanol amine derivatives, and assessed their effects on HCN channels expressed in COS7 cells using a whole-cell patch clamp method. Among them, compound 4e displayed the most potent inhibitory activity with an IC50 of 2.9 ± 1.2 µM at - 120 mV on HCN2 channel expressed in COS7 cells. Further analysis revealed that application of compound 4e (10 µM) caused a slowing of activation and a hyperpolarizing shift (ΔV1/2 = - 30.2 ± 2.9 mV, n = 5) in the voltage dependence of HCN2 channel activation. The inhibitory effect of compound 4e on HCN1 and HCN4 channel expressed in COS7 cells was less potent with IC50 of 17.2 ± 1.3 and 7.3 ± 1.2 µM, respectively. Besides, we showed that application of compound 4e (10 µM) inhibited Ih and action potential firing in acutely dissociated mouse small dorsal root ganglion neurons. Our study provides a new strategy for the design and development of potent HCN channel inhibitors.

Extraction of yellow pear residue polysaccharides and effects on immune function and antioxidant activity of immunosuppressed mice.

Yellow pear residue polysaccharides were extracted via water bath alcohol precipitation, and the extraction conditions were optimized through the response surface method. The yield of polysaccharides maximized to 56.88 mg/g after extraction at 67.45 °C and material-liquid ratio of 1:34.91 for 3.66 h. The crude polysaccharide was further purified to obtain high-purity polysaccharide LPB-C, it was a kind of pyranoid polysaccharide containing a beta glycosidic bond. It consisted of mannose, glucose, rhamnose and xylose and the molar ratio was 3.3:2.3:10.6:23.2. Then the test mice were grouped, modeled and intragastrically administrated and the immune function and antioxidant capacity in immunosuppressed mice were evaluated. The results showed that the administration of yellow pear residue polysaccharides could markedly improve the immune organ index, carbon clearance ability and earlap swelling rate in immunosuppressed mice, significantly increased the secretion of TNF-α, INF-γ, IL-4 and the activities of CAT, SOD, GSH-Px, and decreased MDA levels in liver, kidney and heart. The present study indicated that yellow pear residue polysaccharides might be used as a potential natural immunomodulator and have great development values in the food and medicine fields.

Modified Technique of Cultured Epithelial Cells Transplantation on Facial Segmental Vitiligo.

BACKGROUND: Cultured epithelial cells transplantation is a known surgical technique for vitiligo. OBJECTIVE: To evaluate the factors influencing efficacy and safety of cultured epithelial cells transplantation in 9-month follow-up. METHODS: Demographic, clinical, and repigmentation outcomes were reviewed for patients with facial segmental vitiligo who had undergone cultured epithelial cells transplantation from November 2013 to July 2015 at the clinic of the Department of Dermatology, Huashan Hospital, China. RESULTS: Twenty-eight patients who had undergone cultured epithelial cells transplantation were included. A satisfactory result (>50% repigmentation) was achieved in 79% patients with facial segmental vitiligo in 9 months. The treatment effect was significantly different in 6th month (P = 0.032), 9th month (P = 0.006) compared with 3rd month. Disease stability did significantly affect repigmentation outcome in 9th month (Z = 2.113, P = 0.035). No significant difference was observed between single segmental type versus mixed type (Z = 1.081, P = 0.280). Adverse effects were nearly absent. CONCLUSION: Cultured epithelial cells transplantation is a relatively safe and effective therapy for facial segmental stable vitiligo patients.

Relación entre la expresión de IL-2 e IL-4 y sus polimorfismos y los riesgos de padecer infección por Mycoplasma pneumoniae y asma en niños / Associations of IL-2 and IL-4 Expression and Polymorphisms With the Risks of Mycoplasma pneumoniae Infection and Asthma in Children

Introducción: El asma es una afección inflamatoria de las vías respiratorias. Las infecciones porMycoplasma pneumoniae pueden exacerbar los síntomas del asma. Se ha demostrado que la interleucina2 y la interleucina4 participan en las reacciones inmunitarias e inflamatorias. Hemos estudiado la relación entre los polimorfismos de la IL2 y la IL4 y su expresión y el riesgo de padecer asma e infección por M.pneumoniae en niños. Métodos: Se reclutó a 392 niños asmáticos y 849 controles para el estudio. Se genotiparon 8 polimorfismos en IL2 e IL4 con la plataforma MassARRAY de Sequenom. La infección por M.pneumoniae y el número de copias se establecieron mediante PCR fluorescente. Los niveles séricos de expresión de IL-2 e IL-4 se midieron con ELISA. Resultados: Hallamos una relación significativa entre el polimorfismo rs6534349 de IL2 y el aumento de riesgo de sufrir asma (heterocigóticos, p = 0,029; variantes homocigóticas, p = 0,013), así como entre el polimorfismo rs2227284 de IL4 y una reducción del riesgo de padecer asma (heterocigóticos, p = 0,026; variantes homocigóticas, p = 0,001). Además, la relación con otros polimorfismos, excepto el rs2070874, se hizo evidente al agrupar a los niños asmáticos según la clasificación GINA de control y gravedad del asma. Asimismo, los niveles séricos de expresión de IL-2 e IL-4 fueron significativamente mayores en los sujetos no infectados (p = 0,038) e infectados (p = 0,011) por M.pneumoniae, respectivamente. Esta observación también se cumple entre los pacientes asmáticos (p = 0,016 para IL-2 y p = 0,042 para IL-4), pero en los controles no asmáticos solo se cumple en el caso de la IL-4 (p = 0,032). Del mismo modo, observamos que el genotipo GG rs6534349 estaba claramente relacionado con un aumento de las posibilidades de tener una infección con alta carga de M.pneumoniae (p = 0,0376). Conclusiones: La IL2 y la IL4 podrían ser biomarcadores importantes para calcular el riesgo de padecer asma, así como infección por M.pneumoniae, en niños

Introduction: Asthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 andIL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children. Methods: 392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms inIL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA. Results: We found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P = .029; homozygous variants; P = .013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P = .026; homozygous variants; P = .001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P = .038) and positive (P = .011) subjects respectively. This observation holds true among asthmatic patients (P = .016 for IL-2 and P = .042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P = .032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P = .0376). Conclusions: IL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children

Early and late Iron supplementation for low birth weight infants: a meta-analysis.

BACKGROUND: Iron deficiency in infancy is associated with a range of clinical and developmentally important issues. Currently, it is unclear what is the optimal timing to administer prophylactic enteral iron supplementation in preterm and very low birth weight infants. The objective of this meta-analysis was to evaluate early compared with late iron supplementation in low birth weight infants. METHODS: PubMed and Cochrane Library databases were searched up to May 10, 2014 for studies that compared the benefit of early and late iron supplementation in infants of low birth weight. Sensitivity analysis was carried out using the leave one-out approach and the quality of the included data was assessed. RESULTS: The data base search and detailed review identified four studies that were included in the meta-analysis. The number of included patients was 246 (n=121 for early supplementation and n=125 for late supplementation) and the majority were premature infants. Across studies, early supplementation ranged from as early as enteral feeding was tolerated to 3 weeks, and late supplementation ranged from 4 weeks to about 60 days. Early treatment was associated with significantly smaller decreases in serum ferritin and hemoglobin levels (P<0.001). In addition, the rate of blood transfusions was lower with early compared with late iron supplementation (P=0.022). There was no difference between early and late supplementation in the number of patients with nectorizing enteroclitis (>bell stage 2) (P=0.646). Sensitivity analysis indicated no one study overly influenced the findings and that the data was reliable. CONCLUSION: In conclusion, early iron supplementation resulted in less a decrease in serum ferritin and hemoglobin levels in infants with low birth rate. However, caution should be used when treating infants with iron so as not to result in iron overload and possibly negative long-term effects on neurodevelopment.

Associations of IL-2 and IL-4 Expression and Polymorphisms With the Risks of Mycoplasma pneumoniae Infection and Asthma in Children.

INTRODUCTION: Asthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 and IL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children. METHODS: 392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms in IL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA. RESULTS: We found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P=.029; homozygous variants; P=.013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P=.026; homozygous variants; P=.001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P=.038) and positive (P=.011) subjects respectively. This observation holds true among asthmatic patients (P=.016 for IL-2 and P=.042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P=.032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P=.0376). CONCLUSIONS: IL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children.

Transoral negative-pressure catheter drainage of a retropharyngeal and mediastinal abscess.

PURPOSE: A retropharyngeal abscess (RPA) is an extremely rare entity in adults that has a tendency to spread vertically and cause a mediastinal abscess. Traditionally, immediate aggressive drainage is recommended via a transcervical or transthoracic approach for the treatment of a retropharyngeal abscess with mediastinal extension. Here, we present a case of a retropharyngeal and mediastinal abscess using a transoral negative-pressure catheter drainage approach. PATIENTS AND METHODS: A 24-year-old woman was admitted with a 4-day history of severe sore throat and painful swallowing. Computed tomography identified a retropharyngeal abscess extending to the upper posterior mediastinum. We performed transoral negative-pressure catheter drainage. RESULTS: The postoperative course was uneventful. The patient reported a rapid improvement in symptoms and had a good tolerance of the catheters in the nasal cavity. At 2 years postoperatively, physical examinations revealed no recurrence or surgical complications. CONCLUSIONS: Transoral negative-pressure catheter drainage is a minimally invasive operation for the treatment of RPA in adults with or without a mediastinal abscess. This method could be recommended as an alternative approach in such cases.

Evaluation of fixation of expandable implants in the mandibles of ovariectomized sheep.

PURPOSE: This study aimed to investigate the effects of an expandable implant (EI) in ovariectomized sheep. METHODS: The EI and taper implant (control group) were produced and placed in mandibles of ovariectomized sheep. Twelve weeks after implantation, resonance frequency analysis, biomechanical tests, histomorphometry, and micro-computed tomography were applied to detect the osseointegration in the 2 groups. RESULTS: The implant stability quotient values, maximal pullout forces, and bone-implant contact (BIC) were 60.3 ± 7.9, 511.0 ± 18.7 N, and 53.14% ± 4.56%, respectively, in the EI group and 58.3 ± 8.9, 394.5 ± 54.5 N, and 46.85% ± 5.04%, respectively, in the control group. There was no significant difference between the 2 groups in implant stability quotient values (P > .05); however, in the EI group the maximal pullout force and BIC were increased significantly (P < .05 and P < .01, respectively). Micro-computed tomography analysis showed that the bone volume/total volume ratio and trabecular number increased significantly (P < .01) and trabecular separation decreased significantly (P < .05) in the EI group. CONCLUSIONS: EI could improve osseointegration in osteoporosis after 12 weeks of implantation by increasing BIC around the implant and by supplying an extra osseointegration surface.

EGFR-mediated G1/S transition contributes to the multidrug resistance in breast cancer cells.

Despite the improvement of strategies against cancer therapy, the multidrug resistance (MDR)is the critical problem for successful cancer therapy. Recurrent cancers after initial treatment with chemotherapy are generally refractory to second treatments with these anticancer therapies. Therefore, it is necessary to elucidate the therapy-resistant mechanism for development of effective therapeutic modalities against tumors. Here we demonstrate a phase-specific chemotherapy resistance due to epidermal growth factor receptor (EGFR) in human breast cancer cells. Thymidine-induced G1-arrested cultures showed upregulated chemosensitivity, whereas S-phase arrested cells were more resistant to chemotherapeutic agents. Overexpression of EGFR promoted the MDR phenotypes in breast cancer cells via accelerating the G1/S phase transition, whereas depletion of EGFR exerted the opposite effects. Furthermore, CyclinD1, a protein related to cell cycle, was demonstrated to be involved in above EGFR-mediated effects since EGFR increased the expression of CyclinD1, and the specific RNA interference against CyclinD1 could primarily abolish the EGFR-induced MDR phenotypes. These data provide new insights into the mode by which MDR breast cancers evade cytoxic attacks from chemotherapeutic agents and also suggest a role for EGFR-CyclinD1 axis in this process.

(8S,9S,10R)-4-(4-Chloro-benz-yloxy)-7,8-didehydro-3,7-dimeth-oxy-17-methyl-morphinan-6-one monohydrate.

In the title compound, C(26)H(28)Cl(N)O(4)·H(2)O, the dihedral angle betwene the two aromatic rings is 69.73 (6)°. The N-containing ring exhibits a chair conformation, while the other non-aromatic rings are in approximate envelope conformations. In the crystal, the water mol-ecule forms O-H⋯O and O-H⋯N hydrogen bonds and a C-H⋯O link also occurs.

Influence of oxidative stress and grains on sclerotial biomass and carotenoid yield of Penicillium sp. PT95.

Oxidative stress and grains were evaluated for carotenoid production by solid-state fermentation using Penicillium sp. PT95. When the fungus was grown at high oxidative stress, its sclerotial biomass and carotenoid content in sclerotia increased significantly with respect to low oxidative stress (P < 0.01). High oxidative stress also caused a statistically significant increase in carotenoid yield as compared with low oxidative stress (P < 0.01). Both the sclerotial biomass and the amount of carotenoid accumulated in sclerotia of strain PT95 were strongly dependent on the grain medium used. Among the grain media tested under high oxidative stress, buckwheat medium gave the highest content of carotenoid in sclerotia (828 microg/g dry sclerotia), millet medium gave respectively the highest sclerotial biomass (12.69 g/100 g grain) and carotenoid yield (10.152 mg/100 g grain).