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The intervention of nectar robbers in plant pollination systems will cause some pollinators to modify their foraging behavior to act as secondary robbers, consequently adopting a mixed foraging strategy. The influence of nectar robbing on pollinator behavior may be affected by spatio-temporal difference of robbing intensity, and consequently, may have different effects on the pollination of host plants. However, whether and how the nectar robbing might influence pollinators under different robbing intensity still needs further investigation. In this study, Symphytum officinale was used to detect the effect of nectar robbers on pollinators under different robbing intensity as well as their effects on plant reproductive success. Six robbing levels and three bumblebees with mixed foraging behaviors were used to evaluate the effect of different robbing intensity on pollinator behavior, visitation rate, flower longevity and pollen deposition. Our results indicated that the robbing rate increased gradually with the proportion of robbed flowers, but which did not affect the frequency of legitimate visits. The increase of robbing rate promoted the corolla abscission, and then enhanced the self-pollen deposition, but which had no significant effect on cross-pollen deposition. These results indicate that the overall fitness of S. officinale was improved by combined self and cross-pollination modes when visited by both pollinators and nectar robbers simultaneously. Although nectar robbing is not uncommon, its consequences for pollination in the interaction web have not been well studied. Our results emphasize the significance of indirect impacts in mediating the adaptive outcomes of species interactions.
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Boraginaceae , Flores , Néctar de las Plantas , Polinización , Reproducción , Polinización/fisiología , Flores/fisiología , Animales , Abejas/fisiología , Reproducción/fisiología , Néctar de las Plantas/fisiología , Boraginaceae/fisiología , Polen/fisiologíaRESUMEN
INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and rarely develops after drug therapy. This study describes the clinical, electrodiagnostic (EDX), and ultrasound (US) findings in seven patients who experienced CTS due to anti-cancer therapeutic agents. METHODS: All patients underwent EDX testing, and four patients had an US study. RESULTS: CTS occurred in four patients with aromatase inhibitors, two with immune checkpoint inhibitors, and one with a selective estrogen receptor modulator. The mean duration between initiation of the anti-cancer therapeutic agents and symptom onset was 6 weeks (range: 2-12 weeks). Decreased digit sensation was noted in all patients; wasting and weakness of the abductor pollicis brevis (APB) was observed in three (42.8%) patients. The compound muscle action potentials (CMAP) of the APB and sensory nerve action potentials of the second or third digit could not be recorded in two (28.5%) and four (57.1%) patients, respectively. The needle EMG detected fibrillations and positive sharp waves in the APB in two patients. The motor unit potentials of the APB were decreased with large polyphasics in three (42.8%) patients. Of the four patients who underwent US testing, all had increased cross-sectional area of the median nerve at the carpal tunnel inlet, three (75%) had thenar muscle atrophy, and two (50%) had a loss of fascicular pattern. Three (42.8%) patients underwent a CTR. CONCLUSIONS: Physicians should be cognizant of the relationship between anti-cancer therapeutic agents and CTS. EDX studies and US play important roles in the diagnostic assessment of such patients.
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Antineoplásicos , Síndrome del Túnel Carpiano , Humanos , Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/tratamiento farmacológico , Conducción Nerviosa/fisiología , Nervio Mediano , Músculo Esquelético/inervación , Pulgar , Antineoplásicos/uso terapéuticoRESUMEN
Fruit ripening in tomato (Solanum lycopersicum) is the result of selective expression of ripening-related genes, which are regulated by transcription factors (TFs). The NAC (NAM, ATAF1/2, and CUC2) TF family is one of the largest families of plant-specific TFs and members are involved in a variety of plant physiological activities, including fruit ripening. Fruit ripening-associated NAC TFs studied in tomato to date include NAC-NOR (non-ripening), SlNOR-like1 (non-ripening like1), SlNAC1, and SlNAC4. Considering the large number of NAC genes in the tomato genome, there is little information about the possible roles of other NAC members in fruit ripening, and research on their target genes is lacking. In this study, we characterize SlNAM1, a NAC TF, which positively regulates the initiation of tomato fruit ripening via its regulation of ethylene biosynthesis. The onset of fruit ripening in slnam1-deficient mutants created by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9) technology was delayed, whereas fruit ripening in OE-SlNAM1 lines was accelerated compared with the wild type. The results of RNA-sequencing (RNA-seq) and promoter analysis suggested that SlNAM1 directly binds to the promoters of two key ethylene biosynthesis genes (1-aminocyclopropane-1-carboxylate synthase: SlACS2 and SlACS4) and activates their expression. This hypothesis was confirmed by electrophoretic mobility shift assays and dual-luciferase reporter assay. Our findings provide insights into the mechanisms of ethylene production and enrich understanding of the tomato fruit ripening regulatory network.
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Etilenos/metabolismo , Regulación de la Expresión Génica de las Plantas , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/metabolismo , Solanum lycopersicum/genética , Frutas/genética , Frutas/fisiología , Liasas/genética , Liasas/metabolismo , Solanum lycopersicum/fisiología , Proteínas de Plantas/genética , Regiones Promotoras Genéticas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Limited evidence is known about whether long-term exposures to air borne particulate matters of 2.5 µm or less (PM2.5) impact human hematologic index for women preparing for pregnancy. No study assessed the effect of PM1, which is small enough to reach the blood circulation. OBJECTIVE: To evaluate whether exposure to PM1 and PM2.5 is associated with blood cell count of woman preparing for pregnancy. METHOD: Based on the baseline data of a national birth cohort in China, we analysed the white blood cell (WBC), red blood cells (RBC) and thrombocyte counts of 1,203,565 women who are aged 18-45 years, being Han ethnicity, had no chronic disease and preparing for pregnancy. We matched their home addresses and examination date with daily concentrations of PM1 and PM2.5 which were estimated by a machine learning method with remote sensing, meteorological and land use information. Generalized additive mixed model to examine the associations between exposure to one-year average exposure to PMs prior to the health examination and the blood cells counts, after adjustment for potential individual variables. RESULTS: A 10 µg/m3 PM1 increment was associated with -1.49% (95%CI: 1.56%, -1.42%) difference in WBC count; with 0.33% (95%CI: 0.30%, 0.36%) difference of RBC count; and with 1.08% (95%CI: 1.01%, 1.15%) difference of thrombocyte count. For PM2.5, the corresponding difference was -0.47% (95%CI: 0.54%, -0.39%) for WBC; was 0.06% (95%CI: 0.03%, 0.09%) for RBC; and was 1.10% (95%CI: 1.02%, 1.18%) for thrombocyte. Women working as workers, being overweight and with tobacco smoking exposure had higher associations between PMs and hematologic index than their counterparts (p < 0.05 for interaction test). CONCLUSION: Long-term exposure to PMs were associated with decrement in WBC, as well as increment in RBC and thrombocytes among Han Chinese women preparing for pregnancy. Measures such as using air purifiers and wearing a mask in polluted areas should be improved to prevent women from the impact of PMs.
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Filtros de Aire , Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Recuento de Células Sanguíneas , China , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Material Particulado/análisis , Material Particulado/toxicidad , EmbarazoRESUMEN
The aim of this paper was to study the effect and mechanism of fucoxanthin on insulin resistance of obese mice induced by high-fat diet. Fifty C57 BL/6 J male mice were randomly divided into control group and high-fat diet group. The insulin resistance model was induced with high-fat diet for 12 weeks, and model mice were randomly divided into model group, fucoxanthin-0.2% group, fucoxanthin-0.4% group and metformin group. After dietary treatment for 6 weeks, the body weight and epididymal fat weight in each group were measured. Fasting blood glucose(FBG), fasting insulin(FINS), total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL-C) and high-density lipoprotein(HDL-C) were measured, and insulin resistance index(HOMA-IR) was calcula-ted. The pathological morphology in liver was observed by hematoxylin eosin staining, and the expressions of some key proteins in insulin receptor substrate 1(IRS-1)/posphoinositide 3-kinase(PI3 K)/serine-threonine kinase(Akt) and peroxisome proliferators-activated receptor-γ(PPARγ)/sterol regulatory element binding protein-1(SREBP-1)/fatty acid synthetase(FAS) pathways in liver were detected by Western blot. According to the findings, compared with the model group, levels of body weight, epididymal fat weight, FBG, FINS, TC, TG, LDL-C and HOMA-IR, as well as protein expressions of PPARγ, SREBP-1 and FAS in liver were significantly reduced(P<0.05 or P<0.01), while level of HDL-C and protein expressions of p-IRS-1, IRS-1, PI3 K and p-Akt in liver were signi-ficantly increased after treatment with fucoxanthin(P<0.05 or P<0.01). And the pathological changes of liver tissue in fucoxanthin-treated mice were also improved obviously. The results showed that fucoxanthin could improve obesity, hyperglycemia and hyperlipidemia, and alleviate insulin resistance in obese mice, and its mechanism is possibly related to the regulation of IRS-1/PI3 K/Akt and PPARγ/SREBP-1/FAS pathways.
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Resistencia a la Insulina , Animales , Dieta Alta en Grasa/efectos adversos , Insulina , Hígado , Masculino , Ratones , Ratones Obesos , XantófilasRESUMEN
BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/terapia , Dosificación Radioterapéutica , Carcinoma Pulmonar de Células Pequeñas/terapia , Adulto , Anciano , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Leucopenia/etiología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonía/etiología , Estudios Prospectivos , Fibrosis Pulmonar/etiología , Informe de Investigación , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
No evidence exists concerning the effect of airborne particulate matter of 1 µm or less (PM1) on blood pressure of young adults planning for pregnancy. We collected health examination information of about 1.2 million couples (aged 18-45 years) from a national birth cohort in China from Jan 1, 2013 to Oct 1, 2014 and matched their home address to daily PM1 and PM2.5 concentrations, which were predicted by remote sensing information. Generalized additive mixed models were used to analyze associations between long-term exposure to PM and blood pressure, after controlling for individual factors. A 10 µg/m3 increase in PM1 was associated with increased systolic blood pressure (SBP) for 0.26 (95%CI: 0.24, 0.29) mmHg in females and 0.29 (95%CI: 0.26, 0.31) mmHg in males, respectively. PM1 was also associated with increased DBP for 0.22 (95%CI: 0.20, 0.23) mmHg in females and 0.17 (95%CI: 0.15, 0.19) mmHg in males, respectively. Similar effects on blood pressure were found for PM2.5, meanwhile, the effect of PM2.5 on SBP increased with the scale of PM1 included in PM2.5 (p for interaction term <0.01). In summary, long-term exposure to PM1 as well as PM2.5 was associated with increased SBP and DBP of Chinese young adults planning for pregnancy.
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Contaminantes Atmosféricos , Contaminación del Aire , Presión Sanguínea , Material Particulado , Adolescente , Adulto , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/análisis , Pueblo Asiatico , China , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Material Particulado/análisis , Material Particulado/toxicidad , Adulto JovenRESUMEN
In order to predict the effects of climate change on the global carbon cycle, it is crucial to understand the environmental factors that affect soil carbon storage in grasslands. In the present study, we attempted to explain the relationships between the distribution of soil carbon storage with climate, soil types, soil properties and topographical factors across different types of grasslands with different grazing regimes. We measured soil organic carbon in 92 locations at different soil depth increments, from 0 to 100â¯cm in southwestern China. Among soil types, brown earth soils (Luvisols) had the highest carbon storage with 19.5⯱â¯2.5â¯kgâ¯m-2, while chernozem soils had the lowest with 6.8⯱â¯1.2â¯kgâ¯m-2. Mean annual temperature and precipitation, exerted a significant, but, contrasting effects on soil carbon storage. Soil carbon storage increased as mean annual temperature decreased and as mean annual precipitation increased. Across different grassland types, the mean carbon storage for the top 100â¯cm varied from 7.6⯱â¯1.3â¯kgâ¯m-2 for temperate desert to 17.3⯱â¯2.9â¯kgâ¯m-2 for alpine meadow. Grazing/cutting regimes significantly affected soil carbon storage with lowest value (7.9⯱â¯1.5â¯kgâ¯m-2) recorded for cutting grass, while seasonal (11.4⯱â¯1.3â¯kgâ¯m-2) and year-long (12.2⯱â¯1.9â¯kgâ¯m-2) grazing increased carbon storage. The highest carbon storage was found in the completely ungrazed areas (16.7⯱â¯2.9â¯kgâ¯m-2). Climatic factors, along with soil types and topographical factors, controlled soil carbon density along a soil depth in grasslands. Environmental factors alone explained about 60% of the total variation in soil carbon storage. The actual depth-wise distribution of soil carbon contents was significantly influenced by the grazing intensity and topographical factors. Overall, policy-makers should focus on reducing the grazing intensity and land conversion for the sustainable management of grasslands and C sequestration.
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Carbono , Suelo , Ciclo del Carbono , China , Pradera , PoaceaeRESUMEN
Here an efficient copper-catalyzed cascade cyclization of azide-ynamides via α-imino copper carbene intermediates is reported, representing the first generation of α-imino copper carbenes from alkynes. This protocol enables the practical and divergent synthesis of an array of polycyclic N-heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities. Moreover, an asymmetric azide-ynamide cyclization has been achieved with high enantioselectivities (up to 98:2 e.r.) by employing BOX-Cu complexes as chiral catalysts. Thus, this protocol constitutes the first example of an asymmetric azide-alkyne cyclization. The proposed mechanistic rationale for this cascade cyclization is further supported by theoretical calculations.
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BACKGROUND: The glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process. METHODS: The temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases. RESULTS: The results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function. CONCLUSIONS: This study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.
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Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/metabolismo , Macrófagos/metabolismo , Microglía/metabolismo , Animales , Femenino , Fuerza de la Mano/fisiología , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China. METHODS: Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record Abstraction Forms (MERAFs), which were collated for analysis. RESULTS: Overall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs. CONCLUSIONS: Findings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results.
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Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Encuestas de Atención de la Salud , Neoplasias Pulmonares/epidemiología , Pautas de la Práctica en Medicina , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , China/epidemiología , Femenino , Pruebas Genéticas , Variación Genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Estadificación de NeoplasiasRESUMEN
Canopy temperature is a result of the canopy energy balance and is driven by climate conditions, plant architecture, and plant-controlled transpiration. Here, we evaluated canopy temperature in a rubber plantation (RP) and tropical rainforest (TR) in Xishuangbanna, southwestern China. An infrared temperature sensor was installed at each site to measure canopy temperature. In the dry season, the maximum differences (Tc - Ta) between canopy temperature (Tc) and air temperature (Ta) in the RP and TR were 2.6 and 0.1 K, respectively. In the rainy season, the maximum (Tc - Ta) values in the RP and TR were 1.0 and -1.1 K, respectively. There were consistent differences between the two forests, with the RP having higher (Tc - Ta) than the TR throughout the entire year. Infrared measurements of Tc can be used to calculate canopy stomatal conductance in both forests. The difference in (Tc - Ta) at three gc levels with increasing direct radiation in the RP was larger than in the TR, indicating that change in (Tc - Ta) in the RP was relatively sensitive to the degree of stomatal closure.
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Hevea , Bosque Lluvioso , Temperatura , Cambio Climático , Hevea/fisiología , Rayos Infrarrojos , Hojas de la Planta/fisiología , Transpiración de Plantas , Estaciones del Año , Árboles/fisiología , Clima TropicalRESUMEN
BACKGROUND/AIMS: Salvianolic acid B (Sal B), a major polyphenolic compound of Salvia miltiorrhiza Bunge, has been shown to possess potential antidiabetic activities. However, the action mechanism of SalB in type 2 diabetes has not been investigated extensively. The present study was designed to investigate the effects of Sal B on diabetes-related metabolic changes in a spontaneous model of type 2 diabetes, as well as its potential molecular mechanism. METHODS: Male C57BL/KsJ-db/db mice were orally treated with Sal B (50 and 100 mg/kg) or metformin (positive drug, 300 mg/kg) for 6 weeks. RESULTS: Both doses of Sal B significantly decreased fasting blood glucose, serum insulin, triglyceride and free fatty acid levels, reduced hepatic gluconeogenic gene expression and improved insulin intolerance in db/db mice. High dose Sal B also significantly improved glucose intolerance, increased hepatic glycolytic gene expression and muscle glycogen content, and ameliorated histopathological alterations of pancreas, similar to metformin. Sal B treatment resulted in increased phosphorylated AMP-activated protein kinase (p-AMPK) protein expression in skeletal muscle and liver, increased glucose transporter 4 (GLUT4) and glycogen synthase protein expressions in skeletal muscle, and increased peroxisome proliferator-activated receptor alpha (PPARα) and phosphorylated acetyl CoA carboxylase (p-ACC) protein expressions in liver. CONCLUSION: Our data suggest that Sal B displays beneficial effects in the prevention and treatment of type 2 diabetes at least in part via modulation of the AMPK pathway.
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Proteínas Quinasas Activadas por AMP/metabolismo , Benzofuranos/uso terapéutico , Dislipidemias/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Transducción de Señal , Animales , Benzofuranos/química , Benzofuranos/farmacología , Peso Corporal/efectos de los fármacos , Dislipidemias/sangre , Dislipidemias/complicaciones , Dislipidemias/genética , Regulación de la Expresión Génica/efectos de los fármacos , Gluconeogénesis/efectos de los fármacos , Glucosa/metabolismo , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/complicaciones , Intolerancia a la Glucosa/tratamiento farmacológico , Intolerancia a la Glucosa/genética , Transportador de Glucosa de Tipo 4/metabolismo , Glucógeno/metabolismo , Glucógeno Sintasa/metabolismo , Glucólisis/efectos de los fármacos , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Hiperglucemia/genética , Hiperinsulinismo/sangre , Hiperinsulinismo/complicaciones , Hiperinsulinismo/tratamiento farmacológico , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/enzimología , PPAR alfa/metabolismo , Páncreas/efectos de los fármacos , Páncreas/patología , Fosforilación/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: The objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2 ), an important isoform of PLA2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of spinal cord injury (SCI). METHODS: A combination of molecular, histological, immunohistochemical, and behavioral assessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduced cell death, protected spinal cord tissue, and improved behavioral recovery after a contusive SCI performed at the 10th thoracic level in adult mice. RESULTS: SCI significantly increased cPLA2 expression and activation. Activated cPLA2 was localized mainly in neurons and oligodendrocytes. Notably, the SCI-induced cPLA2 activation was mediated by the extracellular signal-regulated kinase signaling pathway. In vitro, activation of cPLA2 by ceramide-1-phosphate or A23187 induced spinal neuronal death, which was substantially reversed by arachidonyl trifluoromethyl ketone, a cPLA2 inhibitor. Remarkably, blocking cPLA2 pharmacologically at 30 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced cell loss and tissue damage after SCI. INTERPRETATION: cPLA2 may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary tissue damage and promoting recovery of function after SCI.
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Marcación de Gen/métodos , Fosfolipasas A2 Grupo IV/antagonistas & inhibidores , Fosfolipasas A2 Grupo IV/genética , Traumatismos de la Médula Espinal/enzimología , Traumatismos de la Médula Espinal/genética , Animales , Butadienos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Activación Enzimática/genética , Inhibidores Enzimáticos/administración & dosificación , Femenino , Regulación Enzimológica de la Expresión Génica , Fosfolipasas A2 Grupo IV/deficiencia , Inyecciones Espinales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Nitrilos/administración & dosificación , Proyectos Piloto , Ratas , Ratas Sprague-Dawley , Médula Espinal/citología , Médula Espinal/enzimología , Médula Espinal/patología , Traumatismos de la Médula Espinal/patologíaRESUMEN
In this work, InGaN/GaN light-emitting diodes (LEDs) possessing varied quantum well (QW) numbers were systematically investigated both numerically and experimentally. The numerical computations show that with the increased QW number, a reduced electron leakage can be achieved and hence the efficiency droop can be reduced when a constant Shockley-Read-Hall (SRH) nonradiative recombination lifetime is used for all the samples. However, the experimental results indicate that, though the efficiency droop is suppressed, the LED optical power is first improved and then degraded with the increasing QW number. The analysis of the measured external quantum efficiency (EQE) with the increasing current revealed that an increasingly dominant SRH nonradiative recombination is induced with more epitaxial QWs, which can be related to the defect generation due to the strain relaxation, especially when the effective thickness exceeds the critical thickness. These observations were further supported by the carrier lifetime measurement using a pico-second time-resolved photoluminescence (TRPL) system, which allowed for a revised numerical modeling with the different SRH lifetimes considered. This work provides useful guidelines on choosing the critical QW number when designing LED structures.
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Axon regeneration in the central nervous system normally fails, in part because of a developmental decline in the intrinsic ability of CNS projection neurons to extend axons. Members of the KLF family of transcription factors regulate regenerative potential in developing CNS neurons. Expression of one family member, KLF7, is down-regulated developmentally, and overexpression of KLF7 in cortical neurons in vitro promotes axonal growth. To circumvent difficulties in achieving high neuronal expression of exogenous KLF7, we created a chimera with the VP16 transactivation domain, which displayed enhanced neuronal expression compared with the native protein while maintaining transcriptional activation and growth promotion in vitro. Overexpression of VP16-KLF7 overcame the developmental loss of regenerative ability in cortical slice cultures. Adult corticospinal tract (CST) neurons failed to up-regulate KLF7 in response to axon injury, and overexpression of VP16-KLF7 in vivo promoted both sprouting and regenerative axon growth in the CST of adult mice. These findings identify a unique means of promoting CST axon regeneration in vivo by reengineering a developmentally down-regulated, growth-promoting transcription factor.
Asunto(s)
Axones/fisiología , Factores de Transcripción de Tipo Kruppel/metabolismo , Regeneración Nerviosa/fisiología , Tractos Piramidales/fisiología , Animales , Axones/metabolismo , Células Cultivadas , Etopósido , Femenino , Expresión Génica , Ingeniería Genética , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Proteína Vmw65 de Virus del Herpes Simple/genética , Humanos , Inmunohistoquímica , Factores de Transcripción de Tipo Kruppel/genética , Mediciones Luminiscentes/métodos , Ratones , Ratones Endogámicos C57BL , Mutación , Regeneración Nerviosa/genética , Neuritas/metabolismo , Neuritas/fisiología , Neuronas/citología , Neuronas/metabolismo , Neuronas/fisiología , Tractos Piramidales/citología , Tractos Piramidales/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología , Activación TranscripcionalRESUMEN
In this research, a directional reduction charging structure was proposed to solve the problems caused by drilling and blasting method such as serious damage to surrounding rocks, working face low contour flatness and serious over-under break of root base c. Drilling and blasting tests, numerical calculations and field applications were designed and performed for the verification of the blasting advantages of charge structure. Test results showed that the peak positive strain along the protection direction of directional protection shaped charge was significantly smaller than that of ordinary charge, where PVC material presented the strongest effect such that the peak positive strain of specimen 1 at measuring point 4 (protection direction) was only 0.27 times that at measuring point 9 (non-protected direction). Numerical simulations indicated shaped jet formation, damage-reduction and charge penetration process and obtained the force law of cement target plate. Experimental results revealed that application of charge in tunnel controlled blasting achieved a clear controlling effect on contour line excavation. Compared with ordinary smooth blasting method, all technical indicators of the developed method were improved such that half hole mark rate was increased by about 33% and the amount of over-under break was decreased by about two times. Research results are of certain significance for the stability of surrounding reserved rocks and formation of roadway in blasting engineering and the developed method was found to be applicable to mining, shaft excavation and other projects.
RESUMEN
Unilateral calf atrophy may result from several medical conditions, such as lumbar radiculopathy, asymmetric myopathy/dystrophy, a Baker's (popliteal) cyst leading to tibial nerve compression, and disuse atrophy. We present a case series of four patients with unilateral calf atrophy, including chronic neurogenic atrophy (benign focal amyotrophy, one patient), tibial nerve compression at the popliteal fossa by a Baker's cyst (one patient), and disuse atrophy (two patients). All four patients underwent electrodiagnostic (EDX) studies, and two of them had denervation changes of the gastrocnemius. One patient underwent an ultrasound (US), which revealed a large cyst in the popliteal fossa causing compression of the tibial nerve. The differential diagnosis of unilateral calf atrophy as well as diagnostic techniques to confirm the underlying pathology are described. EDX and US studies are useful in differentiating between the varied conditions that may cause asymmetric calf muscle wasting.
RESUMEN
BACKGROUND: The inability to extend the fingers at the metacarpophalangeal and interphalangeal joints leads to finger drop. While wrist drop and foot drop are well recognized, the causes of finger drop are poorly understood. AIMS: This study describes the clinical, electrodiagnostic (EDX), and ultrasound (US) features in patients with finger drop. MATERIALS AND METHODS: This is a retrospective study of 87 patients presenting with finger drop and referred for EDX studies during the past 10 years. We analyzed the clinical picture, EDX data, and US findings. The patients were categorized into global (all five digits) or partial (limited to 1-4 digits) finger drop. RESULTS: Fifty-six (64%) patients had global finger drop, while 31 (36%) had partial finger drop. The frequent cause of finger drop was Parsonage-Turner syndrome (PTS) (29 [33%]), followed by trauma (23 [26%]), cervical radiculopathy (16 [18%]), extensor tendon rupture (four [4%]), and compression/entrapment (two [2%]). In 13 (15%) patients, no cause was identified. A total of 13/16 (81%) patients with cervical radiculopathy and four of the patients with tendon rupture had partial finger drop, while 52/64 (81%) with posterior interosseous nerve (PIN) neuropathy had global finger drop. Of the 16 patients who experienced cervical radiculopathy as the cause of the finger drop, 15 patients had C7 and C8 radiculopathy and one patient had C7 radiculopathy. EDX studies of patients with PTS revealed partial axon loss in 18 (62%) patients, conduction block in eight (28%), and total axon loss in four (14%). Enlarged fascicles were observed by US in 40% of patients with PTS. EDX studies of patients who sustained iatrogenic nerve injury causing finger drop demonstrated total axon loss in six (46%) patients, partial axon loss in four (31%), demyelination in two (15%), and conduction block in two (15%). CONCLUSIONS: PIN neuropathy is the most common cause of finger drop, however, lesser-known causes such as cervical radiculopathy and extensor tendon rupture should also be considered. Global finger drop is suggestive of PIN neuropathy, while partial finger drop occurs more often in cervical radiculopathy and tendon rupture. EDX and US studies provide valuable information for localizing the lesion site and may reveal the cause of the finger drop.