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In this work, the perfluorobenzene-bonded silica sorbent was tested to adsorb polycyclic aromatic hydrocarbons in hexane. In the comparison experiments, the perfluorobenzene-bonded sorbent's performance was better than octadecyl silica sorbent and phenyl-bonded silica sorbents, which indicated that the π-hole···π bonds between perfluorobenzene and the polycyclic aromatic hydrocarbons were stronger than π···π interactions and hydrophobic interactions in hexane. Then the perfluorobenzene-bonded silica sorbent was applied to solid-phase extraction of 15 polycyclic aromatic hydrocarbons from the hexane extracts of soil samples directly without the solvent replacement, which simplified the soil pretreatment process. And the results showed that under the optimal conditions, the proposed method for the determination of polycyclic aromatic hydrocarbons in the environment soil presented good recoveries and stabilities for the 10 heavier polycyclic aromatic hydrocarbons with the recoveries ranging from 75.1% to 104.6% and the relative standard deviations being in the range of 1.4%-5.8%. The limits of detection of the method varied from 0.1 to 2 ng/g. This work reveals the great application potential of the π-hole bond as a new retention mechanism in the field of solid-phase extraction.
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Sustained expression of B-cell receptor (BCR) critically contributes to the development of diffuse large B-cell lymphoma (DLBCL). However, little is known on the mechanism regulating BCR expression. In the present study, we explored the biological significance of functional intergenic repeating RNA element (FIRRE) in DLBCL and its regulation on BCR. Functional impacts of FIRRE on cell viability, transformation, and apoptosis were examined by MTT, colony formation, and flow cytometry, respectively. The interaction between FIRRE and polypyrimidine tract binding protein 1 (PTBP1) was identified by RNA pull-down and verified using RNA immunoprecipitation (RIP) assays. The effects of FIRRE and PTBP1 on Smurf2 mRNA were examined by RIP, RNA pull-down, and mRNA stability assays. Smurf2-mediated BCR ubiquitination was investigated using co-immunoprecipitation, ubiquitination, and protein stability assays. In vivo, xenograft models were used to assess the impacts of targeting FIRRE on DLBCL growth. FIRRE was specifically up-regulated in and essentially maintained multiple malignant behaviors of BCR-dependent DLBCL cells. Through the interaction with PTBP1, FIRRE promoted the mRNA decay of Smurf2, a ubiquitin ligase for the degradation BCR protein. Targeting FIRRE was sufficient to regulat Smurf2 and BCR expressions and inhibit DLBCL malignancy both in vivo and in vitro. FIRRE-PTBP1 interaction, by simulating Smurf2 mRNA decay and stabilizing BCR, promotes the development of DLBCL. Consequently, targeting this signaling mechanism may provide therapeutic benefits for DLBCL.
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Ribonucleoproteínas Nucleares Heterogéneas , Linfoma de Células B Grandes Difuso , Proteína de Unión al Tracto de Polipirimidina , ARN Largo no Codificante , Receptores de Antígenos de Linfocitos B , Ubiquitina-Proteína Ligasas , Línea Celular Tumoral , Ribonucleoproteínas Nucleares Heterogéneas/genética , Humanos , Ligasas/metabolismo , Linfoma de Células B Grandes Difuso/patología , Proteína de Unión al Tracto de Polipirimidina/genética , ARN Largo no Codificante/genética , ARN Mensajero , Receptores de Antígenos de Linfocitos B/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: For patients with spinal canal stenosis in the upper cervical spine who undergo C3-7 laminoplasty alone, it remains impossible to achieve full decompression due to its limited range. This study explores the extension of expansive open-door laminoplasty (EODL) to C1 and C2 for the treatment of cervical spinal stenosis of the upper cervical spine and its effects on cervical sagittal parameters. METHODS: A retrospective analysis of 33 patients presenting with symptoms of cervical spondylosis myelopathy (CSM) and ossification in the posterior longitudinal ligament (OPLL) of the upper cervical spine from February 2013 to December 2015 was performed. Furthermore, the changes in the C0-2 Cobb angle, C1-2 Cobb angle, C2-7 Cobb angle, C2-7 SVA, and T1-Slope in lateral X-rays of the cervical spine were measured before, immediately after, and 1 year after the operation. JOA and NDI scores were used to evaluate spinal cord function. RESULTS: The C0-2 and C1-2 Cobb angles did not significantly increase (P = 0.190 and P = 0.081), but the C2-7 Cobb angle (P = 0.001), C2-7 SVA (P < 0.001), and T1-Slope (P < 0.001) significantly increased from preoperative to 1 year postoperative. In addition, C2-7 SVA was significantly correlated with the T1-Slope (Pearson = 0.376, P < 0.001) and C0-2 Cobb angle (Pearson = 0.287, P = 0.004), and the C2-7 SVA was negatively correlated with the C2-7 Cobb angle (Pearson = - 0.295, P < 0.001). The average preoperative and postoperative JOA scores were 8.3 ± 1.6 and 14.6 ± 1.4 points, respectively, indicating in a postoperative neurological improvement rate of approximately 91.6%. The average preoperative and final follow-up NDI scores were 12.62 ± 2.34 and 7.61 ± 1.23. CONCLUSIONS: The sagittal parameters of patients who underwent EODL extended to C1 and C2 included loss of cervical curvature, increased cervical anteversion and compensatory posterior extension of the upper cervical spine to maintain visual balance in the field of vision. However, the changes in cervical spine parameters were far less substantial than the alarm thresholds reported in previous studies. We believe that EODL extended to C1 and C2 for the treatment of patients with spinal canal stenosis in the upper cervical spine is a feasible and safe procedure with excellent outcomes.
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Vértebras Cervicales/diagnóstico por imagen , Descompresión Quirúrgica/métodos , Laminoplastia/métodos , Osificación del Ligamento Longitudinal Posterior/cirugía , Compresión de la Médula Espinal/cirugía , Espondilosis/cirugía , Anciano , Vértebras Cervicales/cirugía , Descompresión Quirúrgica/efectos adversos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Laminoplastia/efectos adversos , Masculino , Persona de Mediana Edad , Osificación del Ligamento Longitudinal Posterior/complicaciones , Periodo Posoperatorio , Radiografía , Estudios Retrospectivos , Compresión de la Médula Espinal/etiología , Espondilosis/complicaciones , Resultado del TratamientoRESUMEN
Both phototropins (phot1 and phot2) and cryptochromes (cry1 and cry2) were proven as the Arabidopsis thaliana blue light receptors. Phototropins predominately function in photomovement, and cryptochromes play a role in photomorphogenesis. Although cryptochromes have been proposed to serve as positive modulators of phototropic responses, the underlying mechanism remains unknown. Here, we report that depleting sucrose from the medium or adding gibberellic acids (GAs) can partially restore the defects in phototropic curvature of the phot1 phot2 double mutants under high-intensity blue light; this restoration does not occur in phot1 phot2 cry1 cry2 quadruple mutants and nph3 (nonphototropic hypocotyl 3) mutants which were impaired phototropic response in sucrose-containing medium. These results indicate that GAs and sucrose antagonistically regulate hypocotyl phototropism in a cryptochromes dependent manner, but it showed a crosstalk with phototropin signaling on NPH3. Furthermore, cryptochromes activation by blue light inhibit GAs synthesis, thus stabilizing DELLAs to block hypocotyl growth, which result in the higher GAs content in the shade side than the lit side of hypocotyl to support the asymmetric growth of hypocotyl. Through modulation of the abundance of DELLAs by sucrose depletion or added GAs, it revealed that cryptochromes have a function in mediating phototropic curvature.
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Arabidopsis/metabolismo , Criptocromos/metabolismo , Hipocótilo/metabolismo , Hipocótilo/fisiología , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Criptocromos/genética , Fototropinas/metabolismo , Fototropinas/fisiología , Fototropismo/fisiología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
OBJECTIVE: To monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer (mGC). DESIGN: Targeted sequencing of 416 clinically relevant genes was performed in 78 paired plasma and tissue biopsy samples to determine plasma-tissue concordance. Then, we performed longitudinal analyses of 97 serial plasma samples collected from 24 patients who were HER2+ to track the resistance during trastuzumab treatment and validated the identified candidate resistance genes. RESULTS: The results from targeted sequencing-based detection of somatic copy number alterations (SCNA) of HER2 gene were highly consistent with fluorescence in situ hybridisation data, and the detected HER2 SCNA was better than plasma carcinoembryonic antigen levels at predicting tumour shrinkage and progression. Furthermore, most patients with innate trastuzumab resistance presented high HER2 SCNA during progression compared with baseline, while HER2 SCNA decreased in patients with acquired resistance. PIK3CA mutations were significantly enriched in patients with innate resistance, and ERBB2/4 genes were the most mutated genes, accounting for trastuzumab resistance in six (35.3%) and five (29.4%) patients in baseline and progression plasma, respectively. Patients with PIK3CA/R1/C3 or ERBB2/4 mutations in the baseline plasma had significantly worse progression-free survival. Additionally, mutations in NF1 contributed to trastuzumab resistance, which was further confirmed through in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade overcame trastuzumab resistance. CONCLUSION: Longitudinal circulating tumour DNA sequencing provides novel insights into gene alterations underlying trastuzumab resistance in HER2+mGC.
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Antineoplásicos Inmunológicos/uso terapéutico , Resistencia a Antineoplásicos/genética , Genes erbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Trastuzumab/uso terapéutico , Biomarcadores de Tumor/metabolismo , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Humanos , Biopsia Líquida , Mutación , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
BACKGROUND: As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development. AIMS: To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen. METHODS: We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis. RESULTS: After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin-eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened. CONCLUSIONS: We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice.
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Claudinas/genética , Modelos Animales de Enfermedad , Enteritis/genética , Eliminación de Gen , Intestino Delgado/patología , Ratones Noqueados/genética , Adenoma/inducido químicamente , Adenoma/diagnóstico por imagen , Adenoma/genética , Adenoma/patología , Animales , Western Blotting , Enteritis/inducido químicamente , Enteritis/diagnóstico por imagen , Enteritis/patología , Femenino , Hiperplasia/inducido químicamente , Hiperplasia/diagnóstico por imagen , Hiperplasia/genética , Hiperplasia/patología , Inmunohistoquímica , Neoplasias Intestinales/inducido químicamente , Neoplasias Intestinales/diagnóstico por imagen , Neoplasias Intestinales/genética , Neoplasias Intestinales/patología , Intestino Delgado/diagnóstico por imagen , Masculino , Ratones , Microscopía Electrónica de Rastreo , Fenotipo , Tamoxifeno/administración & dosificación , Uniones Estrechas/patologíaRESUMEN
X-linked inhibitor of apoptosis protein functions as an intrinsic regulator of apoptosis by inhibition of caspase activity and possesses a pivotal role in human cancer development and progression. A growing body of literature has demonstrated that microRNAs lead to the degradation or translational repression of messenger RNAs by binding to the non-coding region of messenger RNA at the 3'-untranslated region. Here, we revealed that the expression of HMGA2 is upregulated with X-linked inhibitor of apoptosis protein after transfection of X-linked inhibitor of apoptosis protein 3'-untranslated region in hepatocellular carcinoma cells, suggesting that X-linked inhibitor of apoptosis protein 3'-untranslated region serves as a competitor for microRNAs and prevent the co-targeted messenger RNA, HMGA2, from being suppressed. We further identified that let-7a-5p could bind to both the X-linked inhibitor of apoptosis protein 3'-untranslated region and HMGA2 3'-untranslated region. Moreover, we demonstrated that the forced expression of X-linked inhibitor of apoptosis protein 3'-untranslated region increases the oncogenicity of hepatocellular carcinoma cells in vitro. Cell functional analyses were performed to examine the association of HMGA2 status and X-linked inhibitor of apoptosis protein 3'-untranslated region. We have also measured the functional readout of let-7a-5p and HMGA2, an assay often employed to provide substantial evidence for the effects of X-linked inhibitor of apoptosis protein 3'-untranslated region on hepatocellular carcinoma cells. In general, our findings suggest that X-linked inhibitor of apoptosis protein 3'-untranslated region serves as a competitive endogenous RNA for HMGA2 to activate hepatocellular carcinoma progression by arresting endogenous let-7a-5p.
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Carcinoma Hepatocelular/genética , Proteína HMGA2/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Regiones no Traducidas 3' , Apoptosis/genética , Carcinoma Hepatocelular/patología , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologíaRESUMEN
BACKGROUND: The bone morphologies of intact knees were measured and compared between Chinese and Caucasian populations. However, to assess if distinct designs of implants are necessary for the Chinese population owing to different morphologies and sizes, the knee measurements after osteotomy performed in total knee arthroplasty were evaluated. METHODS: Thirty-seven Caucasian and 50 Chinese patients' knees were examined using computed tomography scans. Mimics were applied to reconstruct 3-dimensional bone models. Dimensions of the 3-dimensional knee models and simulated bone resections during total knee arthroplasty were measured using Geomagic Studio and Pro/ENGINEER. The morphologic measurements of the native and resected femur and tibia included the anteroposterior (AP) depth, mediolateral (ML) width, notch width, knee physical valgus angle, tibial slope angle, and the ML-to-AP ratio of the femur, tibia, and resected femur. Statistical analysis was performed using the independent samples t test and the Pearson correlation coefficient in SPSS for Windows. Values of P < .05 were considered significant. RESULTS: No measurements were significantly different between the Chinese and Caucasian knees. However, the Chinese female showed significant differences compared with the Chinese male on distal femoral measurements both presimulated and postsimulated osteotomy such as a smaller mean ML-to-AP ratio in presimulated (1.3 ± 0.1) and postsimulated (1.3 ± 0.1) osteotomy. CONCLUSION: The necessity of designing a full set of total knee components specifically for the Chinese population is still undetermined. However, we suggest designing femoral components specific for the Chinese females because of different postosteotomy distal femoral ML-to-AP ratio between the Chinese males and the Chinese females.
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Artroplastia de Reemplazo de Rodilla/métodos , Fémur/cirugía , Osteotomía/métodos , Tibia/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Pesos y Medidas Corporales , China , Femenino , Fémur/anatomía & histología , Humanos , Imagenología Tridimensional , Rodilla/anatomía & histología , Rodilla/cirugía , Articulación de la Rodilla/anatomía & histología , Articulación de la Rodilla/cirugía , Prótesis de la Rodilla , Masculino , Persona de Mediana Edad , Examen Físico , Tibia/anatomía & histología , Tomografía Computarizada por Rayos X , Población Blanca , Adulto JovenRESUMEN
BACKGROUND: The promotion effect on proliferation of Streptococcus thermophilus by enzymatic hydrolysates of aquatic products was firstly studied. The effect of influencing factors of the hydrolysis on the growth of S. thermophilus was investigated. RESULT: Grass Carp fish skin was hydrolysed to peptides by enzymatic hydrolysis using protease ProteAX, and for the S. thermophilus growth, the optimal enzymatic hydrolysis conditions were temperature of 60 °C, initial pH of 9.0, enzyme concentration of 10 g kg-1 , hydrolysis time of 80 min, and ratio of material to liquid of 1:2. The Grass Carp fish skin hydrolysate (GCFSH) prepared under the optimum conditions was fractionated to five fragments (GCFSH 1, GCFSH 2, GCFSH 3, GCFSH 4, GCFSH 5) according to molecular weight sizes, in which the fragments GCFSH 4 and GCFSH 5, with molecular weights of less than 1000 Da, significantly promoted the growth of S. thermophilus. CONCLUSION: The hydrolysis process of Grass Carp fish skin can be simplified, and the peptides with molecular weights below 1000 Da in the hydrolysates are the best nitrogen source for proliferation of S. thermophilus. This work can provide a fundamental theoretical basis for the production of multi-component functional foods, especially in milk drinks or yogurt. © 2017 Society of Chemical Industry.
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Carpas , Proteínas de Peces/química , Hidrolisados de Proteína/química , Piel/química , Streptococcus thermophilus/citología , Animales , Biocatálisis , Medios de Cultivo/química , Medios de Cultivo/metabolismo , Proteínas de Peces/metabolismo , Hidrólisis , Péptido Hidrolasas/química , Hidrolisados de Proteína/metabolismo , Streptococcus thermophilus/crecimiento & desarrollo , Streptococcus thermophilus/metabolismoRESUMEN
OBJECTIVE: To evaluate the effect of obesity on total knee arthroplasty, and on patient-reported outcomes. METHODS: The longitudinal study was conducted from September 2013 to August 2015 at The Second Hospital of Jinlin University, Changchun, Jinlin, China, a tertiary hospital. Using universal sampling method, all patients who underwent elective total knee arthroplasty were included in the study. Data was collected using a semi-structured questionnaire, Oxford Knee Score, and Short Form 12 Questionnaire. SPSS 19 was used for statistical analysis. RESULTS: Of the 183 patients, 104(57%) were obese and 79(43%) were non-obese. The mean age was 63.7 ± 8.4 years and 65.0 ± 8.8 years in obese and normal patients respectively (p=0.31). A statistically significant association was observed with regard to Oxford knee score in both groups of patients (p<0.05). Overall, 7(8.9%) patients from the non-obese category and 23(22.1%) from the obese category presented with local complications, while another 7(3.8%) patients had to undergo a revised surgery. CONCLUSIONS: It is very important to equate the outcomes of the surgery in obese and normal individuals.
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Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Obesidad/epidemiología , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , China , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Resultado del TratamientoRESUMEN
Weak gel with PAM cross-linked radical reaction was prepared by being incorporated to side chain of PAM. The structure, gel for ming process and the influence of NaCl concentration to apparent viscosity of gel were studied. The results show that the crosslinking ratios influence to crosslinking time, gel breaking time and gel strength. The crosslinking time decreases and gel strength slightly increases with increase of crosslinking ratio. Apparent viscosity of Polyacrylamide derivative crosslinking system increases with increase of NaCl concentration. The weak gel has good salt tolerance ability.
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BACKGROUND: B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. METHODS: Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. RESULTS: BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. CONCLUSIONS: The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer.
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Neoplasias de la Mama/genética , Carcinogénesis/genética , Carcinogénesis/metabolismo , Animales , Neoplasias de la Mama/patología , Movimiento Celular/genética , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , MicroARNs/genética , Invasividad Neoplásica/genética , Proteínas Proto-Oncogénicas c-bcl-6 , ARN Interferente Pequeño , Transducción de Señal/genéticaRESUMEN
To accurately estimate the age of individual tree and to achieve full-cycle sustainable management of natural Larix gmelinii forest in Great Xing'an Mountains of northeastern China, we constructed individual tree age prediction model using stepwise regression and random forest algorithms based on 44 fixed plots data and 280 stan-dard tree cores obtained from the Pangu Forest Farm. We analyzed the influence of stand structure, site conditions, and competition index on the accuracy of model prediction. The model was evaluated by the coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE). The results showed that the random forest model had the highest prediction accuracy when number of decision trees was 1500 and number of node con-tention variables was 8. The random forest model had better accuracy and prediction ability than the stepwise regression model, with R2, RMSE and MAE of 0.5882, 9.9259 a, 8.1155 a. Diameter at breast height was the most important factor affecting age prediction (83.8%), followed by tree height (34.4%), elevation (17.9%), and basal area per hectare (17.5%). The random forest algorithm exhibited better adaptability and modeling effect on constructing a predictive model for individual tree age. This research contributed to improving the accuracy of growth and harvest estimation for L. gmelinii, and could provide a reference for other scientific studies related to tree age estimation in forests.
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Algoritmos , Bosques , Larix , Larix/crecimiento & desarrollo , China , Conservación de los Recursos Naturales , Ecosistema , Modelos Teóricos , Bosques AleatoriosRESUMEN
Regenerating family protein 2 (Reg2) is a trophic factor which stimulates ß-cell replication and resists islet destruction. However, Reg2 also serves as an islet autoantigen, which makes it complicated to judge the effectiveness in treating diabetes. How Reg2 treatment behaves in non-obese diabetic (NOD) mice is to be investigated. NOD mice were treated with recombinant Reg2 protein, Complete Freund's adjuvant (CFA) + PBS and CFA+Reg2 vaccinations, CFA+PBS- and CFA+Reg2-immunized antisera, and single chain variable fragment (scFv)-Reg2 and mIgG2a-Reg2 antibodies. Glycemic level, bodyweight, serum Reg2 antibody titer, glucose tolerance, and insulin secretion were determined. Islet morphological characteristics, insulitis, cell apoptosis, islet cell components, and T cell infiltration were analyzed by histological examinations. The autoantigenicity of constructed Reg2C and Reg2X fragments was determined in healthy BALB/c mice, and the bioactivity in stimulating cell proliferation and survival was assessed in insulinoma MIN6 cells. Reg2 administration alleviated diabetes in NOD mice with improved glucose tolerance and insulin secretion but elevated serum Reg2 autoantibodies. Histomorphometry showed reduced inflammatory area, TUNEL signal and CD8 + T cell infiltration, and increased ß-cell proportion in support of the islet-protective effect of Reg2 treatment. CFA+PBS and CFA+Reg2 immunizations prevented diabetic onset and alleviated insulitis while injections of the antisera offered mild protections. Antibody treatments accelerated diabetic onset without increasing the overall incidence. Reg2C fragment depletes antigenicity, but reserves protective activity in streptozotocin (STZ)-treated MIN6 cells. In conclusion, Reg2 treatment alleviates type 1 diabetes (T1D) by preserving islet ß-cells, but induces Reg2 autoantibody production which poses a potential risk of accelerating diabetic progression.
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Autoanticuerpos , Islotes Pancreáticos , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Proteínas Asociadas a Pancreatitis , Animales , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Ratones , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Femenino , Proteínas Asociadas a Pancreatitis/inmunología , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/prevención & control , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Litostatina/inmunologíaRESUMEN
OBJECTIVE: As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure. METHODS: A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36-Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line-C7 plumbline [CSVL-C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow-up were compared to their preoperative results. RESULTS: Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p < 0.001). Meanwhile, CSVL-C7PL, SVA, and TK did not change much after surgery (p > 0.05) but improved significantly at follow-up (p < 0.001). There was no significant change in PI at either the postoperative or follow-up timepoint. The operation took 283.90 ± 81.62 min and resulted in a total blood loss of 257.27 ± 213.44 mL. No significant complications occurred. Patients were followed up for to 21.7 ± 9.8 months. VAS, ODI, and SF-36 scores improved considerably at postoperative and final follow-up compared to preoperative levels (p < 0.001). After surgery, the Cobb angle and LL angle had improved significantly compared to preoperative values (p < 0.001). CSVL-C7PL, SVA, and TK were stable after surgery (p > 0.05) but considerably improved during follow-up (p < 0.001). PI showed no significant change at either the postoperative or follow-up timepoints. CONCLUSION: Lateral lumbar intervertebral fusion treatment of DLS significantly improved sagittal and coronal balance of the lumbar spine, as well as compensatory thoracic scoliosis, with good clinical and radiological findings. Furthermore, there was less blood, less trauma, and quicker recovery from surgery.
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Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.
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Bacteriófagos , Bacteriófagos/genética , Ecosistema , Fósforo , Metagenoma/genética , SueloRESUMEN
BACKGROUND: The aim of this study was to investigate the effect of C-reactive protein/oxidised low-density lipoprotein/ß2-glycoprotein I (CRP/oxLDL/ß2GPI) complex on atherosclerosis (AS) in diabetic BALB/c mice. METHODS: BALB/c mice were fed high-fat and normal diet. Eight weeks later, the mice fed with high-fat diet were injected with streptozotocin (STZ) to induce diabetes. The diabetic mice were respectively injected twice monthly with 20 µg oxLDL, 20 µg ß2GPI, 40 µg oxLDL/ß2GPI complex, 44 µg CRP/oxLDL/ß2GPI complex, and PBS. Aortas were stained with Sudan IV to investigate lipid plaque formation. The infiltration condition of smooth muscle cells (SMCs), macrophages, and T cells in the aortas were determined by immunohistochemistry (IH). The mRNA expressions of receptors associated with lipid metabolism were quantified by real-time PCR. The phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and MKK3/6 in aorta tissues were assessed by Western blot. The expression of inflammation cytokines was evaluated by protein chip. RESULTS: The lipid plaques were more extensive, the lumen area was obviously narrower, the ratio of intima and media thickness were increased, and the normal internal elastic lamia structure and endothelial cell disappeared (P < 0.05) in the oxLDL and CRP/oxLDL/ß2GPI groups (P < 0.05). CRP/oxLDL/ß2GPI complex dramatically promoted infiltration of SMCs, macrophages, and T cells, improved the mRNA expression of ABCA1 and ABCG1, but reduced the mRNA expression of SR-BI and CD36 and increased the phosphorylation of p38MAPK and MKK3/6 (all P < 0.05). The highest expression levels of IL-1, IL-9, PF-4, bFGF, and IGF-II were detected in the CRP/oxLDL/ß2GPI group (P < 0.05). CONCLUSIONS: CRP/oxLDL/ß2GPI complex aggravated AS in diabetic BALB/c mice by increasing lipid uptake, the mechanism of which may be mediated by the p38MAPK signal pathway.
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Aterosclerosis/etiología , Aterosclerosis/genética , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/genética , Placa Aterosclerótica/etiología , Placa Aterosclerótica/genética , Transducción de Señal , Animales , Aorta/metabolismo , Aorta/patología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Proteína C-Reactiva/farmacología , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Dieta Alta en Grasa , Regulación de la Expresión Génica , Lipoproteínas LDL/farmacología , MAP Quinasa Quinasa 3/genética , MAP Quinasa Quinasa 3/metabolismo , MAP Quinasa Quinasa 6/genética , MAP Quinasa Quinasa 6/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Estreptozocina , Linfocitos T/metabolismo , Linfocitos T/patología , beta 2 Glicoproteína I/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVE: To evaluate the relationship between cardiovascular risk factors and cognitive function in a healthy population. METHODS: A community-based cross-sectional study was conducted in Shenyang. The Framingham gender-specific risk equation was employed to evaluate the cardiovascular risk factors, calculate Framingham risk score and estimate the risk of 10-year coronary heart disease (CHD). A total of 505 study subjects were divided into 3 groups according to 10-year CHD risk: low risk(<10%), moderate risk (10%-20%) and high risk groups(>20%). They were also divided into 5 groups according to age; ≤ 44 year old; 45-54 year old; 55-64 year old; 65-74 year old and ≥ 75 years old. Clock drawing test and mini-mental state examination (MMSE) were used to evaluate the cognitive function and compare it among different risk groups. And correlation coefficients between Framingham risk score and cognitive function were calculated. RESULTS: Framingham risk score, clock drawing test sore and MMSE score in the low risk group was (2.6 ± 0.8), (4 ± 1) and (27 ± 3). In comparison to low risk group, Framingham risk score increased significantly (P < 0.01), MMSE score(25 ± 4) decreased significantly (P < 0.01) in moderate risk group, Framingham risk score (9.7 ± 1.0) increased significantly (P < 0.05) and clock drawing test scores (3 ± 1) and MMSE scores (23 ± 4) decreased significantly (P < 0.05) in high risk group; in comparison to moderate risk group, clock drawing test and MMSE scores decreased significantly (P < 0.05) in high risk group. There was a significantly inverse correlation between Framingham risk score and cognitive function. And the Pearson correlation coefficients were -0.196(clock drawing test, P < 0.01) and -0.333 (MMSE, P < 0.01) . CONCLUSIONS: An inverse correlation exists between cardiovascular risk factors and cognitive function in healthy population. With more risk factors and greater severity, Framingham risk score increases while cognitive function decreases.
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Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/psicología , Cognición , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores de RiesgoRESUMEN
As an important commercial form of vanadium, vanadium pentoxide (V2O5) is widely used in various modern industries, and its environmental impacts and ecotoxicity have been extensively studied. In this research, the ecotoxicity of V2O5 to earthworms (Eisenia fetida) in soil was tested by exposure to V2O5 at a series of doses, and biochemical response indices, such as the superoxide dismutase (SOD) and catalase (CAT) enzyme activity and malondialdehyde (MDA) content, were analysed to determine the mechanism by which antioxidant enzymes respond to V2O5 exposure. The bioaccumulation factor (BAF) of vanadium pentoxide in the earthworms and soil was also measured to explore the bioaccumulation process of V2O5 in the test period. The results showed that the acute and subchronic lethal toxicity values of V2O5 towards E. fetida were 21.96 mg/kg (LC50, 14 days) and 6.28 mg/kg (LC10, 28 days), respectively. For the antioxidant enzymes, SOD and CAT were synchronously induced or inhibited within the time period, and the enzyme activity had a dose-effect relationship with the V2O5 concentration. MDA analysis indicated that lipid peroxidation in earthworms mainly occurred at the early stage and was eliminated slowly in the later stage during the test time. In addition, the BAFs were much less than 1, which indicated that V2O5 did not easily accumulate in earthworms, and the BAF was positively correlated with the exposure time and negatively linearly correlated with the V2O5 concentration in the soil. These results indicated that the bioconcentration and metabolic mechanism of V2O5 in earthworms differed with the different exposure concentrations, and bioaccumulation became balanced after 14-28 days in earthworms exposed to a relatively lower dose of V2O5. The analysis of the integrated biomarker response (IBR) index indicated that the trends of IBR values were positively related to the changing V2O5 concentration, and the IBR index could reflect the organism's sensitivity to the external stimulus of V2O5. The toxicity of V2O5 is mainly caused by V5+, which is also an important factor in formulating guidelines regarding vanadium levels in soil, and the test earthworm species (Eisenia fetida) is a sensitive biological indicator for risk assessments of vanadium oxidation in the soil.
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Oligoquetos , Contaminantes del Suelo , Animales , Antioxidantes/metabolismo , Bioacumulación , Suelo/química , Vanadio/toxicidad , Vanadio/análisis , Contaminantes del Suelo/análisis , Catalasa/metabolismo , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , Biomarcadores/metabolismo , Malondialdehído/metabolismoRESUMEN
BACKGROUND: Intradural disc herniation(IDH) caused by trauma is a rare type of diseaseï¼which is difficult to diagnose clinically and is easily misdiagnosed. We received a patient with the disease, reported the case to share the process of diagnosis and treatment and put forward our own opinions, so as to increase the probability of correct diagnosis. CASE PRESENTATION: We report the case of a 48-year-old male who fell from a scaffold at a height of 2 m. Later, he developed low back pain, restricted movement, numbness and hyperalgesia of the lower left limb, and decreased left muscle strength. He was diagnosed with IDH. Treatment with posterior decompression and intramedullary decompression with pedicle screw internal fixation was performed. His postoperative course was uneventful, and he underwent regular follow up for 1 year. Good neurologic symptom improvement was achieved. CONCLUSIONS: IDH is rare, and comprehensive consideration and film reading can improve the correct diagnosis rate. Accurate diagnosis and early decompression of laminae and intramedullary decompression can lead to good recovery after neurologic impingement.