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Crossovers create genetic diversity and are required for equal chromosome segregation during meiosis. Crossover number and distribution are highly regulated by different mechanisms that are not yet fully understood, including crossover interference. The chromosome axis is crucial for crossover formation. Here, we explore the function of the axis protein ASYNAPSIS3. To this end, we use the allotetraploid species Brassica napus; due to its polyploid nature, this system allows a fine-grained dissection of the dosage of meiotic regulators. The simultaneous mutation of all four ASY3 alleles results in defective synapsis and drastic reduction of crossovers, which is largely rescued by the presence of only one functional ASY3 allele. Crucially, while the number of class I crossovers in mutants with two functional ASY3 alleles is comparable to that in wild type, this number is significantly increased in mutants with only one functional ASY3 allele, indicating that reducing ASY3 dosage increases crossover formation. Moreover, the class I crossovers on each bivalent in mutants with one functional ASY3 allele follow a random distribution, indicating compromised crossover interference. These results reveal the distinct dosage-dependent effects of ASY3 on crossover formation, and provide insights into the role of the chromosome axis in patterning recombination.
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Functional signals emerge from the structural network, supporting multiple cognitive processes through underlying molecular mechanism. The link between human brain structure and function is region-specific and hierarchical across the neocortex. However, the relationship between hierarchical structure-function decoupling and the manifestation of individual behavior and cognition, along with the significance of the functional systems involved, and the specific molecular mechanism underlying structure-function decoupling remain incompletely characterized. Here, we used the structural-decoupling index (SDI) to quantify the dependency of functional signals on the structural connectome using a significantly larger cohort of healthy subjects. Canonical correlation analysis (CCA) was utilized to assess the general multivariate correlation pattern between region-specific SDIs across the whole brain and multiple cognitive traits. Then, we predicted five composite cognitive scores resulting from multivariate analysis using SDIs in primary networks, association networks, and all networks, respectively. Finally, we explored the molecular mechanism related to SDI by investigating its genetic factors and relationship with neurotransmitter receptors/transporters. We demonstrated that structure-function decoupling is hierarchical across the neocortex, spanning from primary networks to association networks. We revealed better performance in cognition prediction is achieved by using high-level hierarchical SDIs, with varying significance of different brain regions in predicting cognitive processes. We found that the SDIs were associated with the gene expression level of several receptor-related terms, and we also found the spatial distributions of four receptors/transporters significantly correlated with SDIs, namely D2, NET, MOR, and mGluR5, which play an important role in the flexibility of neuronal function. Collectively, our findings corroborate the association between hierarchical macroscale structure-function decoupling and individual cognition and provide implications for comprehending the molecular mechanism of structure-function decoupling. PRACTITIONER POINTS: Structure-function decoupling is hierarchical across the neocortex, spanning from primary networks to association networks. High-level hierarchical structure-function decoupling contributes much more than low-level decoupling to individual cognition. Structure-function decoupling could be regulated by genes associated with pivotal receptors that are crucial for neuronal function flexibility.
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Conectoma , Neocórtex , Fenómenos Fisiológicos del Sistema Nervioso , Humanos , Imagen por Resonancia Magnética/métodos , Cognición/fisiología , Encéfalo/fisiología , Conectoma/métodos , Neocórtex/diagnóstico por imagenRESUMEN
Chromosome axis-associated HORMA domain proteins (HORMADs), e.g. ASY1 in Arabidopsis, are crucial for meiotic recombination. ASY1, as other HORMADs, is assembled on the axis at early meiosis and depleted when homologous chromosomes synapse. Puzzlingly, both processes are catalyzed by AAA+ ATPase PCH2 together with its cofactor COMET. Here, we show that the ASY1 remodeling complex is temporally and spatially differently assembled. While PCH2 and COMET appear to directly interact in the cytoplasm in early meiosis, PCH2 is recruited by the transverse filament protein ZYP1 and brought to the ASY1-bound COMET assuring the timely removal of ASY1 during chromosome synapsis. Since we found that the PCH2 homolog TRIP13 also binds to the ZYP1 homolog SYCP1 in mouse, we postulate that this mechanism is conserved among eukaryotes. Deleting the PCH2 binding site of ZYP1 led to a failure of ASY1 removal. Interestingly, the placement of one obligatory crossover per homologous chromosome pair, compromised by ZYP1 depletion, is largely restored in this separation-of-function zyp1 allele suggesting that crossover assurance is promoted by synapsis. In contrast, this zyp1 allele, similar to the zyp1 null mutant, showed elevated type I crossover numbers indicating that PCH2-mediated eviction of ASY1 from the axis restricts crossover formation.
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Proteínas de Arabidopsis , Arabidopsis , Emparejamiento Cromosómico , Animales , Ratones , Adenosina Trifosfatasas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sitios de Unión , Emparejamiento Cromosómico/genética , Meiosis/genética , Complejo Sinaptonémico/genética , Complejo Sinaptonémico/metabolismoRESUMEN
Ulcerative colitis (UC) is a complex inflammatory disease of colorectum that induces abnormal immune responses and severely affects the quality of life of the patients. Grape seed proanthocyanidin extract (GSPE) exerts anti-inflammatory and antioxidant functions in many inflammatory diseases. The objective of this study was to investigate the potential therapeutic effects and underlying mechanisms of GSPE in UC using a dextran sodium sulfate (DSS)-induced mouse UC model and a lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model. In this study, we found that the GSPE markedly prevented DSS-induced weight loss and colon length shortening in UC mice. Further investigations showed that GSPE significantly attenuated the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, and elevated the expression of anti-inflammatory cytokine IL-10 in the colon tissues and serum of DSS-induced colitis mice by suppressing NF-κB signaling pathway. Furthermore, LPS-induced inflammation in RAW264.7 cells was also reversed by GSPE. Taken together, our results confirm that GSPE can ameliorate inflammatory response in experimental colitis via inhibiting NF-κB signaling pathway. This study advances the research progress on a potentially effective therapeutic strategy for inflammatory bowel diseases.
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Colitis Ulcerosa , Extracto de Semillas de Uva , Proantocianidinas , Animales , Humanos , Ratones , Antiinflamatorios/uso terapéutico , Antiinflamatorios/toxicidad , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Lipopolisacáridos/toxicidad , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Calidad de Vida , Transducción de SeñalRESUMEN
OBJECTIVE: This study aims to elucidate a novel, minimally invasive surgical technique using a biportal endoscope for the implantation of spinal cord stimulation (SCS) paddle leads and to report the preliminary results of its clinical application. MATERIALS AND METHODS: The perioperative data of patients who underwent the biportal endoscopic SCS paddle lead implantation in our department were collected; the surgical procedure was delineated, and the clinical outcomes were assessed. RESULTS: From February 2022 to December 2023, six patients underwent biportal endoscopic SCS paddle lead implantation. The median follow-up time was nine months (range one to three months). The median intraoperative blood loss was 30 mL (range 25-50 mL), and the median operative time was 87.5 minutes (range 75-110 minutes). One patient experienced severe neck pain during the operation, whereas the other five patients experienced no surgical complications. One patient was found to have a slight lead migration three months after surgery, which did not affect the therapeutic effect. The median visual analogue scale (VAS) of the surgical area was 0.5 (range 0-2), 2.5 (range 1-4), and 0.5 (range 0-1) during the operation and one day and one week after the operation, respectively. The median VAS of the six patients' primary disease was 8 (range 7-9) before surgery and 2.5 (range 1-4) at the last postoperative follow-up (pain reduction ≥50%). CONCLUSION: Paddle lead systems for SCS can be implanted successfully using a biportal endoscopic technique.
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Electrodos Implantados , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/métodos , Estimulación de la Médula Espinal/instrumentación , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Resultado del Tratamiento , Endoscopía/métodos , Estudios de SeguimientoRESUMEN
As a valuable biomarker for various tumor, sensitive and reliable quantitative determination of microRNA (miRNA) is crucial for both disease diagnosis and cancer treatment. Herein, we depict a novel simple and sensitive miRNA detection approach by exploiting an elegantly designed target recognition initiated self-dissociation based DNA nanomachine. In this nanomachine, target recognition assists the formation of active DNAzyme secondary conformation, and the active DNAzyme generates a nicking site in H probe, initiating the self-assembly of H probe. With the reflexed sequences as primer, dual signal recycles are formed under the cooperation of DNA polymerase and Nb.BbvCI. Eventually, the method exhibits a high sensitivity with the limit of detection as low as 12 fM. In addition, the method is also demonstrated with a high selectivity that can distinguish one mismatched base pair. We believe the established approach can be a robust tool for the early-diagnosis of a variety of cancers and also in anticancer drug development.
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Técnicas Biosensibles , ADN Catalítico , MicroARNs , MicroARNs/genética , Técnicas Biosensibles/métodos , ADN , Límite de Detección , Técnicas de Amplificación de Ácido Nucleico/métodosRESUMEN
BACKGROUND: Although epidural analgesia is considered the gold standard for pain relief during labor and is safe for maternity and fetus, the association between the epidural analgesia and pelvic floor disorders remains unclear. Thus we estimate the association between epidural analgesia and early postpartum urinary incontinence (UI). METHODS: A propensity score-matched retrospective cohort study was conducted at a university-affiliated hospital in Shanghai, China. Primiparous women with term, singleton, and vaginal delivery between December 2020 and February 2022 were included. UI was self-reported by maternity at 42 to 60 days postpartum and was classified by International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). Using logistic regression models, the associations between epidural analgesia and early postpartum UI were assessed. RESULTS: Among 5190 participants, 3709 (71.5%) choose epidural anesthesia during labor. Analysis of the propensity-matched cohort (including 1447 maternal pairs) showed epidural anesthesia during labor was independently associated with UI in early postpartum period (aOR 1.50, 95% CI 1.24-1.81). This association was mainly contributed to stress UI (aOR 1.38, 95% CI 1.12-1.71) rather than urge UI (aOR 1.45, 95% CI 0.99-2.15) and mixed UI (aOR 1.52, 95% CI 0.95-2.45). Furthermore, we observed that the association between epidural anesthesia and UI was more pronounced among older women (≥ 35 y) and women with macrosomia (infant weight ≥ 4000 g), compared with their counterparts (both P for interaction < 0.01). After further analysis excluding the women with UI during pregnancy, the results remained largely consistent with the main analysis. CONCLUSIONS: The findings support that epidural anesthesia was associated with SUI in the early postpartum period.
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Analgesia Epidural , Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Embarazo , Lactante , Femenino , Humanos , Anciano , Analgesia Epidural/efectos adversos , Puntaje de Propensión , Estudios Retrospectivos , China/epidemiología , Incontinencia Urinaria de Esfuerzo/epidemiología , Incontinencia Urinaria de Esfuerzo/etiología , Periodo PospartoRESUMEN
BACKGROUND: Stress urinary incontinence (SUI) is a common public health issue that negatively impacts the quality of life for women worldwide, of which early detection and rehabilitation are consequently pivotal. The aim of this study is to establish a simple nomogram for identifying women at risk of postpartum SUI. METHODS: A retrospective study was conducted in a tertiary specialized hospital in Shanghai, China. The study included only women with singleton, full-term, and vaginal deliveries. 2,441 women who delivered from July 2019 to November 2019 were included in the training cohort, and 610 women who delivered from January 2022 to February 2022 were included in the validation cohort. SUI was determined by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Univariate and multifactorial logistical regression were used to identify independent risk factors for postpartum SUI and further construct the nomogram accordingly. Based on concordance statistics (C-statistics), calibration curves, and decision curve analyses, we evaluated the performance of the nomogram in the training cohort and the validation cohort. In addition, the model was validated internally in the training cohort through cross-validation. RESULTS: There were no significant statistically differences in important baseline data such as age, pre-pregnancy BMI, and parity between the training and validation cohorts. SUI was observed in 431 (17.6%) and 125 (20.5%) women in the training and validation cohorts, respectively. According to the regression analysis, age, parity, second stage of labor, infant weight, and forceps delivery were included in the nomogram. The nomogram had a C-statistic of 0.80 (95% confidence interval [CI] 0.74-0.85) for predicting SUI. C-statistics were stable in both internally cross-validated training cohort (mean 0.81) and validation cohort (0.83 [95% CI 0.79-0.87]). The nomogram's calibration curve was near the ideal diagonal line. Additionally, the model exhibited a positive net benefit from the decision curve analysis. CONCLUSION: We have created a nomogram that can be utilized to quantify the risk of postpartum SUI for women with vaginal delivery. The model might contribute to predicting early postpartum SUI, thereby facilitating the management of SUI.
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Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Embarazo , Femenino , Humanos , Masculino , Incontinencia Urinaria de Esfuerzo/diagnóstico , Incontinencia Urinaria de Esfuerzo/epidemiología , Incontinencia Urinaria de Esfuerzo/etiología , Estudios Retrospectivos , Calidad de Vida , Nomogramas , China/epidemiología , Parto Obstétrico/efectos adversos , Periodo Posparto , Incontinencia Urinaria/etiologíaRESUMEN
PURPOSE: This study aims to evaluate the efficacy and safety of the full-endoscopic lumbar discectomy (FELD) via lateral superior articular process (LSAP) approach and full-endoscopic transforaminal discectomy (FETD) for treating far lateral lumbar disk herniation (FFLDH). METHODS: From January 2020 to June 2022, patients who were diagnosed as FLLDH underwent the FELD via LSAP approach or FETD. The operation time, estimated blood loss, length of hospital stays, and complications were recorded. The visual analog scale (VAS) for back pain, VAS for leg pain, and the Oswestry Disability Index (ODI) scores was measured during preoperative and postoperative follow-up. RESULTS: Thirty-two patients were enrolled in this study, of which 12 patients were treated with the FELD via LSAP approach (LSAP-FELD group) and 20 patients underwent FETD (FETD group). The LSAP-FELD group exhibited significantly shorter operation times and hospital stays compared to the FETD group, while no statistically significant differences were observed in intraoperative blood loss and complication rates. There were no significant differences in the VAS for back pain, the VAS for leg pain, and the ODI score between the two groups preoperatively and three days, three months, and the last follow-up postoperatively. CONCLUSIONS: Both the FELD via LSAP approach and FETD have demonstrated favourable clinical efficacy in the treatment of FLLDH. Notably, the FELD via LSAP approach shows the advantages of shorter operation time and hospital stays.
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Desplazamiento del Disco Intervertebral , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/etiología , Estudios Retrospectivos , Vértebras Lumbares/cirugía , Discectomía/efectos adversos , Endoscopía/efectos adversos , Dolor de Espalda/etiología , Resultado del TratamientoRESUMEN
INTRODUCTION AND HYPOTHESIS: To evaluate the effect of the second stage of labor (SSL) lasting > 2 h on pelvic floor function. METHODS: This single-center prospective cohort study included primiparous women with SSL > 2 h treated at Tongji Hospital between January 2018 and December 2019 (case group). A matched group of women with similar newborn weight and SSL < 2 h were recruited simultaneously (control group). Stress urinary incontinence (SUI) and pelvic floor muscle (PFM) characteristics were measured at 6 weeks, 6 months, and finally 1 year postpartum. RESULTS: A total of 63 pairs of primiparous women completed 1-year follow-up. The incidence of SUI in the case group was significantly higher than that in the control group at 6 weeks postpartum (P = 0.020); however, the differences were not significant at 1 year postpartum (P=1.00). PFM endurance was significantly lower in the case group at 6 weeks (P = 0.000), 6 months (P = 0.000), and 1 year (P = 0.011) after childbirth. There was no difference in PFM strength between the two groups. The maximal voluntary contraction (MVC) of PFM was significantly lower in the case group at 6 weeks postpartum (P = 0.007), but the differences were not significant at 1 year postpartum (P = 0.197). PFM endurance and MVC were higher at 1 year than at 6 weeks postpartum in both groups. CONCLUSIONS: The SSL > 2 h increased the incidence of SUI at 6 weeks postpartum and decreased PFM endurance for 1 year.
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Diafragma Pélvico , Incontinencia Urinaria de Esfuerzo , Femenino , Humanos , Recién Nacido , Segundo Periodo del Trabajo de Parto , Contracción Muscular/fisiología , Fuerza Muscular/fisiología , Embarazo , Estudios Prospectivos , Incontinencia Urinaria de Esfuerzo/epidemiología , Incontinencia Urinaria de Esfuerzo/etiologíaRESUMEN
Microcystin-leucine-arginine (MC-LR) is a cyclic heptapeptide compound produced by cyanobacteria with strong cytotoxicity. Previous studies have confirmed that MC-LR could exert toxic effects on the genitourinary system, but there are few reports about its toxicity to the bladder. In this study, we investigated the effects of MC-LR on mouse bladder and human bladder epithelial cells (SV-HUC-1 cells). We observed that the bladder weight and the number of bladder epithelial cells were markedly increased in mice following chronic low-dose exposure to MC-LR. Further investigation showed that MC-LR activates AKT/NF-kB signaling pathway to induce the production of proinflammatory cytokines TNF-α and IL-6. In addition, the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in bladder tissue was increased and the relative migration and invasion capacities of SV-HUC-1 cells were enhanced upon exposure to MC-LR. In conclusion, these results suggest that chronic exposure to MC-LR induced epithelial hyperplasia and inflammation, upregulated the expression of matrix metalloproteinases (MMPs) and promoted the migration and invasion of bladder epithelial cells, which provides a basis for further exploring the potential mechanism by which environmental factors increasing the risk of bladder cancer.
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Metaloproteinasa 2 de la Matriz , Microcistinas , Animales , Arginina , Humanos , Hiperplasia , Inflamación/inducido químicamente , Interleucina-6 , Leucina , Metaloproteinasa 9 de la Matriz , Ratones , Microcistinas/toxicidad , FN-kappa B , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Necrosis Tumoral alfa , Vejiga Urinaria/metabolismoRESUMEN
The aim of this retrospective study was to assess the value of using an enema alone for mechanical bowel preparation (MBP) before transvaginal pelvic floor reconstruction (TPFR) in patients ≥65 years old. In total, 190 patients were included [81 in the enema group vs. 109 in the enema + polyethylene glycol (PEG) group]. The levels of serum potassium (p = .004) and calcium (p = .005) were higher in the enema group after surgery. The decrease in serum calcium was more significant in the enema + PEG group (p = .027). More patients in the enema + PEG group developed hypokalaemia (p = .035) or hypocalcaemia (p = .008) after surgery. The incidence of thrombus and surgical site infection was similar and earlier bowel movement was evident in the enema group (p = .000). Overall, the enema group used more laxatives (p = .026). Using enema alone before TPFR reduces the incidence of electrolyte disturbances with no increase in surgical complications in elderly patients.IMPACT STATEMENTWhat is already known on this subject? TPFR is an effective treatment for pelvic organ prolapse (POP) in elderly women. Bowel preparation performed before gynecological surgery can reduce surgical site infection, but increase discomfort and electrolyte disturbance.What do the results of this study add? The levels of serum potassium and calcium were lower in the enema + PEG group than in the enema group after surgery and more patients developed hypokalaemia or hypocalcaemia in the enema + PEG group. The incidence of thrombus and surgical site infection was similar between the two groups. Bowel movement was earlier in the enema group.What are the implications of these findings for clinical practice and/or future research? Using enema alone before TPFR reduces the incidence of electrolyte disturbance and does not increase surgical complications. This conclusion needs to be confirmed by random controlled trial studies in the future.
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Hipocalcemia , Hipopotasemia , Anciano , Calcio , Electrólitos , Enema/métodos , Femenino , Humanos , Hipopotasemia/tratamiento farmacológico , Laxativos/uso terapéutico , Diafragma Pélvico/cirugía , Polietilenglicoles/efectos adversos , Potasio , Estudios Retrospectivos , Infección de la Herida QuirúrgicaRESUMEN
BACKGROUND: Cytoplasmic male sterility (CMS), which naturally exists in higher plants, is a useful mechanism for analyzing nuclear and mitochondrial genome functions and identifying the role of mitochondrial genes in the plant growth and development. Polima (pol) CMS is the most universally valued male sterility type in oil-seed rape. Previous studies have described the pol CMS restorer gene Rfp and the sterility-inducing gene orf224 in oil-seed rape, located in mitochondria. However, the mechanism of fertility restoration and infertility remains unknown. Moreover, it is still unknown how the fecundity restorer gene interferes with the sterility gene, provokes the sterility gene to lose its function, and leads to fertility restoration. RESULT: In this study, we used multi-omics joint analysis to discover candidate genes that interact with the sterility gene orf224 and the restorer gene Rfp of pol CMS to provide theoretical support for the occurrence and restoration mechanisms of sterility. Via multi-omics analysis, we screened 24 differential genes encoding proteins related to RNA editing, respiratory electron transport chain, anther development, energy transport, tapetum development, and oxidative phosphorylation. Using a yeast two-hybrid assay, we obtained a total of seven Rfp interaction proteins, with orf224 protein covering five interaction proteins. CONCLUSIONS: We propose that Rfp and its interacting protein cleave the transcript of atp6/orf224, causing the infertility gene to lose its function and restore fertility. When Rfp is not cleaved, orf224 poisons the tapetum cells and anther development-related proteins, resulting in pol CMS mitochondrial dysfunction and male infertility. The data from the joint analysis of multiple omics provided information on pol CMS's potential molecular mechanism and will help breed B. napus hybrids.
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Brassica napus/genética , Flores/genética , Flores/ultraestructura , Genes de Plantas , Infertilidad Vegetal/genética , Polen/genética , Polen/ultraestructura , Metaboloma , Proteoma , TranscriptomaRESUMEN
The repair of bone defects with irregular shapes, particularly in a minimally invasive manner, remains a major challenge. For synthetic bone grafts, injectable hydrogels are superior to conventional scaffolds because they can adapt satisfactorily to the defect margins and can be injected into deeper areas of injury via a minimally invasive procedure. Based on the poly(lactide-co-glycolide)(PLGA)/1-methyl-2-pyrrolidinone solution reported in our previous study, we successfully synthesized injectable MgO/MgCO3@PLGA (PMM) hydrogels, namely, injectable biomimetic porous hydrogels (IBPHs), to accelerate bone regeneration. In addition to exhibiting excellent injectability, PMM hydrogels could transform into porous scaffolds in situ through a liquid-to-solid phase transition and completely fill irregular bone defects via their superb shape adaptability. Moreover, sustainable and steady release of Mg2+ was achieved by regulating the weight ratio of the incorporated MgO and MgCO3 particles. Via controlled release of Mg2+, PMM hydrogels significantly promoted proliferation, osteogenic differentiation, migration, and biomineral deposition of immortalized mouse embryonic fibroblasts. More importantly, micro-CT imaging and histological analysis indicated that concomitant with their gradual degradation, PMM hydrogels effectively stimulated in situ bone regeneration in rat calvarial defects with an increase in the bone volume fraction of almost 2-fold compared with that in the control group. These findings suggest that injectable PMM hydrogels can satisfactorily match bone defects and form porous scaffolds in situ and can significantly promote bone regeneration via controllable Mg2+ release. The remarkable features of IPBHs may open a new avenue for the exploration of in situ repair systems for irregular bone defects to accelerate bone regeneration and have great potential for clinical translation.
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Magnesio , Osteogénesis , Animales , Biomimética , Regeneración Ósea , Fibroblastos , Hidrogeles , Ratones , Porosidad , Ratas , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
OBJECTIVE AND DESIGN: Database screening indicated that tubulin polymerization-promoting protein 3 (TPPP3) was involved in pathogenesis of multiple cancer types. miR-1827 has a potential role in a variety of human cancers. However, the role of TPPP3 and its underlying molecular mechanism in endometrial cancer (EC) has not been investigated. Herein, we aimed to reveal the role of TPPP3/miR-1827 in EC progression. METHODS: Tumour tissue and whole blood samples were collected for the detection of TPPP3 expression. TPPP3 shRNAs and pcDNA-TPPP3 were applied to knockdown or upregulate the TPPP3 expression, and miR-1827 mimic was used to upregulate miR-1827 level. CCK-8 and colony assays were applied to estimate the cell proliferation. Wound healing and Transwell assays were conducted to assess the cell migration and invasion abilities. The dual-luciferase reporter assay was conducted to validate the putative binding site between TPPP3 and miR-1827. Expression of TPPP3, miR-1827 and related proteins in cell lines, tissue and whole blood sample were detected using western blot, RT-qPCR and immunofluorescence. RESULTS: TPPP3 was observed markedly elevated in EC patients and cells. TPPP3 knockdown displayed evident suppression in cell proliferation, migration and invasion in vitro and in vivo. Moreover, we identified TPPP3 as a direct and functional target gene of miR-1827 in EC cells. The miR-1827 induced regulatory effects on EC cells were partially reversed by TPPP3. Additionally, in vivo study confirmed the findings discovered in vitro. CONCLUSION: TPPP3 exerted oncogenic roles in EC progression by sponging miR-1827. This finding might provide potential targets for EC therapy.
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Movimiento Celular , Neoplasias Endometriales , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , MicroARNsRESUMEN
In this study, broilers were fed with heavy-metal-containing diets (Zn, Cu, Pb, Cr, As, Hg) at three rates (T1: 5 kg premix/ton feed, T2: 10 kg premix/ton feed and T3: 15 kg premix/ton feed) and Doxycycline (DOX) and Gatifloxacin (GAT) at low or high doses (T4: 31.2 mg DOX/bird/day and 78 mg GAT/bird/day, T5: 15.6 mg DOX/bird/day and 48 mg GAT/bird/day) to assess the accumulation of various heavy metals and the fate of two antibiotics in broiler manure after 35 days of aerobic composting. The results indicated that the two antibiotics changed quite differently during aerobic composting. About 14.96-15.84% of Doxycycline still remained at the end of composting, while Gatifloxacin was almost completely removed within 10 days of composting. The half-lives of Doxycycline were 13.75 and 15.86 days, while the half-lives of Gatifloxacin were only 1.32 and 1.38 days. Based on the Redundancy analysis (RDA), the concentration of antibiotics was significantly influenced by physico-chemical properties (mainly temperature and pH) throughout the composting process. Throughout the composting process, all heavy metal elements remained concentrated in organic fertilizer. In this study the Cr content reached 160.16 mg/kg, 223.98 mg/kg and 248.02 mg/kg with increasing premix feed rates, similar to Zn, which reached 258.2 mg/kg, 312.21 mg/kg and 333.68 mg/kg. Zn and Cr concentrations well exceeded the United States and the European soil requirements. This experiment showed that antibiotic residues and the accumulation of heavy metals may lead to soil contamination and pose a risk to the soil ecosystem.
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Doxiciclina/metabolismo , Gatifloxacina/metabolismo , Animales , Compostaje , Estiércol/microbiología , Metales Pesados/metabolismoRESUMEN
BACKGROUND: Aucubin (Au), an iridoid glycoside from natural plants, has antioxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in an H2O2-induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model. METHODS: In vitro experiments, the various concentrations of Au (50 µg/ml, 100 µg/ml, or 200 µg/ml) were added in culture medium at 0 h and 6 h after neurons stimulated by H2O2 (100 µM). After exposed for 12 h, neurons were collected for western blot (WB), immunofluorescence, and M29,79-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In vivo experiments, Au (20 mg/kg or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling. Brain water content, neurological deficits, and cognitive functions were measured at specific time, respectively. Cortical tissue around focal trauma was collected for WB, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry, and enzyme linked immunosorbent assay (ELISA) at 72 h after TBI. RNA interference experiments were performed to determine the effects of nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with Au (40 mg/kg) treatment. Mice were intracerebroventricularly administrated with lentivirus at 72 h before TBI establishment. The cortex was obtained at 72 h after TBI and used for WB and q-PCR. RESULTS: Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS), and reduced cell apoptosis both in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages, and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1 (HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au. CONCLUSIONS: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.
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Lesiones Traumáticas del Encéfalo/patología , Inflamación/patología , Glucósidos Iridoides/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Fármacos Neuroprotectores/farmacología , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Modelos Animales de Enfermedad , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To explore the value of a radiomics approach based on MRI texture analysis (TA) in identifying intraductal carcinoma of the prostate gland (IDCP). METHODS: MRI images of 56 patients with pathological proven prostate cancer were analyzed retrospectively, including 31 patients with pure prostate adenocarcinoma and 25 patients with IDCP component in the prostate adenocarcinoma lesions. After imaging features of lesions were analyzed, then enhanced arterial and venous phase images were imported into Omni-Kinetics software for the extraction the TA features of region of interests' lesion according to the T2-weighted imaging. In order to set up a regression prediction model which based on texture parameters and morphological features. Furthermore, the comparison of diagnostic accuracy of each TA regression models were assessed by operating characteristic curves (ROC). RESULTS: Among the imaging features of peripheral lesions, the incidence of surgical capsule invasion, prostatic capsule involvement, and seminal vesicle invasion in patients with IDCP was higher than that in patients with adenocarcinoma alone ( P<0.05). Among the imaging features of transitional zone lesions, patients with adenocarcinoma containing IDCP had a higher incience of imaging features as benign prostatic hyperplasia, extracapsular invasion of the prostate, seminal vesicles invasion, and vascular nerve bundles than that in pure adenocarcinoma group ( P<0.05). In order to differential diagnosis of simple adenocarcinoma and adenocarcinoma containing IDCP, 4 arterial phase texture features were used to build the regression model in the peripheral zone group, and the area under the curve ( AUC) of the TA model and combined model with or without seminal vesicles invasion were 0.890 and 0.938, respectively. In the transitional zone group, 2 arterial phase texture features and 2 venous phase features were used in TA regression model, and the AUC of texture model and the combined model with or without vascular nerve bundles were 0.844 and 0.901, respectively. CONCLUSION: The incidence of adenocarcinoma with IDCP is higher in high-grade invasive prostate cancer. It is wonderful that when compared with T2WI, enhanced sequential texture analysis is more valuable when using the radiomics approach based on MRI texture analysis in identifying IDCP in prostate cancer.
Asunto(s)
Carcinoma Intraductal no Infiltrante , Imagen por Resonancia Magnética , Neoplasias de la Próstata , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
BACKGROUND With the in-depth development of minimally invasive spine surgery in recent years, robot- and computer-assisted technologies have been increasingly used and successfully applied to spinal surgery. MATERIAL AND METHODS We performed a retrospective analysis of 60 patients with grade I or II lumbar spondylolisthesis who underwent minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) from January 2017 to December 2017. A robot-assisted surgical system was used in 30 patients for pedicle screw placement. The other 30 patients underwent fluoroscopy-guided percutaneous pedicle screw placement. RESULTS There were 130 screws placed under fluoroscopic guidance, with 26.2% penetration of the pedicle wall. There were 130 screws placed in robotic-assisted surgery, with 6.2% penetration of the pedicle wall. Severe screw deviation (Neo grade III) was identified in 4 screws in the fluoroscopy-guided group, while no severe deviation was noted in the robot-assisted group. In the fluoroscopic group, 15.6% of screws penetrated the superior articular process, and 2.1% screws had severe complications (Babu grade III). However, only 5.1% of screws in the robot-assisted group had severe complications. The mean screw insertion angle was significantly greater in the robot-assisted group than in the fluoroscopy-guided group (23.8±6.1° vs. 18.4±7.2°, P=0.017). CONCLUSIONS Compared to fluoroscopy-guided percutaneous pedicle screw placement, robot-assisted percutaneous pedicle screw placement has the following advantages: greater accuracy, lower incidences of screw penetration of the pedicle wall and invasion of the facet joints, and better screw insertion angle. Combined with MIS-TLIF, robot-assisted percutaneous pedicle screw placement is an effective minimally invasive treatment for lumbar spondylolisthesis.
Asunto(s)
Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Espondilolistesis/cirugía , Adulto , Anciano , China , Estudios de Cohortes , Femenino , Humanos , Región Lumbosacra/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Tornillos Pediculares , Estudios Retrospectivos , Robótica , Fusión Vertebral/métodos , Cirugía Asistida por Computador/métodos , Resultado del TratamientoRESUMEN
Heat stress is an environmental factor that causes severe economic loss to the current intensive breeding industry and induces huge impact on the long-term growth in livestock and poultry industry. Many animal experiments confirmed that heat stress is a major cause of heat stroke death, which is due to severe damage to endothelial cells. In order to provide a theoretical basis for the treatment or mitigation of heat stress related diseases in broilers, the effect of taurine on injury and apoptosis of aortic endothelial cells in broilers under heat stress was investigated in the present study. Ten days healthy broilers were sacrificed, then aortic tissue was used to isolate and cultivate primary broiler aortic endothelial cells. The third to the fifth generations of cells were used in the experiment. The cells were randomly divided into five groups, including control group (C), heat stress group (HS), low taurine (HS+LTau) group, mild taurine (HS+MTau) group and high taurine (HS+HTau) group. Cells in all groups were cultivated for 24 h in cell incubator (37 °C, 5% CO2). Then the heat stress group cells were cultivated in a 43 °C thermostatic water bath for 6 h under heat stress, and then re-incubated under 37 °C for 1 h. The results showed that compared with the control group, expression levels of Bax, Caspase-9, Caspase-3, Cyt-c, P53 and other pro-apoptosis factors in HS groups were significantly increased (P < 0.05), while expression levels of anti-apoptosis factor Bcl-2 showed a significant decrease (P < 0.05). Compared with HS group, expression levels of Bcl-2 in endothelial cells were significantly increased by taurine administration (P < 0.05), while expression of Bax, Caspase-9, Caspase-3, Cyt-c and P53 were significantly increased by taurine (P < 0.05). In summary, the present data indicated that taurine could protect against injury and apoptosis of aortic endothelial cells under heat stress by inhibiting the activation of mitochondria-mediated apoptotic pathways.