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Cultivated rice varieties are all diploid, and polyploidization of rice has long been desired because of its advantages in genome buffering, vigorousness, and environmental robustness. However, a workable route remains elusive. Here, we describe a practical strategy, namely de novo domestication of wild allotetraploid rice. By screening allotetraploid wild rice inventory, we identified one genotype of Oryza alta (CCDD), polyploid rice 1 (PPR1), and established two important resources for its de novo domestication: (1) an efficient tissue culture, transformation, and genome editing system and (2) a high-quality genome assembly discriminated into two subgenomes of 12 chromosomes apiece. With these resources, we show that six agronomically important traits could be rapidly improved by editing O. alta homologs of the genes controlling these traits in diploid rice. Our results demonstrate the possibility that de novo domesticated allotetraploid rice can be developed into a new staple cereal to strengthen world food security.
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Productos Agrícolas/genética , Domesticación , Oryza/genética , Sistemas CRISPR-Cas , Seguridad Alimentaria , Edición Génica , Variación Genética , Genoma de Planta , Oryza/clasificación , PoliploidíaRESUMEN
Efficient diode-pumped continuous-wave (CW) and wavelength tunable Tm:YAP lasers based on the vibronic and electronic transitions are investigated. A total maximum output power of 4.1 W is achieved with multi-wavelength output around 2162 nm and 2274 nm, corresponding to a slope efficiency of 29.8% for a 3 at. % Tm:YAP crystal. A maximum output power of 2.48 W with a slope efficiency of 25.4% is obtained at 2146 nm for a 4 at. % Tm:YAP crystal. Using a birefringent filter (BF), the emission wavelengths of the Tm:YAP laser are tuned over spectral ranges of 59 nm from 2115 nm to 2174 nm and 127 nm from 2267 nm to 2394 nm, respectively, which is the first demonstration of wavelength tunable Tm:YAP laser based on the electronic transition 3H4â3H5 and vibronic transition 3F4â3H6, to the best of our knowledge. The results show great potentials of the Tm:YAP crystal for realizing efficient lasers in the spectral range of 2.1-2.4 µm.
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BACKGROUND: Assessing the glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS) may be helpful for mild traumatic brain injury (mTBI) management. PURPOSE: To assess glymphatic function using DTI-ALPS and its associations with global white matter damage and cognitive impairment in mTBI. STUDY TYPE: Prospective. POPULATION: Thirty-four controls (44.1% female, mean age 49.2 years) and 58 mTBI subjects (43.1% female, mean age 48.7 years), including uncomplicated mTBI (N = 32) and complicated mTBI (N = 26). FIELD STRENGTH/SEQUENCE: 3-T, single-shot echo-planar imaging sequence. ASSESSMENT: Magnetic resonance imaging (MRI) was done within 1 month since injury. DTI-ALPS was performed to assess glymphatic function, and peak width of skeletonized mean diffusivity (PSMD) was used to assess global white matter damage. Cognitive tests included Auditory Verbal Learning Test and Digit Span Test (forward and backward). STATISTICAL TESTS: Neuroimaging findings comparisons were done between mTBI and control groups. Partial correlation and multivariable linear regression assessed the associations between DTI-ALPS, PSMD, and cognitive impairment. Mediation effects of PSMD on the relationship between DTI-ALPS and cognitive impairment were explored. P-value <0.05 was considered statistically significant, except for cognitive correlational analyses with a Bonferroni-corrected P-value set at 0.05/3 ≈ 0.017. RESULTS: mTBI showed lower DTI-ALPS and higher PSMD, especially in complicated mTBI. DTI-ALPS was significantly correlated with verbal memory (r = 0.566), attention abilities (r = 0.792), executive function (r = 0.618), and PSMD (r = -0.533). DTI-ALPS was associated with verbal memory (ß = 8.77, 95% confidence interval [CI] 5.00, 12.54), attention abilities (ß = 5.67, 95% CI 4.56, 6.97), executive function (ß = 2.34, 95% CI 1.49, 3.20), and PSMD (ß = -0.79, 95% CI -1.15, -0.43). PSMD mediated 46.29%, 20.46%, and 24.36% of the effects for the relationship between DTI-ALPS and verbal memory, attention abilities, and executive function. DATA CONCLUSION: Glymphatic function may be impaired in mTBI reflected by DTI-ALPS. Glymphatic dysfunction may cause cognitive impairment related to global white matter damage after mTBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
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Conmoción Encefálica , Disfunción Cognitiva , Sistema Glinfático , Sustancia Blanca , Femenino , Humanos , Persona de Mediana Edad , Masculino , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico por imagen , Estudios Prospectivos , Sustancia Blanca/diagnóstico por imagen , Imagen por Resonancia Magnética , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiologíaRESUMEN
Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776-1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893-2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.
What is the context? Currently, the standard treatment for patients who have undergone percutaneous coronary intervention following acute myocardial infarction involves dual antiplatelet therapy with a combination of aspirin and a potent P2Y12 receptor inhibitor.However, the potential benefits of aspirin were partially constrained by the intolerance of some patients.The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.What is new? While both American and European clinical guidelines recommend the use of indobufen as an alternative treatment for patients who cannot tolerate aspirin, there exists a limited body of research on this subject.Our research is the first to address this gap by comparing the efficacy and safety of indobufen and aspirin in patients with AMI.Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.What is the impact? These findings might pave the way for further exploration of alternatives to aspirin in patients with AMI.
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Aspirina , Clopidogrel , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Aspirina/uso terapéutico , Masculino , Femenino , Clopidogrel/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Anciano , Resultado del Tratamiento , Quimioterapia Combinada/métodosRESUMEN
A method for the determination of five microplastics in agricultural soil was established by double-shot pyrolysis-gas chromatography combined with two-step extraction. First, polycarbonate (PC), polystyrene (PS), polypropylene (PP), and polyethylene (PE) were extracted from soil samples using a mixed solvent of cyclohexanone and p-xylene, and then PE terephthalate was extracted with m-methylphenol. Subsequently, PC and PE terephthalate were analyzed by thermochemolysis, and PE, PP, and PS were investigated by direct pyrolysis at 600°C. The linearity of the method was satisfactory for five microplastics and the correlation coefficients were higher than 0.97 in the respective concentration range. The limits of detection and the limits of quantification were 0.2-10.0 and 0.5-20.0 µg/g, respectively. The method provided recoveries of 75.1%-141.5%, with acceptable repeatability within 20.0%. It was a supplementary method for the existing characterization of microplastics in agricultural soil.
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BACKGROUND: Distinguishing high-grade from low-grade chondrosarcoma is extremely vital not only for guiding the development of personalized surgical treatment but also for predicting the prognosis of patients. We aimed to establish and validate a magnetic resonance imaging (MRI)-based nomogram for predicting preoperative grading in patients with chondrosarcoma. METHODS: Approximately 114 patients (60 and 54 cases with high-grade and low-grade chondrosarcoma, respectively) were recruited for this retrospective study. All patients were treated via surgery and histopathologically proven, and they were randomly divided into training (n = 80) and validation (n = 34) sets at a ratio of 7:3. Next, radiomics features were extracted from two sequences using the least absolute shrinkage and selection operator (LASSO) algorithms. The rad-scores were calculated and then subjected to logistic regression to develop a radiomics model. A nomogram combining independent predictive semantic features with radiomic by using multivariate logistic regression was established. The performance of each model was assessed by the receiver operating characteristic (ROC) curve analysis and the area under the curve, while clinical efficacy was evaluated via decision curve analysis (DCA). RESULTS: Ultimately, six optimal radiomics signatures were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging with fat suppression (T2WI-FS) sequences to develop the radiomics model. Tumour cartilage abundance, which emerged as an independent predictor, was significantly related to chondrosarcoma grading (p < 0.05). The AUC values of the radiomics model were 0.85 (95% CI, 0.76 to 0.95) in the training sets, and the corresponding AUC values in the validation sets were 0.82 (95% CI, 0.65 to 0.98), which were far superior to the clinical model AUC values of 0.68 (95% CI, 0.58 to 0.79) in the training sets and 0.72 (95% CI, 0.57 to 0.87) in the validation sets. The nomogram demonstrated good performance in the preoperative distinction of chondrosarcoma. The DCA analysis revealed that the nomogram model had a markedly higher clinical usefulness in predicting chondrosarcoma grading preoperatively than either the rad-score or clinical model alone. CONCLUSION: The nomogram based on MRI radiomics combined with optimal independent factors had better performance for the preoperative differentiation between low-grade and high-grade chondrosarcoma and has potential as a noninvasive preoperative tool for personalizing clinical plans.
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Neoplasias Óseas , Condrosarcoma , Imagen por Resonancia Magnética , Clasificación del Tumor , Nomogramas , Humanos , Condrosarcoma/diagnóstico por imagen , Condrosarcoma/patología , Condrosarcoma/cirugía , Imagen por Resonancia Magnética/métodos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Adulto , Anciano , Curva ROC , Adulto Joven , RadiómicaRESUMEN
STATEMENT OF PROBLEM: Three-dimensional (3D) printing has had extensive applications across dentistry, but a comprehensive bibliometric analysis relating to the application of 3D printing in dentistry is lacking. PURPOSE: The purpose of this study was to conduct a comprehensive bibliometric analysis of the scientific literature concerning the application of 3D printing in dentistry from 2012 to 2023. MATERIAL AND METHODS: The literature search was conducted in the Web of Science Core Collection Database. The retrieved literature data were downloaded as plain text file in "full record and cited references" format, with software programs (VOSviewer, CiteSpace, Biblioshiny, RStudio, Carrot2, and Microsoft Excel) used for bibliometric analysis and quantitative assessment. RESULTS: The bibliometric analysis incorporated 1911 publications. Revilla-León, Marta was the most productive author. Zurich University had the highest number of publications and citations. The United States dominated the research landscape with the highest publication volume and H-index. The Journal of Prosthetic Dentistry was the leading journal in both publication volume and citation frequency. Co-occurrence analysis of keyword and co-cited analysis of reference indicated a robust research environment, characterized by a strong focus on the pursuit of accuracy in dental restorative solutions, biocompatibility of materials, and clinical applications. CONCLUSIONS: Research on 3D printing in the field of dentistry continues to grow. Collaborations with leading organizations and countries have been established, with Revilla-León, Marta et al playing a pivotal role. Top journals represented included the Journal of Prosthetic Dentistry and Dental Materials. Main research domain resided in prosthodontics and implantology. Hot research topics included improvements in accuracy, dental materials, and clinical applications centered on implant guide design.
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There have been several clinical studies using chimeric antigen receptor (CAR)-T cell therapy for different hematological malignancies. It has transformed the therapy landscape for hematologic malignancies dramatically. Nonetheless, in acute myeloid leukemia (AML) and T cell malignancies, it still has a dismal prognosis. Even in the most promising locations, recurrence with CAR-T treatment remains a big concern. Oncolytic viruses (OVs) can directly lyse tumor cells or cause immune responses, and they can be manipulated to create therapeutic proteins, increasing anticancer efficacy. Oncolytic viruses have been proven in a rising number of studies to be beneficial in hematological malignancies. There are limitations that cannot be avoided by using either treatment alone, and the combination of CAR-T cell therapy and oncolytic virus therapy may complement the disadvantages of individual application, enhance the advantages of their respective treatment methods and improve the treatment effect. The alternatives for combining two therapies in hematological malignancies are discussed in this article.
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OBJECTIVE: To investigate and verify the efficiency and effectiveness of a nomogram based on radiomics labels in predicting the treatment of lumbar disc herniation (LDH). METHODS: By reviewing medical records that were analysed over the past three years, clinical and imaging data of 200 lumbar disc patients at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were obtained. The collected cases were randomly divided into a training group (n = 140) and a testing group (n = 60) at a ratio of 7:3. Two radiologists with experience in reading orthopaedics images independently segmented the ROIs. The whole intervertebral disc with the most obvious protrusion in the sagittal plane T2WI lumbar MRI as a mask (ROI) is sketched. The LASSO (Least Absolute Shrinkage And Selection Operator) algorithm was used to filter the features after extracting the radiomics features. The multivariate logistic regression model was used to construct a quantitative imaging RadScore for the selected features with nonzero coefficients. The radiomics labels and nomogram were evaluated using the receiver operating characteristic curve (ROC) and the area under the curve (AUC). The calibration curve was used to evaluate the consistency between the nomogram prediction and the actual treatment plan. The DCA decision curve was used to evaluate the clinical applicability of the nomogram. RESULT: Following feature extraction, 11 radiomics features were used to construct the radiomics label for predicting the treatment plan of LDH. A nomogram was then constructed. The AUC was 0.93 (95% CI: 0.90-0.97), with a sensitivity of 89%, a specificity of 91%, a positive predictive value of 92.7%, a negative predictive value of 89.4%, and an accuracy of 91%. The calibration curve showed that there was good consistency between the prediction and the actual observation. The DCA decision curve analysis showed that the nomogram of the imaging group has great potential for clinical application when the risk threshold is between 5 and 72%. CONCLUSION: A nomogram based on radiomics labels has good predictive value for the treatment of LDH and can be used as a reference for clinical decision-making.
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Desplazamiento del Disco Intervertebral , Disco Intervertebral , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/terapia , Imagen por Resonancia Magnética/métodos , Nomogramas , Estudios RetrospectivosRESUMEN
Vaginal reconstruction is the main solution to the problem of sexuality and gender roles for patients with no vagina. A tissue-engineered vagina may be the best choice. However, many defects have been found in neovaginas reconstructed with a graft only. In this study, we investigated whether a stem cell-seeded graft would accelerate the morphological and functional recovery of neovaginas. CM-DiI-labeled bone marrow mesenchymal stem cell (MSC)-seeded small intestinal submucosa (SIS) (SIS+MSCs group) was used for vaginal reconstruction in a rat model; unseeded SIS (SIS group) was used as a control. The neovaginas of each group were harvested at 4 and 12 weeks after surgery. Morphological analyses were performed using hematoxylin and eosin (H&E) staining and immunohistochemical staining for α-smooth muscle actin (SMA), protein gene product 9.5(PGP9.5), and CD34. Functional recovery was evaluated using an organ bath study. The role of MSCs in the neovagina was analyzed by immunofluorescence and molecular biology methods. At the 4th week, a regenerated epithelium covered the whole neovagina in both groups. A small amount of smooth muscle regeneration was found in the neovagina. Up to the 12th week, nerve fibers appeared. There were more smooth muscle and nerve fibers, along with better contractility, in the neovagina of the SIS+MSCs group. Further study showed that the MSCs differentiated into smooth muscles at the 4th week. A higher microvessel density (MVD) and more vascular endothelial growth factor (VEGF) were found in the neovagina of the SIS+MSCs group. In short, MSCs accelerate the structural and functional recovery of the neovagina.
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Yeyuno/trasplante , Células Madre Mesenquimatosas/fisiología , Estructuras Creadas Quirúrgicamente , Vagina , Animales , Femenino , Ratas Sprague-Dawley , Recuperación de la Función , Porcinos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To study whether small intestine submucosa (SIS) could be a treatment option for preventing the formation of intrauterine adhesions (IUAs). METHODS: The IUAs model was established by mechanical curettage and infectious injury in a rat model. One uterine horn of the rat model was treated with the transplantation of SIS (SIS group) and the other one was left without any treatment (control group). The endometrium was evaluated with endometrial thickness, number of glands and fibrosis area. The endometrial receptive factors were detected by quantitative real-time polymerase chain reaction The number and location of embryos were documented to assess the function of endometrium. RESULTS: In the SIS group, endometrial thickness was significantly thicker than that in the control group on the 14th and 21st day and the percentage of fibrosis area was significantly lower during the entire observation process (p < 0.05). The number of glands was similar between the 2 groups (p > 0.05). Receptive factors changed as follows: in the SIS group, the expression of uteroglobin was higher and peaked on the 21st day (3.42-fold, p < 0.05); the HOXA10 level was significantly higher on the 10th day (2.16-fold, p < 0.05), and it then decreased. More embryos were seen in SIS horns (5.13 vs. 1.25, p < 0.05). CONCLUSIONS: SIS could be a potential physical barrier for the formation of IUAs. It contributes to the regeneration of and improvement of the receptivity of endometrium, and helps in the implantation and development of embryos in a rat model.
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Endometrio/patología , Mucosa Intestinal , Adherencias Tisulares/prevención & control , Enfermedades Uterinas/prevención & control , Animales , Modelos Animales de Enfermedad , Femenino , Proteínas de Homeodominio/análisis , Humanos , Intestino Delgado , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Adherencias Tisulares/patología , Enfermedades Uterinas/patologíaRESUMEN
BACKGROUND: The Internet hospital, an innovative approach to providing health care, is rapidly developing in China because it has the potential to provide widely accessible outpatient service delivery via Internet technologies. To date, China's Internet hospitals have not been systematically investigated. OBJECTIVE: The aim of this study was to describe the characteristics of China's Internet hospitals, and to assess their health service capacity. METHODS: We searched Baidu, the popular Chinese search engine, to identify Internet hospitals, using search terms such as "Internet hospital," "web hospital," or "cloud hospital." All Internet hospitals in mainland China were eligible for inclusion if they were officially registered. Our search was carried out until March 31, 2017. RESULTS: We identified 68 Internet hospitals, of which 43 have been put into use and 25 were under construction. Of the 43 established Internet hospitals, 13 (30%) were in the hospital informatization stage, 24 (56%) were in the Web ward stage, and 6 (14%) were in full Internet hospital stage. Patients accessed outpatient service delivery via website (74%, 32/43), app (42%, 18/43), or offline medical consultation facility (37%, 16/43) from the Internet hospital. Furthermore, 25 (58%) of the Internet hospitals asked doctors to deliver health services at a specific Web clinic, whereas 18 (42%) did not. The consulting methods included video chat (60%, 26/43), telephone (19%, 8/43), and graphic message (28%, 12/43); 13 (30%) Internet hospitals cannot be consulted online any more. Only 6 Internet hospitals were included in the coverage of health insurance. The median number of doctors available online was zero (interquartile range [IQR] 0 to 5; max 16,492). The median consultation fee per time was ¥20 (approximately US $2.90, IQR ¥0 to ¥200). CONCLUSIONS: Internet hospitals provide convenient outpatient service delivery. However, many of the Internet hospitals are not yet mature and are faced with various issues such as online doctor scarcity and the unavailability of health insurance coverage. China's Internet hospitals are heading in the right direction to improve provision of health services, but much more remains to be done.
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Hospitales/normas , Internet/estadística & datos numéricos , Informática Médica/métodos , Adulto , China , Estudios Transversales , Humanos , Encuestas y CuestionariosRESUMEN
During xylitol fermentation, Candida tropicalis is often inhibited by inhibitors in hemicellulose hydrolysate. The mechanisms involved in the metabolic responses to inhibitor stress and the resistances to inhibitors are still not clear. To understand the inhibition mechanisms and the metabolic responses to inhibitors, a GC/MS-based metabolomics approach was performed on C. tropicalis treated with and without complex inhibitors (CI, including furfural, phenol and acetic acid). Partial least squares discriminant analysis was used to determine the metabolic variability between CI-treated groups and control groups, and 25 metabolites were identified as possible entities responsible for the discrimination caused by inhibitors. We found that xylose uptake rate and xylitol oxidation rate were promoted by CI treatment. Metabolomics analysis showed that the flux from xylulose to pentose phosphate pathway increased, and tricarboxylic acid cycle was disturbed by CI. Moreover, the changes in levels of 1,3-propanediol, trehalose, saturated fatty acids and amino acids showed different mechanisms involved in metabolic responses to inhibitor stress. The increase of 1,3-propanediol was considered to be correlated with regulating redox balance and osmoregulation. The increase of trehalose might play a role in protein stabilization and cellular membranes protection. Saturated fatty acids could cause the decrease of membrane fluidity and make the plasma membrane rigid to maintain the integrity of plasma membrane. The deeper understanding of the inhibition mechanisms and the metabolic responses to inhibitors will provide us with more information on the metabolism regulation during xylitol bioconversion and the construction of industrial strains with inhibitor tolerance for better utilization of bioresource.
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Candida tropicalis/efectos de los fármacos , Candida tropicalis/metabolismo , Fermentación , Xilitol/metabolismo , Ácido Acético/farmacología , Candida tropicalis/crecimiento & desarrollo , Cloruros/farmacología , Furaldehído/farmacología , Metaboloma , Metabolómica/métodos , Xilosa/metabolismoRESUMEN
BACKGROUND: Drug-free in vitro activation (IVA) is a new protocol to activate residual dormant follicles for fertility restoration in patients with premature ovarian insufficiency (POI). However, several deficiencies have reduced its clinical efficacy rate. Our previous studies have confirmed that the combination of adipose-derived stem cells (ADSCs) and drug-free IVA can improve the effectiveness of drug-free IVA and restore ovarian function of rats with POI. Increasing evidence has demonstrated that mesenchymal stem cell-derived exosomes have similar therapeutic effects as their source cells. Here, we performed a preclinical study to evaluate the therapeutic effects of ADSCs-derived exosomes (ADSCs-Exos) combined with drug-free IVA in the POI rats and the mechanism in restoring ovarian function. RESULTS: In vivo, the effects of ADSCs-Exos were comparable to those of ADSCs, and the ADSCs-Exos combined with drug-free IVA was better than ADSCs-Exos alone therapy in promoting follicular development. Moreover, transplantation of ADSCs/ADSCs-Exos lead to up-regulation of BCL-2 expression and down-regulation of the expression of Bax and Cleaved Caspase-3, thus reducing the apoptosis of chemotherapy-induced follicle cells, and further promoting the development of the follicles and rescuing ovarian function in POI-damaged ovary. In vitro, ovarian fragmentation could activate follicular growth and development, and in combination with ADSCs-Exos could prevent the loss of follicles, promote follicular proliferation and inhibit apoptosis. CONCLUSIONS: ADSCs-Exos combined drug-free IVA had remarkable therapeutic effects in restoring ovarian function of POI rats, and markedly promoted follicular development and inhibited apoptosis of ovarian cells in vitro. Our study confirmed that the combination therapy might be a promising and effective treatment for POI.
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Exosomas , Ovario , Insuficiencia Ovárica Primaria , Animales , Femenino , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/metabolismo , Exosomas/metabolismo , Exosomas/trasplante , Ratas , Ovario/metabolismo , Apoptosis , Células Madre Mesenquimatosas/metabolismo , Folículo Ovárico/metabolismo , Tejido Adiposo/citología , Ratas Sprague-DawleyRESUMEN
BACKGROUND: 3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction. METHODS: In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography. The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes' effect of promotion vaginal reconstruction and to explore the mechanism in this process. RESULTS: It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway. CONCLUSION: The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.
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Matriz Extracelular Descelularizada , Exosomas , Células Madre Mesenquimatosas , Impresión Tridimensional , Andamios del Tejido , Vagina , Femenino , Exosomas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Animales , Vagina/citología , Andamios del Tejido/química , Matriz Extracelular Descelularizada/química , Estereolitografía , Ratas , Hidrogeles/química , Ratas Sprague-Dawley , Regeneración , Procedimientos de Cirugía Plástica/métodos , Gelatina/química , Humanos , Ingeniería de Tejidos/métodos , Matriz Extracelular/metabolismoRESUMEN
Introduction: Pyruvate kinase M2 (PKM2) was involved in the pathophysiology of atherosclerosis and coronary artery disease (CAD). We tested whether plasma PKM2 concentrations were correlated with clinical severity and major adverse cardiovascular events (MACEs) in CAD patients. Materials and methods: A total of 2443 CAD patients and 238 controls were enrolled. The follow-up time was two years. Plasma PKM2 concentrations were detected by enzyme-linked immunosorbent assay (ELISA) kits (Cloud-Clone, Wuhan, China) using SpectraMax i3x Multi-Mode Microplate Reader (Molecular Devices, San Jose, USA). The predictors of acute coronary syndrome (ACS) were assessed by logistic regression analysis. The association between PKM2 concentration in different quartiles and MACEs was evaluated by Kaplan-Meier (KM) curves with log-rank test and Cox proportional hazard models. The predictive value of PKM2 and a cluster of conventional risk factors was determined by Receiver operating characteristic (ROC) curves. The net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) were utilized to evaluate the enhancement in risk prediction when PKM2 was added to a predictive model containing a cluster of conventional risk factors. Results: In CAD patients, PKM2 concentration was the independent predictor of ACS (P < 0.001). Kaplan-Meier cumulative survival curves and Cox proportional hazards analyses revealed that patients with a higher PKM2 concentration had higher incidence of MACEs compared to those with a lower PKM2 concentration (P < 0.001). The addition of PKM2 to a cluster of conventional risk factors significantly increased its prognostic value of MACEs. Conclusion: Baseline plasma PKM2 concentrations predict the clinical severity and prognosis of CAD.
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Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Humanos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/complicaciones , Pronóstico , Piruvato Quinasa , Factores de RiesgoRESUMEN
BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and α-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of ß-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the ß-catenin/c-Myc/cyclin D1 pathway. CONCLUSION: This study reveals that porcine-derived AVM has potential application for vaginal regeneration.
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Trastornos del Desarrollo Sexual 46, XX , Anomalías Congénitas , Ciclina D1 , Conductos Paramesonéfricos/anomalías , Ingeniería de Tejidos , Humanos , Femenino , Porcinos , Animales , beta Catenina , Porcinos Enanos , Vagina/anomalías , Vagina/cirugíaRESUMEN
BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.
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Angiografía por Tomografía Computarizada , Lipoproteína(a) , Infarto del Miocardio , Placa Aterosclerótica , Humanos , Masculino , Femenino , Lipoproteína(a)/sangre , Infarto del Miocardio/sangre , Infarto del Miocardio/epidemiología , Persona de Mediana Edad , Placa Aterosclerótica/sangre , Placa Aterosclerótica/diagnóstico por imagen , Anciano , Angiografía Coronaria , Estudios Retrospectivos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Estudios Prospectivos , Estudios de Seguimiento , Biomarcadores/sangreRESUMEN
Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24-2.17, p < 0.001), cardiac death (HR 2.15, 95% CI 1.29-3.59, p = 0.003) and repeat revascularization (HR 1.52, 95% CI 1.09-2.11, p = 0.013), but not for non-fatal myocardial infarction (HR 1.66, 95% CI 0.94-2.12, p = 0.081). Newly diagnosed diabetes was associated with an increased risk of 5-year MACE compared with non-diabetes and previously diagnosed diabetes in elderly patients underwent PCI. More attention should be given to those elderly newly diagnosed diabetes population.
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Diabetes Mellitus , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Anciano , Masculino , Femenino , Prevalencia , Diabetes Mellitus/epidemiología , Factores de Riesgo , República de Corea/epidemiología , Anciano de 80 o más Años , Resultado del Tratamiento , Estudios Prospectivos , Modelos de Riesgos ProporcionalesRESUMEN
Certain crops were domesticated from their wild progenitors and have served as the major staple food since then, but now suffered from the limited genetic diversity in breeding. Enormous wild species possess unique advantages such as stress tolerance, polyploidy, perennial habit, and natural nutrition. However, it remains a big challenge to utilize wild species in conventional breeding. With recent advances in biotechnologies, one new breeding strategy, de novo domestication, has emerged and been demonstrated by pioneer work. Here, we review the emergence and milestone progress of de novo domestication and discuss how wild relatives could be exploited into new types of crops. With the understanding of the genetic basis of crop domestication and the development of biotechnologies, various elite wild germplasms will be designed and practiced to fulfill particular breeding goals and create new types of crops. De novo domestication is paving a new way for breeding the future.