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OBJECTIVE: Endometriosis (EMs) commonly occurs in reproductive women. We explored the mechanism of methyltransferase-like 14 (METTL14) on human endometriotic stromal cell (ESC; HEM15A) proliferation, migration and invasion, to provide novel therapy for EMs. METHODS: HEM15A and human endometrial stromal cells (HESCs) were cultured in vitro. HEM15A cells were treated with oe-METTL14 and oe-zinc finger E-box-binding protein 1 (ZEB1) plasmids, N6-methyladenosine (m6A) inhibitor 3-deazaadenosine (3-DAA) and the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway inhibitor isoprenaline (ISO). After identifying HEM15A and HESCs, METTL14, ZEB1, p-ERK1/2/ERK1/2 and p-MEK/MEK levels, and cell proliferation, migration and invasion were assessed. The modification sites of ZEB1 and m6A were predicted using SRAMP database, with m6A modification level assessed by MeRIP. The binding of YT521-B homology domain 2 (YTHDF2) to ZEB1 messenger RNA (mRNA), and ZEB1 stability and mRNA level were tested. RESULTS: Compared with HESCs, METTL14 level in HEM15A was significantly reduced. METTL14 overexpression in HEM15A prominently increased its proliferation, migration and invasion. METTL14 overexpression notably elecated m6A-methylated ZEB1 mRNA level and reduced the stability and expression of ZEB1 mRNA. Further m6A modification inhibition increased ZEB1 mRNA stability and mRNA and protein levels, and decreased ZEB1 m6A modification level. ZEB1 upregulation partially reversed METTL14 overexpression-inhibited HEM15A proliferation, migration and invasion. METTL14 inhibited the MEK/ERK signaling activation by regulating ZEB1, and the MEK/ERK signaling activation partly averted METTL14-suppressed proliferation, migration and invasion. CONCLUSION: METTL14 lowered ZEB1 expression by regulating ZEB1 m6A modification levels, thereby inhibiting the MEK/ERK pathway activation and ESC proliferation, migration and invasion.
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Research assessing the changing epidemiology of infectious diseases in China after the implementation of new healthcare reform in 2009 was scarce. We aimed to get the latest trends and disparities of national notifiable infectious diseases by age, sex, province, and season in China from 2010 to 2019. The number of incident cases and deaths, incidence rate, and mortality of 44 national notifiable infectious diseases by sex, age groups, and provincial regions from 2010 to 2019 were extracted from the China Information System for Disease Control and Prevention and official reports and divided into six kinds of infectious diseases by transmission routes and three classes (A-C) in this descriptive study. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends of incidence and mortality rate. We calculated the concentration index to measure economic-related inequality. Segmented interrupted time-series analysis was used to estimate the impact of the COVID-19 pandemic on the epidemic of notifiable infectious diseases. The trend of incidence rate on six kinds of infectious diseases by transmission routes was stable, while only mortality of sexual, blood-borne, and mother-to-child-borne infectious diseases increased from 0.6466 per 100 000 population in 2010 to 1.5499 per 100 000 population in 2019 by 8.76% per year (95% confidence interval [CI]: 6.88-10.68). There was a decreasing trend of incidence rate on Class-A infectious diseases (EAPC = -16.30%; 95% CI: -27.93 to -2.79) and Class-B infectious diseases (EAPC = -1.05%; 95% CI: -1.56 to -0.54), while an increasing trend on Class-C infectious diseases (EAPC = 6.22%; 95% CI: 2.13-10.48). For mortality, there was a decreasing trend on Class-C infectious diseases (EAPC = -14.76%; 95% CI: -23.46 to -5.07), and an increasing trend on Class-B infectious diseases (EAPC = 4.56%; 95% CI: 2.44-6.72). In 2019, the infectious diseases with the highest incidence rate and mortality were respiratory diseases (340.95 per 100 000 population), and sexual, blood-borne, and mother-to-child-borne infectious diseases (1.5459 per 100 000 population), respectively. The greatest increasing trend of incidence rate was observed in seasonal influenza, from 4.83 per 100 000 population in 2010 to 253.36 per 100 000 population in 2019 by 45.16% per year (95% CI: 29.81-62.33), especially among females and children aged 0-4 years old. The top disease with the highest mortality was still AIDs, which had the highest average yearly mortality in 24 provinces from 2010 to 2019, and its incidence rate (EAPC = 14.99%; 95% CI: 8.75-21.59) and mortality (EAPC = 9.65; 95%CI: 7.71-11.63) both increased from 2010 to 2019, especially among people aged 44-59 years old and 60 or older. Male incidence rate and mortality were higher than females each year from 2010 to 2018 on 29 and 10 infectious diseases, respectively. Additionally, sex differences in the incidence and mortality of AIDS were becoming larger. The curve lay above the equality line, with the negative value of the concentration index, which indicated that economic-related health disparities exist in the distribution of incidence rate and mortality of respiratory diseases (incidence rate: the concentration index = -0.063, p < 0.0001; mortality: the concentration index = -0.131, p < 0.001), sexual, blood-borne, and mother-to-child-borne infectious diseases (incidence rate: the concentration index = -0.039, p = 0.0192; mortality: the concentration index = -0.207, p < 0.0001), and the inequality disadvantageous to the poor (pro-rich). Respiratory diseases (Dec-Jan), intestinal diseases (May-Jul), zoonotic infectious diseases (Mar-Jul), and vector-borne infectious diseases (Sep-Oct) had distinct seasonal epidemic patterns. In addition, segmented interrupted time-series analyses showed that, after adjusting for potential seasonality, autocorrelation, GDP per capita, number of primary medical institutions, and other factors, there was no significant impact of COVID-19 epidemic on the monthly incidence rate of six kinds of infectious diseases by transmission routes from 2018 to 2020 (all p > 0.05). The incidence rates of six kinds of infectious diseases were stable in the past decade, and incidence rates of Class-A and Class-B infectious diseases were decreasing because of comprehensive prevention and control measures and a strengthened health system after the implementation of the new healthcare reform in China since 2009. However, age, gender, regional, and economic disparities were still observed. Concerted efforts are needed to reduce the impact of seasonal influenza (especially among children aged 0-4 years old) and the mortality of AIDs (especially among people aged 44-59 years old and 60 or older). More attention should be paid to the disparities in the burden of infectious diseases.
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Síndrome de Inmunodeficiencia Adquirida , COVID-19 , Enfermedades Transmisibles , Gripe Humana , Femenino , Masculino , Humanos , Recién Nacido , Lactante , Preescolar , Adulto , Persona de Mediana Edad , Gripe Humana/epidemiología , Pandemias , Síndrome de Inmunodeficiencia Adquirida/epidemiología , COVID-19/epidemiología , Transmisión Vertical de Enfermedad Infecciosa , Enfermedades Transmisibles/epidemiología , Incidencia , China/epidemiologíaRESUMEN
Wheat stripe rust (WSR) is a foliar disease that causes destructive damage in the wheat production context. Accurately estimating the severity of WSR in the autumn growing stage can help to objectively monitor the disease incidence level of WSR and predict the nationwide disease incidence in the following year, which have great significance for controlling its nationwide spread and ensuring the safety of grain production. In this study, to address the low accuracy and the efficiency of disease index estimation by traditional methods, WSR-diseased areas are segmented based on Segformer, and the macro disease index (MDI) is automatically calculated for the measurement of canopy-scale disease incidence. The results obtained with different semantic segmentation algorithms, loss functions, and data sets are compared for the segmentation effect, in order to address the severe class imbalance in disease region segmentation. We find that: (1) The results of the various models differed significantly, with Segformer being the best algorithm for WSR segmentation (rust class F1 score = 72.60%), based on the original data set; (2) the imbalanced nature of the data has a significant impact on the identification of the minority class (i.e., the rust class), for which solutions based on loss functions and re-weighting of the minority class are ineffective; (3) data augmentation of the minority class or under-sampling of the original data set to increase the proportion of the rust class greatly improved the F1-score of the model (rust class F1 score = 86.6%), revealing that re-sampling is a simple and effective approach to alleviating the class imbalance problem. Finally, the MDI was used to evaluate the models based on the different data sets, where the model based on the augmented data set presented the best performance (R2 = 0.992, RMSE = 0.008). In conclusion, the deep-learning-based semantic segmentation method, and the corresponding optimization measures, applied in this study allow us to achieve pixel-level accurate segmentation of WSR regions on wheat leaves, thus enabling accurate assessment of the degree of WSR disease under complex backgrounds in the field, consequently providing technical support for field surveys and calculation of the disease level.
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Basidiomycota , Triticum , Resistencia a la Enfermedad , Enfermedades de las Plantas , Hojas de la PlantaRESUMEN
Accurately predicting the impact of point mutation on protein stability has crucial roles in protein design and engineering. In this study, we proposed a novel method (BoostDDG) to predict stability changes upon point mutations from protein sequences based on the extreme gradient boosting. We extracted features comprehensively from evolutional information and predicted structures and performed feature selection by a strategy of sequential forward selection. The features and parameters were optimized by homologue-based cross-validation to avoid overfitting. Finally, we found that 14 features from six groups led to the highest Pearson correlation coefficient (PCC) of 0.535, which is consistent with the 0.540 on an independent test. Our method was indicated to consistently outperform other sequence-based methods on three precompiled test sets, and 7363 variants on two proteins (PTEN and TPMT). These results highlighted that BoostDDG is a powerful tool for predicting stability changes upon point mutations from protein sequences.
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Mutación , Mutación Puntual , Proteínas , Secuencia de Aminoácidos , Estabilidad Proteica , Proteínas/genéticaRESUMEN
BACKGROUND: Although it has been documented that methamphetamine induces astrocyte activation, the mechanism(s) underlying this effect remain poorly understood. We thus sought to examine the molecular mechanisms involved in methamphetamine-mediated activation of astrocytes with a focus on the role of sigma-1 receptor (σ-1R) in this process. METHODS: The expression of σ-1R and glial fibrillary acidic protein (GFAP) was examined by reverse transcription PCR (RT-PCR), real-time PCR, Western blot, and immunofluorescent staining; phosphorylation of cell signaling pathways was detected by Western blot analysis. Immunoprecipitation was used to determine the interaction between σ-1R and p-Src. Chromatin immunoprecipitation (ChIP) assay was employed to discern the binding of cAMP-response element-binding protein (CREB) with the promoter of σ-1R. The role of σ-1R in astrocyte activation was further validated in σ-1R knockout (KO) mice by Western blot combined with immunofluorescent staining. RESULTS: Exposure of primary rat astrocytes to methamphetamine increased the expression of σ-1R via the activation of Src, ERK mitogen-activated protein kinase, and downstream CREB pathways. Subsequently, CREB translocated into nucleus and interacted with the promoter of σ-1R resulting in increased expression of σ-1R with a concomitant increase in expression of GFAP. This effect was inhibited in cells treated with the σ-1R antagonist-BD1047, thereby implicating the role of σ-1R in the activation of astrocytes. In vivo relevance of these findings was further corroborated in σ-1R KO mice that were administered methamphetamine. In the methamphetamine administered mice, there was a failure of the drug to induce activation of astrocytes, an effect that was evident in wild-type (WT) mice exposed to methamphetamine. CONCLUSIONS: The study presented herein demonstrates that methamphetamine-mediated activation of astrocytes involved up-regulation of σ-1R through a positive-feedback mechanism. Understanding the regulation of σ-1R expression could provide insights into the development of potential therapeutic strategies for astrocyte activation induced by methamphetamine.
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Astrocitos/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Metanfetamina/farmacología , Receptores sigma/genética , Receptores sigma/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Animales , Animales Recién Nacidos , Butadienos/farmacología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Etilenodiaminas/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Nitrilos/farmacología , Ratas , Ratas Sprague-Dawley , Receptores sigma/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Receptor Sigma-1RESUMEN
Background: Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 1 (NLRP1) participates in neuroinflammation. This study aimed to identify serum NLRP as a potential prognostic biomarker of acute intracerebral hemorrhage (ICH). Methods: This prospective cohort study enrolled 145 patients with supratentorial ICH and 51 healthy controls. Serum NLRP1 levels were quantified on admission of all 145 patients, on days 1, 3, 5, 7, and 10 after stroke in 51 of 145 patients and at entry into the study of controls. Poststroke 6-month modified Rankin Scale (mRS) scores of 3-6 signified a poor prognosis. Results: Compared to controls, patients had prominently increased serum NLRP1 levels until day 10 after ICH, with the highest levels at days 1 and 3. Serum NLRP1 levels were independently correlated with National Institutes of Health Stroke Scale (NIHSS) scores, hematoma volume and six-month mRS scores, and independently predicted six-month bad prognosis. A linear relationship was observed between serum NLRP1 levels and the risk of poor prognosis in a restricted cubic spline. Under the receiver operating characteristic (ROC) curve, serum NLRP levels efficiently discriminated poor prognosis. Serum NLRP1, NIHSS, and hematoma volume were merged into a prognosis prediction model, which was portrayed using a nomogram. Good performance of the model was verified using calibration curve, decision curve, and ROC curve. Conclusion: Serum NLRP1 levels are elevated during the early period following ICH and are independently related to hemorrhagic severity and poor prognosis, suggesting that serum NLRP1 may represent a promising prognostic biomarker of ICH.
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OBJECTIVE: The triglyceride glucose (TyG) index is regarded as a reliable alternative indicator for measuring insulin resistance. We investigated the association between the prognosis of patients with subarachnoid hemorrhage (SAH)and the TyG index, explored the potential of the TyG index as a new biomarker for forecasting the outcomes of SAH patients, and explored independent risk factors for predicting the condition of SAH patients. METHODS: A retrospective analysis was performed of patients who were admitted to a single center due to SAH. Differences in clinical data and correlation between laboratory indexes, disease severity score on admission, and prognosis score were compared between the 2 groups. The study employed multivariate logistic regression analysis to examine the independent influencing aspects of Glasgow Outcome Scale score. The receiver operating characteristic curve was drawn and the area under the curve (AUC) calculated to predict the best cutoff value of the degree of neurological impairment in patients with SAH. RESULTS: Univariate analysis showed that Glasgow Coma Scale score (86.3% vs. 12.0%, P < 0.001), Hunt-Hess grade (88.2% vs. 15.7%, P < 0.001), white blood cell count (11.20 [7.9, 15.2] vs. 9.1 [7.0, 12.2], P = 0.027), and TyG index (1.49 [1.40, 1.59] vs. 1.16 [1.06, 1.27], P < 0.001) were statistically significantly different. Multivariate analysis showed that TyG index, Hunt-Hess grade, and GCS score were independent risk factors for poor prognosis. CONCLUSIONS: Patients with SAH may benefit from using the TyG index as a predictive method. In our clinical practice, the TyG index is beneficial for managing diseases and making decisions. More research is required to determine if improved TyG index control would lead to better clinical results in the future.
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Glucemia , Hemorragia Subaracnoidea , Triglicéridos , Humanos , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Triglicéridos/sangre , Glucemia/análisis , Glucemia/metabolismo , Anciano , Adulto , Biomarcadores/sangre , Escala de Coma de Glasgow , Factores de RiesgoRESUMEN
Objective: Coagulopathy score has been applied as a new prognostic indicator for sepsis, heart failure and acute respiratory failure. However, its ability to forecast intensive care unit (ICU) mortality in patients with an acute cerebral hemorrhage (ICH) has not been assessed. The purpose of this study was to clarify the relationship between ICU mortality and early coagulation problem score. Methods: Data from the Medical Information Mart for Intensive Care (MIMIC-IV) (v2.0) database were used in this retrospective cohort analysis. The association between the coagulation disorder score and ICU mortality was examined using multivariate logistic regression. Furthermore, the impact of additional variables on the results was investigated by a subgroup analysis. Results: 3174 patients (57.3 % male) were enrolled in total. The ICU mortality reached 18.2 %. After adjusting for potential confounders, the ICU mortality of patients rose with the increase of coagulation disorder score. The ROC curve revealed the predictive accuracy of coagulation dysfunction score to mortality in patients with ICU. The coagulation disorder score had a lower AUC value (0.601, P < 0.001) than the SAPSII(AUCs of 0.745[95 % CI, 0.730-0.761]) and the combined indicators(AUCs of 0.752[95 % CI, 0.737-0.767]), but larger than single indicators platelet, INR and APTT. In the subgroup analysis, most subgroups showed no significant interaction, but only age showed significant interaction in the adjusted model. Conclusion: The coagulopathy score and ICU mortality were found to be strongly positively correlated in this study, and its ability to predict ICU mortality was better than that of a single measure (platelet, INR, or APTT), but worse than that of the SAPSII score, GCS system.
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INTRODUCTION: Functions of existing automatic module systems for synthesis of radiopharmaceuticals mainly focus on the radiolabeling of small molecules. There are few modules which have achieved full-automatic radiolabeling of non-metallic and metallic nuclides on small molecules, peptides, and antibody drugs. This study aimed to develop and test a full-automatic multifunctional module system for the safe, stable, and efficient production of radiopharmaceuticals. METHODS: According to characteristics of labeling process of radioactive drugs, using UG and Solidworks softwares, full-automatic cassette-based synthesis module system Mortenon M1 for synthesis of radiopharmaceuticals with various radionuclides, was designed and tested. Mortenon M1 has at least three significant highlights: the cassettes are disposable, and there is no need of manual cleaning; the synthesis method program is flexible and can be edited freely by users according to special needs; this module system is suitable for radiolabeling of both small-molecule and macromolecular drugs, with potentially various radionuclides including 18F, 64Cu, 68Ga, 89Zr, 177Lu, etc. By program control methods for certain drugs, Mortenon M1 was used for radiolabeling of both small-molecule drugs such as [68Ga]-FAPI-46 and macromolecular drugs such as [89Zr]-TROP2 antibody. Quality control assays for product purity were performed with radio-iTLC and radio-HPLC, and the radiotracers were confirmed for application in microPET imaging in xenograft tumor-bearing mouse models. RESULTS: Functional tests for Mortenon M1 module system were conducted, with [68Ga]-FAPI-46 and [89Zr]-TROP2 antibody as goal synthetic products, and it displayed that with the cassette modules, the preset goals could be achieved successfully. The radiolabeling synthesis yield was good ([68Ga]-FAPI-46, 70.63% ± 2.85%, n = 10; [89Zr]-TROP2, 82.31% ± 3.92%, n = 10), and the radiochemical purity via radio-iTLC assay of the radiolabeled products was above 99% after purification. MicroPET imaging results showed that the radiolabeled tracers had reasonable radioactive distribution in MDA-MB-231 and SNU-620 xenograft tumor-bearing mice, and the tumor targeted radiouptake was satisfactory for diagnosis. CONCLUSION: This study demonstrated that the full-automatic module system Mortenon M1 is efficient for radiolabeling synthesis of both small-molecule and macromolecular substrates. It may be helpful to reduce radiation exposure for safety, provide qualified radiolabeled products and reliable PET diagnosis, and ensure stable production and supply of radiopharmaceuticals.
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Neoplasias , Radiofármacos , Humanos , Animales , Ratones , Radiofármacos/química , Radioisótopos de Galio/química , Radioisótopos/química , Péptidos , AnticuerposRESUMEN
The complex genomics, immunosuppressive tumor microenvironment (TME), and chemotherapeutic resistance of osteosarcoma (OS) have resulted in limited therapeutic effects in the clinic. Ferroptosis is involved in tumor progression and is regulated mainly by glutathione peroxidase 4 (GPX4). Small interfering RNA (siRNA)-based RNA interference (RNAi) can precisely target any gene. However, achieving effective siRNA delivery is highly challenging. Here, we fabricated a TME-responsive metal-organic framework (MOF)-based biomimetic nanosystem (mFeP@si) with siGPX4 delivery and sonodynamic therapy (SDT) to treat OS by targeting ferroptosis. Under ultrasound (US) irradiation, mFeP@si achieves lysosomal escape via singlet oxygen (1O2)-mediated lysosomal membrane disruption and then accelerates ROS generation and glutathione (GSH) depletion. Meanwhile, siGPX4 silences GPX4 expression by binding to GPX4 mRNA and leads to the accumulation of toxic phospholipid hydroperoxides (PL-OOH), further magnifying the ROS storm and triggering ferroptosis. Notably, synergistic therapy remarkably enhances antitumor effects, improves the immunosuppressive TME by inducing potent immunogenic cell death (ICD), and increases the sensitivity of chemotherapy-resistant OS cells to cisplatin. Overall, this novel nanosystem, which targets ferroptosis by integrating RNAi and SDT, exhibits strong antitumor effects both in vitro and in vivo, providing new insights for treating OS.
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Stripe rust of wheat is caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Breeding durably resistant wheat varieties by disrupting the susceptibility (S) gene has an important impact on the control of wheat stripe rust. Mingxian169 (MX169) showed strong stripe rust susceptibility to all the races of Pst. However, molecular mechanisms and responsive genes underlying susceptibility of the wheat variety MX169 to Pst have not been elucidated. Here, we utilized next-generation sequencing technology to analyze transcriptomics data of "MX169" and high-resistance wheat "Zhong4" at 24, 48, and 120 h post-inoculation (hpi) with Pst. Comparative transcriptome analysis revealed 3,494, 2,831, and 2,700 differentially expressed genes (DEGs) at different time points. We observed an upregulation of DEGs involved in photosynthesis, flavonoid biosynthesis, pyruvate metabolism, thiamine metabolism, and other biological processes, suggesting their involvement in MX169's response to Pst. DEGs encoding transcription factors were also identified. Our study suggested the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst. IMPORTANCE: Our study suggests the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst.
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Resistencia a la Enfermedad , Enfermedades de las Plantas , Puccinia , Transcriptoma , Triticum , Triticum/microbiología , Triticum/genética , Triticum/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Basidiomycota/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering, but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber. Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification. Herein, a multi-functional supramolecular peptide, P1R16, is developed by coupling a bioactive factor, parathyroid hormone related peptide 1 (PTHrP-1), to the basic supramolecular peptide RADA16-â via solid-phase synthesis. It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-â to form nanofiber hydrogels, thus coupling PTHrP-1 to hydrogel matrix. P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner, and P1R16/RADA16-â nanofiber hydrogels promote osteogenesis, angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen (Col) scaffolds. Abundant red blood marrow formation, ideal osteointegration and adapted degradation are observed in the 50% P1R16/Col scaffold group. Therefore, this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.
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OBJECTIVE: To compare the diagnostic efficacy of the Chinese Thyroid Imaging Reporting and Data Systems (C-TIRADS) with the well-accepted ACR-TIRADS guidelines in identifying benign from malignant thyroid nodules. METHODS: A total of 2064 nodules were collected from 1627 patients undergoing thyroid ultrasonography in our center between October 2019 and November 2021. Nodules were divided into two groups: "≥1 cm" and "<1 cm". Ultrasound features of each nodule were observed and recorded by two physicians with more than 15 years of experience and classified according to the ACR-TIRADS and C-TIRADS guidelines, respectively. RESULTS: The area under the curve of the ACR-TIRADS guideline was higher than that of the C-TIRADS guideline (0.922, P = 0.017), the specificity and positive predictive value of the C-TIRADS guideline were higher (81.64%, 88.72%, all P < 0.05), which was more significant in the subgroup of nodules <1 cm (P = 0.001). In addition, there was no statistical difference between the two guidelines in the diagnostic efficacy indicators for nodules ≥1 cm. The ACR-TIRADS effectively reduced unnecessary biopsies compared with the C-TIRADS (P < 0.05). CONCLUSIONS: There was high agreement between the two guidelines for the diagnosis of thyroid nodules, C-TIRADS guidelines had a higher specificity and simplicity while were inferior to the ACR-TIRADS guidelines in terms of reducing the number of biopsies.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Biopsia con Aguja Fina , Sistemas de Datos , Estudios Retrospectivos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Ultrasonografía/métodos , China , Guías de Práctica Clínica como Asunto , Estados UnidosRESUMEN
Objective: Caspase activation and recruitment domain-containing protein 4 (NLRC4) is implicated in neuroinflammation. The aim of the study was to discern the potential ability of serum NLRC4 in assessment of prognosis after intracerebral hemorrhage (ICH). Methods: In this prospective, observational study, serum NLRC4 levels were quantified in 148 acute supratentorial ICH patients and 148 controls. Severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume, and poststroke 6-month functional outcome was estimated according to the modified Rankin Scale (mRS). Early neurologic deterioration (END) and 6-month poor outcome (mRS 3-6) were deemed as the two prognostic parameters. Multivariate models were established for investigating associations, and receiver operating characteristic (ROC) curves were configured to indicate predictive capability. Results: Patients had substantially higher serum NLRC4 levels than controls (median, 363.2 pg/ml vs. 74.7 pg/ml). Serum NLRC4 levels had independent correlation with NIHSS scores [ß, 0.308; 95% confidence interval (CI), 0.088-0.520], hematoma volume (ß, 0.527; 95% CI, 0.385-0.675), serum C-reactive protein levels (ß, 0.288; 95% CI, 0.109-0.341) and 6-month mRS scores (ß, 0.239; 95% CI, 0.100-0.474). Serum NLRC4 levels above 363.2 pg/ml were independently predictive of END (odds ratio, 3.148; 95% CI, 1.278-7.752) and 6-month poor outcome (odds ratio, 2.468; 95% CI, 1.036-5.878). Serum NLRC4 levels significantly distinguished END risk [area under ROC curve (AUC), 0.765; 95% CI, 0.685-0.846] and 6-month poor outcome (AUC, 0.795; 95% CI, 0.721-0.870). In terms of predictive ability for 6-month poor outcome, serum NLRC4 levels combined with NIHSS scores and hematoma volume was superior to NIHSS scores combined with hematoma volume, NIHSS scores and hematoma volume (AUC, 0.913 vs. 0.870, 0.864 and 0.835; all P < 0.05). Nomograms were built to reflect prognosis and END risk of combination models, where serum NLRC4, NIHSS scores and hematoma volume were enforced. Calibration curves confirmed stability of combination models. Conclusions: Markedly raised serum NLRC4 levels following ICH, in close relation to illness severity, are independently associated with poor prognosis. Such results are indicative of the notion that determination of serum NLRC4 may aid in severity assessment and prediction of functional outcome of ICH patients.
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OBJECTIVE: Resolvin D1 (RvD1) has anti-inflammatory properties and may be neuroprotective. This study was designed to assess usability of serum RvD1 as a prognostic biomarker after intracerebral hemorrhage (ICH). METHODS: In this prospective, observational study of 135 patients and 135 controls, serum RvD1 levels were measured. Its relations to severity, early neurologic deterioration (END) and poststroke 6-month worse outcome (modified Rankin Scale scores of 3-6) were determined via multivariate analysis. Predictive effectiveness was evaluated based on area under receiver operating characteristic curve (AUC). RESULTS: Patients had markedly lower serum RvD1 levels than controls (median, 0.69 ng/ml versus 2.15 ng/ml). Serum RvD1 levels were independently correlated with the National Institutes of Health Stroke Scale (NIHSS) [ß, -0.036; 95 % confidence interval (CI), -0.060--0.013; VIF, 2.633; t = -3.025; P = 0.003] and hematoma volume (ß, -0.019; 95 % CI, -0.056--0.009; VIF, 1.688; t = -2.703; P = 0.008). Serum RvD1 levels substantially discriminated risks of END and worse outcome with AUCs at 0.762 (95 % CI, 0.681-0.831) and 0.783 (95 % CI, 0.704-0.850) respectively. A RvD1 cut-off value of 0.85 ng/ml was effective in predicting END with a sensitivity of 95.0 % and specificity of 48.4 % and its levels <0.77 ng/ml distinguished patients at risk of worse outcome with a sensitivity of 84.5 % and specificity of 63.6 %. Under restricted cubic spline, serum RvD1 levels were linearly related to risk of END and worse outcome (both P > 0.05). Serum RvD1 levels and NIHSS scores independently predicted END with odds ratio (OR) values of 0.082 (95 % CI, 0.010-0.687) and 1.280 (95 % CI, 1.084-1.513) respectively. Serum RvD1 levels (OR, 0.075; 95 % CI, 0.011-0.521), hematoma volume (OR, 1.084; 95 % CI, 1.035-1.135) and NIHSS scores (OR, 1.240; 95 % CI, 1.060-1.452) were independently associated with worse outcome. END prediction model containing serum RvD1 levels and NIHSS scores, and prognostic prediction model containing serum RvD1 levels, hematoma volumes and NIHSS scores displayed efficient predictive ability with AUCs at 0.828 (95 % CI, 0.754-0.888) and 0.873 (95 % CI, 0.805-0.924) respectively. Such two models were visually shown via building two nomograms. Using Hosmer-Lemeshow test, calibration curve and decision curve, the models were comparatively stable and had clinical benefit. CONCLUSION: There is a dramatical declination of serum RvD1 levels after ICH, which is tightly related to stroke severity and is independently predictive of poor clinical outcome, implying that serum RvD1 may be of clinical significance as a prognostic marker of ICH.
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Hemorragia Cerebral , Accidente Cerebrovascular , Humanos , Pronóstico , Estudios Prospectivos , Estudios Longitudinales , Hemorragia Cerebral/diagnóstico , Accidente Cerebrovascular/diagnóstico , HematomaRESUMEN
In recent years, the utilization of antibiotics in animal feed has been restricted, probiotics have been increasingly used to replace antibiotics in maintaining animal health. The aim of this study was to screen and evaluate probiotics with excellent probiotic potential from the gut of healthy goslings for clinical application. Thirteen strains of Bacillus (named AH-G201 to AH-G2013), including 2 strains of Bacillus subtilis (B. subtilis), 6 strains of Bacillus licheniformis (B. licheniformis) and 5 strains of Bacillus amyloliquefaciens (B. amyloliquefaciens), were isolated and identified. Then, acid and bile salts tolerance tests were performed to screen probiotics strains that could survive under different environments. The effects of screened probiotics on the growth of pathogenic Escherichia coli (E. coli) and Salmonella were assessed. Furthermore, we performed the drug resistance tests and safety tests in animals. The results showed that B. Subtilis AH-G201, B. licheniformis AH-G202 and AH-G204 exhibited higher gastrointestinal resistance under in vitro conditions, and showed a moderate level of resistance to the tested antibiotics. Importantly, AH-G201 and AH-G202 showed 24 to 60% inhibition rate against pathogenic E. coli and Salmonella. Moreover, the safety analysis of AH-G201 and AH-G202 suggested that the 2 probiotics strains have no adverse effects on body weight gain and feed intake in the broilers, and in addition, they have significantly improved growth performance. Finally, we analyzed effects of B. Subtilis AH-G201and B. licheniformis AH-G202 on growth performance, immune organ index and the feces microbes of broilers. The results showed that broilers fed with high doses (5 × 109 CFU/mL, for single strain) of a mixture of AH-G201 and AH-G202 exhibited good growth performance, and exhibited the greatest gain in spleen weight and the highest lactic acid bacteria counts. These findings indicate that the combined addition of B. Subtilis AH-G201 and B. licheniformis AH-G202 has the potential to replace antibiotics and to improve the growth performance of broilers.
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Bacillus , Probióticos , Animales , Pollos , Dieta/veterinaria , Escherichia coli , Gansos , Probióticos/farmacología , Bacillus subtilis/fisiología , Alimentación Animal/análisis , Antibacterianos/farmacologíaRESUMEN
COVID-19 appears to put people living with HIV and AIDS (PLWHA) at a higher risk of catastrophic consequences and mortality. However, investigations on the hesitancy and vaccination behavior of PLWHA in China were lacking compared to the general population. From January 2022 to March 2022, we conducted a multi-center cross-sectional survey of PLWHA in China. Logistic regression models were used to examine factors associated to vaccine hesitancy and COVID-19 vaccine uptake. Among 1424 participants, 108 participants (7.6%) were hesitant to be vaccinated while 1258 (88.3%) had already received at least one dose of the COVID-19 vaccine. Higher COVID-19 vaccine hesitancy was associated with older age, a lower academic level, chronic disease, lower CD4+ T cell counts, severe anxiety and despair, and high perception of illness. Lower education level, lower CD4+ T cell counts, and significant anxiety and depression were all associated with a lower vaccination rate. When compared to vaccinated participants, those who were not hesitant but nevertheless unvaccinated had a higher presence of chronic disease and lower CD4+ T cell count. Tailored interventions (e.g. targeted education programs) based on these linked characteristics were required to alleviate concerns for PLWHA in promoting COVID-19 vaccination rates, particularly for PLWHA with lower education levels, lower CD4+ T cell counts, and severe anxiety and depression.
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COVID-19 , Infecciones por VIH , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios Transversales , China/epidemiología , Infecciones por VIH/complicaciones , VacunaciónRESUMEN
In recent years, the convolution neural network has been the most widely used deep learning algorithm in the field of plant disease diagnosis and has performed well in classification. However, in practice, there are still some specific issues that have not been paid adequate attention to. For instance, the same pathogen may cause similar or different symptoms when infecting plant leaves, while the same pathogen may cause similar or disparate symptoms on different parts of the plant. Therefore, questions come up naturally: should the images showing different symptoms of the same disease be in one class or two separate classes in the image database? Also, how will the different classification methods affect the results of image recognition? In this study, taking rice leaf blast and neck blast caused by Magnaporthe oryzae, and rice sheath blight caused by Rhizoctonia solani as examples, three experiments were designed to explore how database configuration affects recognition accuracy in recognizing different symptoms of the same disease on the same plant part, similar symptoms of the same disease on different parts, and different symptoms on different parts. The results suggested that when the symptoms of the same disease were the same or similar, no matter whether they were on the same plant part or not, training combined classes of these images can get better performance than training them separately. When the difference between symptoms was obvious, the classification was relatively easy, and both separate training and combined training could achieve relatively high recognition accuracy. The results also, to a certain extent, indicated that the greater the number of images in the training data set, the higher the average classification accuracy.
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Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a crucial disease for wheat worldwide and constantly threatens wheat production in southwestern and northwestern China, where the environment is a good fit for Pst oversummering and overwintering. However, the underlying genetic dynamics of spring epidemic Pst populations across large areas of continuous planting in the southwestern and northwestern regions are poorly understood. A total of 2,103 Pst isolates were sampled in the spring of 2019 from the two agroecosystems and grouped into three horizontal spatial scales (countywide, provincial, and regional subpopulations) and two vertical spatial scales that consisted of elevational and geomorphic subpopulations. A total of 776 multilocus genotypes were identified, with the highest genetic diversity found in the northern and Sichuan populations, particularly in the Ningxia and Sichuan Basins, while the lowest genetic diversity was found in the Yunnan and Guizhou populations. Multivariate discriminant analysis of principal components (DAPC) and STRUCTURE (STRUCTURE 2.3.4) analyses revealed variation in the genotypic compositions of the molecular groups on horizontal and vertical dimensions from north to south or vice versa and from low to high or vice versa, respectively. The regional neighbor-joining tree revealed three large spatial structures consisting of the southwestern, the northwestern, and the Xinjiang regions, while the Tibetan population connected the southwestern and northwestern regions. The isolates of the Sichuan Basin were scattered over the four quartiles by principal coordinate analysis, which indicated frequent genotype interchange with others. Greater genetic differentiation was observed between the southwestern and northwestern regions. Linkage equilibrium (P ≥ 0.05) was detected on different spatial scales, suggesting that Pst populations are using sexual reproduction or mixed reproduction (sexual and clonal reproduction) in southwestern and northwestern China. IMPORTANCE Understanding the epidemiology and population genetics of plant pathogens is crucial to formulate efficient predictions of disease outbreaks and achieve sustainable integrated disease management, especially for pathogens with migratory capability. Here, this study covers the genetic homogeneity and heterogeneity of different geographical Pst populations on broad to fine spatial scales from the key epidemic regions of the two agroecosystems in China, where wheat stripe rust occurs annually. We provide knowledge of the population genetics of Pst and reveal that, for instance, there is greater genetic diversity in northwestern China, there are close genetic relationships between Yunnan and Guizhou and between Gansu-Ningxia and Qinghai, and there are effects of altitude on genetic compositions, etc. All of these findings clarify the genetic relationships and expand the insights into the population dynamics and evolutionary mechanisms of Pst in southwestern and northwestern China, providing a theoretical basis for achieving sustainable control of wheat stripe rust in key epidemic regions.
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Basidiomycota , Enfermedades de las Plantas , Basidiomycota/genética , China , Puccinia , TriticumRESUMEN
BACKGROUND: Dysregulated osteoclast activity due to altered osteoclast differentiation causes multiple bone diseases. Osteoclasts are multinucleated giant cells derived from hematopoietic stem cells and play a major role in bone absorption. However, the mechanisms underlying the tight regulation of osteoclast differentiation in multiple pathophysiological status remain unknown. RESULTS: We showed that Bhlhe40 upregulation is tightly associated with osteoclast differentiation and osteoporosis. Functionally, Bhlhe40 promoted osteoclast differentiation in vitro, and Bhlhe40 deficiency led to increased bone mass and decreased osteoclast differentiation in vivo. Moreover, Bhlhe40 deficient mice resisted estrogen deficiency and aging-induced osteoporosis. Mechanism study showed that the increase in bone mass due to Bhlhe40 deficiency was a cell intrinsic defect in osteoclast differentiation in these mice. BHLHE40 upregulated the gene expression of Fos and Nfatc1 by directly binding to their promoter regions. Notably, inhibition of Fos/Nfatc1 abrogated the enhanced osteoclast differentiation induced by BHLHE40 overexpression. CONCLUSIONS: Our research reveals a novel Bhlhe40/c-Fos/Nfatc1 axis involved in regulating osteoclastogenesis and shows that osteoporosis caused by estrogen deficiency and aging can be rescued by regulating Bhlhe40 in mice. This may help in the development of a new strategy for the treatment of osteoporosis.