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Alzheimer's disease (AD) has gradually received enthusiastic attention with the aging process, and studying its biological relevance is expected. Excitingly, fluorescence probes were considered to be powerful tools for exploring biological correlations. Therefore, a highly selective near-infrared (NIR) fluorescent probe (DCM-Cl-Acr) for imaging cysteine (Cys) in AD was designed and synthesized. Through structural optimization, the probe exhibited high fluorescence quantum yield and low detection limit (20 nM) towards Cys. Meanwhile, based on the high selectivity and high sensitivity response exhibited by the probe to Cys, it was successfully applied to visualize endogenous and exogenous Cys in living cells and zebrafish, and showed good discrimination from homocysteine (Hcy) and glutathione (GSH). Further, the correlation between AD and Cys concentration was clarified by imaging studies in hippocampus tissue of AD mouse, and the abnormal accumulation of Cys in the hippocampus of AD brain was demonstrated.
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Enfermedad de Alzheimer , Cisteína , Colorantes Fluorescentes , Pez Cebra , Cisteína/análisis , Cisteína/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Animales , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico , Ratones , Humanos , Hipocampo/diagnóstico por imagen , Hipocampo/metabolismo , Hipocampo/química , Imagen Óptica/métodos , Rayos InfrarrojosRESUMEN
The pharmacokinetics (PK) of Rhodiola crenulata in rats were studied, and pharmacokinetic-pharmacodynamic (PK-PD) correlation analysis was performed to elucidate their time-concentration-effect relationship. The myocardial ischemia model was made with pituitrin. Rats were divided into sham operation, sham operation administration, model, and model administration groups (SG, SDG, MG, and MDG, respectively; n = 6). Blood was collected from the fundus venous plexus at different time points after oral administration. The HPLC-QQQ-MS/MS method was established for the quantification of five components of Rhodiola crenulata. CK, HBDH, SOD, LDH, and AST at different time points were detected via an automatic biochemical analyzer. DAS software was used to analyze PK parameters and PK-PD correlation. The myocardial ischemia model was established successfully. There were significant differences in the PK parameters (AUC0-t, AUC0-∞, Cmax) in MDG when compared with SDG. Two PD indicators, CK and HBDH, conforming to the sigmoid-Emax model, had high correlation with the five components, which indicated a delay in the pharmacological effect relative to the drug concentration in plasma. The difference in the PK parameters between modeled and normal rats was studied, and the time-concentration-effect of composition and effect indicators were investigated. This study can provide reference for the rational clinical application of Rhodiola crenulata and for related studies of other anti-myocardial ischemia drugs.
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Triboelectric polymers have attracted extensive attention due to their great electron-accepting and electron-donating properties in contact electrification as well as their flexible and low-cost merits and have become promising electrode materials in triboelectric nanogenerators (TENGs). However, most research has exclusively focused on improving the electron capture capability of the triboelectric layer, neglecting to enhance the electron-donating capability, which leads to a low output performance of TENG and limits its practical application. In this study, we developed a method to fabricate highly tribo-positive Nylon-11 film through roll-to-roll processing. Paired with the poly(tetrafluoroethylene) triboelectric layer, the transferred charge density of contact-separation TENG based on Nylon-11 film prepared by this method reaches 291.1 µC/m2, which has been improved by 12.4% compared with the conventional compression molding sample. The novel fabricating method can regulate the surface functional groups to achieve higher surface potential and obtain a favorable pseudohexagonal crystal phase, leading to an increasing transferred charge density in triboelectrification. Additionally, it has been analyzed that higher chemical potential of materials can facilitate the transfer of electrons from the triboelectric polymer surface. This study provides a nonadditive, simple, and effective strategy to fabricate excellent tribo-positive material, which can significantly enhance the performance of TENG.
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ß-Galactosidase (ß-gal), an enzyme related to cell wall degradation, plays an important role in regulating cell wall metabolism and reconstruction. However, activatable fluorescence probes for the detection and imaging of ß-gal fluctuations in plants have been less exploited. Herein, we report an activatable fluorescent probe based on intramolecular charge transfer (ICT), benzothiazole coumarin-bearing ß-galactoside (BC-ßgal), to achieve distinct in situ imaging of ß-gal in plant cells. It exhibits high sensitivity and selectivity to ß-gal with a fast response (8 min). BC-ßgal can be used to efficiently detect the alternations of intracellular ß-gal levels in cabbage root cells with considerable imaging integrity and imaging contrast. Significantly, BC-ßgal can assess ß-gal activity in cabbage roots under heavy metal stress (Cd2+, Cu2+, and Pb2+), revealing that ß-gal activity is negatively correlated with the severity of heavy metal stress. Our work thus facilitates the study of ß-gal biological mechanisms.
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Brassica , Colorantes Fluorescentes , Metales Pesados , Raíces de Plantas , beta-Galactosidasa , beta-Galactosidasa/metabolismo , beta-Galactosidasa/química , Brassica/química , Brassica/metabolismo , Brassica/enzimología , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Colorantes Fluorescentes/química , Metales Pesados/metabolismo , Metales Pesados/análisis , Imagen Óptica , Proteínas de Plantas/metabolismoRESUMEN
OBJECTIVE: Pure tone audiometry has played a critical role in audiology as the initial diagnostic tool, offering vital insights for subsequent analyses. This study aims to develop a robust deep learning framework capable of accurately classifying audiograms across various commonly encountered tasks. DESIGN, SETTING, AND PARTICIPANTS: This single-centre retrospective study was conducted in accordance with the STROBE guidelines. A total of 12 518 audiograms were collected from 6259 patients aged between 4 and 96 years, who underwent pure tone audiometry testing between February 2018 and April 2022 at Tongji Hospital, Tongji Medical College, Wuhan, China. Three experienced audiologists independently annotated the audiograms, labelling the hearing loss in degrees, types and configurations of each audiogram. MAIN OUTCOME MEASURES: A deep learning framework was developed and utilised to classify audiograms across three tasks: determining the degrees of hearing loss, identifying the types of hearing loss, and categorising the configurations of audiograms. The classification performance was evaluated using four commonly used metrics: accuracy, precision, recall and F1-score. RESULTS: The deep learning method consistently outperformed alternative methods, including K-Nearest Neighbors, ExtraTrees, Random Forest, XGBoost, LightGBM, CatBoost and FastAI Net, across all three tasks. It achieved the highest accuracy rates, ranging from 96.75% to 99.85%. Precision values fell within the range of 88.93% to 98.41%, while recall values spanned from 89.25% to 98.38%. The F1-score also exhibited strong performance, ranging from 88.99% to 98.39%. CONCLUSIONS: This study demonstrated that a deep learning approach could accurately classify audiograms into their respective categories and could contribute to assisting doctors, particularly those lacking audiology expertise or experience, in better interpreting pure tone audiograms, enhancing diagnostic accuracy in primary care settings, and reducing the misdiagnosis rate of hearing conditions. In scenarios involving large-scale audiological data, the automated classification system could be used as a research tool to efficiently provide a comprehensive overview and statistical analysis. In the era of mobile audiometry, our deep learning framework can also help patients quickly and reliably understand their self-tested audiograms, potentially encouraging timely consultations with audiologists for further evaluation and intervention.
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Audiometría de Tonos Puros , Aprendizaje Profundo , Pérdida Auditiva , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Audiometría de Tonos Puros/métodos , Adolescente , Anciano , Masculino , Femenino , Adulto , Anciano de 80 o más Años , Niño , Preescolar , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/clasificación , Adulto Joven , ChinaRESUMEN
BACKGROUND: Many studies have found an association between mood-disorder-related traits and endometriosis and adenomyosis. However, the cause-effect relationship remains unclear. AIMS: We conducted Mendelian randomisation analyses to evaluate any causal relationship between mood disorders and endometriosis as well as different sites of endometriosis. METHOD: Summary-level statistics for mood-disorder-related traits and endometriosis (8288 cases, 68 969 controls) in European populations were derived from large-scale data-sets of genome-wide association studies. A two-sample Mendelian randomisation was performed using the inverse-variance weighted and weight median methods. Further sensitivity analyses, including heterogeneity, pleiotropy and leave-one-out analyses, were conducted to test the consistency of the results. RESULTS: Genetically determined mood swings (odds ratio = 2.557, 95% CI: 1.192-5.483, P = 0.016) and major depression (odds ratio = 1.233, 95% CI: 1.019-1.493, P = 0.031) were causally associated with an increased risk of endometriosis. Mood swings (odds ratio = 4.238, 95% CI: 1.194-15.048, P = 0.025) and major depression (odds ratio = 1.512, 95% CI: 1.052-2.173, P = 0.025) were also causally associated with the risk of adenomyosis. Sensitivity analyses confirmed the reliability of the results. CONCLUSIONS: Our results suggest that mood-disorder-related traits increase the risk of endometriosis and adenomyosis. This study provides new insights into the potential pathogenesis of endometriosis and adenomyosis, and highlights the importance of preventing endometriosis and adenomyosis in patients with mood-disorder-related traits.
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Universal approximation capability, also referred to as universality, is an important property of deep neural networks, endowing them with the potency to accurately represent the underlying target function in learning tasks. In practice, the architecture of deep neural networks largely influences the performance of the models. However, most existing methodologies for designing neural architectures, such as the heuristic manual design or neural architecture search, ignore the universal approximation property, thus losing a potential safeguard about the performance. In this paper, we propose a unified framework to design the architectures of deep neural networks with a universality guarantee based on first-order optimization algorithms, where the forward pass is interpreted as the updates of an optimization algorithm. The (explicit or implicit) network is designed by replacing each gradient term in the algorithm with a learnable module similar to a two-layer network or its derivatives. Specifically, we explore the realm of width-bounded neural networks, a common practical scenario, showcasing their universality. Moreover, adding operations of normalization, downsampling, and upsampling does not hurt the universality. To the best of our knowledge, this is the first work that width-bounded networks with universal approximation guarantee can be designed in a principled way. Our framework can inspire a variety of neural architectures including some renowned structures such as ResNet and DenseNet, as well as novel innovations. The experimental results on image classification problems demonstrate that the newly inspired networks are competitive and surpass the baselines of ResNet, DenseNet, as well as the advanced ConvNeXt and ViT, testifying to the effectiveness of our framework.
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STUDY QUESTION: Does a matrix-free culture system supplemented with neurotrophic factor 4 (NT4) improve human in vitro follicular development and meiotic maturation, ultimately resulting in fertilizable oocytes? SUMMARY ANSWER: NT4 supplementation of in vitro culture significantly enhances the growth, steroid hormone production, and maturity potential of human secondary follicles derived from fresh ovarian medulla (from post- and pre-pubertal patients), thereby yielding fertilizable oocytes. WHAT IS KNOWN ALREADY: Reconstituting folliculogenesis in vitro is of paramount importance in the realms of fertility preservation, reproductive biology research, and reproductive toxicity assessments. However, the efficiency of in vitro culture systems remains suboptimal, as the attainment of fertilizable oocytes from in vitro growth (IVG) of human follicles remains unachieved, with the data being particularly scant regarding follicles from prepubertal girls. We have previously found that mouse oocytes from secondary follicles derived from IVG are deficient in neuroendocrine regulation. NT4 and its corresponding receptor have been identified in human follicles. Significantly, the addition of NT4 during the IVG process markedly enhances both follicle growth and oocyte maturation rates in mice. STUDY DESIGN SIZE DURATION: Fresh medulla tissue obtained during tissue preparation for ovarian tissue cryopreservation (OTC) were collected from 10 patients aged from 6 to 21 years old, all of whom had undergone unilateral oophorectomy as a means of fertility preservation. Isolated secondary follicles were individually cultured in vitro with or without NT4 in a matrix-free system. PARTICIPANTS/MATERIALS SETTING METHODS: Secondary follicles, extracted via enzymatic digestion and mechanical disruption from each patient, were randomly allocated to either a control group or an NT4-supplemented group (100 ng/ml), followed by individual culture on an ultra-low attachment plate. Follicle growth and viability were assessed by microscopy. Levels of anti-Müllerian hormone (AMH), estradiol, and progesterone in the medium were quantified. An oocyte-specific marker was identified using confocal fluorescence microscopy following DEAD box polypeptide 4 (DDX4) staining. The competence of individual oocytes for maturation and fertilization were assessed after IVM and ICSI with donated sperm samples. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, isolated follicles from both groups survived up to 6 weeks with increasing diameters over the duration (P < 0.05), reaching terminal diameters of almost 1 mm with confirmed steroidogenesis and expression of oocyte marker (DDX4), and producing morphologically normal MII oocytes. When compared with the control group, the NT4 group had a similar initial follicular diameter (206 ± 61.3 vs 184 ± 93.4 µm) but exhibited a significant increase in follicular diameter from the ninth day of culture onwards (P < 0.05). From Week 3, estradiol and progesterone production were significantly increased in the NT4 group, while no significant difference was observed in AMH production between groups. The proportion of 'fast-growth' follicles in the NT4 group was significantly higher than that in the control group (13/23 vs 6/24, P < 0.05). An increased efficiency of MII oocyte maturation per live follicle in the NT4 group was also observed (control group vs NT4 group, 4/24 vs 10/23, P < 0.05). It is noteworthy that an MII oocyte obtained from the control group exhibited abnormal fertilization after ICSI. In contrast, an MII oocyte acquired from the NT4 group progressed to the blastocyst stage and showed potential for transfer. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The cohort examined in this study was all patients diagnosed with beta-thalassemia major. Whether this culture system is effective for patients with other diseases remains unknown. Since the chosen dose of NT4 was established based on dose finding in mice, the optimal dose for use in a human IVG system needs further confirmation. The oocytes and embryos procured from this study have not been quantified for ploidy status or epigenetic signatures. WIDER IMPLICATIONS OF THE FINDINGS: Fresh medulla tissue obtained during tissue preparation for OTC may serve as a precious source of fertilizable oocytes for female fertility preservation, even for pre-pubertal girls, without the threat of tumour reintroduction. After further characterization and optimization of the system, this culture system holds the potential to provide a powerful future research tool, for the comprehensive exploration of human follicular development mechanisms and for conducting reproductive toxicity evaluations. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Key R&D Program of China (grant number 2022YFC2703000) and National Natural Science Foundation of China (grant numbers 82271651 and 81871214). The medium used in human follicle in vitro culture in this study has been applied for a national invention patent in China (No. 202211330660.7). The inventors of the patent, in order, are: Y.G., C.F., and X.L.
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Cerebral ischemia-reperfusion injury (CIRI), a cause of cerebral dysfunction during cerebral infarction treatment, is closely associated with mitochondrial viscosity and hydrogen peroxide (H2O2). However, the accurate measurement of mitochondrial viscosity and H2O2 levels in CIRI is challenging because of the lack of sufficient selectivity and blood-brain barrier (BBB) penetration of existing monitoring tools related to CIRI, hampering the exploration of the role of mitochondrial viscosity and H2O2 in CIRI. To address this issue, we designed an activatable fluorescent probe, mitochondria-targeting styryl-quinolin-ium (Mito-IQS), with excellent properties including high selectivity, mitochondrial targeting, and BBB penetration, for the visualization of mitochondrial viscosity and H2O2 in the brain. Based on the real-time monitoring capabilities of the probe, bursts of mitochondrial viscosity and H2O2 levels were visualized during CIRI. This probe can be used to monitor the therapeutic effects of butylphthalein treatment. More importantly, in vivo experiments further confirmed that CIRI was closely associated with the mitochondrial viscosity and H2O2 levels. This discovery provides new insights and tools for the study of CIRI and is expected to accelerate the process of CIRI diagnosis, treatment, and drug design.
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Isquemia Encefálica , Daño por Reperfusión , Humanos , Peróxido de Hidrógeno , Colorantes Fluorescentes , Viscosidad , MitocondriasRESUMEN
Lysine crotonylation (Kcr), a newly discovered post-translational modification, played a crucial role in physiology and disease progression. However, the roles of crotonylation in oocyte meiotic resumption remain elusive. As abnormal cumulus cell development will cause oocyte maturation arrest and female infertility, we report that cumulus cells surrounding human meiotic arrested oocytes showed significantly lower crotonylation, which was associated with decreased EP300 expression and blocked cumulus cell expansion. In cultured human cumulus cells, exogenous crotonylation or EP300 activator promoted cell proliferation and reduced cell apoptosis, whereas EP300 knockdown induced the opposite effect. Transcriptome profiling analysis in human cumulus cells indicated that functions of crotonylation were associated with activation of epidermal growth factor receptor (EGFR) pathway. Importantly, we characterized the Kcr proteomics landscape in cumulus cells by LC-MS/MS analysis, and identified that annexin A2 (ANXA2) was crotonylated in cumulus cells in an EP300-dependent manner. Crotonylation of ANXA2 enhanced the ANXA2-EGFR binding, and then activated the EGFR pathway to affect cumulus cell proliferation and apoptosis. Using mouse oocytes IVM model and EP300 knockout mice, we further confirmed that crotonylation alteration in cumulus cells affected the oocyte maturation. Together, our results indicated that EP300-mediated crotonylation is important for cumulus cells functions and oocyte maturation.
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Anexina A2 , Células del Cúmulo , Animales , Ratones , Femenino , Humanos , Células del Cúmulo/metabolismo , Anexina A2/metabolismo , Anexina A2/farmacología , Cromatografía Liquida , Espectrometría de Masas en Tándem , Oocitos , Receptores ErbB/metabolismo , Proteína p300 Asociada a E1A/metabolismoRESUMEN
OBJECTIVE: The probability of embryo implantation in an abnormal location is significantly higher in assisted reproductive technology (ART) than in natural pregnancies. Angular pregnancy is an eccentric intrauterine pregnancy with embryo implantation in the lateral superior angle of the uterine cavity. Cycle-level factors associated with angular pregnancy in patients conceived with ART needed to be explored. METHODS: A total of 11 336 clinical pregnancies cycles were included. Angular pregnancy rate was compared among groups according to the type of embryos transferred. Among them, 53 cases of angular pregnancy and 159 cases of normal intrauterine pregnancy were screened out using propensity score matching. Risk factors of angular pregnancy were explored. RESULTS: The angular pregnancy rate was 0.31% (14/4572) in the day 5 blastocyst transfer group, 0.58% (39/6764) in non-day 5 embryo transfer group, with 0.55% (29/5280) in day 3 embryo transfer and 0.67% (10/1484) in the day 6 blastocyst group, respectively. A multifactor regression analysis was performed and indicated that the number of embryos transferred was significantly associated with angular pregnancy (P = 0.031, OR, 2.23, 95% CI: 1.09-4.68). CONCLUSION: Multiple embryo transfer could possibly be associated with an increased incidence of angular pregnancy in patients conceived with ART.
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Embarazo Angular , Embarazo Múltiple , Embarazo , Femenino , Humanos , Fertilización In Vitro , Transferencia de Embrión/efectos adversos , Índice de Embarazo , Blastocisto , Estudios RetrospectivosRESUMEN
To explore an appropriate time interval between oocyte retrieval and intracytoplasmic sperm injection (ICSI) for optimal embryological and clinical outcomes in ICSI cycles over 40 years of maternal age. A retrospective analysis of 1476 ICSI fresh cycles from women aged over 40 years, was performed at the Reproduction Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University, between December 2013 and August 2020. The fertilization rate and clinical pregnancy rate were the main outcomes. Multivariate linear regression and logistic regression analysis of factors showed that fertilization rate (P = 0.024) and clinical pregnancy rate (P = 0.011) were significantly associated with oocyte pick up (OPU)-ICSI interval. A longer OPU-ICSI interval (no more than 6 h) was associated with a higher fertilization rate but significantly decreased the clinical pregnancy rate when the OPU-ICSI interval was over 4 h (P < 0.05). The optimal OPU-ICSI interval is between 3 and 4 h for excellent embryological and clinical outcomes in ICSI cycles over 40 years of maternal age.
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Recuperación del Oocito , Semen , Masculino , Embarazo , Humanos , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas , HospitalesRESUMEN
The ongoing epidemic of SARS-CoV-2 is taking a substantial financial and health toll on people worldwide. Assessing the level and duration of SARS-CoV-2 neutralizing antibody (Nab) would provide key information for government to make sound healthcare policies. Assessed at 3-, 6-, 12-, and 18-month postdischarge, we described the temporal change of IgG levels in 450 individuals with moderate to critical COVID-19 infection. Moreover, a data imputation framework combined with a novel deep learning model was implemented to predict the long-term Nab and IgG levels in these patients. Demographic characteristics, inspection reports, and CT scans during hospitalization were used in this model. Interpretability of the model was further validated with Shapely Additive exPlanation (SHAP) and Gradient-weighted Class Activation Mapping (GradCAM). IgG levels peaked at 3 months and remained stable in 12 months postdischarge, followed by a significant decline in 18 months postdischarge. However, the Nab levels declined from 6 months postdischarge. By training on the cohort of 450 patients, our long-term antibody prediction (LTAP) model could predict long-term IgG levels with relatively high area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score, which far exceeds the performance achievable by commonly used models. Several prognostic factors including FDP levels, the percentages of T cells, B cells and natural killer cells, older age, sex, underlying diseases, and so forth, served as important indicators for IgG prediction. Based on these top 15 prognostic factors identified in IgG prediction, a simplified LTAP model for Nab level prediction was established and achieved an AUC of 0.828, which was 8.9% higher than MLP and 6.6% higher than LSTM. The close correlation between IgG and Nab levels making it possible to predict long-term Nab levels based on the factors selected by our LTAP model. Furthermore, our model identified that coagulation disorders and excessive immune response, which indicate disease severity, are closely related to the production of IgG and Nab. This universal model can be used as routine discharge tests to identify virus-infected individuals at risk for recurrent infection and determine the optimal timing of vaccination for general populations.
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COVID-19 , Aprendizaje Profundo , Humanos , Anticuerpos Neutralizantes , SARS-CoV-2 , Cuidados Posteriores , Estudios Prospectivos , COVID-19/diagnóstico , Alta del Paciente , China/epidemiología , Anticuerpos Antivirales , Inmunoglobulina GRESUMEN
Dual-atom catalysts, particularly those with heteronuclear active sites, have the potential to outperform the well-established single-atom catalysts for oxygen evolution reaction, but the underlying mechanistic understanding is still lacking. Herein, a large-scale density functional theory is employed to explore the feasibility of *O-*O coupling mechanism, which can circumvent the scaling relationship with improving the catalytic performance of N-doped graphene supported Fe-, Co-, Ni-, and Cu-containing heteronuclear dual-atom catalysts, namely, M'M@NC. Based on the constructed activity maps, a rationally designed descriptor can be obtained to predict homonuclear catalysts. Seven heteronuclear and four homonuclear dual-atom catalysts possess high activities that outperform the minimum theoretical overpotential. The chemical and structural origin in favor of *O-*O coupling mechanism thus leading to enhanced reaction activity have been revealed. This work not only provides additional insights into the fundamental understanding of reaction mechanisms, but also offers a guideline for the accelerated discovery of efficient catalysts.
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Atomically precise copper nanoclusters (Cu NCs) have attracted tremendous attention for their huge potential in many applications. However, the uncertainty of the growth mechanism and complexity of the crystallization process hinder the in-depth understanding of their properties. In particular, the ligand effect has been rarely explored at the atomic/molecular level due to the lack of feasible models. Herein, three isostructural Cu6 NCs ligated with diverse mono-thiol ligands (2-mercaptobenzimidazole, 2-mercaptobenzothiazole, and 2-mercaptobenzoxazole, respectively) are successfully synthesized, which provide an ideal platform to unambiguously address the intrinsic role of ligands. The overall atom-by-atom structural evolution process of Cu6 NCs is mapped out with delicate mass spectrometry (MS) for the first time. It is intriguingly found that the ligands, albeit only atomic difference (NH, O, and S), can profoundly affect the building-up processes, chemical properties, atomic structures, as well as catalytic activities of Cu NCs. Furthermore, ion-molecule reactions combined with density functional theory (DFT) calculations demonstrate that the defective sites formed on ligand can significantly contribute to the activation of molecular oxygen. This study provides fundamental insights into the ligand effect, which is vital for the delicate design of high-efficient Cu NCs-based catalysts.
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Poly(lactic acid) (PLA), as a biodegradable material, finds wide applications in packaging, automotive, and biological industries. However, achieving high strength, toughness, ultra-transparency, and heat resistance simultaneously in pure PLA through continuous one-step manufacturing remains a significant challenge. In this study, we addressed this challenge by utilizing the eccentric rotor extruder (ERE) in combination with cooling rolls to manufacture PLA sheets with outstanding mechanical performance. The ERE's elongational flow field combined with the cooling roller's weak stretching action induced orientation in the PLA molecular chains and promoted the formation of more mesophase, significantly improving mechanical properties. When the extrusion-stretch ratio (λ) value was 3.5, the tensile yield strength, Young's modulus, and elongation at break of ERE-fabricated samples ER-3.5 reached 86.2 MPa, 1777 MPa, and 57.9 %, respectively. Compared to the SE-3.5 samples manufactured with traditional methods, the increases were 38.8 %, 25.8 %, and 9.4 times, respectively. Additionally, the ERE manufactured samples maintained ultra-transparency and high heat resistance, making them suitable for food packaging, biomedicine, and other related fields. This methodology provides an efficient industrial-scale approach for manufacturing neat, biodegradable PLA with outstanding mechanical performance and ultra-transparency.
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Calor , Poliésteres , Transición de Fase , FríoRESUMEN
Microporous organic polymers (MOPs) are a new type of porous materials, which have advantages of synthetic diversity, chemical and physical stability, microporous size controllability, etc. MOPs indicate broad applications in various fields such as heterogeneous catalysis, gas adsorption, separation, and storage. In recent years, MOPs have attracted an enormous attention in greenhouse gas capture due to their great potential in physisorptive gas storage. Carbazole and its derivatives have been studied extensively as Metal-Organic Polyhedra (MOPs) building blocks due to their unique structural features and versatile functionalization possibilities. This paper systematically reviews the synthesis, characterization and application of carbazole-based polymers, and relationship of structures and properties of these polymers. The application of the polymers in carbon dioxide (CO2) capture field is analysed taking advantage of their adjustable microporous structure and electron rich properties. This review also provides novel insights regarding functional polymer materials that have high ability of greenhouse gas capture and absorbing selectivity will be obtained by reasonable molecular design and efficient synthesis.
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The aim of the study was to compare retrospectively the extent of blastulation timing (Day 5 or later) and expansion grade to predict the ability of blastocysts to give rise to a pregnancy. Blastocysts frozen on day 5 with a lower expansion grade (group D5) or day 6 with a higher expansion grade (group D6) were included. A single embryo was thawed and transferred on day 5 after ovulation or progesterone supplementation. Differences in patient baseline characteristics, endometrial preparation and pregnancy outcomes between groups were stratified by patient age and anti-Müllerian hormone (AMH) levels. Logistic regression was used to analyse the results. A total of 617 blastocysts in group D5 and 1134 blastocysts in group D6 were assessed. Stratified analyses showed higher biochemical pregnancy, clinical pregnancy and live birth rates for patients aged less than 30 years old, and higher ongoing pregnancy rate for patients with AMH ≥ 1.1 ng/ml. For patients aged less than 30 years old, the biochemical pregnancy, clinical pregnancy and live birth rates in group D5 were higher than those in group D6.
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Criopreservación , Implantación del Embrión , Embarazo , Femenino , Humanos , Adulto , Estudios Retrospectivos , Criopreservación/métodos , Transferencia de Embrión/métodos , Resultado del Embarazo , Índice de Embarazo , BlastocistoRESUMEN
We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.
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COVID-19 , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19 , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Glicoproteína de la Espiga del Coronavirus/química , Pruebas de NeutralizaciónRESUMEN
Objective: To explore the possible mechanisms of cholestasis induced by Polygoni Multiflori Radix (PM). Methods: Low and high doses of water extract of PM were given to mice by gavage for 8 weeks. The serum biochemical indexes of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (GGT) alkaline phosphatase (ALP) and so on were detected in the second, fourth, sixth, and eighth weeks after administration. At the end of the eighth week of administration, the bile acid metabolic profiles of liver and bile were screened by high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS). Liver pathological changes were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA transcription of the target genes and Western blotting (WB) was used to the detect target protein expression. Results: Biochemical tests results showed the values of ALP and GGT were two and three times greater than the normal values respectively, and the value of R was less than 2. Histopathology also showed that PM caused lymphocyte infiltration, a small amount of hepatocyte necrosis and nuclear fragmentation in mouse liver. The proliferation of bile duct epithelial cells was observed in the high group. These results indicated that PM may lead to cholestatic liver injury. HPLC-QQQ-MS/MS analysis with the multivariate statistical analysis revealed significant alterations of individual bile acids in liver and gallbladder as compared to those of the control group. RT-qPCR showed that the transcription of Fxr, Shp, Bsep, Bacs, Mdr2, and Ugt1a1 were downregulated and that of Cyp7a1, Mrp3, and Cyp3a11 was significantly upregulated in the treatment group. WB demonstrated that PM also markedly downregulated the protein expression of FXR, BSEP, and MDR2, and upregulated CYP7A1. Conclusion: PM inhibited the expression of FXR, which reduced the expression of MDR2 and BSEP, leading to the obstruction of bile acids outflow, and increased the expression of CYP7A1, resulting in an increase of intrahepatic bile acid synthesis, which can lead to cholestasis.