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The mammalian brain is composed of diverse, specialized cell populations. To systematically ascertain and learn from these cellular specializations, we used Drop-seq to profile RNA expression in 690,000 individual cells sampled from 9 regions of the adult mouse brain. We identified 565 transcriptionally distinct groups of cells using computational approaches developed to distinguish biological from technical signals. Cross-region analysis of these 565 cell populations revealed features of brain organization, including a gene-expression module for synthesizing axonal and presynaptic components, patterns in the co-deployment of voltage-gated ion channels, functional distinctions among the cells of the vasculature and specialization of glutamatergic neurons across cortical regions. Systematic neuronal classifications for two complex basal ganglia nuclei and the striatum revealed a rare population of spiny projection neurons. This adult mouse brain cell atlas, accessible through interactive online software (DropViz), serves as a reference for development, disease, and evolution.
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Encéfalo/metabolismo , Linhagem da Célula , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Análise de Célula Única/métodos , Transcriptoma , Animais , Encéfalo/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
(1) Currently, the survival prognosis for patients with relapsed and refractory acute myeloid leukemia (R/R AML) is extremely poor. Therefore, the exploration of novel drugs is imperative to enhance the prognosis of patients with R/R AML. The therapeutic efficacy and mechanism of Chidamide, a novel epigenetic regulatory drug, in the treatment of R/R AML remain unclear. METHODS: The mechanism of action of Chidamide has been explored in various AML cell lines through various methods such as cell apoptosis, cell cycle analysis, high-throughput transcriptome sequencing, gene silencing, and xenograft models. RESULTS: Here, we have discovered that chidamide potently induces apoptosis, G0/G1 phase arrest, and mitochondrial membrane potential depolarization in R/R AML cells, encompassing both primary cells and cell lines. Through RNA-seq analysis, we further revealed that chidamide epigenetically regulates the upregulation of differentiation-related pathways while suppressing those associated with cell replication and cell cycle progression. Notably, our screening identified NR4A3 as a key suppressor gene whose upregulation by chidamide leads to P21-dependent cell cycle arrest in the G0/G1 phase. CONCLUSIONS: We have discovered a novel epigenetic regulatory mechanism of chidamide in the treatment of relapsed and refractory acute myeloid leukemia (R/R AML).
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Deep learning holds great potential for expediting the discovery of new polymers from the vast chemical space. However, accurately predicting polymer properties for practical applications based on their monomer composition has long been a challenge. The main obstacles include insufficient data, ineffective representation encoding, and lack of explainability. To address these issues, we propose an interpretable model called the Polymer Graph Convolutional Neural Network (PGCNN) that can accurately predict various polymer properties. This model is trained using the RadonPy data set and validated using experimental data samples. By integrating evidential deep learning with the model, we can quantify the uncertainty of predictions and enable sample-efficient training through uncertainty-guided active learning. Additionally, we demonstrate that the global attention of the graph embedding can aid in discovering underlying physical principles by identifying important functional groups within polymers and associating them with specific material attributes. Lastly, we explore the high-throughput screening capability of our model by rapidly identifying thousands of promising candidates with low and high thermal conductivity from a pool of one million hypothetical polymers. In summary, our research not only advances our mechanistic understanding of polymers using explainable AI but also paves the way for data-driven trustworthy discovery of polymer materials.
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Aprendizado Profundo , Polímeros , Polímeros/química , Incerteza , Redes Neurais de ComputaçãoRESUMO
A two-stage decoupling model based on an artificial neural network with polynomial regression is proposed for the six-component force sensor load decoupling problem in the case of multidimensional mixed loading. The six-dimensional load categorization stage model constructed in the first stage combines 63 load category label sets with a deep BP neural network. The six-dimensional load regression stage model was constructed by combining polynomial regression with a BP neural network in the second stage. Meanwhile, the six-component force sensor with a fiber Bragg grating (FBG) sensor as the sensitive element was designed, and the elastomer simulation and calibration experimental dataset was established to realize the validation of the two-stage decoupling model. The results based on the simulation data show that the accuracy of the classification stage is 93.65%. The MAPE for the force channel in the regression stage is 6.29%, and 3.24% for the moment channel. The results based on experimental data show that the accuracy of the classification stage is 87.80%. The MAPE for the force channel in the regression phase is 5.63%, and 4.82% for the moment channel.
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Introduction: It was intended to research the level changes and clinical significance of interleukin (IL)-10, transforming growth factor ß1 (TGF-ß1), and CD4+CD25 cytokines in paediatric allergic rhinitis (AR) accompanied with allergic asthma (AA). Material and methods: Eighty children of AA with AR receiving immunotherapy indications were included as the experimental group (EG), while another 40 healthy children in the same period were selected as the control group (CG). IL-10, TGF-ß1, and CD4+CD25 levels in cells of the two groups before and after treatment were compared and analysed. Results: The serum TGF-ß1 level was determined as 1,045.7 ±44.7 pg/ml in the EG at admission, remarkably higher than that in the CG (p < 0.05). The IL-10 level was 21.4 ±2.8 pg/ml; CD4+CD25 cells accounted for 9.2 ±2.4%, CD4+CD25high cells accounted for 0.6 ±0.3%. These were all greatly lower than those in the CG (p < 0.05). At discharge, the serum TGF-ß1 level in the EG was 903.7 ±29.4 pg/ml, which was still memorably higher than that in the CG (p < 0.05). The IL-10 level changed to 32.8 ±3.7 pg/ml; the percentage of CD4+CD25 was 11.3 ±1.8, respectively, among CD4+T cells. These were also notably lower than those in the CG at discharge (p < 0.05). Conclusions: IL-10, TGF-ß1, and CD4+CD25 level changes in cells might be of reference value as therapeutic indicators for clinical treatment or evaluation of paediatric AR with AA.
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Neuropeptides play pivotal roles in different physiological processes and are related to different kinds of diseases. Identification of neuropeptides is of great benefit for studying the mechanism of these physiological processes and the treatment of neurological disorders. Several state-of-the-art neuropeptide predictors have been developed by using a two-layer stacking ensemble algorithm. Although the two-layer stacking ensemble algorithm can improve the feature representability, these models are complex, which are not as efficient as the models based on one classifier. In this study, we proposed a new model, NeuroPpred-SVM, to predict neuropeptides based on the embeddings of Bidirectional Encoder Representations from Transformers and other sequential features by using a support vector machine (SVM). The experimental results indicate that our model achieved a cross-validation area under the receiver operating characteristic (AUROC) curve of 0.969 on the training data set and an AUROC of 0.966 on the independent test set. By comparing our model with the other four state-of-the-art models including NeuroPIpred, PredNeuroP, NeuroPpred-Fuse, and NeuroPpred-FRL on the independent test set, our model achieved the highest AUROC, Matthews correlation coefficient, accuracy, and specificity, which indicate that our model outperforms the existing models. We believed that NeuroPpred-SVM could be a useful tool for identifying neuropeptides with high accuracy and low cost. The data sets and Python code are available at https://github.com/liuyf-a/NeuroPpred-SVM.
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Neuropeptídeos , Máquina de Vetores de Suporte , Algoritmos , Curva ROC , Área Sob a CurvaRESUMO
Recent developments in molecular biological technologies and genetic diagnostic methods, accompanying with updates of relevant terminologies, have enabled the improvements of new strategies of preimplantation genetic testing for monogenic (single gene) disorders (PGT-M) to prevent the transmission of inherited diseases. However, there has been much in the way of published consensus on PGT-M. To properly regulate the application of PGT-M, Chinese experts in reproductive medicine and genetics have jointly developed this consensus statement. The consensus includes indications for patient selection, genetic and reproductive counseling, informed consent, diagnostic strategies, report generation, interpretation of results and patient follow-ups. This consensus statement serves to assist in establishment of evidence-based clinical and laboratory practices for PGT-M.
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Diagnóstico Pré-Implantação , Feminino , Humanos , Gravidez , Aneuploidia , Aconselhamento , Testes Genéticos/métodos , Diagnóstico Pré-Implantação/métodos , ChinaRESUMO
The modification of metal-organic framework (MOF) materials to facilitate their practical applications is an extremely challenging and meaningful topic. In this work, two stepwise modification strategies for MOFs were conducted. First, we have demonstrated a single-crystal-to-single-crystal (SCSC) transformation from a microporous three-dimensional (3D) MOF to a two-dimensional (2D) coordination polymer (CP). The centrosymmetric [Cd(3-bpdb)(MeO-ip)]n (1) transforms into a chiral [Cd2(3-bpdb)(MeO-ip)2(CH3OH)2]n (2), which is triggered by the reaction time with methanol that acts as a structure-directing agent. The conversion relationship of 1 to 2 at different reaction times was studied in detail. Density functional theory (DFT) calculations clearly state that the irreversible formation of 2 is thermodynamically favorable. Intriguingly, 2 exhibits good proton conduction of 1.34 × 10-3 S cm-1 under 363 K and 98% relative humidity (RH) due to unique H-bond network characteristics. To the best of our knowledge, there are very few cases of 3D to 2D SCSC transformation stimulated by reaction time. The results have important implications for understanding the SCSC transformation mechanism and synthetic chemistry. On the other hand, the lanthanide3+-functionalized hybrids (Ln3+-MOF), Ln3+@1, were continuously prepared by incorporating luminescent Ln3+ ions into the structure of 1 through encapsulating post-synthesis modification (PSM). Tb3+@1 exhibits double emission in water and shows visual ratiometric fluorescence behavior for sensing glutamic acid (Glu), tryptophan (Trp), and Al3+, which is more reliable and accurate than single emission. Our work may not only provide new insights into the multiple modification of MOF materials but also promote the practical application of such materials.
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Thanks to the tremendous advancement of deep sequencing and large-scale profiling, epitranscriptomics has become a rapidly growing field. As one of the most important parts of epitranscriptomics, ribonucleic acid (RNA) methylation has been focused on for years for its fundamental role in regulating the many aspects of RNA function. Thanks to the big data generated in sequencing, machine learning methods have been developed for efficiently identifying methylation sites. In this review, we comprehensively explore machine learning based approaches for predicting 10 types of methylation of RNA, which include m6A, m5C, m7G, 5hmC, m1A, m5U, m6Am, and so on. Firstly, we reviewed three main aspects of machine learning which are data, features and learning algorithms. Then, we summarized all the methods that have been used to predict the 10 types of methylation. Furthermore, the emergent methods which were designed to predict multiple types of methylation were also reviewed. Finally, we discussed the future perspectives for RNA methylation sites prediction.
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Aprendizado de Máquina , RNA , Sequência de Bases , Metilação , RNA/genética , RNA/metabolismoRESUMO
Receptor-interacting protein kinase 1 (RIPK1) and RIPK3, two imperative targets of the necroptosis pathway, are associated with various inflammatory-related diseases. Regulating kinase activity with inhibitors has been confirmed as a promising strategy for inflammation treatment. However, most of the reported type I and II kinase inhibitors of RIPK1 and RIPK3, including benzothiazole compounds discovered by our group, have selective limitations due to interaction with ATP-binding pockets. Fortunately, a solvent exposure E0 region of the kinase domain, which extends into the linker region, has been reported to be related to the potency and selectivity of inhibitors. Hence, based on our previous study, a series of benzothiazole necroptosis inhibitors with chiral substitutions in the linker region were developed to investigate RIPK1/3 inhibitory potency. The results showed a 2-to 6-fold increase in anti-necroptotic activity for these chiral compounds. The improved selectivity on RIPK1 or RIPK3 was demonstrated on different derivatives. Predicted binding conformations of enantiomers with RIPK1/3 gave an explanation for their activity differences, guiding further rational design of chiral necroptosis inhibitors.
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Necroptose , Proteínas Quinases , Proteínas Quinases/metabolismo , Fosforilação , Benzotiazóis/farmacologia , ApoptoseRESUMO
As a class of microtubule targeting agents, colchicine binding site inhibitors (CBSIs) are considered as promising drug candidates for cancer therapy. However, due to adverse reactions, there are currently no CBSIs approved by FDA for cancer treatment. Therefore, extensive efforts are still encouraged to find novel CBSIs with different chemical structures and better anticancer efficacies. In this work, we designed and synthesized a new coumarin-dihydroquinoxalone derivative, MY-673, and evaluated its anticancer potency in vitro and in vivo. We confirmed that MY-673 was a potent CBSI that it not only inhibited tubulin polymerization, but also exhibited significant inhibitory potency on the growth of 13 cancer cells with IC50 values from 11.7 nM to 395.9 nM. Based on the results of kinase panel screening, MY-673 could inhibit ERK (extracellular regulated protein kinases) pathways-related kinases. We further confirmed that MY-673 could inhibit ERK signaling pathway in MGC-803 and HGC-27 cells, and then affected the expression level of SMAD4 protein in TGF-ß (transforming growth factor ß) /SMAD (small mother against decapentaplegic) signaling pathway using the western blotting assay. In addition, compound MY-673 could effectively inhibit cell proliferation, migration and induce cell apoptosis. We also further confirmed the in vivo efficacy of MY-673 in inhibiting tumor growth using the MGC-803 xenograft tumor model. At 20 mg/kg, the TGI rate was 85.9%, and it did not cause obvious toxicity to the main organs of mice. Together, the results we report here indicated that MY-673 was a promising CBSI for cancer treatment, which was capable of inhibiting the ERK pathway with potent antiproliferative activities in vitro and in vivo.
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Antineoplásicos , Neoplasias Gástricas , Humanos , Animais , Camundongos , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêutico , Moduladores de Tubulina/química , Sistema de Sinalização das MAP Quinases , Tubulina (Proteína)/metabolismo , Microtúbulos , Colchicina/metabolismo , Proliferação de Células , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder resulting from a deficient secretion of the episodic gonadotropin-releasing hormone, leading to delayed or absent puberty and infertility. In female patients with CHH, the most commonly used treatment is gonadotropin (Gn) therapy. Due to the rarity of the disease in females, there are limited case reports available. This article offers a management approach for this unusual disease that can be helpful for clinicians. CASE PRESENTATION: We report the case of a 29-year-old woman who successfully achieved pregnancy and delivered healthy twin girls after ovulation induction therapy. The patient was diagnosed with CHH at 18 years of age due to primary amenorrhea and the absence of secondary sexual characteristics. After experiencing infertility for three years, the patient sought medical assistance for conceiving. The patient was treated with gonadotropin therapy due to anovulation. In her first treatment cycle, the initial dose of HMG used for treatment was 75IU, which was increased to 150IU after six days. However, the cycle was canceled due to follicular dysplasia. In the second cycle, the treatment began with an initial dose of 150IU, and the follicles grew normally, but the estrogen level was low. Consequently, the treatment was interrupted. In a third ovulation stimulation cycle, HMG was adjusted to 150IU, and recombinant LH was added. After 12 days of ovulation, three mature follicles grew, the estrogen level was normal,and the treatment resulted in successful ovulation and subsequent pregnancy. At 35 weeks of gestation, the patient underwent a cesarean section and delivered two healthy female infants weighing 2,405 g and 2,755 g with an Apgar score of 10/10. CONCLUSIONS: Early diagnosis and timely and appropriate hormone replacement therapy are important for future pregnancy. Ovulation induction therapy is necessary to stimulate fertility. Gn therapy is a feasible and effective treatment for reproduction in CHH females, but the selection of Gn type and dosage must be personalized to maximize fertility outcomes. Effective treatment is available not only for inducing estrogenization and promoting fertility, but also for addressing concerns about psychological and emotional well-being.
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Hipogonadismo , Infertilidade , Humanos , Gravidez , Feminino , Adulto , Cesárea/efeitos adversos , Hipogonadismo/tratamento farmacológico , Gonadotropinas/uso terapêutico , Hormônio Liberador de Gonadotropina/uso terapêutico , Indução da Ovulação/métodos , Estrogênios/uso terapêutico , OvulaçãoRESUMO
Myocardium baseline impedance (BI) is an important factor in ablation effectiveness. This study examined the performance of low-power and long-duration (LPLD), high-power and short-duration (HPSD) ablation at different BIs by computer simulation. A 3D model of the ablation region was constructed for simulation, and in vitro experiments were performed to validate the simulation. Three ablation power and duration configurations of 30 W/30 s, 50 W/10 s, and 90 W/5 s were used for simulation with BI values of 90, 100, 110, 120, 130, and 140 Ω. Roll-off time and ablation volume were measured to evaluate ablation results. The simulation is consistent with the in vitro experiments. When BI is changed from 90 [Formula: see text] to 140 [Formula: see text], the lesion volume over 50 °C with BI of 140 [Formula: see text] was reduced by 6.3%, 6.7%, and 7.3% for 30 W/30 s, 50 W/10 s, and 90 W/5 s configurations, respectively, and the lesion volume over 100 °C was reduced by 62.8%, 49.7%, and 22.5% under 30 W/30 s, 50 W/10 s, and 90 W/5 s, respectively. Simulation results revealed that HPSD (vHPSD) and LPLD ablation were more affected by changes in BI in the lesion volumes over 50 °C and 100 °C, respectively, and demonstrated that resistive and conductive heating were the main heating effects in HPSD (vHPSD) and LPLD, respectively.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Simulação por Computador , Impedância Elétrica , Ablação por Cateter/métodos , Miocárdio/patologia , Fatores de Tempo , Fibrilação Atrial/cirurgia , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
INTRODUCTION: To date, many studies have shown a link between siesta and cardiovascular events. Little is known regarding the connection between siesta and brachial-ankle pulse wave velocity (baPWV) levels, even though baPWV can determine the degree of atherosclerosis and vascular stiffness. Thus, we examined the relationship between siesta time and baPWV in a cross-sectional study. METHODS: Interviews, physical examinations, lab testing, and electron beam computed tomography were all part of the baseline evaluation for participants aged older than 35. Baseline data were compared for 3 different siesta habits: irregular or no siestas, daily short siestas (1 h or less), and daily long siestas (> 1 h). Utilizing logistic regression models and multivariate linear regression, the link between siesta time and baPWV was determined. RESULTS: Among all 6566 participants, the different siesta groups had a significant difference of the degrees of AS (P < 0.001). The same outcome was true for both males (P < 0.001) and females (P < 0.001). Numerous cardiovascular risk variables and markers of subclinical atherosclerosis were positively correlated with daily extended siestas. Results from the fully adjusted model showed that long siestas (> 60 min, OR = 1.18, 95%CI: 1.06-1.31, P = 0.002) were linked to a more severe level of the baPWV. For age or gender stratification, we found significant differences between non-siesta and > 60 min siesta groups. Multiple linear regression analysis revealed a positive connection between siesta duration and baPWV (ß = 0.197, P = 0.038). CONCLUSIONS: An elevated risk of atherosclerosis was shown to accompany prolonged siestas. These results need to be followed up on with prospective studies and additional lab work.
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Aterosclerose , Rigidez Vascular , Masculino , Feminino , Humanos , Idoso , Estudos Transversais , Índice Tornozelo-Braço/métodos , Estudos Prospectivos , Fatores de Risco , Análise de Onda de Pulso/métodos , China , Aterosclerose/diagnóstico , Aterosclerose/epidemiologiaRESUMO
Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are important causative agents for foodborne diseases worldwide. Besides antibiotic treatment, vaccination has been deemed as the most effective strategy for preventing EPEC- and EHEC-caused foodborne illnesses. Despite substantial progress made in identifying promising antigens and efficacious vaccines, no vaccines against EPEC or EHEC have yet been licensed. Mice are inherently resistant to EPEC and EHEC infections; infection with Citrobacter rodentium (CR), the murine equivalent of EPEC and EHEC, in mice has been widely used as a model to study bacterial pathogenesis and develop novel vaccine strategies. Mirroring the severe outcomes of EPEC and EHEC infections in immunocompromised populations, immunocompromised mouse strains such as interleukin-22 knockout (Il22-/-) are susceptible to CR infection with severe clinical symptoms and mortality. Live attenuated bacterial vaccine strategies have been scarcely investigated for EPEC and EHEC infections, in particular in immunocompromised populations associated with severe outcomes. Here we examined whether live attenuated CR strain with rational genetic manipulation generates protective immunity against lethal CR infection in the susceptible Il22-/- mice. Our results demonstrate that oral administration of live ΔespFΔushA strain promotes efficient systemic and humoral immunity against a wide range of CR virulence determinants, thus protecting otherwise lethal CR infection, even in immunocompromised Il22-/- mice. This provides a proof of concept of live attenuated vaccination strategy for preventing CR infection in immunocompromised hosts associated with more severe symptoms and lethality.
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Infecções por Enterobacteriaceae , Escherichia coli Êntero-Hemorrágica , Escherichia coli Enteropatogênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Administração Oral , Animais , Citrobacter rodentium , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli Enteropatogênica/genética , Hospedeiro Imunocomprometido , CamundongosRESUMO
Recurrent implantation failure (RIF) is a challenge in the field of reproductive medicine, but mechanisms for its occurrence remain still unclear. Long non-coding RNAs (lncRNAs) have been found to play a vital role in many different diseases. In recent years, the differentially expressed lncRNAs have been reported in endometrial tissues. Here, we profiled dysregulated lncRNAs and mRNAs in the endometrial tissues of RIF patients and performed correlation analysis. We found that LINC02190 was upregulated in RIF endometrium and was bound to the integrin αD (ITGAD) mRNA promoter. Immunofluorescence assays were used to detect the location of ITGAD in the Ishikawa cell line and patients' endometrial biopsies. Overexpressed LINC02190 could decrease the expression of ITGAD and the adhesion rate of Ishikawa and JAR cells. Knockdown of the expression of LINC02190 significantly increased the ITGAD level, as well as the adhesion rate of Ishikawa and JAR cells. Furthermore, we demonstrated that the 150-250 bps of LINC02190 were the cis-elements involved in the regulation of ITGAD promoter activities. In conclusion, the results demonstrated that LINC02190 plays an important role in the occurrence of RIF, and the molecular mechanism may be associated with the embryo-endometrial attachment mediated by ITGAD. This study emphasizes the importance of lncRNAs in the occurrence of RIF and provides a potential new biomarker for diagnosis and therapies.
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Integrinas , RNA Longo não Codificante , Antígenos CD11 , Implantação do Embrião/genética , Endométrio/metabolismo , Feminino , Humanos , Cadeias alfa de Integrinas , Integrinas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genéticaRESUMO
Invited for the cover of this issue are the groups of Lin Du and Qi-Hua Zhao at Yunnan University. The image depicts astronauts as protons moving along the hydrogen-bond network in the channel of Eu-ETTB/Gd-ETTB. Read the full text of the article at 10.1002/chem.202202154.
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In this work, the two example rare earth-based metal-organic frameworks (LaIII -based MOFs), Eu-ETTB and Gd-ETTB, were obtained by self-assembly. Both materials showed extremely high proton conductivity, with the proton conductivity of Eu-ETTB being 1.53×10-2 â S cm-1 at 98 % relative humidity (RH) and 85 °C and that of Gd-ETTB being 2.63×10-2 â S cm-1 at 98 % RH and 75 °C. This was almost the best performance observed for three-dimensional porous MOFs without post-synthetic modification and was based on milder conditions than for most materials. Furthermore, cycle test experiments and continuous work tests showed that both materials had excellent performance both in terms of stability and durability. Water vapor adsorption experiments showed that a large number of water molecules are adsorbed the hydrogen-bond network's being rebuilt by the adsorbed water molecules in the pore channel and thus optimizing the channels for proton transfer explained the MOF's high performance.
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BACKGROUND: To compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. METHODS: This was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20-40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10-11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%). RESULTS: 378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3-11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa. CONCLUSION: Follitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. CLINICAL TRIAL REGISTRATION NUMBER: NCT03296527.
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Síndrome de Hiperestimulação Ovariana , Injeções de Esperma Intracitoplásmicas , Adulto , Hormônio Antimülleriano , Feminino , Fertilização in vitro/métodos , Hormônio Foliculoestimulante Humano/uso terapêutico , Hormônio Liberador de Gonadotropina , Humanos , Masculino , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Proteínas Recombinantes , Sêmen , Injeções de Esperma Intracitoplásmicas/métodos , Adulto JovemRESUMO
The recognition and adsorption of silver ions (Ag+) from industrial wastewater are necessary but still challenging. Herein, we constructed four Zn(II)-based coordination polymers (CPs), namely, [Zn(btap)2(NO3)2]n (1), [Zn(btap)(SO4)(H2O)3]n (2), {[Zn(btap)2(H2O)2]·(ClO4)2}n (3), and [Zn(btap)Cl2]n (4), by using 3,5-bis(triazol-1-yl)pyridine (btap) with different anionic Zn(II) salts. The crystal structures of 1-4, varying from one-dimensional beaded (1) and zigzag chain (2) to two-dimensional sql (3) and bex (4) typologies, were regulated by the coordination modes of btap and the counter-anions. The water stability, pH stability, thermostability, and luminescent properties of the CPs were investigated. The luminescence performances in a series of cations and anions were also explored. Considering the high density of chloride groups in the structure, 4 showed luminescence sensing for Ag+ [KSV = 9188.45 M-1 and a limit of detection (LOD) of 4.9 µM], as well as an excellent ability for Ag+ adsorption in aqueous solution (maximum adsorption capacity, 653.3 mg/g). Additionally, anti-interference experiments revealed that 4 had excellent recognition and adsorption capacities for Ag+ even when multiple ions coexisted. Moreover, XRD, EDS, and XPS analyses confirmed that the coordination of Ag+ with chloride groups in 4 resulted in excellent adsorption capacity and prevented ligand-to-ligand electron transfer, showing excellent detection ability. Suitable coordination sites were introduced to interact strongly with Ag+, along with detection and large adsorption capacity. Our strategy can effectively design and develop multifunctional CP-based materials, which are applicable in removal processes and environmental protection, by regulating anions in the self-assembly and introducing CP functional groups.