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Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor ß1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.
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Complemento C1q , Leucemia Mieloide Aguda , Humanos , Proteômica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Medula Óssea/metabolismo , Prognóstico , Doença Crônica , RecidivaRESUMO
Dopamine (DA) is a neurotransmitter synthesized in the human body that acts on multiple organs throughout the body, reaching them through the blood circulation. Neurotransmitters are special molecules that act as messengers by binding to receptors at chemical synapses between neurons. As ligands, they mainly bind to corresponding receptors on central or peripheral tissue cells. Signalling through chemical synapses is involved in regulating the activities of various body systems. Lack of DA or a decrease in DA levels in the brain can lead to serious diseases such as Parkinson's disease, schizophrenia, addiction and attention deficit disorder. It is widely recognized that DA is closely related to neurological diseases. As research on the roles of brain-gut peptides in human physiology and pathology has deepened in recent years, the regulatory role of neurotransmitters in digestive system diseases has gradually attracted researchers' attention, and research on DA has expanded to the field of digestive system diseases. This review mainly elaborates on the research progress on the roles of DA and DRs related to digestive system diseases. Starting from the biochemical and pharmacological properties of DA and DRs, it discusses the therapeutic value of DA- and DR-related drugs for digestive system diseases.
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Doenças do Sistema Digestório , Doença de Parkinson , Humanos , Dopamina/metabolismo , Receptores Dopaminérgicos , Doença de Parkinson/metabolismo , NeurotransmissoresRESUMO
Bilateral diffuse metastatic lung adenocarcinoma (BLDM-LUAD) is a special imaging pattern of lung adenocarcinoma (LUAD). We retrospectively assessed survival outcomes and co-mutation characteristics of BLDM-LUAD patients harboring epidermal growth factor receptor (EGFR) mutations who were treated with EGFR-yrosine kinase inhibitors (TKIs). From May 2016 to May 2021, among 458 patients who submitted samples for next generation sequencing (NGS) detection in 1125 patients with non-small-cell lung cancer (NSCLC), and 44 patients were diagnosed as BLDM-LUAD. In order to analyze the survival outcomes of BLDM-LUAD patients harboring EGFR mutations who were treated with EGFR-TKIs, the factors age, gender, smoking history, hydrothorax, site of EGFR mutations and EGFR-TKIs treatment were adjusted using propensity score-matching (PSM). The Kaplan-Meier survival curves and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The co-mutation characteristics of BLDM-LUAD patients harboring EGFR mutations were analyzed by NGS panels. 64 patients with advanced lung adenocarcinoma harboring EGFR mutations and first-line treatment of EGFR-TKIs were successfully matched. BLDM-LUAD (n = 32) have significantly longer median PFS than control group (n = 32) (mPFS: 14 vs 6.2 months; p = .002) and insignificantly longer median OS than control group (mOS: 45 vs 25 months; p = .052). The patients with BLDM-LUAD have the higher frequency of EGFR mutation than control group (84.1% vs 62.0%) before PSM. The co-mutation genes kirsten rat sarcoma viral oncogene homolog (KRAS) (9.4%), ataxia telangiectasia-mutated (ATM) (7.4%) and mesenchymal-epithelial transition (MET) (3.1%) only appeared in the control group after PSM. The BLDM-LUAD harboring EGFR mutations was associated with a favorable prognosis to EGFR-TKI.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos RetrospectivosRESUMO
Epinephrine (EP) is an essential catecholamine in the human body. Currently, most EP detection methods are not suitable for in vivo detection due to material limitations. An organic small molecule fluorescent probe based on a chemical cascade reaction for the detection of EP was designed. Anionic heptamethine cyanine dye was selected as a fluorescent dye because of its NIR fluorescence emission with excellent biocompatibility. The secondary amine of EP nucleophilically attacks the carbonate of the probe with its stronger nucleophilicity and further undergoes intramolecular nucleophilic cyclization to release the fluorophore. Other substances containing only primary amines or no ß-OH lack reaction competitiveness due to their weaker nucleophilicity or inability to undergo further cyclization. The fluorescence recovery of the probe was linearly related to the EP concentration of 2-75 µmol/L. The detection limit was 0.4 µmol/L. The recovery rate was 94.78-111.32%. Finally, we successfully achieved bioimaging of EP in living cells and EP analogue in nematodes.
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Carbocianinas , Epinefrina , Corantes Fluorescentes , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Humanos , Epinefrina/análise , Carbocianinas/química , Animais , Imagem Óptica , Ânions/química , Ânions/análise , Caenorhabditis elegans , Limite de Detecção , Raios Infravermelhos , Células HeLa , Estrutura MolecularRESUMO
The functionalization of metal-organic frameworks (MOFs) with organic small molecules by in situ postsynthetic modification has garnered considerable attention. However, the precise engineering of recognition sites using this method remains rarely explored in optically controlled bioelectronics. Herein, employing the Schiff base reaction to embed the small molecule (THBA) into a Zr-MOF, we fabricated a hydroxyl-rich MOF on the surface of titanium dioxide nanorod arrays (U6H@TiO2 NRs) to develop light-sensitive gate electrodes with tailored recognition capabilities. The U6H@TiO2 NR gate electrodes were integrated into organic photoelectrochemical transistor (OPECT) sensing systems to tailor a sensitive device for bilirubin (I-Bil) detection. In the presence of I-Bil, coordination effects, hydrogen bonding, and π-π interactions facilitated strong binding between U6H@TiO2 NRs and the target I-Bil. The electron-donating property of I-Bil influenced the gate voltage, enabling precise control of the channel status and modulation of the channel current. The OPECT device exhibited exceptional analytical performance toward I-Bil with wide linearity ranging from 1 × 10-16 to 1 × 10-9 M and a low limit detection of 0.022 fM. Leveraging the versatility of small molecules for boosting the functionalization of materials, this work demonstrates the great potential of the small molecule family for OPECT bioanalysis and holds promise for the advancement of OPECT sensors.
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Bilirrubina , Técnicas Eletroquímicas , Estruturas Metalorgânicas , Titânio , Estruturas Metalorgânicas/química , Bilirrubina/análise , Técnicas Eletroquímicas/instrumentação , Titânio/química , Limite de Detecção , Transistores Eletrônicos , Humanos , Eletrodos , Processos Fotoquímicos , Nanotubos/química , Zircônio/químicaRESUMO
Meningeal metastasis (LM) is commonly seen in the advanced stages of cancer patients, often leading to a rapid decline in survival time and quality of life. Currently, there is still a lack of standardized treatments. Oncolytic viruses (OVs) are a class of emerging cancer therapeutics with the advantages of selectively replicating in cancer cells, delivering various eukaryotic transgenes, inducing immunogenic cell death, and promoting anti-tumor immunity. Some studies applying OVs intrathoracically or intraperitoneally for the treatment of malignant pleural and peritoneal effusions have shown promising therapeutic effects. If OVs could be applied to treat LM, it would bring significant survival benefits to patients with LM. In this review, we analyzed past research on the use of viruses to treat meningeal metastasis, summarized the efficacy and safety demonstrated by the research results, and analyzed the feasibility of oncolytic virus therapy for meningeal metastasis. We also summarized the existing data to provide guidance for the development of OVs that can be injected into the cerebrospinal fluid (CSF).
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Neoplasias Meníngeas , Terapia Viral Oncolítica , Vírus Oncolíticos , Terapia Viral Oncolítica/métodos , Humanos , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/terapia , Animais , Vírus Oncolíticos/fisiologiaRESUMO
Oligoasthenoteratozoospermia (OAT) is a common type of male infertility; however, its genetic causes remain largely unknown. Some of the genetic determinants of OAT are gene defects affecting spermatogenesis. BCORL1 (BCL6 corepressor like 1) is a transcriptional corepressor that exhibits the OAT phenotype in a knockout mouse model. A hemizygous missense variant of BCORL1 (c.2615T > G:p.Val872Gly) was reported in an infertile male patient with non-obstructive azoospermia (NOA). Nevertheless, the correlation between BCORL1 variants and OAT in humans remains unknown. In this study, we used whole-exome sequencing to identify a novel hemizygous nonsense variant of BCORL1 (c.1564G > T:p.Glu522*) in a male patient with OAT from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Further population screening identified four BCORL1 missense variants in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%), but no pathogenic BCORL1 variants among 362 fertile subjects. In conclusion, our findings indicate that BCORL1 is a potential candidate gene in the pathogenesis of OAT and NOA, expanded its disease spectrum and suggested that BCORL1 may play a role in spermatogenesis by interacting with SKP1.
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Sequenciamento do Exoma , Infertilidade Masculina , Proteínas Repressoras , Masculino , Humanos , Proteínas Repressoras/genética , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Oligospermia/genética , Oligospermia/patologia , Adulto , Linhagem , Azoospermia/genética , Azoospermia/patologia , Mutação com Perda de Função/genética , Predisposição Genética para Doença , Proteína-Arginina N-Metiltransferases/genética , Mutação de Sentido Incorreto/genética , Espermatogênese/genéticaRESUMO
Empty follicle syndrome (EFS) is a disorder characterised by the unsuccessful retrieval of oocytes from matured follicles following ovarian stimulation for in vitro fertilisation (IVF). Genetic factors significantly contribute to this pathology. To date, an increasing number of genetic mutations associated with GEFS have been documented, however, some cases still remain unexplained by these previously reported mutations. Here, we identified a novel homozygous missense ZP1 variant (c.1096 C > T, p.Arg366Trp) in a female patient with GEFS from a consanguineous family who failed to retrieve any oocytes during two cycles of IVF treatment. We conducted a molecular dynamics simulation analysis on the mutant ZP1 model, revealing that the mutant ZP1 protein has an altered 3D structure, lower fluctuation, higher compactness and higher instability than wild-type ZP1. Immunostaining, immunoblotting and co-immunoprecipitation results showed that the homozygous missense mutation in ZP1 impaired protein secretion and weakened interactions between ZP1 and other ZP proteins, which may affect the ZP assembly. This study contributes to a more comprehensive understanding of the genetic aetiopathogenesis of GEFS.
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Active control of induced reflection is crucial for many potential applications ranging from slowing light to biosensing devices. However, most previous approaches require patterned nanostructures to achieve controllable induced reflection, which hinders their further applications due to complicated architectures. Herein, we propose a lithography-free multilayered structure to achieve the induced reflection through the coupling of dual-topological-interface-states. The multilayers consist of two one-dimensional (1D) photonic crystals (PCs) and an Ag film separated by a Spacer, topological edge state (TES) and topological Tamm state (TTS) can be excited simultaneously and their coupling induces the reflection window. The coupled-oscillator model is proposed to mimic the coupling between the TES and TTS, and the analytical results are in good agreement with finite element method (FEM). In addition, the TES-TTS induced reflection is robust to the variation of structural parameters. By integrating an ultra-thin phase-change film of Ge2Sb2Te5 (GST) into the multilayers, the induced reflection can be switched through the phase transition of the GST film. The multipole decomposition reveals that the vanished reflection window is arising from the disappearance of TTS associated with the toroidal dipole (TD) mode.
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Optical chirality is highly demanded for biochemical sensing, spectral detection, and advanced imaging, however, conventional design schemes for chiral metamaterials require highly computational cost due to the trial-and-error strategy, and it is crucial to accelerate the design process particularly in comparably simple planar chiral metamaterials. Herein, we construct a bidirectional deep learning (BDL) network consists of spectra predicting network (SPN) and design predicting network (DPN) to accelerate the prediction of spectra and inverse design of chiroptical response of planar chiral metamaterials. It is shown that the proposed BDL network can accelerate the design process and exhibit high prediction accuracy. The average process of prediction only takes â¼15â ms, which is 1 in 40000 compared to finite-difference time-domain (FDTD). The mean-square error (MSE) loss of forward and inverse prediction reaches 0.0085 after 100 epochs. Over 95.2% of training samples have MSE ≤ 0.0042 and MSE ≤ 0.0044 for SPN and DPN, respectively; indicating that the BDL network is robust in the inverse deign without underfitting or overfitting for both SPN and DPN. Our founding shows great potentials in accelerating the on-demand design of planar chiral metamaterials.
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BACKGROUND: Glioma recurrence, subsequent to maximal safe resection, remains a pivotal challenge. This study aimed to identify key clinical predictors influencing recurrence and develop predictive models to enhance neurological diagnostics and therapeutic strategies. METHODS: This longitudinal cohort study with a substantial sample size (n = 2825) included patients with non-recurrent glioma who were pathologically diagnosed and had undergone initial surgical resection between 2010 and 2018. Logistic regression models and stratified Cox proportional hazards models were established with the top 15 clinical variables significantly influencing outcomes screened by the least absolute shrinkage and selection operator (LASSO) method. Preoperative and postoperative models predicting short-term (within 6 months) postoperative recurrence in glioma patients were developed to explore the risk factors associated with short- and long-term recurrence in glioma patients. RESULTS: Preoperative and postoperative logistic models predicting short-term recurrence had accuracies of 0.78 and 0.87, respectively. A range of biological and early symptomatic characteristics linked to short- and long-term recurrence have been pinpointed. Age, headache, muscle weakness, tumor location and Karnofsky score represented significant odd ratios (t > 2.65, p < 0.01) in the preoperative model, while age, WHO grade 4 and chemotherapy or radiotherapy treatments (t > 4.12, p < 0.0001) were most significant in the postoperative period. Postoperative predictive models specifically targeting the glioblastoma and IDH wildtype subgroups were also performed, with an AUC of 0.76 and 0.80, respectively. The 50 combinations of distinct risk factors accommodate diverse recurrence risks among glioma patients, and the nomograms visualizes the results for clinical practice. A stratified Cox model identified many prognostic factors for long-term recurrence, thereby facilitating the enhanced formulation of perioperative care plans for patients, and glioblastoma patients displayed a median progression-free survival (PFS) of only 11 months. CONCLUSION: The constructed preoperative and postoperative models reliably predicted short-term postoperative glioma recurrence in a substantial patient cohort. The combinations risk factors and nomograms enhance the operability of personalized therapeutic strategies and care regimens. Particular emphasis should be placed on patients with recurrence within six months post-surgery, and the corresponding treatment strategies require comprehensive clinical investigation.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/complicações , Estudos Longitudinais , Glioma/patologia , Estudos de Coortes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Encefálicas/patologiaRESUMO
BACKGROUND: Glioma is the most common primary brain tumor with high mortality and disability rates. Recent studies have highlighted the significant prognostic consequences of subtyping molecular pathological markers using tumor samples, such as IDH, 1p/19q, and TERT. However, the relative importance of individual markers or marker combinations in affecting patient survival remains unclear. Moreover, the high cost and reliance on postoperative tumor samples hinder the widespread use of these molecular markers in clinical practice, particularly during the preoperative period. We aim to identify the most prominent molecular biomarker combination that affects patient survival and develop a preoperative MRI-based predictive model and clinical scoring system for this combination. METHODS: A cohort dataset of 2,879 patients was compiled for survival risk stratification. In a subset of 238 patients, recursive partitioning analysis (RPA) was applied to create a survival subgroup framework based on molecular markers. We then collected MRI data and applied Visually Accessible Rembrandt Images (VASARI) features to construct predictive models and clinical scoring systems. RESULTS: The RPA delineated four survival groups primarily defined by the status of IDH and TERT mutations. Predictive models incorporating VASARI features and clinical data achieved AUC values of 0.85 for IDH and 0.82 for TERT mutations. Nomogram-based scoring systems were also formulated to facilitate clinical application. CONCLUSIONS: The combination of IDH-TERT mutation status alone can identify the most distinct survival differences in glioma patients. The predictive model based on preoperative MRI features, supported by clinical assessments, offers a reliable method for early molecular mutation prediction and constitutes a valuable scoring tool for clinicians in guiding treatment strategies.
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Biomarcadores Tumorais , Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Imageamento por Ressonância Magnética , Telomerase , Humanos , Glioma/genética , Glioma/mortalidade , Glioma/diagnóstico por imagem , Glioma/patologia , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Isocitrato Desidrogenase/genética , Pessoa de Meia-Idade , Telomerase/genética , Mutação , Adulto , Nomogramas , Prognóstico , IdosoRESUMO
Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti6O6(OiPr)8(TTFTC)(phen)2]2 (1, where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1, in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity (qex) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1.
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Optimizing the width of depletion region is a key consideration in designing high performance photovoltaic photodetectors, as the electron-hole pairs generated outside the depletion region cannot be effectively separated, leading to a negligible contribution to the overall photocurrent. However, currently reported photovoltaic mid-infrared photodetectors based on two-dimensional heterostructures usually adopt a single pn junction configuration, where the depletion region width is not maximally optimized. Here, we demonstrate the construction of a high performance broadband mid-infrared photodetector based on a MoS2/b-AsP/MoS2npn van der Waals heterostructure. The npn heterojunction can be equivalently represented as two parallel-stacked pn junctions, effectively increasing the thickness of the depletion region. Consequently, the npn device shows a high detectivity of 1.3 × 1010cmHz1/2W-1at the mid-infrared wavelength, which is significantly improved compared with its single pn junction counterpart. Moreover, it exhibits a fast response speed of 12 µs, and a broadband detection capability ranging from visible to mid-infrared wavelengths.
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PURPOSE: In this study, we aim to explore the efficacy of paxlovid on reducing mortality of COVID-19 patients in clinical setting, especially whether paxlovid modifies the risk of death in these severe and critical patients. METHODS: Our retrospective cohort study was conducted on the medical records of patients, consecutively admitted for COVID-19 to five hospitals in Chongqing, China from Dec 8, 2022 to Jan 20, 2023. Based on whether patients received paxlovid during their hospitalization, patients were grouped as paxlovid group and non-paxlovid group. We used 1:1 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between groups. Statistical analysis were performed by SPSS 23.0. The differences in 28-day mortality between these two groups and its influencing factors were the main results we focused on. RESULTS: There were 1018 patients included in our study cohort. With 1:1 ratio PSM, each of the paxlovid group and non-paxlovid group included 237 patients. The results showed that patients using paxlovid have a lower 28-day mortality in overall population either before PSM (OR 0.594, 95% CI 0.385-0.917, p = 0.019) or after PSM (OR 0.458, 95% CI 0.272-0.774, p = 0.003) with multivariable adjusted logistic regression models. Meanwhile, in severe subgroup, it showed similar findings.With paxlovid treatment, it showed a significantly lower 28-day mortality in severe subgroup both before PSM (28% vs.41%, p = 0.008) and after PSM (19% vs.32%, p = 0.007). CONCLUSION: Paxlovid can significantly reduce the risk of 28-day mortality in overall population and severe subgroup patients.This study distinguished the severe subgroup patients with COVID-19 who benefit more from paxlovid treatment.
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COVID-19 , SARS-CoV-2 , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , COVID-19/mortalidade , Idoso , China/epidemiologia , Adulto , Pontuação de Propensão , Tratamento Farmacológico da COVID-19 , Hospitalização/estatística & dados numéricosRESUMO
Insecticide resistance poses a significant challenge in managing generalist herbivores such as the tobacco cutworm (TCW), Spodoptera litura. This study investigates the potential risks associated with using the novel diamide insecticide tetraniliprole to control TCW. A tetraniliprole-resistant strain was developed through twelve generations of laboratory selection, indicating an intermediate risk of resistance development. Field monitoring in China revealed a significant incidence of resistance, particularly in the Nanchang (NC) population (>100-fold). Tetraniliprole showed moderate to high cross-resistance to multiple insecticides and was autosomally inherited with incomplete dominance, controlled by multiple genes, some of which belong to the cytochrome P450 family associated with enhanced detoxification. Life table studies indicated transgenerational hormesis, stimulating TCW female fecundity and increasing population net reproduction rates (R0). These findings suggest a potential for pest resurgence under tetraniliprole use. The integrated risk assessment provides a basis for the sustainable management of TCW using tetraniliprole.
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Inseticidas , Spodoptera , Animais , Medição de Risco , Spodoptera/efeitos dos fármacos , Inseticidas/toxicidade , Resistência a Inseticidas/genética , Herbivoria , China , Feminino , Larva/efeitos dos fármacosRESUMO
BACKGROUND: Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL. METHODS: In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR. RESULTS: BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes. CONCLUSION: Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.
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Aborto Espontâneo , Biomarcadores , Transferência Embrionária , MicroRNAs , Humanos , Feminino , Gravidez , MicroRNAs/sangue , Adulto , Biomarcadores/sangue , Aborto Espontâneo/sangue , Implantação do Embrião , Aprendizado de MáquinaRESUMO
BACKGROUND: The genetic causes for most male infertility due to severe oligoasthenoteratozoospermia (OAT) remain unclear. OBJECTIVE: To identify the genetic cause of male infertility characterised by OAT. METHODS: Variant screening was performed by whole-exome sequencing from 325 infertile patients with OAT and 392 fertile individuals. In silico and in vitro analyses were performed to evaluate the impacts of candidate disease-causing variants. A knockout mouse model was generated to confirm the candidate disease-causing gene, and intracytoplasmic sperm injection (ICSI) was used to evaluate the efficiency of clinical treatment. RESULTS: We identified biallelic CFAP61 variants (NM_015585.4: c.1654C>T (p.R552C) and c.2911G>A (p.D971N), c.144-2A>G and c.1666G>A (p.G556R)) in two (0.62%) of the 325 OAT-affected men. In silico bioinformatics analysis predicted that all four variants were deleterious, and in vitro functional analysis confirmed the deleterious effects of the mutants. Notably, H&E staining and electron microscopy analyses of the spermatozoa revealed multiple morphological abnormalities of sperm flagella, the absence of central pair microtubules and mitochondrial sheath malformation in sperm flagella from man with CFAP61 variants. Further immunofluorescence assays revealed markedly reduced CFAP61 staining in the sperm flagella. In addition, Cfap61-deficient mice showed the OAT phenotype, suggesting that loss of function of CFAP61 was the cause of OAT. Two individuals accepted ICSI therapy using their own ejaculated sperm, and one of them succeeded in fathering a healthy baby. CONCLUSIONS: Our findings indicate that CFAP61 is essential for spermatogenesis and that biallelic CFAP61 variants lead to male infertility in humans and mice with OAT.
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Anormalidades Múltiplas , Astenozoospermia , Infertilidade Masculina , Oligospermia , Humanos , Masculino , Animais , Camundongos , Infertilidade Masculina/genética , Oligospermia/genética , Astenozoospermia/genética , Sêmen , Espermatozoides , Anormalidades Múltiplas/genéticaRESUMO
Phase measuring profilometry (PMP) has been widely used in industries for three-dimensional (3D) shape measurement. However, phase information is often lost due to image saturation results from high-reflection object surfaces, leading to subsequent 3D reconstruction errors. To address the problem, we propose an adaptive phase retrieval algorithm that can accurately fit the sinusoidal fringes damaged by high reflection in the saturated regions to retrieve the lost phase information. Under the proposal, saturated regions are first identified through a minimum error thresholding technique to narrow down regions of interest and so that computation costs are reduced. Then, images with differing exposures are fused to locate peak-valley coordinates of the fitting sinusoidal fringes. And the corresponding values of peak-valley pixels are obtained based on a least squares method. Finally, an adaptive piecewise sine function is constructed to recover the sinusoidal fringe pattern by fitting the pattern intensity distribution. And the existing PMP technology is used to obtain phase information from the retrieved sinusoidal fringes. To apply the developed method, only one (or two) image with different exposure times is needed. Compared with existing methods for measuring reflective objects, the proposed method has the advantages of short operation time, reduced system complexity, and low demand on hardware equipment. The effectiveness of the proposed method is verified through two experiments. The developed methodology provides industry an alternative way to measure high-reflection objects in a wide range of applications.
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BACKGROUND AND OBJECTIVES: The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions. METHODS: A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale. RESULTS: The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect. CONCLUSION: The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.