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1.
J Obstet Gynaecol ; 44(1): 2338235, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38619096

RESUMO

BACKGROUND: Selection of high-quality blastocysts is the most important factor determining the success of assisted reproductive technology. The objective of this study is to assess the values of blastocyst morphological quality and development speed for predicting euploidy and clinical pregnancy outcome. METHODS: A total of 155 preimplantation genetic testing cycles including 959 blastocysts and 154 euploid blastocyst transfer cycles conducted between January 2018 and December 2019 were retrospectively analysed. The associations of blastocyst morphological quality and development speed (D) with chromosomal status, clinical pregnancy rate, early miscarriage rate, and ongoing pregnancy rate were evaluated by univariate and multivariate regression. RESULTS: The euploidy rate of development speed D5 blastocysts was significantly greater than that of D6 blastocysts (61.4% vs. 38.1%, P < 0.001), and the euploid rate of morphologically high-grade blastocysts was significantly greater than that of non-high-grade blastocysts. Development speed D5 (OR = 1.6, 95% CI 1.2-2.2, P = 0.02) and high-grade morphology (OR = 2.1, 95% CI 1.5-2.9, P = 0.01) were independent predictors of euploidy. The ongoing pregnancy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (62.3% vs. 43.8%, P = 0.04). Transfer of euploid blastocysts with high-grade morphology resulted in a greater ongoing pregnancy rate than transfer of non-high-grade euploid blastocysts (60.7% vs. 43.2%, P = 0.049). Alternatively, D6 development speed was an independent risk factor for early pregnancy loss after euploid blastocyst transfer. Multivariate regression analysis adjusting for confounding factors identified maternal age, blastocyst development speed, and blastocyst morphological grade as independent predictors of euploidy but not of clinical pregnancy. CONCLUSION: The recommended sequence of embryo transfer based on the present study is D5 high-grade > D6 high-grade > D5 non-high-grade > D6 non-high-grade.


Assisted reproductive technology physicians are actively exploring methods to improve the accuracy of embryo selection for successful pregnancy. We evaluated the associations of embryo morphological grade and development speed with chromosomal status and clinical outcome for couples without a history of infertility, in vitro fertilisation failure, or recurrent miscarriage receiving euploid embryo transfer. Blastocysts from females younger than 35 years, of high morphological grade, and demonstrating faster development speed were most likely to be euploid (least likely to have chromosomal abnormalities). Alternatively, patients implanted with slower developing euploid blastocysts were at higher risk of early pregnancy loss. To maximise the probability of implanting euploid embryos and minimise the risk of pregnancy loss, the selection order of embryo transferred should be based on embryo development speed followed by morphological grades.


Assuntos
Aborto Espontâneo , Resultado da Gravidez , Gravidez , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Transferência de Embrião Único , Estudos Retrospectivos , Blastocisto , Embrião de Mamíferos , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia
2.
Nat Cell Biol ; 26(4): 552-566, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38561547

RESUMO

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7FBXW8 in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P-CUL7FBXW8-ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.


Assuntos
Glicemia , Lipólise , Fosfatos de Fosfatidilinositol , Camundongos , Animais , Humanos , Lipólise/genética , Lipase/genética , Lipase/metabolismo , Glucose , Ácidos Graxos/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
3.
Sci Total Environ ; : 172622, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642761

RESUMO

The phyllosphere is a vital yet often neglected habitat hosting diverse microorganisms with various functions. However, studies regarding how the composition and functions of the phyllosphere microbiome respond to agricultural practices, like nitrogen fertilization, are limited. This study investigated the effects of long-term nitrogen fertilization with different levels (CK, N90, N210, N330) on the functional genes and pathogens of the rice phyllosphere microbiome. Results showed that the relative abundance of many microbial functional genes in the rice phyllosphere was significantly affected by nitrogen fertilization, especially those involved in C fixation and denitrification genes. Different nitrogen fertilization levels have greater effects on fungal communities than bacteria communities in the rice phyllosphere, and network analysis and structural equation models further elucidate that fungal communities not only changed bacterial-fungal inter-kingdom interactions in the phyllosphere but also contributed to the variation of biogeochemical cycle potential. Besides, the moderate nitrogen fertilization level (N210) was associated with an enrichment of beneficial microbes in the phyllosphere, while also resulting in the lowest abundance of pathogenic fungi (1.14 %). In contrast, the highest abundance of pathogenic fungi (1.64 %) was observed in the highest nitrogen fertilization level (N330). This enrichment of pathogen due to high nitrogen level was also regulated by the fungal communities, as revealed through SEM analysis. Together, we demonstrated that the phyllosphere fungal communities were more sensitive to the nitrogen fertilization levels and played a crucial role in influencing phyllosphere functional profiles including element cycling potential and pathogen abundance. This study expands our knowledge regarding the role of phyllosphere fungal communities in modulating the element cycling and plant health in sustainable agriculture.

4.
Microb Pathog ; 190: 106633, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38554778

RESUMO

Interferon-stimulated gene product 15 (ISG15) can be conjugated to substrates through ISGylation. Currently, the E3 ligase for porcine ISGylation remains unclear. Here, we identified porcine HERC5 and HERC6 (pHERC5/6) as ISGylation E3 ligases with pHERC6 acting as a major one by reconstitution of porcine ISGylation system in HEK-293 T cell via co-transfecting E1, E2 and porcine ISG15(pISG15) genes. Meanwhile, our data demonstrated that co-transfection of pISG15 and pHERC5/6 was sufficient to confer ISGylation, suggesting E1 and E2 of ISGylation are interchangeable between human and porcine. Using an immunoprecipitation based ISGylation analysis, our data revealed pHERC6 was a substrate for ISGylation and confirmed that K707 and K993 of pHERC6 were auto-ISGylation sites. Mutation of these sites reduced pHERC6 half-life and inhibited ISGylation, suggesting that auto-ISGylation of pHERC6 was required for effective ISGylation. Conversely, sustained ISGylation induced by overexpression of pISG15 and pHERC6 could be inhibited by a well-defined porcine ISGylation antagonist, the ovarian tumor (OTU) protease domain of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-nsp2 and PRRSV-nsp1ß, further indicating such method could be used for identification of virus-encoded ISG15 antagonist. In conclusion, our study contributes new insights towards porcine ISGylation system and provides a novel tool for screening viral-encoded ISG15 antagonist.

5.
Front Public Health ; 12: 1364579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463156

RESUMO

Introduction: Many women experience fear toward pregnancy, which can impact their desire to have children and the national birth rate. Thus, assessing women's fear of pregnancy is of great importance. However, there is currently no specialized tool for assessing women's fear of pregnancy in China. The purpose of this study is to translate the Fear of Pregnancy Scale into Chinese and test its reliability and validity among women of childbearing age. Methods: Using convenience sampling combined with a snowballing method, a cross-sectional survey was conducted on 886 women of childbearing age in two cities in China. The translation was strictly carried out according to the Brislin model. Item analysis, validity analysis, and reliability analysis were employed for psychometric assessment. Results: The Chinese version of the Fear of Pregnancy Scale comprises 28 items. Exploratory factor analysis extracted four factors with a cumulative variance contribution rate of 72.578%. Confirmatory factor analysis showed: NFI = 0.956, CFI = 0.986, GFI = 0.927, IFI = 0.986, TLI = 0.985, RMSEA = 0.032, and χ2/df = 1.444. The scale's Cronbach's α coefficient is 0.957, split-half reliability is 0.840, and test-retest reliability is 0.932. Conclusion: The Chinese version of the Fear of Pregnancy Scale possesses robust psychometric properties and can assess the degree of pregnancy fear among Chinese women of childbearing age. It provides a reference for formulating relevant policies in the prenatal care service system and implementing targeted intervention measures.


Assuntos
Medo , Gravidez , Criança , Humanos , Feminino , Inquéritos e Questionários , Psicometria , Estudos Transversais , Reprodutibilidade dos Testes
6.
Clinics (Sao Paulo) ; 79: 100348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38552386

RESUMO

OBJECTIVE: This study aimed to systematically evaluate the efficacy and safety of Endoscopic Ultrasonography (EUS) for the treatment of pancreatic cancer. METHODS: The PubMed, Embase, Web of Science, and Google Scholar databases were searched from the inception of the databases to June 2022. RevMan 5.3.0 software was utilized for data analysis. In total, 13 self-descriptive studies, which enrolled 382 patients, were finally included. RESULTS: It was revealed that EUS for the treatment of pancreatic cancer exhibited a lower incidence of adverse reactions (Relative Risk Ration [RR = 0.23], 95 % Confidence interval [95 % CI 0.23-0.23]), a higher success rate (RR = 0.90, 95 % CI 0.90-0.90), and a low failure rate (RR = 0.06, 95 % CI 0.06-0.06). Moreover, EUS-guided Celiac Plexus Neurolysis (EUS-CPN) not only significantly relieved pancreatic cancer patients' pain (RR = 0.83, 95 % CI 0.83-0.83), but also significantly eliminated pain in some patients (RR = 0.09, 95 % CI 0.09-0.09). The effects of EUS on pancreatic cancer treatment were satisfactory, and few adverse reactions were found. CONCLUSION: Owing to the restricted sample size in this meta-analysis, primarily consisting of descriptive studies, it was imperative to conduct more rigorously designed, multi-center, long-term follow-up, larger sample, and Randomized Controlled Trials (RCTs) to validate the findings.


Assuntos
Bloqueio Nervoso , Neoplasias Pancreáticas , Humanos , Endossonografia/efeitos adversos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Dor Abdominal/etiologia
7.
Vet Microbiol ; 292: 110035, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38484577

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the global pork industry, resulting in substantial economic losses. Current control measures rely on modified live virus (MLV) vaccines with safety concerns. However, the lack of consensus on protective PRRSV antigens is impeding the development of effective and safety subunit vaccines. In this study, we conducted in vitro virus neutralization (VN) assays in MARC-145 and CRL-2843CD163/CD169 cell lines and primary porcine alveolar macrophages (PAMs) to systemically identify PRRSV structural proteins (SPs) recognized by virus-neutralizing antibodies in hyperimmune serum collected from piglets infected with highly pathogenic PRRSV (HP-PRRSV). Additionally, piglets immunized with different combinations of recombinant PRRSV-SPs were challenged with HP-PRRSV to evaluate their in vivo protection potential. Intriguingly, different in vitro VN activities of serum antibodies elicited by each PRRSV SP were observed depending on the cell type used in the VN assay. Notably, antibodies specific for GP3, GP4, and M exhibited highest in vitro VN activities in PAMs, correlating with complete protection (100% survival) against HP-PRRSV challenge in vivo after immunization of piglets with combination of GP3, GP4, M and N (GP3/GP4/M/N). Further analysis of lung pathology, weight gain, and viremia post-challenge revealed that the combination of GP3/GP4/M/N provided superior protective efficacy against severe infection. These findings underscore the potential of this SP combination to serve as an effective PRRSV subunit vaccine, marking a significant advancement in pork industry disease management.


Assuntos
Guanidinas , Piperazinas , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Doenças dos Suínos , Vacinas Virais , Animais , Suínos , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Macrófagos Alveolares , Anticorpos Antivirais
8.
Ann Thorac Surg ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38499219

RESUMO

BACKGROUND: We aimed to validate the prognostic implication of uncertain resection, R(un), proposed by International Association for the Study of Lung Cancer (IASLC) and evaluate the prognostic value of spread through air spaces (STAS) in reclassifying the R classification among patients with lung adenocarcinoma after segmentectomy. METHODS: We enrolled 1007 patients who underwent segmentectomy for c-stage IA lung adenocarcinoma between 2014 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were compared to evaluate the prognostic value of IASLC-R(un) and STAS. Whether STAS would skip into complementary lobectomy was evaluated in a prospective cohort. RESULTS: The current IASLC-R(un) failed to significantly stratify the RFS (P = .078) in segmentectomy, and STAS was a stronger risk factor of poor prognosis for both RFS and OS (P < .001). Moreover, the presence of STAS was associated with increased locoregional recurrence in patients undergoing segmentectomy (P < .001) but not in those treated with lobectomy (P = .187), indicating that only STAS-positive segmentectomy was consistent with the concept of R(un) in relapse pattern. After reclassifying STAS-positive segmentectomy into the R(un) category, the proposed R(un) showed an improvement in prognosis stratification. In addition, 2 of 30 patients (6.2%) in the prospective cohort who underwent initial segmentectomy and complementary lobectomy had STAS clusters in the complementary lobectomy specimens. CONCLUSIONS: Unfavorable prognosis, relapse patterns consistent with R(un), and pathologic verification that saltatory spread of STAS observed in complementary lobectomy specimens supported reclassifying STAS-positive segmentectomy as R(un). STAS is a critical concern for the surgical completeness evaluation after segmentectomy.

9.
J Pharm Biomed Anal ; 243: 116080, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38479306

RESUMO

Cancer antigen 125 (CA125) is pivotal as a tumor marker in early ovarian cancer prevention and diagnosis. In this work, we introduced an ultrasensitive label-free electrochemical immunosensor tailored for CA125 detection, leveraging nanogold-functionalized copper-cobalt oxide nanosheets (CuCo-ONSs@AuNPs) as nanocomposites. For the inaugural application, copper-cobalt oxide nanosheets delivered the requisite DPV electrochemical response for the immunosensors. Their large specific surface area and commendable electrical conductivity amplify electron transfer and enable significant gold nanoparticle loading. Concurrently, AuNPs offer a plethora of active sites, facilitating easy immobilization of biomolecules via the bond between amino groups and AuNPs. We employed scanning electron microscopy, transmission electron microscopy, and x-ray photoelectron spectroscopy to characterize the nanomaterials' surface morphology and elemental composition. The electrochemical sensor response signals were ascertained using differential pulse voltammetry. Under optimal conditions, the immunosensor exhibited a linear detection range from 1×10-7 U/mL to 1×10-3 U/mL and a detection limit of 3.9×10-8 U/mL (S/N=3). The proposed label-free electrochemical immunosensor furnishes a straightforward, dependable, and sensitive approach for CA125 quantification and stands as a promising method for clinical detection of other tumor markers.


Assuntos
Técnicas Biossensoriais , Cobalto , Nanopartículas Metálicas , Nanocompostos , Neoplasias , Óxidos , Ouro/química , Técnicas Biossensoriais/métodos , Cobre , Limite de Detecção , Técnicas Eletroquímicas/métodos , Antígeno Ca-125 , Nanopartículas Metálicas/química , Imunoensaio/métodos , Biomarcadores Tumorais , Nanocompostos/química
10.
Nat Biomed Eng ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374224

RESUMO

The blood-brain barrier (BBB) restricts the systemic delivery of messenger RNAs (mRNAs) into diseased neurons. Although leucocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, it is difficult to efficiently load long mRNAs into the EVs and to enhance their neuronal uptake. Here we show that the packaging of mRNA into leucocyte-derived EVs and the endocytosis of the EVs by neurons can be enhanced by engineering leucocytes to produce EVs that incorporate retrovirus-like mRNA-packaging capsids. We transfected immortalized and primary bone-marrow-derived leucocytes with DNA or RNA encoding the capsid-forming activity-regulated cytoskeleton-associated (Arc) protein as well as capsid-stabilizing Arc 5'-untranslated-region RNA elements. These engineered EVs inherit endothelial adhesion molecules from donor leukocytes, recruit endogenous enveloping proteins to their surface, cross the BBB, and enter the neurons in neuro-inflammatory sites. Produced from self-derived donor leukocytes, the EVs are immunologically inert, and enhanced the neuronal uptake of the packaged mRNA in a mouse model of low-grade chronic neuro-inflammation.

11.
Lung Cancer ; 189: 107472, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38320371

RESUMO

OBJECTIVES: The Lepidic Component (LP) identifies a subgroup with an excellent prognosis for lung adenocarcinoma (LUAD). Our research aimed to propose an improved pathological T (pT) stage for LUAD based on LP. MATERIALS AND METHODS: Totally, 3335 surgical patients with pathological stage I LUAD were incorporated. Factors affecting survival were investigated by analyzing recurrence-free survival (RFS) and overall survival (OS) using the Kaplan-Meier method and Cox regression analyses. Subgroup analysis based on Lepidic Ratio (LR) was further evaluated. The net benefit from the modified pT category (pTm) was assessed using the Area Under the time-dependent Receiver Operating Curve (AUC), Harrell's Concordance Index (C-index), Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). RESULTS: The presence of LP (LP+) was identified in 1425 (42.7 %) patients, indicating a significantly better RFS (P < 0.001) and OS (P < 0.001) than those without LP, and similar results were reproduced in pT1a-pT2a subcategory (P < 0.050 for all). Multivariable Cox analysis revealed LP+ as an independent prognostic factor for both RFS (HR, 0.622; P < 0.001) and OS (HR, 0.710; P = 0.019). However, lepidic ratio (LR) was not independently associated with both RFS and OS for LP+ patients. The 5-year RFS and OS rates between T1a (LP-) and T1b (LP+), T1b (LP-) and T1c (LP+), and T1b (LP-) and T2a (LP+) were comparable (P > 0.050 for all). After modification, compared with current 8th edition pT stage system (pT8), pTm independently predicted RFS and OS, and AUCs, c-index, NRI, and IDI analysis all demonstrated pTm holds better discrimination performances than pT8 for LUAD prognosis. CONCLUSION: LP can be an additional down-staged T descriptor for pathological stage I LUAD and improve the survival predictive performance of reclassification.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Área Sob a Curva
12.
J Cancer Res Clin Oncol ; 150(2): 98, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381215

RESUMO

OBJECTIVE: The initial therapeutic approach for diffuse large B-cell lymphoma (DLBCL) entails a rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen. However, 40% of patients exhibit suboptimal responses, with some experiencing relapse and refractory conditions. This study aimed to explore novel therapeutic strategies and elucidate their underlying mechanisms in DLBCL. METHODS: Bioinformatics techniques were employed to scrutinize correlations between the HDAC1, HDAC2, HDAC3, HDAC10, BTK, MYC, TP53, and BCL2 genes in DLBCL. In vitro experiments were conducted using DB and SU-DHL-4 cells treated with chidamide, orelabrutinib, and a combination of both. Cell viability was assessed by cell counting kit-8. Cell apoptosis and the cell cycle were determined using flow cytometry. Reactive oxygen species (ROS) production and mitochondrial function were assessed through ROS and JC-1 staining. RNA sequencing and western blot analyses were conducted to elucidate the molecular mechanisms underlying the combined action of chidamide and orelabrutinib in DLBCL cells. RESULTS: This investigation revealed markedly enhanced antiproliferative effects when chidamide was combined with orelabrutinib. Compusyn software analysis indicated a synergistic effect of chidamide and orelabrutinib in inhibiting DLBCL cell proliferation, with a combination index (CI) < 1. This synergy further manifested as augmented cell cycle arrest, apoptosis induction, the downregulation of cell cycle-associated and antiapoptotic proteins, and the upregulation of proapoptotic proteins. Furthermore, the western blot and RNA-Seq findings suggested that combining chidamide and orelabrutinib modulated the PI3K/AKT/mTOR signaling pathway, thereby promoting DLBCL cell cycle arrest and apoptosis. CONCLUSION: The findings of this study provide a compelling justification for the clinical utilization of chidamide and orelabrutinib to treat relapsed/refractory DLBCL.


Assuntos
Aminopiridinas , Benzamidas , Linfoma Difuso de Grandes Células B , Fosfatidilinositol 3-Quinases , Piperidinas , Piridinas , Humanos , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio , Recidiva Local de Neoplasia , Apoptose , Pontos de Checagem do Ciclo Celular , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Serina-Treonina Quinases TOR , Histona Desacetilases
14.
Cell Host Microbe ; 32(3): 349-365.e4, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38367621

RESUMO

Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.


Assuntos
Transtorno do Espectro Autista , Infecções por Clostridium , Microbioma Gastrointestinal , Humanos , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/genética , Trato Gastrointestinal , Fezes , Resultado do Tratamento
15.
Talanta ; 272: 125606, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394747

RESUMO

Carbohydrate antigen 199 (CA199) is the most sensitive marker reported for pancreatic cancer, and it is a difficult task to develop a highly sensitive assay for CA199. During the experiment, a ratiometric electrochemical immunosensor for quantitative analysis of CA199 was prepared for NiCo@Fc-MWCNTs-LDH as the electrode sensing surface and 3D-rGOF@Ag/Au as the label of Ab2. NiCo@Fc-MWCNTs-LDH not only provide the required signal for the immunosensor, but also have a layered structure to obtain a large specific surface area, which can provide more sites for the placement of biological molecules. rGOF has the advantages of large specific surface area and high porosity, which can adsorb Ag electrochemical probe through redox reaction. The modification of gold nanoparticles can not only enhance the electrical conductivity of nano-composites, but also immobilize more biomolecules to improve the sensitivity of electrochemical sensors. With the beefing up of CA199 concentration, the oxidation peak current of Ag increases and the oxidation peak current of Fc-COOH decreases. The ratio (y = IAg/IFc-COOH) of two different signals was linear with the logarithm of CA199 concentration in a certain value range. Under optimal conditions, the immunosensor showed excellent performance in the concentration range of 0.0001 U/mL to 10 U/mL, and the detection limit was 5.55 × 10-4 U/mL. The strategy could clearly discriminate between matched and mismatched targets, demonstrating high specifificity. This approach further detects CA199 in human plasma to differentiate pancreatic cancer patients from healthy individuals with high accuracy. This method also provided a new idea for the ultrasensitive quantitative detection of other biomarkers.


Assuntos
Técnicas Biossensoriais , Grafite , Nanopartículas Metálicas , Neoplasias Pancreáticas , Humanos , Ouro/química , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , Biomarcadores Tumorais , Neoplasias Pancreáticas/diagnóstico , Limite de Detecção , Grafite/química
16.
Clin Nucl Med ; 49(4): 361-363, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38350075

RESUMO

ABSTRACT: A 72-year-old man with fever and weakness in both lower limbs underwent thoracolumbar MRI and 18 F-FDG PET/CT. The PET/CT scan revealed diffused FDG uptake along the spinal dura mater from T7 to S2 level like a "bottle brush." Pathologic examination after biopsy of spinal canal lesions manifested granulomatous inflammation. The blood test showed cytoplasmic antineutrophil cytoplasmic antibody (ANCA) and myeloperoxidase-ANCAs were positive, whereas the perinuclear ANCA was negative. Eventually, he was diagnosed with granulomatosis with polyangiitis.


Assuntos
Granulomatose com Poliangiite , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Masculino , Humanos , Idoso , Fluordesoxiglucose F18 , Anticorpos Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico por imagem , Dura-Máter/diagnóstico por imagem
17.
Clin Lab ; 70(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345975

RESUMO

BACKGROUND: Bloodstream infections (BSI) represent a common cause of sepsis and mortality in children. Blood culture (BC) is the gold standard for diagnosis of BSI. The low sensitivity of BC in the pediatric population is usually due to the small volume of blood used for inoculation and to the antibiotics used before sampling. Here, we explore the ways to effectively reduce antibiotic activity to maximize the chances of pathogen recovery, and to enhance the growth of microorganisms in lower blood volume and bacterial counts. METHODS: The recovery of common pathogens causing blood stream infections was analyzed after exposure to cefo-perazone/sulbactam, vancomycin, and caspofung by using resin-containing or not BacT/Alert PF Plus and BD FX400 peds plus pediatric bottles. The microbial growth in the resin-containing bottles was assessed using 0.5 colony-forming units (CFU) bacterial inoculum to mimic the bacteremia/fungemia condition. The usefulness of a diagnosis to confirm or exclude BSI was evaluated by lower than recommended blood culture sampling (102 CFU/mL, 0.3 mL). RESULTS: Staphylococcus aureus (S. aureus), and Candida glabrata (C. glabrata) were recovered from 100% of two types of resin-containing bottles in the presence of a sufficient antibiotic dose, while Escherichia coli (E. coli) was not restored to 100% in BD FX400 peds plus pediatric bottles. The shorter TTD for S. aureus, C. glabrata, and E. coli were observed in antibiotic-containing BacT/Alert PF Plus bottles. Both the PF Plus and BD resin test bottles showed consistently good TTD performances to Gram-negative, Gram-positive, and yeast species in low inoculum levels, with the exception of S. aureus. The lower volume of blood inoculated into culture bottles hardly affected the growth of most bacteria, but optimized PF Plus resin-bottles accelerated the detection of infectious agents, especially S. aureus, Streptococcus pneumoniae, and C. glabrata. CONCLUSIONS: It is possible to enhance recovery from antibiotic-containing pediatric bottles and shorten TTD for the identification of pathogens by using the BacT/Alert blood culture system combination with new resin-containing media.


Assuntos
Bacteriemia , Sepse , Infecções Estafilocócicas , Criança , Humanos , Antibacterianos/farmacologia , Escherichia coli , Meios de Cultura , Staphylococcus aureus , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Bactérias , Técnicas Bacteriológicas
18.
J Environ Manage ; 352: 120083, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38237331

RESUMO

Modeling and predicting forest landscape dynamics are crucial for forest management and policy making, especially under the context of climate change and increased severities of disturbances. As forest landscapes change rapidly due to a variety of anthropogenic and natural factors, accurately and efficiently predicting forest dynamics requires the collaboration and synthesis of domain knowledge and experience from geographically dispersed experts. Owing to advanced web techniques, such collaboration can now be achieved to a certain extent, for example, discussion about modeling methods, consultation for model use, and surveying for stakeholders' feedback can be conducted on the web. However, a research gap remains in terms of how to facilitate online joint actions in the core task of forest landscape modeling by overcoming the challenges from decentralized and heterogeneous data, offline model computation modes, complex simulation scenarios, and exploratory modeling processes. Therefore, we propose an online collaborative strategy to enable collaborative forest landscape dynamic prediction with four core modules, namely data preparation, forest landscape model (FLM) computation, simulation scenario configuration, and process organization. These four modules are designed to support: (1) voluntary data collection and online processing, (2) online synchronous use of FLMs, (3) collaborative simulation scenario design, altering, and execution, and (4) participatory modeling process customization and coordination. We used the LANDIS-II model as a representative FLM to demonstrate the online collaborative strategy for predicting the dynamics of forest aboveground biomass. The results showed that the online collaboration strategy effectively promoted forest landscape dynamic prediction in data preparation, scenario configuration, and task arrangement, thus supporting forest-related decision making.


Assuntos
Mudança Climática , Florestas , Biomassa , Simulação por Computador , Formulação de Políticas , Árvores
19.
Ecotoxicol Environ Saf ; 271: 115991, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237395

RESUMO

Heavy metal toxicity is a significant global health concern, with particular attention given to lead (Pb) exposure due to its adverse effects on cognitive development, especially in children exposed to low concentrations. While Pb neurotoxicity has been extensively studied, the analysis and molecular mechanisms underlying the transgenerational effects of Pb exposure-induced neurotoxicity remain poorly understood. In this study, we utilized Drosophila, a powerful developmental animal model, to investigate this phenomenon. Our findings demonstrated that Pb exposure during the developmental stage had a profound effect on the neurodevelopment of F0 fruit flies. Specifically, we observed a loss of correlation between the terminal motor area and muscle fiber area, along with an increased frequency of the ß-lobe midline crossing phenotype in mushroom bodies. Western blot analysis indicated altered expression levels of synaptic vesicle proteins, with a decrease in Synapsin (SYN) and an increase in Bruchpilot (BRP) expression, suggesting changes in synaptic vesicle release sites. These findings were corroborated by electrophysiological data, showing an increase in the amplitude of evoked excitatory junctional potential (EJP) and an increase in the frequency of spontaneous excitatory junctional potential (mEJP) following Pb exposure. Importantly, our results further confirmed that the developmental neurotoxicity resulting from grandparental Pb exposure exhibited a transgenerational effect. The F3 offspring displayed neurodevelopmental defects, synaptic function abnormalities, and repetitive behavior despite lacking direct Pb exposure. Our MeDIP-seq analysis further revealed significant alterations in DNA methylation levels in several neurodevelopmental associated genes (eagle, happyhour, neuroglian, bazooka, and spinophilin) in the F3 offspring exposed to Pb. These findings suggest that DNA methylation modifications may underlie the inheritance of acquired phenotypic traits resulting from environmental Pb exposure.


Assuntos
Drosophila melanogaster , Síndromes Neurotóxicas , Animais , Criança , Humanos , Chumbo/metabolismo , Metilação de DNA , Síndromes Neurotóxicas/genética , Genoma
20.
Cell ; 187(1): 184-203.e28, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38181741

RESUMO

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.


Assuntos
Neoplasias Pulmonares , Proteogenômica , Carcinoma de Pequenas Células do Pulmão , Humanos , Linhagem Celular , Neoplasias Pulmonares/química , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/química , Carcinoma de Pequenas Células do Pulmão/genética , Xenoenxertos , Biomarcadores Tumorais/análise
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