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1.
Medicine (Baltimore) ; 103(36): e39587, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252239

RESUMO

To understand the prevalence of cognitive impairment (CI) in middle-aged and elderly individuals in Anhui Province and to develop a CI risk prediction model. From May to June 2022, a multistage, stratified cluster-sampling method was used to select 3200 middle-aged and elderly people over 45 years old in Anhui Province for a questionnaire survey, and the Chinese version of the Mini-Mental State Examination (MMSE) was used to assess cognitive function. SPSS 25.0 was used for univariate and multivariate analyses, and R software was used to establish and validate the nomogram. A total of 3059 valid questionnaires were included, of which 384 were from participants who were diagnosed with CI, and the prevalence rate was 12.6%. Multivariate logistic analysis showed that female sex, advanced age, family history, etc., were closely related to the occurrence of CI. The area under curve (AUC) values in the modeling and validation groups were 0.845 (95% CI: 0.822-0.868) and 0.868 (95% CI: 0.835-0.902), respectively, indicating that the predictive ability of the model was good. The Hosmer-Lemeshow test suggested that the model had good goodness-of-fit, and the decision-curve evaluation nomogram had a high benefit within the threshold, which had a certain clinical importance. The prevalence rate of CI among middle-aged and elderly individuals in Anhui Province was 12.6%. Female sex, elderly age, family history, low educational status, current smoking status, sleep disorders, hypertension, stroke, and diabetes were shown to be risk factors for CI, while exercise was shown to be a protective factor.


Assuntos
Disfunção Cognitiva , Humanos , Feminino , Disfunção Cognitiva/epidemiologia , Masculino , China/epidemiologia , Prevalência , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Testes de Estado Mental e Demência , Inquéritos e Questionários , Nomogramas , Idoso de 80 Anos ou mais , Fatores Etários , Fatores Sexuais , Estudos Transversais
2.
J Am Heart Assoc ; 13(19): e035075, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39291499

RESUMO

BACKGROUND: Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long-term clinical outcomes after acute ischemic stroke. METHODS AND RESULTS: We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all-cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log-corin was associated with a 21% (95% CI, 11-30), 16% (95% CI, 6-26), and 12% (95% CI, 3-21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all-cause mortality and cardiovascular events, as shown by C-statistics (all P<0.05). CONCLUSIONS: Serum soluble corin was associated with decreased risks of long-term clinical outcomes, and may be a promising prognostic biomarker for risk stratification in patients with acute ischemic stroke.


Assuntos
Biomarcadores , AVC Isquêmico , Recidiva , Serina Endopeptidases , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , AVC Isquêmico/sangue , AVC Isquêmico/mortalidade , AVC Isquêmico/diagnóstico , Biomarcadores/sangue , Idoso , Serina Endopeptidases/sangue , Prognóstico , China/epidemiologia , Fatores de Risco , Medição de Risco , Fatores de Tempo
3.
Int J Pharm ; 664: 124580, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39142464

RESUMO

The tumor stroma plays a crucial role in tumor progression, and the interactions between the extracellular matrix, tumor cells, and stromal cells collectively influence tumor progression and the efficacy of therapeutic agents. Currently, utilizing components of the tumor stroma for drug delivery is a noteworthy strategy. A number of targeted drug delivery systems designed based on tumor stromal components are entering clinical trials. Therefore, this paper provides a thorough examination of the function of tumor stroma in the advancement of targeted drug delivery systems. One approach is to use tumor stromal components for targeted drug delivery, which includes certain stromal components possessing inherent targeting capabilities like HA, laminin, along with targeting stromal cells homologously. Another method entails directly focusing on tumor stromal components to reshape the tumor stroma and facilitate drug delivery. These drug delivery systems exhibit great potential in more effective cancer therapy strategies, such as precise targeting, enhanced penetration, improved safety profile, and biocompatibility. Ultimately, the deployment of these drug delivery systems can deepen our comprehension of tumor stroma and the advanced development of corresponding drug delivery systems.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Neoplasias , Células Estromais , Humanos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Animais , Células Estromais/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Microambiente Tumoral/efeitos dos fármacos , Matriz Extracelular/metabolismo
4.
J Transl Med ; 22(1): 737, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103915

RESUMO

BACKGROUND: Cancer stem-like cells (CSCs) play an important role in initiation and progression of aggressive cancers, including esophageal cancer. Natural killer (NK) cells are key effector lymphocytes of innate immunity that directly attack a wide variety of cancer cells. NK cell-based therapy may provide a new treatment option for targeting CSCs. In this study, we aimed to investigate the sensitivity of human esophageal CSCs to NK cell-mediated cytotoxicity. METHODS: CSCs were enriched from human esophageal squamous cell carcinoma cell lines via sphere formation culture. Human NK cells were selectively expanded from the peripheral blood of healthy donors. qRT-PCR, flow cytometry and ELISA assays were performed to examine RNA expression and protein levels, respectively. CFSE-labeled target cells were co-cultured with human activated NK cells to detect the cytotoxicity of NK cells by flow cytometry. RESULTS: We observed that esophageal CSCs were more resistant to NK cell-mediated cytotoxicity compared with adherent counterparts. Consistently, esophageal CSCs showed down-regulated expression of ULBP-1, a ligand for NK cells stimulatory receptor NKG2D. Knockdown of ULBP-1 resulted in significant inhibition of NK cell cytotoxicity against esophageal CSCs, whereas ULBP-1 overexpression led to the opposite effect. Finally, the pro-differentiation agent all-trans retinoic acid was found to enhance the sensitivity of esophageal CSCs to NK cell cytotoxicity. CONCLUSIONS: This study reveals that esophageal CSCs are more resistant to NK cells through down-regulation of ULBP-1 and provides a promising approach to promote the activity of NK cells targeting esophageal CSCs.


Assuntos
Citotoxicidade Imunológica , Regulação para Baixo , Neoplasias Esofágicas , Células Matadoras Naturais , Células-Tronco Neoplásicas , Humanos , Células Matadoras Naturais/imunologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Regulação para Baixo/efeitos dos fármacos , Linhagem Celular Tumoral , Citotoxicidade Imunológica/efeitos dos fármacos , Proteínas Ligadas por GPI/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
5.
Aging Clin Exp Res ; 36(1): 150, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060791

RESUMO

BACKGROUND: Fine particular matter (PM2.5) has been associated with dementia, but limited information is available regarding the association between PM2.5 components and dementia. AIMS: We aimed to identify the major components of PM2.5 that affect cognitive function to further investigate its mechanism of action, and develop a prevention strategy for dementia. METHODS: In this study, we included 7804 participants aged ≥ 60 years recruited from seven counties in Zhejiang province, eastern China. The participants completed the baseline survey between 2014 and 2015, and were followed up until the end of 2020. We adopted single-component robust Poisson regression models for analyses, and estimated relative risks and 95% confidence intervals describing associations between the chemical constituents of PM2.5 exposure and incident cognitive impairment in those who were free from cognitive impairment at baseline. RESULTS: Significantly positive associations were observed between sulfate, nitrate, ammonium, and organic matter in PM2.5 and incident cognitive impairment across different exposure periods; the relative risks of 10-year exposure before enrollment ranged from 1.01 to 1.02. However, we did not find a significant association between black carbon and cognitive impairment. The point estimates of the relative risk values did not change substantially after performing the sensitivity analyses. CONCLUSIONS: Our findings strengthen the idea that long-term exposure to PM2.5 mass and its chemical components is associated with an elevated risk of incident cognitive impairment among older adults.


Assuntos
Disfunção Cognitiva , Vida Independente , Material Particulado , Humanos , Idoso , Disfunção Cognitiva/epidemiologia , Masculino , Material Particulado/análise , Material Particulado/efeitos adversos , Feminino , China/epidemiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Exposição Ambiental/efeitos adversos , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos
6.
Cell Death Dis ; 15(7): 502, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003255

RESUMO

Dysfunction of the ubiquitin-proteasome system (UPS) is involved in the pathogenesis of various malignancies including colorectal cancer (CRC). Ubiquitin domain containing 1 (UBTD1), a ubiquitin-like protein, regulates UPS-mediated protein degradation and tumor progression in some cancer types. However, the biological function and mechanism of UBTD1 are far from being well elucidated, and its role in CRC has not been explored yet. In our study, we analyzed CRC patients' clinical information and UBTD1 expression data, and found that the expression of UBTD1 in cancer tissue was significantly higher than that in adjacent normal tissue. Higher UBTD1 expression was significantly associated with poorer survival and more lymph node metastasis. Overexpression of UBTD1 could facilitate, while knockdown could inhibit CRC cell proliferation and migration, respectively. RNA-seq and proteomics indicated that c-Myc is an important downstream target of UBTD1. Metabolomics showed the products of the glycolysis pathway were significantly increased in UBTD1 overexpression cells. In vitro, we verified UBTD1 upregulating c-Myc protein and promoting CRC cell proliferation and migration via regulating c-Myc. UBTD1 promoted CRC cells' glycolysis, evidenced by the increased lactate production and glucose uptake following UBTD1 overexpression. Mechanistically, UBTD1 prolonged the half-life of the c-Myc protein by binding to E3 ligase ß-transducin repeat-containing protein (ß-TrCP), thereby upregulated the expression of glycolysis rate-limiting enzyme hexokinase II (HK2), and enhanced glycolysis and promoted CRC progression. In conclusion, our study revealed that UBTD1 promotes CRC progression by upregulating glycolysis via the ß-TrCP/c-Myc/HK2 pathway, suggesting its potential as a prognostic biomarker and therapeutic target in CRC.


Assuntos
Proliferação de Células , Neoplasias Colorretais , Progressão da Doença , Glicólise , Proteínas Proto-Oncogênicas c-myc , Regulação para Cima , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Hexoquinase/metabolismo , Hexoquinase/genética , Camundongos Nus , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Ubiquitinas/metabolismo , Ubiquitinas/genética
7.
Comput Biol Med ; 179: 108913, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39047508

RESUMO

Machine learning has been employed in recognizing protein localization at the subcellular level, which highly facilitates the protein function studies, especially for those multi-label proteins that localize in more than one organelle. However, existing works mostly study the qualitative classification of protein subcellular locations, ignoring fraction of one multi-label protein in different locations. Actually, about 50 % proteins are multi-label proteins, and the ignorance of quantitative information highly restricts the understanding of their spatial distribution and functional mechanism. One reason of the lack of quantitative study is the insufficiency of quantitative annotations. To address the data shortage problem, here we proposed a generative model, PLocGAN, which could generate cell images with conditional quantitative annotation of the fluorescence distribution. The model was a conditional generative adversarial network, in which the condition learning utilized partial label learning to overcome the lack of training labels and allowed training with only qualitative labels. Meanwhile, it used contrastive learning to enhance diversity of the generated images. We assessed the PLocGAN on four pixel-fused synthetic datasets and one real dataset, and demonstrated that the model could generate images with good fidelity and diversity, outperforming existing state-of-the-art generative methods. To verify the utility of PLocGAN in the quantitative prediction of protein subcellular locations, we replaced the training images with generated quantitative images and built prediction models, and found that they had a boosting effect on the quantitative estimation. This work demonstrates the effectiveness of deep generative models in bioimage analysis, and provides a new solution for quantitative subcellular proteomics.


Assuntos
Aprendizado Profundo , Humanos , Proteínas/metabolismo , Proteínas/química , Proteínas/análise , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência/métodos , Aprendizado de Máquina
8.
J Agric Food Chem ; 72(31): 17377-17391, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39051843

RESUMO

Bufadienolides (BDs) are a class of naturally occurring toxins present in amphibian toads. Serving as the chemical weapons, they exist not only in the adult toads but also in toad eggs. Guided by mass spectrometry (MS)-based component analysis and feature-based molecular networking (FBMN), 30 bufadienolide-fatty acid conjugates (BDFs) were isolated from the fertilized eggs of toad Bufo gargrizans, including 25 previously undescribed compounds (1-25). Their chemical structures were elucidated by extensive spectroscopic analysis, chemical methods, and GC-MS. The toxicities of all BDFs and their corresponding free BDs were assessed using the zebrafish model. The structure-toxicity relationship analysis showed that the modification of BDs by hydroxy fatty acids can cause a significant increase of the toxicity. Furthermore, all the isolated compounds were evaluated for their antiproliferative activities in pancreatic cancer cell lines ASPC-1 and PANC10.05. The structure-activity relationship (SAR) analysis revealed that BDFs with hellebrigenin as the bufogenin moiety (6 and 7) exhibited the most potent antiproliferative effect. Further investigation into their functional mechanism demonstrated that 6 and 7 induced apoptosis in pancreatic cancer cells PANC10.05 and significantly suppressed the expression of the apoptosis-related gene c-MYC. In addition, 6 and 7 effectively inhibited the expression of the PI3K/Akt/mTOR pathway in PANC10.05. Moreover, we assessed the efficacy of 6 and 7 on cancer cells from various tissues and observed their broad-spectrum antiproliferative activity.


Assuntos
Bufanolídeos , Bufonidae , Proliferação de Células , Ácidos Graxos , Peixe-Zebra , Animais , Bufanolídeos/química , Bufanolídeos/farmacologia , Bufanolídeos/toxicidade , Bufanolídeos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Humanos , Linhagem Celular Tumoral , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Ácidos Graxos/toxicidade , Relação Estrutura-Atividade , Zigoto/efeitos dos fármacos , Zigoto/química , Estrutura Molecular
9.
Environ Sci Technol ; 58(31): 13624-13635, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39051940

RESUMO

Cohorts of pregnant women in 2018 and 2020 were selected to explore prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS). Maternal serum during the whole pregnancy (first to third trimesters) and matched cord serum were collected for the analysis of 50 PFAS. Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and 6:2 fluorotelomer sulfonic acid (6:2 FTS) were the dominant PFAS in both the maternal and cord serum. The median ∑PFAS concentration was 14.18 ng/mL, and the ∑PFAS concentration was observed to decline from the first trimester to the third trimester. The transplacental transfer efficiencies (TTE) of 29 PFAS were comprehensively assessed, and a "U"-shaped trend in TTE values with increasing molecular chain length of perfluoroalkyl carboxylic acid (PFCA) was observed in this study. Moreover, the maternal concentrations of 9-chlorohexadecafluoro-3-oxanonane-1-sulfonic acid (6:2 Cl-PFESA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), PFOS, and hexafluoropropylene oxide dimer acid (HFPO-DA) in the 2020 cohort were significantly lower than those in the 2018 cohort, declining by about 23.85-43.2% from 2018 to 2020 (p < 0.05). Higher proportions of emerging PFAS were observed in fetuses born in 2020. This birth cohort was collected during the COVID-19 epidemic period. The change in the PFAS exposure scene might be in response to the different exposure profiles of the 2018 and 2020 cohorts, which are attributed to the impact of COVID-19 on the social activities and environment of pregnant women. Finally, by application of a multiple informant model, the third trimester was identified as the critical window of vulnerability to PFAS exposure that affects birth weight and birth length.


Assuntos
Fluorocarbonos , Humanos , Feminino , Gravidez , Adulto , COVID-19/epidemiologia , Ácidos Alcanossulfônicos , Estudos de Coortes , Exposição Materna , Poluentes Ambientais , Caprilatos
10.
Front Public Health ; 12: 1375106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827624

RESUMO

Introduction: Depressive symptoms are often experienced by patients with arthritis and are correlated with poor health outcomes. However, the association between depressive symptoms and multidimensional factors (sociodemographic characteristics, health conditions, health behaviors, and social support) among older patients with arthritis in China remains poorly understood. This study aimed to explore the prevalence of depressive symptoms in older patients with arthritis in eastern China and identify the associated factors. Methods: We analyzed data of 1,081 older patients with arthritis using secondary data from 2014 to 2020 from a community-based ongoing study initiated in 2014 in eastern China. The prevalence of depressive symptoms was calculated, and univariate and multilevel logistic regression analyses were used to identify the associated factors. Results: The mean age of older patients with arthritis was 69.16 ± 7.13 years; 42.92% were men and 57.08% were women. The prevalence of depressive symptoms in older patients with arthritis was 14.99% (95% confidence interval: 12.91-17.26%), about 1.8 times higher than that in older adults without arthritis (8.49%, p < 0.001). Multilevel logistic regression identified perception of poor economic status (odds ratio [OR] = 5.52, p < 0.001), multimorbidity (OR = 1.96, p = 0.001), limitations in activities of daily living (OR = 2.36, p = 0.004), and living alone (OR = 3.13, p = 0.026) as factors positively associated with depressive symptoms. Patients diagnosed with arthritis at an older age had lower odds of experiencing depressive symptoms (OR = 0.67, p = 0.046). Conclusion: Screening for depressive symptoms is essential among older patients with arthritis, especially those who perceive themselves as having a poor economic status, are diagnosed at an earlier age, have multimorbidity, have limitations in activities of daily living, and live alone. The associations of age at arthritis diagnosis and dietary behaviors with depressive symptoms require further research.


Assuntos
Artrite , Depressão , Humanos , Masculino , Feminino , Idoso , China/epidemiologia , Artrite/epidemiologia , Depressão/epidemiologia , Prevalência , Pessoa de Meia-Idade , Fatores de Risco , Estudos Transversais , Apoio Social , Idoso de 80 Anos ou mais , Modelos Logísticos , Atividades Cotidianas , Fatores Socioeconômicos
11.
J Hazard Mater ; 476: 134896, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38909464

RESUMO

Cadmium(Cd) contamination can exert significantly adverse effects on soil microbiota in reclaimed areas, however, its effects on bacterial network structure are still limitedly understood. Here we collected soil samples from typical reclaimed wetlands (RW) and ditch wetlands (DW) in coastal reclamation areas and examined the effects of Cd contamination on the bacterial network complexity and stability. The results showed that the bacterial networks were destabilized by the Cd contamination, while bacteria in DW soils showed robust invulnerability characterized by higher node constancy and compositional stability compared with RW soils. Soil bacteria resisted Cd stress by forming a network with intensive connections in the module but sparser connections among the modules. Especially, network modularity was higher in DW soils than in RW soils, but made it more vulnerable to nodes removal. In addition, Cd contamination promoted bacterial positive cohesion but decreased negative cohesion in RW soils. Flavobacteriaceae, Xanthomonadaceae, and Alcaligenaceae were identified as core phylotypes, which played pivotal roles in regulating interspecies interactions due to higher contributions to cohesion and significant correlations with soil nutrients. The findings of this work indicate the changes of bacterial network structure and the indispensable role of core phylotypes in regulating interactions and maintaining network sustainability under Cd contamination.


Assuntos
Bactérias , Cádmio , Microbiologia do Solo , Poluentes do Solo , Áreas Alagadas , Cádmio/toxicidade , Cádmio/análise , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Microbiota/efeitos dos fármacos
12.
Blood Sci ; 6(2): e00189, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742239

RESUMO

An accurate prognostic model for acute myeloid leukemia (AML) can guide personalized treatment. In our prospective cohort of 591 patients newly diagnosed with AML, we evaluated the prognostic significance of serum albumin levels. We recognized baseline serum albumin as a prognostic factor by univariate Cox regression analysis (albumin-high vs albumin-low: overall survival [OS]: hazard ratio [HR]: 0.679, 95% confidence interval [CI]: 0.529-0.870, P = .002; cumulative incidence of relapse [CIR]: HR: 0.705, 95% CI: 0.530-0.938, P = .017) and multivariate Cox regression analysis (OS: HR per g/L: 0.966, 95% CI: 0.940-0.993, P = .014; CIR: HR per g/L: 0.959, 95% CI: 0.927-0.993, P = .017). In the subgroup analysis, serum albumin was prognostic significant in patients who received intermediate-dose cytarabine combined with daunorubicin and omacetaxine mepesuccinate induction (albumin-high vs albumin-low: OS: HR: 0.585, 95% CI: 0.397-0.863, P = .007; CIR: HR: 0.551, 95% CI: 0.353-0.861, P = .009) rather than those receiving conventional-dose induction regimens. In addition, the impact of baseline serum albumin level was evident in patients with intermediate European LeukemiaNet risk (albumin-high vs albumin-low: OS: HR: 0.617, 95% CI: 0.424-0.896, P = .011; CIR: HR: 0.617, 95% CI: 0.388-0.979, P = .040). Gene set enrichment analysis revealed that leukemia stem cell signatures were enriched in patients with low serum albumin levels. Our study suggested that baseline serum albumin level was associated with the inherent properties of AML and correlated with patient outcomes.

13.
Anal Chem ; 96(18): 7289-7296, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38666489

RESUMO

Quantitative glycosylation analysis serves as an effective tool for detecting changes in glycosylation patterns in cancer and various diseases. However, compared with N-glycans, O-glycans present challenges in both qualitative and quantitative mass spectrometry analysis due to their low abundance, ease of peeling, lack of a universal enzyme, and difficult accessibility. To address this challenge, we developed O-GlycoIsoQuant, a novel O-glycome quantitative approach utilizing superbase release and isotopic Girard's P labeling. This method facilitates rapid and efficient nonreducing ß-elimination to dissociate O-glycans from proteins using the organic superbase, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), combined with light and heavy isotopic Girard's reagent P (GP) labeling for relative quantification of O-glycans by mass spectrometry. Employing this method, labeled O-glycans exhibit a double peak with a mass difference of 5 Da, suitable for stable relative quantification. The O-GlycoIsoQuant method is characterized by its high labeling efficiency, excellent reproducibility (CV < 20%), and good linearity (R2 > 0.99), across a dynamic range spanning a 100-fold range. This method was applied to various complex sample types, including human serum, porcine spermatozoa, human saliva, and urinary extracellular vesicles, detecting 33, 39, 49, and 37 O-glycans, respectively, thereby demonstrating its broad applicability.


Assuntos
Glicômica , Marcação por Isótopo , Polissacarídeos , Polissacarídeos/análise , Polissacarídeos/química , Polissacarídeos/metabolismo , Humanos , Glicômica/métodos , Animais , Glicosilação , Masculino , Espectrometria de Massas
14.
JAMA Netw Open ; 7(4): e244592, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602679

RESUMO

Importance: Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear. Objectives: To explore the different patterns in cervical length trajectories in singleton and twin pregnancies and to analyze whether the immunological mechanisms of sPTB are consistent among these cervical length patterns. Design, Setting, and Participants: This cohort study recruited pregnant individuals who received antenatal care and delivered at Peking University Third Hospital in Beijing, China, between January 1, 2014, and December 31, 2022. Individuals with singleton and twin pregnancies were included. Exposures: Cervical length measurements and white blood cell (WBC) indicators. Main Outcomes and Measures: The primary outcome was sPTB. Longitudinal trajectory cluster analysis was used to identify patterns of changes in cervical length in singleton and twin pregnancies. A random-effects model with cubic spline was used to fit and compare the longitudinal trajectory of WBC indicators among early preterm birth, moderate to late preterm birth, and term birth. Results: A total of 43 559 pregnant individuals were included; of these, 41 706 had singleton pregnancies (mean [SD)] maternal age, 33.0 [4.0] years) and 1853 had twin pregnancies (mean [SD] maternal age, 33.3 [3.6] years). Two distinct patterns of cervical length changes were observed in both singleton and twin pregnancies: shortened (21 366 singletons and 546 twins) and stable (20 340 singletons and 1307 twins). In singleton pregnancies, WBC count was associated with early sPTB in individuals with both shortened cervix (odds ratio [OR], 1.35; 95% CI, 1.00-1.82) and stable cervix (OR, 1.64; 95% CI, 1.07-2.50). However, for twin pregnancies, the association of WBC count (OR, 3.13; 95% CI, 1.58-6.18) with the risk of early sPTB was observed only in individuals with a shortened cervix. Conclusions and Relevance: This study identified 2 distinct cervical length patterns: shortened and stable. These patterns revealed 2 preterm birth mechanisms in twin pregnancies, with the immunopathogenesis of sPTB found only in the shortened cervix pattern; in singleton pregnancies, maternal immune response was associated with a higher risk of sPTB regardless of a shortened or stable cervix.


Assuntos
Gravidez de Gêmeos , Nascimento Prematuro , Recém-Nascido , Gravidez , Humanos , Feminino , Adulto , Medida do Comprimento Cervical , Estudos de Coortes , Nascimento Prematuro/epidemiologia , China/epidemiologia
15.
Carbohydr Polym ; 335: 122084, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38616102

RESUMO

Mapping the N-glycome of porcine sperm before and after sperm capacitation is important for understanding the rearrangement of glycoconjugates during capacitation. In this work, we characterized the N-glycome on the membranes of 18 pairs of fresh porcine sperm before capacitation and porcine sperm after capacitation by MALDI-MS (Matrix-assisted laser desorption/ionization-mass spectrometry). A total of 377 N-glycans were detected and a comprehensive N-glycome map of porcine sperm membranes before and after capacitation was generated, which presents the largest N-glycome dataset of porcine sperm cell membranes. Statistical analysis revealed a significantly higher level of high mannose glycosylation and a significantly lower level of fucosylation, galactosylation, and α-2,6-NeuAc after capacitation, which is further verified by flow cytometry and lectin blotting. This research reveals new insights into the relationship between N-glycosylation variations and sperm capacitation, including the underlying mechanisms of the capacitation process.


Assuntos
Peróxido de Benzoíla , Sêmen , Masculino , Suínos , Animais , Membranas , Membrana Celular , Espermatozoides
16.
Exp Hematol ; 133: 104206, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508299

RESUMO

Many prognostic factors have been identified in acute myeloid leukemia (AML). In this study, we investigated novel prognostic biomarkers using machine learning and Cox regression models in a prospective cohort of 591 patients with AML and tried to identify potential therapeutic targets based on transcriptomic data. We found that elevated red blood cell distribution width (RDW) at diagnosis was an adverse prognostic factor for AML, independent of the 2022 European LeukemiaNet (ELN2022) genetic risk. As a continuous variable, higher RDW was associated with shorter overall survival (OS) (hazard ratio [HR] 1.087, 95% confidence interval [CI] 1.036-1.139, p < 0.001) and event-free survival (EFS) (HR 1.078, 95% CI 1.033-1.124, p < 0.001). Elevated RDW returned to normal after consolidation therapy, which indicated that leukemia cells resulted in abnormal RDW. We further investigated the relationship between RDW and transcriptome in another cohort of 191 patients with AML and public datasets using gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). We found that patients in the high-RDW group were significantly enriched in the positive regulation of erythroid differentiation and inflammation-related pathways. Finally, we identified the inflammation-associated gene IL12RB2 and verified its prognostic relevance with patients with AML in public databases, suggesting it as a potential therapy target.


Assuntos
Índices de Eritrócitos , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Transcriptoma , Estudos Prospectivos
17.
Cell Death Dis ; 15(3): 236, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553452

RESUMO

Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial-mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Metabolismo Energético , Retroalimentação , Regulação Neoplásica da Expressão Gênica , Biossíntese de Proteínas , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia
18.
Biomed Opt Express ; 15(3): 1668-1681, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38495701

RESUMO

Laser ablation is an effective treatment modality. However, current laser scanners suffer from laser defocusing when scanning targets at different depths in a 3D surgical scene. This study proposes a deep learning-assisted 3D laser steering strategy for minimally invasive surgery that eliminates laser defocusing, increases working distance, and extends scanning range. An optofluidic laser scanner is developed to conduct 3D laser steering. The optofluidic laser scanner has no mechanical moving components, enabling miniature size, lightweight, and low driving voltage. A deep learning-based monocular depth estimation method provides real-time target depth estimation so that the focal length of the laser scanner can be adjusted for laser focusing. Simulations and experiments indicate that the proposed method can significantly increase the working distance and maintain laser focusing while performing 2D laser steering, demonstrating the potential for application in minimally invasive surgery.

19.
Medicine (Baltimore) ; 103(10): e37366, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457568

RESUMO

To investigate the infection status of coronavirus disease 2019 (COVID-19) among people in Anhui Province, China after the epidemic prevention and control measures were lifted, and to study and analyze its related influencing factors. From March 11 to May 20, 2023, questionnaires on COVID-19 were distributed on the Questionnaire Star platform, and Statistical Product and Service Solutions software (version 19.0) was used for statistical processing. The results showed that the infection rate of COVID-19 among respondents reached 72.24%. 58.81% of the infected people reported post COVID-19 symptoms. Fever, fatigue, and cough were the main symptoms during infection. The results of multi-factor logistic regression analysis showed that there is statistical significance between age (P = .002), residential area (P = .025), number of vaccine injections (P < .001) and the risk of new coronavirus infection. COVID-19 had a high infection rate, and children had a lower risk of COVID-19. People living in cities were more susceptible to COVID-19, and it was necessary to increase the number of vaccine doses.


Assuntos
COVID-19 , Vacinas , Criança , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , SARS-CoV-2 , Prevalência , China/epidemiologia , Fatores de Risco
20.
J Contam Hydrol ; 262: 104318, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38354450

RESUMO

Ecological water replenishment is a crucial and effective measure to improve the water quality and ecological function of lakes. However, the effects of ecological water replenishment on the pollution characteristics and ecological risks of trace elements and bacterial communities in lake surface water are still kept unclear. We investigated the pollution levels and potential ecological risks for trace elements, as well as variation of the bacterial community in surface water in the BYD lake before and after ecological water replenishment. Our results revealed that higher levels and pollution indexes (Igeo) of trace metals (e.g., As, Cd, Co, Cu and Ni; p < 0.05) after ecological water replenishment were observed than before ecological water replenishment and their total potential ecological risk (∑RI) were increased. In contrast, the network complexity of these trace elements, including nodes, edges, average diameter, modularity, clustering coefficient and average pathlength showed a decrease after ecological water replenishment than before. The diversity (community richness, community diversity and phylogenetic diversity decreased) and community structure of the bacterial community in the surface water (p < 0.05) were greatly changed after ecological water replenishment than before, with the increase in heavy metal-resistant phylum (e.g., Acidobacteriota). Moreover, the concentration of trace elements and ∑RI were significantly correlated with the alpha diversity of bacterial community, as well as dissolved organic carbon (DOC) and ORP, after ecological water replenishment. The findings indicate that it is very necessary to continuously monitor trace metal pollution levels and heavy metal-resistant phylum and identify their potential pollution sources for water environment control and lake ecosystem health.


Assuntos
Metais Pesados , Oligoelementos , Poluentes Químicos da Água , Lagos/química , Ecossistema , Filogenia , Monitoramento Ambiental , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Medição de Risco , Metais Pesados/análise , China , Qualidade da Água
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