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1.
Sci Rep ; 14(1): 6459, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499679

RESUMO

Physical activity (PA) is linked to a decreased risk of type 2 diabetes mellitus (T2DM). However, the influence of circadian PA trajectories remains uncertain. This study aims to explore the optimal circadian PA trajectory pattern for reducing the risk of T2DM. Methods: A total of 502,400 participants were recruited from the UK Biobank between 2006 and 2010, and 102,323 participants provided valid accelerometer-captured acceleration data. After excluding individuals with prior T2DM, 99,532 participants were included in the final analysis. We initially investigated the association between PA intensity at 24 hourly time points and T2DM. Subsequently, PA trajectories were identified using K-means cluster analysis. Cox proportional hazard models were employed to estimate hazard ratios (HR). Four distinct PA trajectories were identified: consistently low, single peak, double peak, and intense trajectories. Compared to consistently low, single peak, double peak and intense PA trajectory reduced the risk of T2DM progressively. Sensitivity analyses, further excluding individuals with glycated hemoglobin (HbA1c) ≥ 6.5% or random glucose ≥ 11.1 mmol/L and adjusted for daily average acceleration, yielded consistent results. This confirms that the ideal circadian PA trajectory serves as a protective factor, independently of PA intensity. Subgroup analyses indicated that these effects were more pronounced in men and individuals with eGFR < 60 mL/(min*1.73 m2). In conclusion, ideal circadian PA trajectory patterns (especially intense and then double peak) reduced risk of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Masculino , Bancos de Espécimes Biológicos , Diabetes Mellitus Tipo 2/epidemiologia , Exercício Físico , Hemoglobinas Glicadas , Fatores de Risco , Biobanco do Reino Unido , Feminino
2.
RSC Adv ; 14(15): 10152-10160, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38544946

RESUMO

Umami peptides are new ingredients for the condiment and seasoning industries, with healthy and nutrition characteristics, some of which were identified from aquatic proteins. This study aims to further explore novel umami peptides from Atlantic cod (Gadus morhua) by combining in silico, nano-HPLC-MS/MS, sensory evaluation, and electronic tongue analysis. Two novel peptides, Leu-Val-Asp-Lys-Leu (LVDKL) and Glu-Ser-Lys-Ile-Leu (ESKIL), from the myosin heavy chain of Atlantic cod (Gadus morhua), were screened and confirmed to have strong umami tastes with the thresholds of 0.427 mM and 0.574 mM, respectively. The molecular docking was adopted to explore the interactions between the umami peptides and the umami taste receptor T1R1/T1R3, which showed that the umami peptides interacted with T1R1/T1R3 mainly by electrostatic interaction, hydrogen bond interaction, and hydrophobic interaction. Furthermore, the physicochemical properties of the peptides were investigated by in silico methods and cell viability experiments. This study will provide a better understanding of the umami taste in Atlantic cod and will promote the development of condiments and seasonings.

3.
Nat Commun ; 15(1): 1333, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351003

RESUMO

Commensal bacteria generate immensely diverse active metabolites to maintain gut homeostasis, however their fundamental role in establishing an immunotolerogenic microenvironment in the intestinal tract remains obscure. Here, we demonstrate that an understudied murine commensal bacterium, Dubosiella newyorkensis, and its human homologue Clostridium innocuum, have a probiotic immunomodulatory effect on dextran sulfate sodium-induced colitis using conventional, antibiotic-treated and germ-free mouse models. We identify an important role for the D. newyorkensis in rebalancing Treg/Th17 responses and ameliorating mucosal barrier injury by producing short-chain fatty acids, especially propionate and L-Lysine (Lys). We further show that Lys induces the immune tolerance ability of dendritic cells (DCs) by enhancing Trp catabolism towards the kynurenine (Kyn) pathway through activation of the metabolic enzyme indoleamine-2,3-dioxygenase 1 (IDO1) in an aryl hydrocarbon receptor (AhR)-dependent manner. This study identifies a previously unrecognized metabolic communication by which Lys-producing commensal bacteria exert their immunoregulatory capacity to establish a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in DCs. This metabolic circuit represents a potential therapeutic target for the treatment of inflammatory bowel diseases.


Assuntos
Colite , Firmicutes , Cinurenina , Humanos , Animais , Camundongos , Cinurenina/metabolismo , Lisina , Receptores de Hidrocarboneto Arílico/metabolismo , Colite/induzido quimicamente , Bactérias/metabolismo , Tolerância Imunológica , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo
4.
BMC Geriatr ; 24(1): 193, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408910

RESUMO

BACKGROUND: There is a lack of relevant studies evaluating the long-term impact of cardiovascular health factor (CVH) metrics on chronic kidney disease (CKD). OBJECTIVE: This study investigates the long-term change in CVH metrics in older people and explores the relationship between CVH metrics trajectory and CKD. METHODS: In total, 27,635 older people aged over 60 from the community-based Tianjin Chronic Kidney Disease Cohort study were enrolled. The participants completed five annual physical examinations between January 01, 2014, and December 31, 2018, and a subsequent follow-up between January 01, 2019, and December 31, 2021. CVH metrics trajectories were established by the group-based trajectory model to predict CKD risk. The relationships between baseline CVH, CVH change (ΔCVH), and CKD risk were also explored by logistic regression and restricted cubic spline regression model. In addition, likelihood ratio tests were used to compare the goodness of fit of the different models. RESULTS: Six distinct CVH metrics trajectories were identified among the participants: low-stable (11.19%), low-medium-stable (30.58%), medium-stable (30.54%), medium-high-decreased (5.46%), medium-high-stable (18.93%), and high-stable (3.25%). After adjustment for potential confounders, higher CVH metrics trajectory was associated with decreased risk of CKD (P for trend < 0.001). Comparing the high-stable with the low-stable group, the risk of CKD decreased by 46%. All sensitivity analyses, including adjusting for baseline CVH and removing each CVH component from the total CVH, produced consistent results. Furthermore, the likelihood ratio test revealed that the model established by the CVH trajectory fit better than the baseline CVH and Δ CVH. CONCLUSION: The higher CVH metrics trajectory and improvement of CVH metrics were associated with decreased risk of CKD. This study emphasized the importance of improving CVH to achieve primary prevention of CKD in older people.


Assuntos
Doenças Cardiovasculares , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Estudos Prospectivos , Indicadores de Qualidade em Assistência à Saúde , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , China/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco , Nível de Saúde
5.
Dalton Trans ; 53(11): 5020-5033, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38294042

RESUMO

Due to the radioactivity of uranium, the discharged nuclear wastewater not only causes certain damage to the ecology, but also causes certain harm to human life and health. Adsorption is considered to be one of the most effective ways to remove uranium. In this paper, a kind of MoS2 adsorbent was prepared by the solid phase synthesis method and functionalized with NiCo-LDH. The raw materials of MoS2 are cheap and easy to obtain, and the preparation conditions are simple, and large quantities can be obtained without limitations. MoS2 functionalized with NiCo-LDH provides more adsorption sites for the adsorbent and at the same time improves the hydrophilicity of the adsorbent, so that the active sites can fully combine with uranyl ions. The maximum adsorption capacity of the Langmuir isothermal adsorption model is 492.83 mg g-1. The selective adsorption capacity of uranium can reach 76.12% in the multi-ion coexistence system. By analyzing the adsorption mechanism with FT-IR and XRD, it is believed that on the one hand, UO22+ forms a covalent bond with Mo in MoS2 and coordinates with S on the surface of MoS2. On the other hand, UO22+ enters the NiCo-LDH layer for ion exchange with NO3- and coordinates with -OH on the surface of NiCo-LDH. The successful preparation of the MoS2/NiCo-LDH composite provides a certain application prospect for the uranium adsorption field.

6.
Macromol Biosci ; 24(5): e2300469, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38197551

RESUMO

In order to achieve long-term and controllable release of anti-tumor drugs at specific sites, temperature/pH responsive nanoparticles encapsulating 5-fluorouracil and methotrexate in situ are prepared through dispersion photopolymerization under green LED irradiation. The physicochemical properties of nanoparticles are characterized by scanning electron microscopy, Fourier transform infrared, dynamic light scattering, thermogravimetric/differential scanning calorimetry, and X-ray diffraction. In vitro drug release at different temperatures and pH values is examined to ascertain the release pattern of two drugs, which can be well described by Korsmeyer-Peppas kinetic model. The cytotoxicity evaluation illustrates that the tumor cells could be more effectively killed by the drug-loaded nanoparticles, and the improved therapeutic effect is attributed to the controllable and sustainable drug release as well as the enhanced cellular uptake. The blood safety and good biocompatibility of nanoparticles are further confirmed by hemolysis assay, indicating the prepared nanoparticles are potential candidates for effective tumor treatment.


Assuntos
Fluoruracila , Metotrexato , Nanopartículas , Polimetil Metacrilato , Temperatura , Fluoruracila/farmacologia , Fluoruracila/química , Metotrexato/farmacologia , Metotrexato/química , Nanopartículas/química , Concentração de Íons de Hidrogênio , Humanos , Polimetil Metacrilato/química , Polimerização , Hemólise/efeitos dos fármacos , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Animais , Difração de Raios X , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/química , Linhagem Celular Tumoral
7.
Int J Cardiol ; 399: 131770, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38211679

RESUMO

BACKGROUND: Physical activity (PA) is associated with mortality and cardiovascular disease (CVD). However, the effect of circadian PA trajectories remains ambiguous. This study aimed to explore ideal circadian PA patterns to reduce mortality and CVD, and potential mediators. METHODS: 502,400 participants from UK Biobank were recruited between 2006 and 2010. Among them, 102,323 participants got valid continuously capturing acceleration data over 7 days by wrist-worn accelerometer. K-means cluster analysis was used to identify PA trajectories. The associations of PA with all-cause, cause-specific mortality and CVD were assessed by cox regression. A sensitivity test was also conducted, starting from the time of acceleration collection and excluding participants with corresponding disease prior to it. Furthermore, the mediation of aging and inflammation were explored. RESULTS: During a median follow-up of 12.9 years, 3482 deaths were recorded (704 were due to CVD). Five distinct PA trajectories were identified: Persistently Low, Moderate and Stable, Single Increase, Double Increase, and Vigorous patterns. Ideal PA trajectory patterns offered progressively protective benefits against all-cause, CVD caused mortality and CVD, especially in Double Increase and Vigorous patterns. Other cause-specific mortality and renal failure incidence showed similar trend. The sensitivity result was consistent. The mediating effects of phenotypic age and inflammation markers were statistically significant. CONCLUSION: Ideal PA trajectories offered protective benefits against all-cause, cause-specific mortality and CVD. The protection was associated with both intensity and circadian distribution. Double Increase and Vigorous activity patterns decreased these risks more significantly. Crucially, this protection was mediated by aging deceleration and inflammation regulation.


Assuntos
Bancos de Espécimes Biológicos , Doenças Cardiovasculares , Humanos , Causas de Morte , Desaceleração , Biobanco do Reino Unido , Exercício Físico/fisiologia , Doenças Cardiovasculares/epidemiologia , Envelhecimento/fisiologia , Inflamação
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(1): 98-102, 2024 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-38269467

RESUMO

Multisystem inflammatory syndrome in children (MIS-C) is a complex syndrome characterized by multi-organ involvement that has emerged in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. The clinical presentation of MIS-C is similar to Kawasaki disease but predominantly presents with fever and gastrointestinal symptoms, and severe cases can involve toxic shock and cardiac dysfunction. Epidemiological findings indicate that the majority of MIS-C patients test positive for SARS-CoV-2 antibodies. The pathogenesis and pathophysiology of MIS-C remain unclear, though immune dysregulation following SARS-CoV-2 infection is considered a major contributing factor. Current treatment approaches for MIS-C primarily involve intravenous immunoglobulin therapy and symptomatic supportive care. This review article provides a comprehensive overview of the definition, epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of MIS-C.


Assuntos
COVID-19 , Criança , Humanos , SARS-CoV-2 , Pandemias , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia
9.
Abdom Radiol (NY) ; 49(2): 399-405, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37792056

RESUMO

INTRODUCTION: The image quality of continuously acquired free-breathing Dynamic Contrast-Enhanced (DCE) golden-angle radial Magnetic Resonance Imaging (MRI) of abdomen suffers from motion artifacts and motion-related blurring. We propose a scheme by minimizing patients' motion status from breathing as well as optimizing the acquiring parameters to improve image quality and diagnostic performance of DCE-MRI with Golden-Angle Radial Sparse Parallel (GRASP) sequence of abdomen. METHODS: The optimization scheme follows two principles: (1) reduce the impact on images from unpredictable and irregulate motions during examination and (2) adjust the sequence parameters to increase the number of radial views in each partition. For the assessment of image quality, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), the severity of radial artifact, the degree of image sharpness, and a visual scoring of image quality with a 5-point scale were assessed. RESULTS: A total of 64 patients were included in this study before (16 men, 14 women, age: 54.9 ± 17.0) and after (18 men, 16 women, age: 58.6 ± 12.6) the optimization scheme was performed. The results showed that the SNR values of right and left lobe of liver in both plain phase and arterial phase were significantly increased (All P < 0.001) after the GRASP sequence been optimized. Significant improvements in CNR values were observed in the arterial phase (All P < 0.05). The significant differences in scores at each phase for visual scoring of image quality, noise of the right and left lobe of liver, radial artifact, and sharpness indicating that the image quality was significantly improved after the optimization (All P < 0.001). CONCLUSION: Our study demonstrated that the optimized scheme significantly improved the image quality of liver DCE-MRI with GRASP sequence both in plain and arterial phases. The optimized scheme of GRASP sequence could be a superior alternative to conventional approach for the assessment of liver.


Assuntos
Abdome , Meios de Contraste , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Abdome/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Fígado/diagnóstico por imagem , Respiração , Artefatos , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos
10.
Inflammation ; 47(1): 227-243, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37777674

RESUMO

Diabetic kidney disease (DKD) is characterized by macrophage infiltration, which requires further investigation. This study aims to identify immune-related genes (IRGs) in macrophage and explore their potential as therapeutic targets. This study analyzed isolated glomerular cells from three diabetic mice and three control mice. A total of 59 glomeruli from normal kidney samples and 66 from DKD samples were acquired from four kidney transcriptomic profiling datasets. Bioinformatics analysis was conducted using both single-cell RNA (scRNA) and bulk RNA sequencing data to investigate inflammatory responses in DKD. Additionally, the "AUCell" function was used to investigate statistically different gene sets. The significance of each interaction pair was determined by assigning a probability using "CellChat." The study also analyzed the biological diagnostic importance of immune hub genes for DKD and validated the expression of these immune genes in mice models. The top 2000 highly variable genes (HVGs) were identified after data normalization. Subsequently, a total of eight clusters were identified. It is worth mentioning that macrophages showed the highest percentage increase among all cell types in the DKD group. Furthermore, the present study observed significant differences in gene sets related to inflammatory responses and complement pathways. The study also identified several receptor-ligand pairs and co-stimulatory interactions between endothelial cells and macrophages. Notably, SYK, ITGB2, FCER1G, and VAV1 were identified as immunological markers of DKD with promising predictive ability. This study identified distinct cell clusters and four marker genes. SYK, ITGB2, FCER1G, and VAV1 may be important roles. Consequently, the present study extends our understanding regarding IRGs in DKD and provides a foundation for future investigations into the underlying mechanisms.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Animais , Camundongos , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Células Endoteliais/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Glomérulos Renais/metabolismo , Macrófagos/metabolismo
11.
Prev Med ; 179: 107831, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145876

RESUMO

BACKGROUND: Physical activity (PA) has been linked with cancer incidence. However, the effects and mechanisms underpinning circadian PA trajectories on cancer remain elusive. This study aimed to explore the optimal PA patterns in reducing cancer incidence and the associated potential mediators. METHODS: Between 2006 and 2010, 502,400 participants were recruited from the UK Biobank. Out of these, 102,323 participants wore accelerometers, which allowed for collecting acceleration data continuously over 7 days. After excluding participants with previous cancer history, 96,687 participants were included in K-means cluster analysis to identify PA trajectories. The association between PA and cancer incidence was assessed using Cox regression analysis. Additionally, we investigated the mediating role of inflammation. RESULTS: A total of 5995 cancer cases were recorded during a median follow-up of 7.1 years. Four distinct PA trajectories (persistent low, single peak, double peak, and vigorous) were identified. The ideal PA patterns reduced the risk of 7 out of 17 site-specific cancers, with the lowest hazard ratios and 95% confidence intervals of cancer for bladder (0.59, 0.40-0.86), breast (0.73, 0.60-0.89), kidney (0.45, 0.26-0.78), lung (0.59, 0.41-0.84), myeloma (0.49, 0.27-0.88), and oral & pharynx (0.51, 0.26-0.98) in the vigorous pattern and for colorectal (0.71, 0.54-0.93) in the double peak pattern. Moreover, the mediating effects of inflammation were significant. CONCLUSION: Optimal PA trajectories reduced cancer incidence, especially in double peak and vigorous patterns. The protective effect was associated with both intensity and circadian rhythm. Crucially, this protection was mediated by inflammation regulation.


Assuntos
Bancos de Espécimes Biológicos , Neoplasias , Humanos , Incidência , Biobanco do Reino Unido , Exercício Físico , Inflamação/epidemiologia , Neoplasias/epidemiologia , Neoplasias/prevenção & controle
12.
Endocrine ; 2023 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-38141061

RESUMO

BACKGROUND: Machine learning is increasingly recognized as a viable approach for identifying risk factors associated with diabetic kidney disease (DKD). However, the current state of real-world research lacks a comprehensive systematic analysis of the predictive performance of machine learning (ML) models for DKD. OBJECTIVES: The objectives of this study were to systematically summarize the predictive capabilities of various ML methods in forecasting the onset and the advancement of DKD, and to provide a basic outline for ML methods in DKD. METHODS: We have searched mainstream databases, including PubMed, Web of Science, Embase, and MEDLINE databases to obtain the eligible studies. Subsequently, we categorized various ML techniques and analyzed the differences in their performance in predicting DKD. RESULTS: Logistic regression (LR) was the prevailing ML method, yielding an overall pooled area under the receiver operating characteristic curve (AUROC) of 0.83. On the other hand, the non-LR models also performed well with an overall pooled AUROC of 0.80. Our t-tests showed no statistically significant difference in predicting ability between LR and non-LR models (t = 1.6767, p > 0.05). CONCLUSION: All ML predicting models yielded relatively satisfied DKD predicting ability with their AUROCs greater than 0.7. However, we found no evidence that non-LR models outperformed the LR model. LR exhibits high performance or accuracy in practice, while it is known for algorithmic simplicity and computational efficiency compared to others. Thus, LR may be considered a cost-effective ML model in practice.

13.
Heliyon ; 9(12): e22916, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144265

RESUMO

O-GlcNAcylation is a post-translational modification of proteins that regulates various biological processes. However, its involvement in peritoneal dialysis fibrosis remains unclear. This study aimed to investigate the impact of O-GlcNAcylation on human peritoneal mesothelial cells (HPMCs) cultured in control and high-glucose medium. To manipulate cellular conditions, we employed knockdown techniques targeting HIF-1α and OGT, along with the administration of pharmacological agents (PUGNAc, OSMI-1, MG-132, FG-4592, and HIF-1α inhibitor). Our findings revealed that elevated glucose levels increased global O-GlcNAcylation and the abundance of HIF-1α, α-SMA, fibronectin, and COL1A2. Conversely, the expression of E-Cadherin was decreased. Significantly, a positive correlation was observed between O-GlcNAcylation, HIF-1α, mesothelial-to-mesenchymal transition (MMT), and fibrosis in HPMCs. Notably, O-GlcNAcylation was found to regulate HIF-1α, thereby promoting MMT and fibrosis under high glucose conditions. Furthermore, we discovered that high glucose levels induced O-GlcNAcylation of HIF-1α, preventing its ubiquitination and proteasomal degradation. In summary, our study demonstrates the critical role of O-GlcNAcylation-mediated regulation of HIF-1α in MMT and fibrosis during peritoneal dialysis.

14.
J Geriatr Cardiol ; 20(9): 673-683, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37840627

RESUMO

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS: The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

15.
BMC Vet Res ; 19(1): 151, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684673

RESUMO

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) and porcine delta-coronavirus (PDCoV) are economically important pathogens that cause diarrhea in sows and acute death of newborn piglets. Moreover, the emerging PDCoV was reported to infect children. The current situation is that vaccine prevention has not met expectations, and emergency containment strategies following outbreaks cannot prevent the damages and losses already incurred. Therefore, a more sensitive detection method, that is both convenient and enables accurate and effective sequencing, that will provide early warning of PEDV and PDCoV is necessary. This will enable active, effective, and comprehensive prevention and control, which will possibly reduce disease occurrences. RESULTS: Duplex nested RT-PCR (dnRT-PCR) is an ideal method to achieve early warning and monitoring of PEDV and PDCoV diseases, and to additionally investigate any molecular epidemiological characteristics. In this study, two pairs of primers were designed for each virus based upon the highly conserved N protein sequences of both PEDV and PDCoV strains retrieved from the NCBI Genbank. After optimization of the reaction conditions, the dnRT-PCR assay amplified a 749-bp fragment specific to PEDV and a 344-bp fragment specific to PDCoV. Meanwhile, the specificity and sensitivity of the primers and clinical samples were tested to verify and establish this dnRT-PCR method. The limit of detection (LoD)for both PEDV and PDCoV was 10 copies/µL. The results showed that among 251 samples, 1 sample contained PEDV infection, 19 samples contained a PDCoV infection, and 8 samples were infected with both viruses, following the use of dnRT-PCR. Subsequently, the positive samples were sent for sequencing, and the sequencing results confirmed that they were all positive for the viruses detected using dnRT-PCR, and conventional RT-PCR detection was conducted again after the onset of disease. As these results were consistent with previous results, a detection method for PEDV and PDCoV using dnRT-PCR was successfully established. In conclusion, the dnRT-PCR method established in this study was able to detect both PEDV and PDCoV, concomitantly. CONCLUSIONS: The duplex nested RT-PCR method represents a convenient, reliable, specific, sensitive and anti-interference technique for detecting PEDV and PDCoV, and can additionally be used to simultaneously determine the molecular epidemiological background.


Assuntos
Infecções por Coronavirus , Coronavirus , Vírus da Diarreia Epidêmica Suína , Animais , Suínos , Feminino , Coronavirus/genética , Vírus da Diarreia Epidêmica Suína/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Reação em Cadeia da Polimerase/veterinária , Primers do DNA
16.
Org Lett ; 25(29): 5426-5430, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37458365

RESUMO

[2 + 2]-Cycloaddition is the most straightforward approach to the construction of cyclobutanes. In this paper, the intermolecular [2 + 2]-cycloaddition reaction of 3-alkylideneindolin-2-ones with alkenes was achieved. This reaction can be used in the synthesis of 3-spirocyclobutyl oxindoles, polycyclic oxindoles, and late stage modification of some drug molecules.

17.
Medicine (Baltimore) ; 102(30): e34486, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37505137

RESUMO

BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC). METHODS: For this integrated analysis, from inception to January 2, 2023, we searched PubMed, Web of Science, Embase, and Cochrane library databases for prospective studies that evaluated SC in RM-TNBC patients. Primary endpoints were survival outcomes and responses. Secondary endpoints were all grade and grade ≥ 3 toxicities. RESULTS: Six hundred potentially relevant records were screened. Our analysis included 3 trials (412 patients). Median overall survival was 12.9 months (95% confidence interval [CI], 11.5-14.4), progression-free survival was 5.7 months (5% CI, 5.1-6.3), and duration of objective response was 7.4 months (5% CI, 5.8-9.0). The objective response rate was 34%, and the disease control rate was 71%. Key grade ≥ 3 toxicities (in over 10% of the patients) included neutropenia (46%), leukopenia (12%), febrile neutropenia (11%), diarrhea (11%), and anemia (10%). Four treatment-related deaths were reported. CONCLUSION: SG was associated with effectiveness in patients with RM-TNBC. Myelosuppression and diarrhea were the primary treatment-related adverse events.


Assuntos
Imunoconjugados , Neoplasias de Mama Triplo Negativas , Humanos , Antígenos de Neoplasias , Camptotecina/efeitos adversos , Diarreia/induzido quimicamente , Imunoconjugados/efeitos adversos , Estudos Prospectivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
18.
BMC Ophthalmol ; 23(1): 287, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353735

RESUMO

BACKGROUND: To assess the anxiety and depression levels in patients with Posner-Schlossman syndrome (PSS) and to determine the potential risk factors. METHODS: In this cross-sectional study, a total of 195 participants, including 93 PSS patients and 102 healthy controls were recruited. Sociodemographic and clinical information were collected for all participants. Hospital Anxiety and Depression scale (HADS) was administered to evaluate the anxiety and depression levels. Visual function (VF) and quality-of-life (QOL) questionnaires were administered to assess variables potentially associated with anxiety and depression. RESULTS: Increased anxiety level was observed in 22 (23.7%) PSS patients as compared to 10 (9.8%) of controls (P = 0.009). While the frequency of depression between the two groups was not significantly different (P = 0.349). The mean anxiety and depression scores were 6.98 ± 4.20 and 6.44 ± 3.66 in PSS patients as compared to 6.67 ± 3.21 (P = 0.564) and 5.96 ± 2.93 (P = 0.311) in controls. Logistic regression analysis showed mental well-being was significantly associated with anxiety (odds ratio [OR] = 0.920, 95% confidence interval [CI] = 0.881-0.962, P < 0.001) and depression (OR = 0.959, CI = 0.926-0.994, P = 0.023) in PSS patients. CONCLUSION: More patients with PSS may experience anxiety as compared to healthy controls. Mental well-being is an independent risk factor for anxiety and depression. It is important for ophthalmologists to be aware of these factors and should pay more attention on mental health when PSS is managed in clinic.


Assuntos
Depressão , Qualidade de Vida , Humanos , Depressão/diagnóstico , Depressão/etiologia , Estudos Transversais , Ansiedade/diagnóstico , Ansiedade/psicologia , Transtornos de Ansiedade/diagnóstico
19.
PLoS One ; 18(5): e0282350, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37146014

RESUMO

OBJECTIVES: Breast cancer is a major health problem with high mortality rates. Early detection of breast cancer will promote treatment. A technology that determines whether a tumor is benign desirable. This article introduces a new method in which deep learning is used to classify breast cancer. METHODS: A new computer-aided detection (CAD) system is presented to classify benign and malignant masses in breast tumor cell samples. In the CAD system, (1) for the pathological data of unbalanced tumors, the training results are biased towards the side with the larger number of samples. This paper uses a Conditional Deep Convolution Generative Adversarial Network (CDCGAN) method to generate small samples by orientation data set to solve the imbalance problem of collected data. (2) For the high-dimensional data redundancy problem, this paper proposes an integrated dimension reduction convolutional neural network (IDRCNN) model, which solves the high-dimensional data dimension reduction problem of breast cancer and extracts effective features. The subsequent classifier found that by using the IDRCNN model proposed in this paper, the accuracy of the model was improved. RESULTS: Experimental results show that IDRCNN combined with the model of CDCGAN model has superior classification performance than existing methods, as revealed by sensitivity, area under the curve (AUC), ROC curve and accuracy, recall, sensitivity, specificity, precision,PPV,NPV and f-values analysis. CONCLUSION: This paper proposes a Conditional Deep Convolution Generative Adversarial Network (CDCGAN) which can solve the imbalance problem of manually collected data by directionally generating small sample data sets. And an integrated dimension reduction convolutional neural network (IDRCNN) model, which solves the high-dimensional data dimension reduction problem of breast cancer and extracts effective features.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Redes Neurais de Computação , Mama/patologia , Curva ROC , Área Sob a Curva , Hidrolases
20.
Behav Brain Res ; 449: 114472, 2023 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-37146721

RESUMO

Post-stroke depression (PSD) negatively affects the prognosis of post-stroke animals. Ramelteon has neuroprotection for chronic ischemia animals, but the effect and the biological mechanism of it on PSD is still unclear. This study explored the effects of ramelteon with prophylactic administration on blood-brain barrier in rats with middle cerebral artery occlusion (MCAO) and the oxygen-glucose deprivation/reperfusion (OGD/R) bEnd.3 cells and found that ramelteon pretreatment improved the depressive-like behaviors and decreased infarct area in MCAO rats. Also, this study found ramelteon pretreatment improved viability and inhibited permeability in OGD/R cells. In addition, this study found that MCP-1, TNF-α, and IL-1 levels were raised in the MCAO rats and that occludin protein and mRNA levels were decreased in the MCAO and the OGD/R models, while the Egr-1 level was up-regulated. All of these were antagonized by ramelteon pretreatment. In addition, overexpression of Egr-1 could reverse the effect of 100 nM ramelteon pretreatment on FITC and occludin levels in OGD/R cells. In short, this study has demonstrated that the protective effect on PSD of ramelteon pretreatment on MCAO rats is related to the development of BBB permeability and that ramelteon regulates occludin to protect the BBB by inhibiting Egr-1.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Ratos , Camundongos , Animais , Barreira Hematoencefálica/metabolismo , Ocludina/metabolismo , Células Endoteliais/metabolismo , Depressão , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
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