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BACKGROUND: Aortic dissection (AD) is a life-threatening cardiovascular emergency that is often misdiagnosed as other chest pain conditions. Physiologically, AD may cause abnormalities in peripheral blood flow, which can be detected using pulse oximetry waveforms. PURPOSE: This study aimed to assess the feasibility of identifying AD based on pulse oximetry waveforms and to highlight the key waveform features that play a crucial role in this diagnostic method. METHODS: This prospective study employed high-risk chest pain cohorts from two emergency departments. The initial cohort was enriched with AD patients (n = 258, 47% AD) for model development, while the second cohort consisted of chest pain patients awaiting angiography (n = 71, 25% AD) and was used for external validation. Pulse oximetry waveforms from the four extremities were collected for each patient. After data preprocessing, a recognition model based on the random forest algorithm was trained using patients' gender, age, and waveform difference features extracted from the pulse oximetry waveforms. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). The importance of features was also assessed using Shapley Value and Gini importance. RESULTS: The model demonstrated strong performance in identifying AD in both the training and external validation sets. In the training set, the model achieved an area under the ROC curve of 0.979 (95% CI: 0.961-0.990), sensitivity of 0.918 (95% CI: 0.873-0.955), specificity of 0.949 (95% CI: 0.912-0.985), and accuracy of 0.933 (95% CI: 0.904-0.959). In the external validation set, the model attained an area under the ROC curve of 0.855 (95% CI: 0.720-0.965), sensitivity of 0.889 (95% CI: 0.722-1.000), specificity of 0.698 (95% CI: 0.566-0.812), and accuracy of 0.794 (95% CI: 0.672-0.878). Decision curve analysis (DCA) further showed that the model provided a substantial net benefit for identifying AD. The median mean and median variance of the four limbs' signals were the most influential features in the recognition model. CONCLUSIONS: This study demonstrated the feasibility and strong performance of identifying AD based on peripheral pulse oximetry waveforms in high-risk chest pain populations in the emergency setting. The findings also provided valuable insights for future human fluid dynamics simulations to elucidate the impact of AD on blood flow in greater detail.
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BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.
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Função Retardada do Enxerto , Transplante de Rim , Aprendizado de Máquina , Doadores de Tecidos , Humanos , Transplante de Rim/efeitos adversos , Feminino , Masculino , Criança , Estudos Retrospectivos , Adolescente , Pré-Escolar , LactenteRESUMO
BACKGROUND: Low-intensity training with blood flow restriction (BFR) training could induce endurance adaptations, its impact on myocardial markers is still unclear compared to training without BFR. Consequently, the influence of low-intensity interval exercise with and without BFR and high-intensity interval exercise (HIIE) on cardiac troponin was determined in this study. METHODS: Twelve physically active males between 18 and 26 years volunteered as participants. The participants completed 3 exercise tests in random order, which included 40% VO2max low-intensity cycling without BFR (group L), 40% VO2max low-intensity cycling with BFR set at 60% limb occlusion pressure (LOP) (group B), and 80% VO2max high-intensity cycling without BFR (group H). Participant muscle oxygen, blood flow, oxygen uptake, heart rate (HR), perceived exertion (RPE) rating, and pain levels were determined before and after exercise, after cuff inflation, and pre- and post-each exercise. Moreover, before each protocol, immediately after the exercises, and 3-4 hours after each exercise, elbow vein blood samples were collected to evaluate lactate (LA) and high-sensitivity cardiac troponin T (cTnT). RESULTS: Increased LA was recorded after exercise by the individuals in group H, which was more significant than in group B. Moreover, group B documented a more significant LA increment than group L (P < .05). The peak cTnT of groups B and H after exercise was significantly higher (P < .05). Furthermore, the increase was more significant than the values recorded by group L (P < .05). CONCLUSION: The present study demonstrated that low-intensity interval exercise combined with BFR could cause cTnT elevations compared to training without BFR. The increase was similar to HIIE protocols.
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The conventional anaerobic-anoxic-oxic (AAO) process for wastewater treatment is associated with high energy consumption and pollutant emissions due to its reliance on heterotrophic denitrification. In contrast, membrane aerated biofilm reactors (MABR) coupled with hydrogenotrophic denitrification (H2-MABR) offers a more promising alternative. This study conducts a life cycle assessment (LCA) to evaluate the environmental and economic benefits of H2-MABR compared to traditional AAO processes. Results indicate that even with a limited reactor life, the application of MABR in actual wastewater treatment plants can yield over 30 % reduction in environmental and economic impacts. Using CO2 from biogas as a carbon source significantly reduces carbon emissions during the anaerobic stage, while the efficient nitrogen removal minimizes the need for wastewater recirculation and electricity consumption. The H2-driven denitrification process also avoids emissions and secondary pollution risks associated with organic electron donors. Furthermore, coupling H2-MABR with renewable energy source and Power-to-Gas technology further enhances sustainability by ensuring a stable hydrogen supply. Given the significant potential of H2-MABR for improving wastewater treatment, further research and large-scale implementation are highly encouraged.
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Primary breast Burkitt lymphoma (PB-BL) is an exceedingly rare form of primary breast lymphoma. Ultrasonography is the preferred modality for diagnosing breast diseases; however, the ultrasonic features of Burkitt lymphoma have rarely been reported. Herein, we report a case of ultrasonically diagnosed bilateral PB-BL in a lactating patient and present a literature review. A 28-year-old female patient experienced bilateral breast engorgement starting more than a month after childbirth. At three months postpartum, the patient experienced extreme bilateral breast engorgement, with the skin appearing dark purple and jaundiced. Based on the imaging diagnosis, pathological, immunohistochemical, and molecular biological findings, she was diagnosed with Burkitt lymphoma involves bilateral breasts, right adrenal glands, uterus, and multiple bones. After 4 cycles of combination chemotherapy, the tumor basically disappeared, and then after autologous stem cell transplantation and one cycle of combination chemotherapy, the patient is generally in good condition and is under follow-up. We found that the ultrasonic characteristics of PB-BL are different from those of common breast cancer or lactation mastitis. PB-BL lesions are often multiple, large masses, and even involve the whole breast. The characteristic reticular structures are common in lesions, and irregular hyperechoic masses can be seen around it. The mass has abundant peripheral and internal blood flow signals, but internal calcification and attenuated posterior echoes of masses are rarely observed. Thus, the ultrasonic features of breast Burkitt lymphoma are somewhat specific and understanding these features is conducive to its early identification.
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Against the traditional view, a recently published theory argued that isotope ratios are higher in convective precipitation but lower in stratiform precipitation and proposed that isotope ratios reflect rain type proportions. This theory has been widely cited despite some early reservations. Whether the theory represents a faithful reflection of signals of water isotope ratios remains unclear. Here, we reassess its validity from different timescales and broader observations from the pantropics. Unexpectedly, our findings contradict the theory on daily, monthly, and even annual timescales. Pantropical precipitation isotope ratios remain strongly correlated to convection intensity but are independent of rain type proportions because stratiform precipitation isotope ratios cover a large range of values. We find that the theory has many serious weaknesses related to preferential data selection and suggest that new theories need to be validated at more locations on different timescales before gaining widespread acceptance.
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OBJECTIVE: The objectively was to study the effect of long-snake moxibustion intervention on gut microbiota of patients with ankylosing spondylitis (AS) by 16S rDNA sequencing technology. METHODS: Thirty AS patients and 30 healthy volunteers were recruited and treated with long-snake moxibustion once a week for 12 weeks. AS patients were divided into pretreatment and posttreatment groups. VAS, BASDAI, and BASFI scores of AS patients before and after treatment were collected. 16S rDNA high-throughput sequencing technology was used to analyze the characteristics and differences of gut microbiota in AS patients before and after treatment and in healthy volunteers. RESULTS: VAS, BASDAI, and BASFI scores of AS patients after long-snake moxibustion treatment were lower than those of pretreatment group (p < 0.05). The results of gut microbiota alpha diversity showed that Ace and Chao1 index of the posttreatment group were higher than those of the health group (p < 0.05), but there was no statistical significance in Ace and Chao1 index between the pretreatment group and the posttreatment group (p > 0.05). Beta diversity analysis showed that mild classification aggregation occurred between the health group and the pretreatment group but did not reach a significant level, and there was no significant difference between the pretreatment group and the posttreatment group. The results of species abundance showed that, at the phylum level, compared with the health group, the relative abundance of Firmicutes and Proteobacteria decreased in the pretreatment group, while the relative abundance of Bacteroidetes and Actinobacteria increased. Compared with the pretreatment group, the relative abundance of Firmicutes increased and the relative abundance of Actinobacteria decreased in the posttreatment group, but there were no statistically significant differences in the above changes (p > 0.05). At the genus level, compared with the health group, the relative abundances of Subdoligranulum in the pretreatment group were increased (p < 0.05), while the relative abundances of Bifidobacterium and Streptococcus were decreased (p < 0.05). Compared with the pretreatment group, the relative abundance of Romboutsia in the posttreatment group was increased (p < 0.05). CONCLUSION: Long-snake moxibustion can obviously improve the clinical symptoms of AS patients. The possible mechanism of action is related to regulating the abundance of gut microbiota, increasing beneficial bacteria, and restoring the homeostasis of gut microorganisms.
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Chemodynamic therapy is an appealing modality in cancer treatment. However, its therapeutic effectiveness is impeded by insufficient catalytic efficiency and overexpression of glutathione (GSH) at the tumor site. In this study, a poly(o-phenylenediamine) (PoPD)@copper sulfide (CuS) nanoplatform was developed as dual-level reactive oxygen species (ROS) amplifier for enhanced photothermal-chemodynamic therapy. The PoPD@CuS nanoplatform exhibited photothermal performance, chemodynamic performance, and GSH-depleting capability. Alongside its improved photothermal conversion efficiency with tumor pH-responsiveness, the photothermal behavior of PoPD@CuS could elevate chemodynamic activity by regulating the temperature spatiotemporally, leading to increased ROS production. Moreover, GSH depletion of PoPD@CuS could suppress ROS scavenging, further enhancing oxidative stress in the tumor region. Consequently, functioning as a dual-level ROS amplifier, PoPD@CuS showcased remarkable effectiveness in photothermal-chemodynamic combination therapy.
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Cobre , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Cobre/química , Cobre/farmacologia , Humanos , Animais , Fenilenodiaminas/química , Fenilenodiaminas/farmacologia , Glutationa/metabolismo , Glutationa/química , Camundongos , Terapia Fototérmica , Fototerapia/métodos , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
BACKGROUND: We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. METHODS: We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. RESULTS: During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. CONCLUSIONS: Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.
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Demência , Osteoartrite , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/epidemiologia , Demência/epidemiologia , Demência Vascular/epidemiologia , Demência Vascular/diagnóstico , Incidência , Modelos Lineares , Imageamento por Ressonância Magnética , Osteoartrite/epidemiologia , Osteoartrite/terapia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Biobanco do Reino Unido , Reino Unido/epidemiologiaRESUMO
To study a new method for establishing animal models of prenatal bronchopulmonary dysplasia (BPD), we used lung ultrasound score (LUS) to semi-quantitatively assess the severity of lung lesions in model rats. Lipopolysaccharide (LPS) was injected into the right lung of the fetus of the rat under ultrasound-guided, and the right lung of the neonates were scanning for LUS. Specimens were collected for pathological scoring and detection of pulmonary surfactant-associated glycoprotein (SP)-C and vascular endothelial growth factor (VEGF) expression quantity. The correlation between LUS and pathological scores was analyzed. (1) The animal models were consistent with the pathological manifestations of BPD. (2) It showed a strong positive correlation between LUS and pathological scores in animal models (r = 0.84, P < 0.005), and the expression quantity of SP-C and VEGF in lung tissue were decreased (both P < 0.05). Animal models established by ultrasound-guided puncture of the lung of rats and injection of LPS were consistent with the manifestation of BPD. This method could be used to establish animal models of BPD before birth, and the severity of BPD could be assessed by using LUS.
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Displasia Broncopulmonar , Modelos Animais de Doenças , Pulmão , Fator A de Crescimento do Endotélio Vascular , Animais , Displasia Broncopulmonar/diagnóstico por imagem , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patologia , Ratos , Feminino , Pulmão/diagnóstico por imagem , Pulmão/metabolismo , Pulmão/patologia , Gravidez , Fator A de Crescimento do Endotélio Vascular/metabolismo , Lipopolissacarídeos , Animais Recém-Nascidos , Índice de Gravidade de Doença , Ratos Sprague-Dawley , Ultrassonografia Pré-Natal/métodosRESUMO
The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM-1 s-1 and 5.323 mM-1 s-1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.
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Purpose: To evaluate the impact of high-risk optic disc (HROD) on central retinal vein occlusion (CRVO) in patients with metabolic disorder(s). Design: Retrospective case-control study. Methods: A case-control study involving CRVO patients with metabolic disorder(s) was performed. PART I. All eligible patients with CRVO were included in CRVO group, and a similar number of patients with metabolic disorder(s) without CRVO were matched by sex, age and blood glucose level in the non-CRVO group. Various parameters were compared between groups. The impact of risk factors associated with CRVO was presented as odds ratios (ORs) and 95% confidence interval (95% CI). PART II. All eyes with CRVO that underwent intravitreal treatment (IVT) with a follow-up duration of ≥1 year were divided into non-HROD and HROD groups, and the differences between the two groups were compared. Results: In PART I, a total of 45 and 63 eyes were enrolled in the CRVO and non-CRVO groups, respectively, with a significant statistical difference in HROD (51.16% vs 26.98%, p = 0.010) between them. In further multivariate regression analysis, HROD was the independent risk factor for CRVO (OR = 5.036, 95% CI 1.847-13.729, p = 0.002). In PART II, demographic, follow-up information, treatment, and prognosis showed no significant statistical difference between the two groups (all p > 0.05). Conclusion: HROD was likely to be an independent risk factor for CRVO occurrence in patients with metabolic disorder(s), but it did not affect the treatment and prognosis of CRVO eyes with HROD.
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BACKGROUND: Melanoma is an aggressive malignancy primarily impacting the skin, mucous membranes, and pigment epithelium. The tumor microbial microenvironment encompasses both the microorganisms inhabiting the tumor vicinity and the environmental factors influencing their interactions. Emerging evidence highlights the pivotal role of the microbial immune microenvironment in melanoma. METHODS: We conducted an extensive review of scholarly works published from 2012 to 2022, utilizing The Web of Science Core Collection. Subsequently, we employed analytical tools such as VOSviewer, CiteSpace, and the R programming language to scrutinize prevailing research patterns within this domain. RESULTS: A sum of 513 articles were pinpointed, with notable input coming from the United States and China. Harvard University stood out as the top-contributing institution, while the journal Science received the most citations. Current research within this sphere chiefly focuses on two principal domains: the gut microbiota and the PD-L1 pathway concerning melanoma treatment. CONCLUSION: The study offers an extensive analysis and overview of the worldwide research landscape concerning the immune microenvironment with a focus on microbes in melanoma. It underscores the promising prospects for harnessing the microbial immune microenvironment's potential in melanoma. These findings furnish valuable insights and guidance for advancing scientific inquiry and refining clinical approaches within this dynamic field.
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Bibliometria , Melanoma , Neoplasias Cutâneas , Microambiente Tumoral , Melanoma/imunologia , Melanoma/microbiologia , Humanos , Microambiente Tumoral/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/microbiologia , Microbioma Gastrointestinal , Pesquisa BiomédicaRESUMO
Targeted membrane protein degradation (TMPD) offers significant therapeutic potential by enabling the removal of harmful membrane-anchored proteins and facilitating detailed studies of complex biological pathways. However, existing TMPD methodologies face challenges such as complex molecular architectures, scarce availability, and cumbersome construction requirements. To address these issues, this study presents a highly efficient TMPD system (TMPDS) that integrates an optimized bivalent aptamer glue with a potent protein transport shuttle. Utilizing this approach, we successfully degraded both the highly expressed protein tyrosine kinase 7 in CCRF-CEM cells and the poorly expressed PTK7 in MV-411 cells. This system represents significant advancement in the field of molecular medicine, offering a new avenue for targeted therapeutic interventions and the exploration of cellular mechanisms.
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OBJECTIVE: Pyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study explored the efficacy and safety of pyrotinib in the treatment of HER2-positive MBC patients in the real world. METHODS: From September 2018 to February 2022, 137 female patients with HER2-positive MBC treated in this center were enrolled in this study. The follow-up period ended on January 12, 2023. The primary endpoint of this study was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), central nervous system (CNS)-PFS, CNS-ORR, CNS-CBR, CNS-DCR, and adverse event (AE) were the secondary endpoints. RESULTS: The ORR, DCR and CBR were 41.98 % (55/131), 87.79 % (115/131) and 44.27 % (58/131) in this cohort, respectively. The median PFS for this cohort was 10.37 months [95 % confidence interval (CI): 9.205-11.535] and the median OS was 37.53 months (not reached). Univariate and multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio (HR): 0.579 (0.371-0.904, p=0.016)] and improved OS [0.410 (0.213-0.790, p=0.008)]. Patients treated with a pyrotinib-based regimen as second-line and third-or-post-line therapy had poorer PFS [second-line: 3.315 (1.832-6.000, p<0.001); third-or-post-line: 3.304 (1.749-6.243, p<0.001)] and OS [second-line: 4.631 (1.033-20.771, p=0.045); third-or-post-line: 5.738 (1.212-27.174, p=0.028)]. There were 38 brain metastases (BM) patients in this study, the CNS-mPFS [14.37 months (7.815-20.925) vs. 7.83 months (7.047-8.613), p=0.375] and mOS [not reached vs. 36.40 months (18.551-54.249), p=0.034] were better in brain radiotherapy (BRT) group than NBRT group. 18.98 % (26/137) of patients experienced grade 3 or higher diarrhea. No AE-related death was reported. CONCLUSION: This study confirms the promising antitumor activity and acceptable safety of real-world pyrotinib-based regimens for the treatment of HER2-positive MBC patients, particularly those who are trastuzumab-sensitive and who are receiving pyrotinib-based regimens as advanced first-line therapy. It has also been demonstrated that these regimens combined with BRT, provide better intracranial responses and long-term survival benefits for these patients with BM.
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Acrilamidas , Neoplasias da Mama , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Receptor ErbB-2/metabolismo , Pessoa de Meia-Idade , Idoso , Adulto , Estudos Retrospectivos , Acrilamidas/uso terapêutico , Aminoquinolinas/uso terapêutico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Metástase Neoplásica , Idoso de 80 Anos ou maisRESUMO
Phasic cardiac vagal activity (CVA), reflecting ongoing, moment-to-moment psychophysiological adaptations to environmental changes, can serve as a predictor of individual difference in executive function, particularly executive performance. However, the relationship between phasic CVA and executive function demands requires further validation because of previous inconsistent findings. Moreover, it remains unclear what types of phasic changes of CVA may be adaptive in response to heightened executive demands. This study used the standard N-back task to induce different levels of working memory (WM) load and combined functional Near-Infrared Spectroscopy (fNIRS) with a multipurpose polygraph to investigate the variations of CVA and its interactions with cognitive and prefrontal responses as executive demands increased in fifty-two healthy young subjects. Our results showed phasic decreases in CVA as WM load increased (t (51) = -3.758, p < 0.001, Cohen's d = 0.526). Furthermore, phasic changes of CVA elicited by increased executive demands moderated the association of cognitive and cerebral hemodynamic variations in the prefrontal cortex (B = 0.038, SE = 0.014, p < 0.05). Specifically, as executive demands increased, individuals with larger phasic CVA withdrawal showed a positive relationship between cognitive and hemodynamic variations in the prefrontal cortex (ß = 0.281, p = 0.031). No such significant relationship was observed in individuals with smaller phasic CVA withdrawal. The current findings demonstrate a decrease in CVA with increasing executive demands and provide empirical support for the notion that a larger phasic CVA withdrawal can be considered adaptive in situations requiring high executive function demands.
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Função Executiva , Memória de Curto Prazo , Córtex Pré-Frontal , Espectroscopia de Luz Próxima ao Infravermelho , Nervo Vago , Humanos , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Masculino , Feminino , Adulto Jovem , Nervo Vago/fisiologia , Adulto , Função Executiva/fisiologia , Memória de Curto Prazo/fisiologia , Cognição/fisiologia , Hemodinâmica/fisiologia , Frequência Cardíaca/fisiologia , Circulação Cerebrovascular/fisiologiaRESUMO
Although trait and state rumination play a central role in the exacerbation of negative affect, evidence suggests that they are weakly correlated and exert distinct influences on emotional reactivity to stressors. Whether trait and state rumination share a common or exhibit distinct neural substrate remains unclear. In this study, we utilized functional near-infrared spectroscopy (fNIRS) combined with connectome-based predictive modeling (CPM) to identify neural fingerprints associated with trait and state rumination. CPM identified distinctive functional connectivity (FC) profiles that contribute to the prediction of trait rumination, primarily involving FC within the default mode network (DMN) and the dorsal attention network (DAN) as well as FC between the DMN, control network (CN), DAN, and salience network (SN). Conversely, state rumination was predominantly associated with FC between the DMN and CN. Furthermore, the predictive features of trait rumination can be robustly generalized to predict state rumination, and vice versa. In conclusion, this study illuminates the importance of both DMN and non-DMN systems in the emergence and persistence of rumination. While trait rumination was associated with stronger and broader FC than state rumination, the generalizability of the predictive features underscores the presence of shared neural mechanisms between the two forms of rumination. These identified connectivity fingerprints may hold promise as targets for innovative therapeutic interventions aimed at mitigating rumination-related negative affect.
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Conectoma , Rede de Modo Padrão , Ruminação Cognitiva , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Ruminação Cognitiva/fisiologia , Masculino , Feminino , Adulto Jovem , Adulto , Rede de Modo Padrão/fisiologia , Rede de Modo Padrão/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Personalidade/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , AdolescenteRESUMO
Objective: Kisspeptin, a protein encoded by the KISS1 gene, functions as an essential factor in suppressing tumor growth. The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway, which assumes a central role in maintaining cellular homeostasis. In the specific context of this investigation, the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization. This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway, aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion (RSA). Methods: We enrolled a cohort comprising 45 individuals diagnosed with RSA, who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020. On the other hand, an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included. To comprehensively assess the molecular landscape, Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin (and its gene KISS1), IGFBP1 (an established marker of decidualization), Notch1, Akt, and Foxo1 within the decidua. Human endometrial stromal cells (hESC) were given targeted interventions, including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10 (the bioactive fragment of kisspeptin), and were subsequently designated as the siKP group or the KP10 group, respectively. A control group comprised hESC was transfected with blank siRNA, and cell proliferation was meticulously evaluated with CCK8 assay. Following in vitro induction for decidualization across the three experimental groups, immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups. Furthermore, RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1, Notch1, Akt, and Foxo1 across the three cell groups. Subsequently, decidualization was induced in hESC by adding inhibitors targeting Notch1, Akt, and Foxo1. The expression profiles of the aforementioned proteins and genes in the four groups were then examined, with hESC induced for decidualization without adding inhibitors serving as the normal control group. To establish murine models of normal pregnancy (NP) and RSA, CBA/J×BALB/c and CBA/J×DBA/2 mice were used. The mice were respectively labeled as the NP model and RSA model. The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234 (acting as a blocker) and were designated as RSA-KP10 and NP-KP234 groups. On the other hand, the control groups received intraperitoneal injections of normal saline (NS) and were referred to as RSA-NS and NP-NS groups. Each group comprised 6 mice, and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes. Results: The analysis revealed that the expression levels of kisspeptin, IGFBP1, Notch1, Akt, and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP (P<0.01 for kisspeptin and P<0.05 for IGFBP1, Notch1, Akt, and Foxo1). After the introduction of kisspeptin10 to hESC, there was an observed enhancement in decidualization capability. Subsequently, the expression levels of Notch1, Akt, and Foxo1 showed an increase, but they decreased after interference with KISS1. Through immunofluorescence analysis, it was observed that proliferative hESC displayed a slender morphology, but they transitioned to a rounder and larger morphology post-decidualization. Concurrently, the expression of Notch1 increased, suggesting enhanced decidualization upon the administration of kisspeptin10, but the expression decreased after interference with KISS1. Further experimentation involved treating hESC with inhibitors specific to Notch1, Akt, and Foxo1 separately, revealing a regulatory sequence of Notch1/Akt/Foxo1 (P<0.05). In comparison to the NS group, NP mice administered with kisspeptin234 exhibited increased fetal absorption rates (P<0.001) and decreased expression of IGFBP1, Notch1, Akt, and Foxo1 (P<0.05). Conversely, RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates (P<0.001) and increased expression levels of the aforementioned molecules (P<0.05). Conclusion: It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade. A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization, which in turn might contribute to the development or progression of RSA.
Assuntos
Aborto Habitual , Decídua , Endométrio , Kisspeptinas , Proteínas Proto-Oncogênicas c-akt , Receptor Notch1 , Transdução de Sinais , Adulto , Feminino , Humanos , Gravidez , Aborto Habitual/metabolismo , Aborto Habitual/genética , Proliferação de Células , Decídua/metabolismo , Decídua/citologia , Endométrio/metabolismo , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Kisspeptinas/metabolismo , Kisspeptinas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Notch1/metabolismo , Receptor Notch1/genéticaRESUMO
Metal nanozymes have offered attractive opportunities for biocatalysis and biomedicine. However, fabricating nanozymes simultaneously possessing highly catalytic selectivity and activity remains a great challenge due to the lack of three-dimensional (3D) architecture of the catalytic pocket in natural enzymes. Here, we integrate rhodium nanocluster (RhNC), reduced graphene oxide (rGO), and protamine (PRTM, a typical arginine-rich peptide) into a composite facilely based on the single peptide. Remarkably, the PRTM-RhNC@rGO composite displays outstanding selectivity, activity, and stability for the catalytic degradation of uric acid. The reaction rate constant of the uric acid oxidation catalyzed by the PRTM-RhNC@rGO composite is about 1.88 × 10-3 s-1 (4 µg/mL), which is 37.6 times higher than that of reported RhNP (k = 5 × 10-5 s-1, 20 µg/mL). Enzyme kinetic studies reveal that the PRTM-RhNC@rGO composite exhibits a similar affinity for uric acid as natural uricase. Furthermore, the uricase-like activity of PRTM-RhNC@rGO nanozymes remains in the presence of sulfur substances and halide ions, displaying incredibly well antipoisoning abilities. The analysis of the structure-function relationship indicates the PRTM-RhNC@rGO composite features the substrate binding site near the catalytic site in a confined space contributed by 2D rGO and PRTM, resulting in the high-performance of the composite nanozyme. Based on the outstanding uricase-like activity and the interaction of PRTM and uric acid, the PRTM-RhNC@rGO composite can retard the urate crystallization significantly. The present work provides new insights into the design of metal nanozymes with suitable binding sites near catalytic sites by mimicking pocket-like structures in natural enzymes based on simple peptides, conducing to broadening the practical application of high-performance nanozymes in biomedical fields.