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1.
World J Gastrointest Oncol ; 16(9): 3752-3760, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39350995

RESUMO

With continuous advancements in interventional radiology, considerable progress has been made in transarterial therapies for hepatocellular carcinoma (HCC) in recent years, and an increasing number of research papers on transarterial therapies for HCC have been published. In this editorial, we comment on the article by Ma et al published in the recent issue of the World Journal of Gastro intestinal Oncology: "Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC". We focus specifically on the current research status and future directions of transarterial therapies. In the future, more studies are needed to determine the optimal transarterial local treatment for HCC. With the emergence of checkpoint immunotherapy modalities, it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

2.
J Hepatocell Carcinoma ; 11: 1675-1687, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39229347

RESUMO

Purpose: To predict the efficacy of patients treated with hepatectomy and transarterial chemoembolization (TACE) based on machine learning models using clinical and radiomics features. Patients and Methods: Patients with HCC whose first treatment was hepatectomy or TACE from June 2016 to July 2021 were collected in the retrospective cohort study. To ensure a causal effect of treatment effect and treatment modality, perfectly matched patients were obtained according to the principle of propensity score matching and used as an independent test cohort. Inverse probability of treatment weighting was used to control bias for unmatched patients, and the weighted results were used as the training cohort. Clinical characteristics were selected by univariate and multivariate analysis of cox proportional hazards regression, and radiomics features were selected using correlation analysis and random survival forest. The machine learning models (Deathhepatectomy and DeathTACE) were constructed to predict the probability of patient death after treatment (hepatectomy and TACE) by combining clinical and radiomics features, and an optimal treatment regimen was recommended. In addition, a prognostic model was constructed to predict the survival time of all patients. Results: A total of 418 patients with HCC who received either hepatectomy (n=267, mean age, 58 years ± 11 [standard deviation]; 228 men) or TACE (n=151, mean age, 59 years ± 13 [standard deviation]; 127 men) were recruited. After constructing the machine learning models Deathhepatectomy and DeathTACE, patients were divided into the hepatectomy-preferred and TACE-preferred groups. In the hepatectomy-preferred group, hepatectomy had a significantly prolonged survival time than TACE (training cohort: P < 0.001; testing cohort: P < 0.001), and vise versa for the TACE-preferred group. In addition, the prognostic model yielded high predictive capability for overall survival. Conclusion: The machine learning models could predict the outcomes difference between hepatectomy and TACE, and prognostic models could predict the overall survival for HCC patients.

3.
Nature ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232171

RESUMO

The long-term physiological consequences of respiratory viral infections, particularly in the aftermath of the COVID-19 pandemic-termed post-acute sequelae of SARS-CoV-2 (PASC)-are rapidly evolving into a major public health concern1-3. While the cellular and molecular aetiologies of these sequelae are poorly defined, increasing evidence implicates abnormal immune responses3-6 and/or impaired organ recovery7-9 after infection. However, the precise mechanisms that link these processes in the context of PASC remain unclear. Here, with insights from three cohorts of patients with respiratory PASC, we established a mouse model of post-viral lung disease and identified an aberrant immune-epithelial progenitor niche unique to fibroproliferation in respiratory PASC. Using spatial transcriptomics and imaging, we found a central role for lung-resident CD8+ T cell-macrophage interactions in impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Specifically, IFNγ and TNF derived from CD8+ T cells stimulated local macrophages to chronically release IL-1ß, resulting in the long-term maintenance of dysplastic epithelial progenitors and lung fibrosis. Notably, therapeutic neutralization of IFNγ + TNF or IL-1ß markedly improved alveolar regeneration and pulmonary function. In contrast to other approaches, which require early intervention10, we highlight therapeutic strategies to rescue fibrotic disease after the resolution of acute disease, addressing a current unmet need in the clinical management of PASC and post-viral disease.

4.
Sci Transl Med ; 16(756): eadn0136, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39018367

RESUMO

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with few focusing on samples derived from affected tissues. Furthermore, clinical studies alone often provide correlative insights rather than causal mechanisms. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to understand the etiology of PASC. In this study, we comprehensively compared bronchoalveolar lavage fluid single-cell RNA sequencing data derived from clinical PASC samples and a mouse model of PASC. This revealed a pro-fibrotic monocyte-derived macrophage response in respiratory PASC, as well as abnormal interactions between pulmonary macrophages and respiratory resident T cells, in both humans and mice. Interferon-γ (IFN-γ) emerged as a key node mediating the immune anomalies in respiratory PASC. Neutralizing IFN-γ after the resolution of acute SARS-CoV-2 infection reduced lung inflammation and tissue fibrosis in mice. Together, our study underscores the importance of performing comparative analysis to understand the cause of PASC and suggests that the IFN-γ signaling axis might represent a therapeutic target.


Assuntos
Líquido da Lavagem Broncoalveolar , COVID-19 , Interferon gama , SARS-CoV-2 , Análise de Célula Única , Animais , Feminino , Humanos , Masculino , Camundongos , Líquido da Lavagem Broncoalveolar/virologia , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , COVID-19/complicações , Modelos Animais de Doenças , Interferon gama/metabolismo , Pulmão/patologia , Pulmão/virologia , Macrófagos Alveolares/imunologia , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia
5.
Int J Stroke ; : 17474930241255031, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38699977

RESUMO

BACKGROUND: Many studies have explored the impact of body mass index (BMI) on stroke prognosis, yet findings remain inconsistent. AIMS: The aims of this study were to conduct a systematic review and meta-analyses to summarize the existing evidence on BMI and stroke outcomes. METHODS: PubMed, Web of Science, Embase, The Cochrane Library, CNKI, CBM, Wanfang Database, and VIP Database were systematically searched from inception to 1 January 2023. Cohort studies were included if they reported on a population of patients with stroke, evaluated BMI on stroke outcomes (mortality/recurrence/score of modified Rankin scale (mRs)), and reported original data. Data extraction and quality assessment were independently undertaken by two reviewers. Stata 16.0 software was used for meta-analysis. RESULTS: Thirty-two studies involving 330,353 patients (5 Chinese language articles) were included in the analysis. The proportion of underweight, overweight, and obese patients was 1.85%, 18.2%, and 15.6%, respectively. Compared with normal weight, being underweight was associated with an increased risk of mortality (relative risk (RR) = 1.78, 95% confidence interval (CI) = 1.60-1.96), poor functional outcomes defined as modified Rankin scale ⩾ 3 (RR = 1.33, 95% CI = 1.22-1.45), and stroke recurrence (RR = 1.19, 95% CI = 1.04-1.37). Being overweight but not obese was associated with reduced mortality (RR = 0.81, 95% CI = 0.74-0.89) and better functional outcomes (RR = 0.92, 95% CI = 0.89-0.96), but did not alter the risk of stroke recurrence (RR = 1.03, 95% CI = 0.90-1.17). Obesity was associated with lower risk of mortality (RR = 0.76, 95% CI = 0.72-0.81) and better functional outcomes (RR = 0.89, 95% CI = 0.84-0.94). CONCLUSIONS: Our findings indicate that in patients with stroke, being underweight is associated with an increased risk of mortality, poor functional outcomes, and stroke recurrence. In contrast, being overweight but not obese, or being obese, was associated with a decreased risk of mortality and better functional outcomes. This is consistent with the obesity paradox in stroke, whereby obesity increases stroke risk in the general population but is associated with improved outcome in patients suffering stroke.

6.
J Stroke Cerebrovasc Dis ; 33(7): 107712, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38599473

RESUMO

BACKGROUND: Previous studies have indicated the potential occurrence of alexithymia among stroke patients, yet the prevalence of alexithymia in this population remains disparate across different investigations without a synthesized overview. AIM: To systematically evaluate the prevalence and characteristics of alexithymia in stroke patients. METHODS: A systematic review and meta-analysis was conducted following the PRISMA guidelines. PubMed, Embase, Web of Science, The Cochrane Library, CINAHL, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, Chinese Biomedical Database, and Weipu Database (VIP) were searched from inception to December 31,2022, two independent researchers extracted data and evaluated article quality. RESULTS: Seventeen studies were included, reporting on the prevalence of alexithymia or Toronto Alexithymia Scale-20 (TAS-20) scores among stroke patients. The pooled prevalence was found to be 35.0% (95%CI= 23.0-47.0%; I2 =97.5%), and the total scores (TS) of TAS-20 was 59.90 (95% CI=56.34-63.47; I2 =100.0%). Subgroup analysis revealed significant variation in TAS-20 scores across different geographical regions. Specifically, the total TAS-20 score in Chinese stroke patients (62.95, 95%CI=58.75-67.14; I2=100%) was higher compared to non-Chinese stroke patients (52.58, 95%CI=49.12-56.04; I2 = 99.0%). CONCLUSIONS: The prevalence of alexithymia is high among stroke patients, with TAS-20 scores surpassing those observed in patients with certain other medical conditions. This underscores the importance of addressing alexithymia in stroke patients promptly through assessment and intervention to mitigate negative emotional consequences and enhance overall quality of life. Future research could explore the influence of demographic factors such as age and sex on alexithymia in stroke patients, enabling a more comprehensive understanding of alexithymia.


Assuntos
Sintomas Afetivos , Acidente Vascular Cerebral , Humanos , Sintomas Afetivos/epidemiologia , Sintomas Afetivos/diagnóstico , Sintomas Afetivos/psicologia , Prevalência , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/diagnóstico , Feminino , Masculino , Fatores de Risco , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais
7.
J Clin Nurs ; 33(5): 1739-1750, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38345142

RESUMO

INTRODUCTION: In 2015, the term 'intrinsic capacity' (IC) was proposed by the World Health Organisation to promote healthy aging. However, the factors associated with IC are still discrepant and uncertain. AIM: We aim to synthesise the factors connected with IC. METHODS: This scoping review followed the five-stage framework of Arksey and O'Malley and was reported using PRISMA-ScR guidelines. RESULTS: In all, 29 articles were included. IC of older adults is associated with demographic characteristics, socioeconomic factors, disease conditions, behavioural factors, and biomarkers. Age, sex, marital status, occupation status, education, income/wealth, chronic diseases, hypertension, diabetes, disability, smoking status, alcohol consumption, and physical activity were emerged as important factors related to the IC of older adults. CONCLUSIONS: This review shows that IC is related to multiple factors. Understanding these factors can provide the healthcare personnel with the theoretical basis for intervening and managing IC in older adults. RELEVANCE TO CLINICAL PRACTICE: The influencing factors identified in the review help to guide older adults to maintain their own intrinsic capacity, thereby promoting their health and well-being. The modifiable factors also provide evidence for healthcare personnel to develop targeted intervention strategies to delay IC decline. NO PATIENT OR PUBLIC CONTRIBUTION: As this is a scoping review, no patient or public contributions are required.


Assuntos
Envelhecimento Saudável , Humanos , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Envelhecimento Saudável/fisiologia
8.
Arch Gerontol Geriatr ; 120: 105335, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38422884

RESUMO

Background and Purpose Intrinsic capacity (IC) has been shown to have the greatest impact on an individual's health status and health trajectory and can independently predict adverse outcomes such as mortality and care dependency in older adults. However, the current understanding of adverse outcomes associated with IC is incomplete. Methods A scoping review of the literature from PubMed, Web of Science (WOS), The Cochrane Library, CINAHL, and Embase databases was conducted from January 2015 to March 2023 to identify articles related to the adverse outcomes associated with IC in older adults. Results 711 studies met screening criteria, and 25 studies met inclusion criteria. These studies reported a total of 17 adverse outcomes related to IC across four domains. (1) Adverse outcomes in the physiological function domains included frailty, pneumonia onset, memory impairment, polypharmacy, incontinence, and poor/fair self-rated health. (2) Clinical outcomes domains included IADL disability, ADL disability, mortality, falls, autonomy decline, and incident dependence. (3) The resource utilization domains included hospitalization, nursing home stays, polypharmacy healthcare costs, and emergency department visits. (4) The other domains mainly included poor quality of life. Conclusion It is evident that IC decline in older adults is associated with a broad spectrum of adverse outcomes spanning cognitive function, activity ability, sensory perception, physical and mental health and living standards. Future studies should further deepen the exploration of IC.


Assuntos
Pessoas com Deficiência , Fragilidade , Humanos , Idoso , Qualidade de Vida , Nível de Saúde , Polimedicação
9.
Virol Sin ; 39(2): 277-289, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38246238

RESUMO

Influenza A virus (IAV) binds sialic acid receptors on the cell surface to enter the host cells, which is the key step in initiating infection, transmission and pathogenesis. Understanding the factors that contribute to the highly efficient entry of IAV into human cells will help elucidate the mechanism of viral entry and pathogenicity, and provide new targets for intervention. In the present study, we reported a novel membrane protein, C1QTNF5, which binds to the hemagglutinin protein of IAV and promotes IAV infection in vitro and in vivo. We found that the HA1 region of IAV hemagglutinin is critical for the interaction with C1QTNF5 protein, and C1QTNF5 interacts with hemagglutinin mainly through its N-terminus (1-103 aa). In addition, we further demonstrated that overexpression of C1QTNF5 promotes IAV entry, while blocking the interaction between C1QTNF5 and IAV hemagglutinin greatly inhibits viral entry. However, C1QTNF5 does not function as a receptor to mediate IAV infection in sialic acid-deficient CHO-Lec2 cells, but promotes IAV to attach to these cells, suggesting that C1QTNF5 is an important attachment factor for IAV. This work reveals C1QTNF5 as a novel IAV attachment factor and provides a new perspective for antiviral strategies.


Assuntos
Vírus da Influenza A , Infecções por Orthomyxoviridae , Ligação Viral , Internalização do Vírus , Animais , Humanos , Camundongos , Células A549 , Células CHO , Cricetulus , Células HEK293 , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A/patogenicidade , Influenza Humana/genética , Influenza Humana/metabolismo , Infecções por Orthomyxoviridae/metabolismo , Ligação Proteica , Receptores Virais/metabolismo , Receptores Virais/genética , Colágeno/genética , Colágeno/metabolismo
10.
J Am Chem Soc ; 146(3): 2072-2079, 2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38189785

RESUMO

Rapid visualization of latent fingerprints, preferably at their point of origin, is essential for effective crime scene evaluation. Here, we present a new class of green fluorescent protein chromophore-based fluorescent dyes (LFP-Yellow and LFP-Red) that can be used for real-time visualization of LFPs within 10 s. Compared with traditional chemical reagents for LFPs, these fluorescent dyes are completely water-soluble, exhibit low cytotoxicity, and are harmless to users. Level 1-3 details of the LFPs could be clearly revealed through "off-on" fluorescence signal readout. Additionally, the fluorescent dyes were constructed based on an imidazolinone core and so do not contain pyridine groups or metal ions, which ensures that the DNA is not contaminated during extraction and identification after the LFPs are treated with the dyes. Combined with our as-developed portable system for capturing LFPs, LFP-Yellow and LFP-Red enabled the rapid capture of LFPs. Therefore, these green fluorescent protein chromophore-based probes provide an approach for the rapid identification of individuals who were present at a crime scene.


Assuntos
Corantes Fluorescentes , Humanos , Proteínas de Fluorescência Verde , Fluorescência
11.
J Colloid Interface Sci ; 659: 639-649, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38198941

RESUMO

In this work, a covalent organic framework (TADM-COF) with high crystallinity and large specific surface area (2597 m2 g-1) has been successfully synthesized using 1,3,5-(4-aminophenyl) benzene (TAPB) and 2,5-dimethoxy-p-phenyldiformaldehyde (DMTP). The COF was grown in situ on oxide particles to form core-shell nanocomposites (SiO2@TADM COF, Fe3O4@TADM COF and Co3O4@TADM COF) to realize its function as a shell material. Among them, the Co3O4@TADM COF with the highest electrochemical response to purine bases was further cross-linked with multi-walled carbon nanotubes (MWCNT) to construct a novel electrochemical sensor (Co3O4@TADM COF/MWCNT/GCE) for detection of purine bases. In this nanocomposite, Co3O4 possesses rich catalytic active sites, MWCNT ensures superior electrical conductivity and COF provides a stable environment for electrocatalytic reactions as the shell. At the same time, regular pore structure of the COFs also offers smooth channels for the transfer of analytes to the catalytic site. The synergistic effect among the three components showed remarkable sensing performance for the simultaneous detection of guanine (G) and adenine (A) with a wide linear range of 0.6-180 µM and low limits of detection (LODs) of 0.020 µM for G and 0.024 µM for A (S/N = 3), respectively. The developed sensor platform was also successfully applied in the detection of purine bases in thermally denatured herring DNA extract. The work provided a general strategy for amplifying signal of COF and its composite in the electrochemical sensing.

12.
J Neurol ; 271(3): 1160-1169, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38036920

RESUMO

BACKGROUND: Stroke is a significant medical condition, and blood pressure stands out as the most prevalent treatable risk factor associated with it. Researches link blood pressure variability (BPV) with stroke; however, the specific relationship between with the outcomes of stroke patients remains unclear. As blood pressure variability and mean blood pressure are interrelated, it remains uncertain whether BPV adds additional information to understanding the outcome of acute stroke patients. OBJECTIVE: To systematically review studies investigating the association between blood pressure variability and prognosis in acute stroke patients. METHODS: Embase, PubMed, Web of Science, and the Cochrane Library were searched for English language full-text articles from the inception to 1 January 2023. Stroke patients aged ≥ 18 years were included in this analysis. Stroke types were not restricted. RESULTS: This meta-analysis shows that higher systolic blood pressure variability is linked to a higher risk of poor outcome, including function disability, mortality, early neurological deterioration, and stroke recurrence, among acute stroke patients without thrombolysis. A higher diastolic blood pressure variability is linked with to a higher risk of mortality and functional disability. CONCLUSIONS: This review reveals that blood pressure variability is a novel and clinically relevant risk factor for stroke patients' outcome. Future studies should investigate how best to measure and define BPV in acute stroke. Larger studies are warranted to provide more robust evidence in this area.


Assuntos
Doenças do Sistema Nervoso Autônomo , Acidente Vascular Cerebral , Humanos , Pressão Sanguínea/fisiologia , Prognóstico , Determinação da Pressão Arterial , Terapia Trombolítica
13.
Talanta ; 269: 125493, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38043342

RESUMO

It is of great significance to propose simple methods to detect DNA bases sensitively for biological analysis and medical diagnosis. Herein, a highly crystalline polyimide covalent organic framework (TAPM-COF) has been successfully synthesized via a solvothermal route using pyromellitic dianhydride (PMDA) and tris(4-aminophenyl) amine (TAPA), which possessed large specific surface area (2286 m2 g-1) and excellent thermal stability. Intriguingly, the crystallinity of the TAPM-COF improved significantly with the increase of water content in the reaction medium. To verify this phenomenon, we synthesized TPPM-COF with two pores by pyromellitic dianhydride (PMDA) and N,N,N',N'-tetrakis(4-aminophenyl)-1,4-benzenediamine (TPDA), which bonding was similar to TAPM-COF. Furthermore, the prepared TAPM-COF-0.3 was used to construct a novel and independent electrochemical biosensor on glassy carbon electrode for simultaneously determination of adenine (A) and guanine (G) without other additives. However, to further improve signal of TAPM-COF in electrochemical sensing, the crystalline TAPM-COF-0.3 can be readily integrated with amino-functionalized multiwalled carbon nanotubes (NH2-MWCNT) to form core-shell TAPM-COF-0.3@NH2-MWCNT driven by a π-π stacking interaction for more sensitive electrochemical sensing toward purine bases. In comparison to TAPM-COF/GCE, the TAPM-COF@NH2-MWCNT/GCE exhibited more favorable linear range and lower limit of detection. The work provided a new strategy for amplifying signal of COF in the field of electrochemical sensors.


Assuntos
Estruturas Metalorgânicas , Nanotubos de Carbono , Estruturas Metalorgânicas/química , Nanotubos de Carbono/química , Purinas , DNA/química
14.
Res Sq ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38077031

RESUMO

The long-term physiological consequences of SARS-CoV-2, termed Post-Acute Sequelae of COVID-19 (PASC), are rapidly evolving into a major public health concern. The underlying cellular and molecular etiology remain poorly defined but growing evidence links PASC to abnormal immune responses and/or poor organ recovery post-infection. Yet, the precise mechanisms driving non-resolving inflammation and impaired tissue repair in the context of PASC remain unclear. With insights from three independent clinical cohorts of PASC patients with abnormal lung function and/or viral infection-mediated pulmonary fibrosis, we established a clinically relevant mouse model of post-viral lung sequelae to investigate the pathophysiology of respiratory PASC. By employing a combination of spatial transcriptomics and imaging, we identified dysregulated proximal interactions between immune cells and epithelial progenitors unique to the fibroproliferation in respiratory PASC but not acute COVID-19 or idiopathic pulmonary fibrosis (IPF). Specifically, we found a central role for lung-resident CD8+ T cell-macrophage interactions in maintaining Krt8hi transitional and ectopic Krt5+ basal cell progenitors, thus impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Mechanistically, CD8+ T cell derived IFN-γ and TNF stimulated lung macrophages to chronically release IL-1ß, resulting in the abnormal accumulation of dysplastic epithelial progenitors and fibrosis. Notably, therapeutic neutralization of IFN-γ and TNF, or IL-1ß after the resolution of acute infection resulted in markedly improved alveolar regeneration and restoration of pulmonary function. Together, our findings implicate a dysregulated immune-epithelial progenitor niche in driving respiratory PASC. Moreover, in contrast to other approaches requiring early intervention, we highlight therapeutic strategies to rescue fibrotic disease in the aftermath of respiratory viral infections, addressing the current unmet need in the clinical management of PASC and post-viral disease.

15.
bioRxiv ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37745354

RESUMO

The long-term physiological consequences of SARS-CoV-2, termed Post-Acute Sequelae of COVID-19 (PASC), are rapidly evolving into a major public health concern. The underlying cellular and molecular etiology remain poorly defined but growing evidence links PASC to abnormal immune responses and/or poor organ recovery post-infection. Yet, the precise mechanisms driving non-resolving inflammation and impaired tissue repair in the context of PASC remain unclear. With insights from three independent clinical cohorts of PASC patients with abnormal lung function and/or viral infection-mediated pulmonary fibrosis, we established a clinically relevant mouse model of post-viral lung sequelae to investigate the pathophysiology of respiratory PASC. By employing a combination of spatial transcriptomics and imaging, we identified dysregulated proximal interactions between immune cells and epithelial progenitors unique to the fibroproliferation in respiratory PASC but not acute COVID-19 or idiopathic pulmonary fibrosis (IPF). Specifically, we found a central role for lung-resident CD8+ T cell-macrophage interactions in maintaining Krt8hi transitional and ectopic Krt5+ basal cell progenitors, thus impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Mechanistically, CD8+ T cell derived IFN-γ and TNF stimulated lung macrophages to chronically release IL-1ß, resulting in the abnormal accumulation of dysplastic epithelial progenitors and fibrosis. Notably, therapeutic neutralization of IFN-γ and TNF, or IL-1ß after the resolution of acute infection resulted in markedly improved alveolar regeneration and restoration of pulmonary function. Together, our findings implicate a dysregulated immune-epithelial progenitor niche in driving respiratory PASC. Moreover, in contrast to other approaches requiring early intervention, we highlight therapeutic strategies to rescue fibrotic disease in the aftermath of respiratory viral infections, addressing the current unmet need in the clinical management of PASC and post-viral disease.

16.
Anal Bioanal Chem ; 415(27): 6785-6798, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37733258

RESUMO

The development of a simple and sensitive electrochemical sensing platform for levofloxacin (LVF) analysis is of great significance to human health. In this work, a covalent organic framework (TP-COF) was in situ grown on the surface of Sn-MoC nanospheres with nanoflower-like morphology through a one-pot method to obtain the TP-COF@Sn-MoC composite. The prepared composite was used to modify a glassy carbon electrode (GCE) to realize the sensitive detection of levofloxacin. TP-COF was formed by polycondensation of 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and pyromellitic dianhydride (PMDA), in which C = O and C = N groups served as double active centers for the recognition and electrocatalytic oxidation of the target molecule. Meanwhile, the introduction of Sn-MoC improved the conductivity of the electrode. The TP-COF@Sn-MoC composite produced a strong synergistic effect and showed a high electrocatalytic ability toward levofloxacin oxidation. The linear range of LVF was 0.6-1000 µM and the limit of detection (LOD) was 0.029 µM (S/N = 3). In addition, the sensor has been successfully applied for the analysis of LVF in human urine and blood serum samples with acceptable recovery rates, demonstrating that the sensor was promising in practical applications.

17.
Behav Brain Res ; 452: 114520, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37268252

RESUMO

Vitamin A deficiency (VAD) has been linked to autism spectrum disorder (ASD) in multiple studies, and autistic children with gastrointestinal (GI) symptoms have been found to have lower VA levels than those without GI symptoms. However, the exact mechanism by which VAD causes both core symptoms and GI symptoms in ASD is ill defined. We constructed VAD and vitamin A normal (VAN) rat models from maternal gestation onwards. Autism-related behaviors were tested using the open-field test and the three-chamber test, and GI function was assessed with the GI transit time, the colonic transit time and fecal water content. Untargeted metabolomic analysis on the prefrontal cortex (PFC) and fecal samples was performed. VAD rats displayed autistic-like behaviors and impaired GI function compared to VAN rats. Metabolic profiles of both PFC and feces from VAD and VAN rats were significantly different. The differential metabolites in both PFC and feces between the VAN and VAD rats were mostly enriched in the purine metabolic pathway. Moreover, the most significantly affected metabolic pathway in PFC of VAD rats was the phenylalanine, tyrosine and tryptophan biosynthesis pathway, and the most remarkably altered metabolic pathway in the feces of VAD rats was the tryptophan metabolism pathway. These results indicate that VAD starting from maternal gestation might be linked to core symptoms of ASD and its GI co-occurring disorders through the purine and tryptophan-related metabolism disorders.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Gastroenteropatias , Deficiência de Vitamina A , Ratos , Animais , Gravidez , Feminino , Transtorno do Espectro Autista/metabolismo , Triptofano , Purinas
18.
J Colloid Interface Sci ; 645: 76-85, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37146381

RESUMO

Component regulation and microstructure design are two effective strategies to adjust electromagnetic parameters and improve the microwave absorption performance of materials. In this study, a facile synthesis strategy consisting of ultrasonic dispersion, blast drying, and roasting is proposed to build a sandwich-like graphene-based absorbent, in which Fe3O4 nanoparticles with adjustable content are sandwiched uniformly between reduced graphene oxide nanosheets. The sandwich structure can form multiple interfaces, prevent the aggregation of nanoparticles, facilitate interface polarization, and endow the material with multiple electromagnetic loss mechanisms, which is very beneficial for impedance matching and microwave attenuation. Notably, the effective absorption bandwidth achieves 5.7 GHz, and the minimum reflection loss value is -49.9 dB. In addition, the synthesis process is simple and suitable for large-scale production and possible industrial applications. Thus, this facile route to fabricate sandwich-like graphene-based absorbents provides new ideas and approaches for designing new graphene-based nanocomposites.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 299: 122844, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37196552

RESUMO

Carbonate ion (CO32-) is an anion essential for the maintenance of life activities and is of great importance to human health. Here, a novel ratiometric fluorescent probe Eu/CDs@UiO-66-(COOH)2 (ECU) was prepared by introducing europium ions (Eu3+) and carbon dots (CDs) into the UiO-66-(COOH)2 parent framework under the guidance of a post-synthetic modification strategy and used for the detection of CO32- ion in the aqueous environment. Interestingly, when CO32- ions were added to the ECU suspension, the characteristic emission of carbon dots at 439 nm was significantly enhanced, while the characteristic emission of Eu3+ ions at 613 nm was reduced. Therefore, the detection of CO32- ions can be realized through the peak height ratio of the two emissions. The probe had a low detection limit (about 1.08 µM) and a wide linear range (0-350 µM) for the detection of carbonate. In addition, the presence of CO32- ions can cause a significant ratiometric luminescence response and resulted obvious red-to-blue color shift of the ECU under UV light, which will facilitate visual analysis by the naked eye.

20.
Int J Stroke ; 18(8): 908-916, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37190789

RESUMO

BACKGROUND: Post-stroke cognitive impairment (PSCI) is one of the serious complications of stroke. The Montreal Cognitive Assessment (MoCA), as a brief cognitive impairment screening tool, is widely used in stroke survivors. However, some studies have suggested that the use of the universal cutoff value of 26 may be inappropriate for detecting cognitive impairments in stroke settings. AIM: We conducted this study to identify the optimal cutoff value of the MoCA in screening for PSCI. METHODS: PubMed, CINAHL, Embase, the Cochrane Library, and Web of Science were searched for eligible studies until March 23, 2023. All studies were screened by two independent researchers. The quality of each article was evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate mixed-effects model was used to pool sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the summary receiver operating characteristic curve. RESULTS: Twenty-four studies with a total of 4231 patients were included in this review. Despite the lack of evidence of publication bias, a high degree of heterogeneity was observed. A meta-analysis revealed that a cutoff value of 21/22 yielded the best diagnostic accuracy. The optimal cutoff varied in different regions, stroke types, and stroke phases as well. CONCLUSION: The optimal cutoff of MoCA was 21/22 for stroke populations rather than the initially recommended cutoff of 26. A revised (lower) cutoff should be considered for stroke survivors.


Assuntos
Disfunção Cognitiva , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Testes de Estado Mental e Demência , Exame Neurológico , Testes Diagnósticos de Rotina , Sensibilidade e Especificidade
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