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1.
Anal Chem ; 96(23): 9570-9575, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38822787

RESUMO

MicroRNA (miRNA) and apurinic/apyrimidinic endonuclease 1 (APE1) have been reported to be closely associated with cancers, making them potential crucial biomarkers and therapeutic targets. However, focusing on the detection of a single target is not conducive to the diagnosis and prognosis assessment of diseases. In this study, an AND logic-gate-based dual-locking hairpin-mediated catalytic hairpin assembly (DL-CHA) was developed for sensitive and specific detection of microRNA and APE1. By addition of a lock to each of the hairpins, with APE1 and microRNA serving as keys, fluorescence signals could only be detected in the presence of simultaneous stimulation by APE1 and miRNA-224. This indicated that the biosensor could operate as an AND logic gate. DL-CHA exhibited advantages such as a low background, rapid response, and high logic capability. Therefore, the biosensor serves as a novel approach to cancer diagnosis with significant potential applications.


Assuntos
Técnicas Biossensoriais , DNA Liase (Sítios Apurínicos ou Apirimidínicos) , MicroRNAs , MicroRNAs/análise , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Humanos , Técnicas Biossensoriais/métodos , Lógica , Limite de Detecção
2.
Langmuir ; 40(26): 13496-13504, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38875122

RESUMO

Developing highly active electrocatalysts is crucial for the application of electrocatalytic water splitting. In this study, we prepared vanadium oxide-graphene carbon nanocomposites (VxOy/C) with abundant defects using a carbon- and oxygen-rich hexavanadate derivative Na2[V6O7{(OCH2)3CCH3}4] as a precursor without the addition of an extra carbon source. Subsequently, the VxOy/C was used as a catalyst support to load a small amount of Ir, forming the Ir/VxOy/C nanoelectrocatalyst. This catalyst exhibited low hydrogen evolution overpotentials of only 18.90 and 13.46 mV at a working current density of 10 mA cm-2 in 1.0 M KOH and 0.5 M H2SO4 electrolyte systems, outperforming the commercial Pt/C catalysts. Additionally, the catalyst showed excellent chemical stability and long-term durability. This work provides a new strategy for the design and synthesis of highly active electrocatalysts for water splitting.

3.
Langmuir ; 40(1): 744-750, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38103033

RESUMO

To explore, highly active electrocatalysts are essential for water splitting materials. Polyoxometalates (POMs) have drawn interesting attention in recent years due to their abundant structure and unique electrocatalytic properties. In this study, by using a POM-based precursor Co2Mo10, novel bimetallic sulfide (CoS2-MoS2) nanocomposites are rationally designed and synthesized under hydrothermal conditions. The incorporation of Co2+ to the host electrocatalyst could effectively increase the exposure of active sites of MoS2. Compared to pure MoS2, the CoS2-MoS2 nanocomposite exhibited a perfect hydrogen evolution reaction (HER) ability, for it merely requires overpotentials of 120 and 153 mV for 10 mA cm-2 working current density toward the HER in 1 M KOH and 0.5 M H2SO4 electrolyte systems, respectively. Additionally, the nanocomposite exhibited outstanding chemical stability and long-term durability. This study presents a novel strategy that utilizes POMs to enrich the exposed edge sites of MoS2, resulting in the preparation of efficient electrocatalysts.

4.
Langmuir ; 40(23): 12089-12096, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38804669

RESUMO

Developing inexpensive, efficient, and stable catalysts is crucial for reducing the cost of electrolytic hydrogen production. Recently, polyoxometalates (POMs) have gained attention and widespread use due to their excellent electrocatalytic properties. This study designed and synthesized three composite materials, NF/PMonW12-n, by using phosphomolybdic-tungstic heteropolyacids as precursors to grow in situ on nickel foam via the hydrothermal process and subsequent calcination. Then, their catalytic performances are systematically investigated. This work demonstrates that the NF/PMonW12-n catalysts generate more low valent oxides under the synergistic effect of Mo and W, further enhancing activity for hydrogen evolution reaction (HER). Among these electrocatalysts, NF/PMo6W6 exhibits the perfect HER performance, η10 is only 74 mV. It also shows great stability during long-term electrolysis. The current study introduces a fresh approach for producing electrocatalysts that are both cost-effective and highly efficient.

5.
J Geriatr Psychiatry Neurol ; : 8919887241275044, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179523

RESUMO

OBJECTIVE: To conduct the association between vitamin D levels in the acute phase of stroke and post-stroke depression (PSD) in stroke patients. METHODS: Five international databases (PubMed, Web of Science, Embase, Ovid MEDLINE(R), Cochrane Library) and one Chinese database (Wanfang Data) were searched for observational studies in any language reporting on PSD and vitamin D levels tested in the acute phase of stroke in stroke patients from inception to May 2024. Data extraction and study quality assessment were conducted by two authors independently. Qualitative and quantitative analyses of data were performed. The meta-analysis was registered in the PROSPERO database (CRD42023398581). RESULTS: We included 7 studies containing 3537 participants in the systematic review and meta-analysis. All studies that met the inclusion and exclusion criteria were conducted in China. Vitamin D levels in the acute phase of stroke were lower in PSD patients compared with non-PSD patients (weighted mean difference = -14.97 nmol/L; 95% confidence interval = -19.54, -10.40). Stroke patients with vitamin D deficiency (<50 nmol/L) had an increased risk of PSD compared with stroke patients with vitamin D sufficiency (≥75 nmol/L) (odds ratio = 3.59; 95% confidence interval = 2.05, 6.27). However, the association between vitamin D insufficiency (50-75 nmol/L) and PSD were not statistically significant (odds ratio = 4.15; 95% confidence interval = 0.87, 19.78). CONCLUSION: Vitamin D deficiency in the acute phase of stroke may be a risk factor for PSD.

6.
Nutr J ; 23(1): 76, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010125

RESUMO

PURPOSE: This study aimed to identify and quantify the association and investigate whether serum vitamin B12 alone or vitamin B12 combined with folate and plasma total homocysteine (tHcy) levels could be used to predict the risk of acute ischemic stroke. MATERIALS AND METHODS: This retrospective case-control study was conducted in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University. It included 259 inpatients experiencing their first-ever acute ischemic stroke and 259 age-matched, sex-matched healthy controls. Patients were categorized into groups based on the etiology of their stroke: large-artery atherosclerosis (LAAS, n = 126), cardio embolism (CEI, n = 35), small vessel disease (SVD, n = 89), stroke of other determined etiology (ODE, n = 5), and stroke of undetermined etiology (UDE, n = 4). The associations of serum vitamin B12, folate, and plasma tHcy levels with the risk of ischemic stroke were evaluated using multivariable logistic regression analysis. Receiver operator characteristic (ROC) curves were used to assess the diagnostic power of vitamin B12, folate, and tHcy levels for ischemic stroke. RESULTS: Serum vitamin B12 and folate levels were significantly lower in ischemic stroke patients compared to controls, while plasma tHcy levels were significantly higher. The first quartile of serum vitamin B12 levels was significantly associated with an increased risk of LAAS (aOR = 2.289, 95% CI = 1.098-4.770), SVD (aOR = 4.471, 95% CI = 1.110-4.945) and overall ischemic stroke (aOR = 3.216, 95% CI = 1.733-5.966). Similarly, the first quartile of serum folate levels was associated with an increased risk of LAAS (aOR = 3.480, 95% CI = 1.954-6.449), CEI (aOR = 2.809, 95% CI = 1.073-4.991), SVD (aOR = 5.376, 95% CI = 1.708-6.924), and overall ischemic stroke (aOR = 3.381, 95% CI = 1.535-7.449). The fourth quartile of tHcy levels was also significantly associated with an increased risk of LAAS (aOR = 2.946, 95% CI = 1.008-5.148), CEI (aOR = 2.212, 95% CI = 1.247-5.946), SVD (aOR = 2.957, 95% CI = 1.324-6.054), and overall ischemic stroke (aOR = 2.233, 95% CI = 1.586-4.592). For predicting different types of ischemic stroke, vitamin B12 alone demonstrated the best diagnostic value for SVD, evidenced by a sensitivity of 71.0% and negative predictive value of 90.3%, along with the highest positive likelihood ratio (+ LR) for SVD. Vitamin B12 + tHcy + folate are valuable in predicting different types of ischemic stroke, with the most significant effect observed in SVD, followed by LAAS, and the weakest predictive effect in CEI. Additionally, vitamin B12 alone in combination with other indicators, such as folate alone, tHcy alone, and folate + tHcy could reduce negative likelihood ratio (-LR) and improve + LR. CONCLUSIONS: Vitamin B12 was an independent risk factor for acute ischemic stroke. The risk calculation model constructed with vitamin B12 + tHcy + folate had the greatest diagnostic value for SVD.


Assuntos
Ácido Fólico , Homocisteína , AVC Isquêmico , Vitamina B 12 , Humanos , Vitamina B 12/sangue , Ácido Fólico/sangue , Homocisteína/sangue , Estudos Retrospectivos , Feminino , Masculino , Estudos de Casos e Controles , Pessoa de Meia-Idade , AVC Isquêmico/sangue , AVC Isquêmico/epidemiologia , Idoso , Fatores de Risco , Curva ROC , Acidente Vascular Cerebral/sangue
7.
Skin Res Technol ; 30(2): e13595, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38279591

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common inherited disorder characterized by cutaneous neurofibromas and other features. It is still a challenge in managing inoperable patients and the complex nature of the disease. Bibliometric analyses for cutaneous neurofibromas (cNF) could offer insights into impactful research and collaborations, guiding future efforts to improve patient care and outcomes. METHODS: We conducted a comprehensive literature search of the Web of Science Core Collection database for the period 2003-2022. Data processing and analysis were performed using bibliometric tools including VOSviewer, CiteSpace, and "Bibliometrix" package. Our analysis assessed the publication or collaboration of countries, institutions, authors, and journals, as well as the co-citation and burst of references and keywords. RESULTS: The analysis included 927 articles from 465 journals and 1402 institutions in 67 countries. Research on cNF has been increasing in recent years. The United States leads the field. Pierre Wolkenstein was the top author, while The University of Hamburg was the most productive institution. The American Journal of Medical Genetics Part A published the most articles in cNF. Co-citation analysis revealed major research topics and trends over time, showing growing interest in evaluating quality of life and genotype-phenotype correlation for cNF patients. Emerging topical MEK inhibitors show potential as a promising therapy. CONCLUSION: In conclusion, our bibliometric analysis of cNF research over the past two decades highlights the growing interest in this complex genetic disorder. Leading countries, authors, institutions, and journals have played significant roles in shaping the field. Notably, recent trends emphasize the importance of evaluating quality of life and genotype-phenotype correlations in cNF patients. Furthermore, the emergence of promising topical therapy marks an exciting development in the quest to improve patient care and outcomes for those affected by cNF, paving the way for future research and collaboration.


Assuntos
Neurofibroma , Neoplasias Cutâneas , Humanos , Qualidade de Vida , Bibliometria , Bases de Dados Factuais
8.
BMC Public Health ; 24(1): 2312, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187780

RESUMO

BACKGROUND: Despite readiness for hospital discharge widespread popularity since readiness for hospital discharge introduction in 1979 and extensive study, readiness for hospital discharge among pulmonary tuberculosis (PTB) patients has not yet been investigated. Moreover, the factors influencing this process remain unclear. OBJECTIVE: The objective of this study was to investigate the factors influencing readiness for hospital discharge in initially treated PTB patients using the capability, opportunity, motivation-behavior (COM-B) model. METHODS: This phenomenological study was conducted from December 2023 to March 2024. Face-to-face individual interviews were conducted with 18 initially treated patients with PTB according to a semistructured interview guide developed on the basis of the COM-B model. The interview data were subjected to analysis using NVivo 14 software and Colaizzi's method. RESULTS: As a result, 6 themes and 14 subthemes were identified. Physical capability for readiness for hospital discharge (subthemes included poor health status, early acquisition of adequate knowledge about PTB, inadequate knowledge about readiness for hospital discharge), psychological capability for readiness for hospital discharge(subthemes included false perceptions about readiness for hospital discharge, high treatment adherence), physical opportunity for readiness for hospital discharge (subthemes included high continuity of transition healthcare, insufficient financial support, insufficient informational support), social opportunity for readiness for hospital discharge (subthemes included stigmatization, inadequate emotional support), reflective motivation for readiness for hospital discharge (subthemes included lack of reflection on coping with difficulties, intention to develop a readiness for hospital discharge plan), and automatic motivation for readiness for hospital discharge (subthemes included strong desire to be cured, negative emotions). CONCLUSION: We established factors related to readiness for hospital discharge in initially treated PTB patients in terms of capability, opportunity and motivation, which can inform the future development of readiness for hospital discharge plans. To improve patients' readiness for hospital discharge, patients need to be motivated to plan and desire readiness for hospital discharge, patients' knowledge and treatment adherence should be improved, and patients' transition healthcare continuity and emotional support should be focused on. Moreover, the quality of readiness for hospital discharge and discharge education should be assessed in a timely manner to identify impeding factors and provide interventions.


Assuntos
Alta do Paciente , Pesquisa Qualitativa , Tuberculose Pulmonar , Humanos , Tuberculose Pulmonar/psicologia , Tuberculose Pulmonar/terapia , Tuberculose Pulmonar/tratamento farmacológico , Masculino , Feminino , China , Adulto , Pessoa de Meia-Idade , Motivação , Entrevistas como Assunto , Conhecimentos, Atitudes e Prática em Saúde , Idoso
9.
Appetite ; 203: 107694, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39341080

RESUMO

The human brain works as a hierarchical organization that is a continuous axis spanning sensorimotor cortex to transmodal cortex (referring to cortex that integrates multimodal sensory information and participates in complex cognitive functions). Previous studies have demonstrated abnormalities in several specific networks that may account for their multiple behavioral deficits in patients with bulimia nervosa (BN), but whether and how the network hierarchical organization changes in BN remain unknown. This study aimed to investigate alterations of the hierarchy organization in BN network and their clinical relevance. Connectome gradient analyses were applied to depict the network hierarchy patterns of fifty-nine patients with BN and thirty-nine healthy controls (HCs). Then, we evaluated the network- and voxel-level gradient alterations of BN by comparing gradient values in each network and each voxel between patients with BN and HCs. Finally, the association between altered gradient values and clinical variables was explored. In the principal gradient, patients with BN exhibited reduced gradient values in dorsal attention network and increased gradient values in subcortical regions compared to HCs. In the secondary gradient, patients with BN showed decreased gradient values in ventral attention network and increased gradient values in limbic network. Regionally, the areas with altered principal or secondary gradient values in BN group were mainly located in transmodal networks, i.e., the default-mode and frontoparietal network. In BN group, the principal gradient values of right inferior frontal gyrus were negatively associated with external eating behavior. This study revealed the disordered network hierarchy patterns in patients with BN, which suggested a disturbance of brain information integration from attention network and subcortical regions to transmodal networks in these patients. These findings may provide insight into the neurobiological underpinnings of BN.

10.
Aging Clin Exp Res ; 36(1): 202, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39368008

RESUMO

OBJECTIVE: To investigate the association between depression, accelerated biological aging, and mortality risk, and to assess whether accelerated aging mediates the relationship between major depression and mortality risk. METHODS: A prospective cohort of 12,761 participants aged 20 years or older from the 2005-2010 cycle of the National Health and Nutrition Examination Survey (NHANES) was analyzed. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores of ≥ 10 indicating major depression. Accelerated biological aging was measured using phenotypic age acceleration (PhenoAgeAccel). Multivariable linear regression models and subgroup analyses were used to examine the association between depression and accelerated aging, while weighted multivariable Cox proportional hazards regression models and subgroup analyses assessed the impact of major depression on mortality risk. Mediation analysis was performed to assess whether PhenoAgeAccel mediated the relationship between major depression and mortality outcomes. RESULTS: Among the 12,761 adults, the weighted mean age was 46.6 years, with 48.8% being male, and 6.9% experiencing major depression. The results showed a positive association between major depression and PhenoAgeAccel (ß: 0.61, 95% CI: 0.06-1.16). Over a median follow-up duration of 11.3 years (interquartile range: 9.9-13.1), major depression was associated with increased all-cause mortality (HR: 1.35, 95% CI: 1.13-1.62) and cardiovascular mortality (HR: 1.73, 95% CI: 1.18-2.54). However, the relationship with cancer mortality was not statistically significant after full adjustment for confounding factors. The mediation analysis further revealed that PhenoAgeAccel accounted for 10.32% and 5.12% of the associations between major depression and all-cause mortality, and cardiovascular mortality, respectively. CONCLUSION: Depression is associated with accelerated aging and contributes to increased all-cause and cardiovascular mortality. Accelerated aging partially mediates the association between major depression and mortality risk. Our findings highlight the urgent need to incorporate mental health care into public health strategies to delay population aging and reduce mortality risk.


Assuntos
Transtorno Depressivo Maior , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Transtorno Depressivo Maior/mortalidade , Transtorno Depressivo Maior/epidemiologia , Depressão/mortalidade , Senilidade Prematura/mortalidade , Senilidade Prematura/psicologia , Idoso , Fatores de Risco , Mortalidade/tendências , Envelhecimento/psicologia , Modelos de Riscos Proporcionais
11.
Appl Nurs Res ; 77: 151789, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38796252

RESUMO

OBJECTIVE: To understand the relationship between the need for continuing care services and influencing factors, social support, readiness for discharge among discharged pulmonary tuberculosis (PTB) patients. METHODS: A cross-sectional study was conducted among 170 patients from a database of discharged patients with PTB from September 2023 to January 2024. A demographic and disease characteristics questionnaire, continuing care services basic modality questionnaire, continuing care services need questionnaire, the Social Support Rating Scale (SSRS), and the Readiness for Hospital Discharge Scale (RHDS) were used for this investigation. Univariate analysis and multiple linear regression analysis were used to analyze the associated factors. RESULTS: The mean total score for the need for continuing care services among patients with PTB discharged from the hospital was (121.61 ± 22.98). The dimension with the highest score was health education guidance need. Compared to the the original hospital medical personnel, the primary source of care information after discharge was the local medical institutions was statistically significant and negatively correlated with continuing care service need (P = 0.005). Social support was positively associated with need for continuing care services (P = 0.042). CONCLUSION: Discharged PTB patients had a high degree of continuing care service need. Factors influencing the need for continuing care services are the primary source of care information after discharge was the local medical institutions, the social support. Medical staff need to provide targeted continuing care services based on relevant influencing factors to meet the discharge needs of patients.


Assuntos
Alta do Paciente , Apoio Social , Tuberculose Pulmonar , Humanos , Estudos Transversais , Alta do Paciente/estatística & dados numéricos , Feminino , Masculino , China , Pessoa de Meia-Idade , Adulto , Tuberculose Pulmonar/psicologia , Inquéritos e Questionários , Idoso , Continuidade da Assistência ao Paciente/estatística & dados numéricos
12.
Nurs Crit Care ; 29(5): 1067-1077, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39207037

RESUMO

BACKGROUND: Early mobilization (EM) is acknowledged for its safety and benefits in the recovery of critically ill patients, yet its implementation in intensive care units (ICU) remains inconsistently aligned with established guidelines. This discrepancy highlights a gap between theoretical endorsement and practical application. While barriers to EM have been extensively studied, the intentions and perceived practices of ICU nurses towards EM, especially in certain geographical regions, have not been adequately understood. AIM: The objective of this study is to assess the perceptions, actual practices and intentions of ICU nurses regarding the implementation of EM for patients in the ICU setting. STUDY DESIGN: A cross-sectional, multi-centre, survey-based study. RESULTS: The study collected data through an electronic questionnaire from 227 ICU nurses across eight hospitals in Beijing, China, concerning their experiences, practices and intentions related to EM. The survey response rate was 50% (114 of 227), indicating a moderate level of engagement by the target population. Among the surveyed participants, 68.7% (n = 156) reported having experience with EM for critically ill patients. Of these experienced nurses, 49.3% (n = 77) indicated they carried out EM less frequently than once per week, while only 29.5% (n = 46) reported dedicating more than 20 min to EM activities per patient. Only 24.2% (n = 55) of participants confirmed the presence of specific EM guidelines in their workplace. Notably, guideline adherence could be influenced by the patient's condition severity, which may affect how these protocols are applied. Notably, the approach and frequency of EM practices showed significant variation across different ICUs. A substantial majority (75%, n = 170) of participants expressed a strong intention towards implementing EM, correlating significantly with factors such as having a higher education level (bachelor's degree or higher), receiving departmental support, encountering fewer perceived barriers, and belonging to specific departments like respiratory (SICU) and surgery (RICU). The EM guidelines mentioned by participants were primarily focused on specific protocols and guidance, highlighting the emphasis on structured approaches to EM in their clinical settings. CONCLUSIONS: Despite the recognized experience with EM among ICU nurses, there is a notable divergence between their practices and the recommendations outlined in EM guidelines. This study underscores the need for the establishment of clear, actionable guidelines, alongside the provision of targeted educational programmes and robust support systems, to foster the consistent and effective implementation of EM in ICU settings. RELEVANCE TO CLINICAL PRACTICE: This study underscores the clinical relevance of EM in ICU settings, advocating for the development of precise EM guidelines to improve patient outcomes.


Assuntos
Enfermagem de Cuidados Críticos , Deambulação Precoce , Unidades de Terapia Intensiva , Intenção , Humanos , Estudos Transversais , Deambulação Precoce/enfermagem , Feminino , Masculino , Inquéritos e Questionários , Adulto , China , Atitude do Pessoal de Saúde , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/psicologia , Estado Terminal/enfermagem
13.
Eur J Neurosci ; 58(3): 2874-2887, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37423618

RESUMO

Accumulating evidence supports the hypothesis that white matter (WM) abnormalities are involved in the pathophysiology of bulimia nervosa (BN); however, findings from in vivo neuroimaging studies have been inconsistent. We aimed to investigate the possible brain WM alterations, including WM volume and microstructure, in patients with BN. We recruited 43 BN patients and 31 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging. Differences in WM volume and microstructure were evaluated using voxel-based morphometry, tract-based spatial statistics, and automated fibre quantification analysis. Compared with HCs, BN patients showed significantly decreased fractional anisotropy in the middle part of the corpus callosum (nodes 31-32) and increased mean diffusivity in the right cranial nerve V (CN V) (nodes 27-33 and nodes 55-88) and vertical occipital fasciculus (VOF) (nodes 58-85). Moreover, we found decreased axial diffusivity in the right inferior fronto-occipital fasciculus (node 67) and increased radial diffusivity in the CN V (nodes 22-34 and nodes 52-89) and left VOF (nodes 60-66 and nodes 81-85). Meanwhile, WM microstructural changes were correlated with patients' clinical manifestations. We did not find any significant differences in WM volume and the main WM fibre bundle properties between BN patients and HCs. Taken together, these findings provide that BN shows significant brain WM reorganization, but primarily in microstructure (part of WM fibre bundle), which is not sufficient to cause changes in WM volume. The automated fibre quantification analysis could be more sensitive to detect the subtle pathological changes in a point or segment of the WM fibre bundle.


Assuntos
Bulimia Nervosa , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imagem de Tensor de Difusão/métodos , Bulimia Nervosa/diagnóstico por imagem , Encéfalo/patologia , Corpo Caloso/patologia
14.
BMC Cancer ; 23(1): 1200, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057772

RESUMO

BACKGROUND: The mammalian target of rapamycin (mTOR) kinase, a central component of the PI3K/AKT/mTOR pathway, plays a critical role in tumor biology as an attractive therapeutic target. We conducted this first-in-human study to investigate the safety, pharmacokinetics (PK), and pilot efficacy of LXI-15029, an mTORC1/2 dual inhibitor, in Chinese patients with advanced malignant solid tumors. METHODS: Eligible patients with advanced, unresectable malignant solid tumors after failure of routine therapy or with no standard treatment were enrolled to receive ascending doses (10, 20, 40, 60, 80, 110, and 150 mg) of oral LXI-15029 twice daily (BID) (3 + 3 dose-escalation pattern) until disease progression or intolerable adverse events (AEs). The primary endpoints were safety and tolerability. RESULTS: Between June 2017 and July 2021, a total of 24 patients were enrolled. LXI-15029 was well tolerated at all doses. Only one dose-limiting toxicity (grade 3 increased alanine aminotransferase) occurred in the 150 mg group, and the maximum tolerated dose was 110 mg BID. The most common treatment-related AEs were leukocytopenia (41.7%), increased alanine aminotransferase (20.8%), increased aspartate aminotransferase (20.8%), prolonged electrocardiogram QT interval (20.8%), and hypertriglyceridemia (20.8%). No other serious treatment-related AEs were reported. LXI-15029 was absorbed rapidly after oral administration. The increases in the peak concentration and the area under the curve were greater than dose proportionality over the dose range. Eight patients had stable disease. The disease control rate was 40.0% (8/20; 95% CI 21.7-60.6). In evaluable patients, the median progression-free survival was 29 days (range 29-141). CONCLUSIONS: LXI-15029 demonstrated reasonable safety and tolerability profiles and encouraging preliminary antitumor activity in Chinese patients with advanced malignant solid tumors, which warranted further validation in phase II trials. TRIAL REGISTRATION: NCT03125746(24/04/2017), http://ClinicalTrials.gov/show/NCT03125746.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Alanina Transaminase , Antineoplásicos/uso terapêutico , População do Leste Asiático , Inibidores Enzimáticos/uso terapêutico , Dose Máxima Tolerável , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases , Serina-Treonina Quinases TOR
15.
BMC Cancer ; 23(1): 285, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36978046

RESUMO

BACKGROUND: The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle. Of note, ORC6, the smallest subunit of ORC, has been reported to be dysregulated in some types of cancers (including prostate cancer), however, its prognostic and immunological significances remain yet to be elucidated. METHODS: In the current study, we comprehensively investigated the potential prognostic and immunological role of ORC6 in 33 human tumors using multiple databases, such as TCGA, Genotype-Tissue Expression, CCLE, UCSC Xena, cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2 databases. RESULTS: ORC6 expression was significantly upregulated in 29 types of cancers compared to the corresponding normal adjacent tissues. ORC6 overexpression correlated with higher stage and worse prognostic outcomes in most cancer types analyzed. Additionally, ORC6 was involved in the cell cycle pathway, DNA replication, and mismatch repair pathways in most tumor types. A negative correlation was observed between the tumor endothelial cell infiltration and ORC6 expression in almost all tumors, whereas the immune infiltration of T regulatory cell was noted to be statistically positively correlated with the expression of ORC6 in prostate cancer tissues. Furthermore, in most tumor types, immunosuppression-related genes, especially TGFBR1 and PD-L1 (CD274), exhibited a specific correlation with the expression of ORC6. CONCLUSIONS: This comprehensive pan-cancer analysis revealed that ORC6 expression serves as a prognostic biomarker and that ORC6 is involved in the regulation of various biological pathways, the tumor microenvironment, and the immunosuppression status in several human cancers, suggesting its potential diagnostic, prognostic, and therapeutic value in pan-cancer, especially in prostate adenocarcinoma.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Próstata , Neoplasias da Próstata/genética , Adenocarcinoma/genética , Biomarcadores , Microambiente Tumoral , Complexo de Reconhecimento de Origem
16.
Int J Eat Disord ; 56(11): 2084-2095, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37530570

RESUMO

OBJECTIVE: Although studies have demonstrated the involvement of the nucleus accumbens (NAc) in the neurobiology of eating disorders, its alterations in bulimia nervosa (BN) remain largely unknown. This study investigated the structural and functional properties of NAc in patients with BN. METHOD: Based on the resting-state functional MRI and high-resolution anatomical T1-weighted imaging data acquired from 43 right-handed BN patients and 40 sex-, age- and education-matched right-handed healthy controls (HCs), the group differences in gray matter volume (GMV) and fractional amplitude of low-frequency fluctuation (fALFF) in slow-4 and -5 bands and functional connectivity (FC) of NAc subregions (core and shell) were compared. The relationships between MRI and clinical data were explored in the BN group. RESULTS: Compared with HCs, BN patients showed preserved GMV, decreased fALFF in slow-5 band of the left NAc core and shell, decreased FC between left NAc core and right caudate, and increased FC between all NAc subregions and frontal regions, between all NAc subregions (except the right NAc core) and the supramarginal gyrus (SMG), and between right NAc shell and left middle temporal gyrus. FC between the NAc and SMG was correlated with emotional eating behaviors. DISCUSSION: Our study revealed preserved GMV, local neuronal activity reduction and functional network reorganization of the NAc in BN. The functional network reorganization of the NAc mainly occurred in the frontal cortex and was correlated with emotional eating behavior. These findings may provide novel insights into the BN using NAc as an entry point. PUBLIC SIGNIFICANCE: Although studies have demonstrated the involvement of the nucleus accumbens (NAc) in the neurobiology of eating disorders, its alterations in bulimia nervosa (BN) remain largely unknown. We used a multimodal MRI technique to systematically investigate structural and functional alterations in NAc subregions of BN patients and explored the associations between such alterations and maladaptive eating behaviors, hoping to provide novel insights into BN.


Assuntos
Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Bulimia Nervosa/psicologia , Núcleo Accumbens/diagnóstico por imagem , Córtex Cerebral , Imageamento por Ressonância Magnética/métodos , Comportamento Alimentar
17.
J Environ Manage ; 345: 118651, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37499413

RESUMO

Organic solid wastes (OSWs) are important reservoirs for antibiotic resistance genes (ARGs). Aerobic composting transforms OSWs into fertilizers. In this study, we investigated ARGs dynamics and their driving mechanisms in three OSW composts: pig manure (PM), kitchen waste (KC), and sewage sludge (SG). The dominant ARGs were different in each OSW, namely tetracycline, aminoglycoside, and macrolide resistance (PM); tetracyclines and aminoglycosides (KC); and sulfonamides (SG). ARGs abundance decreased in PM (71%) but increased in KC (5.9-fold) and SG (1.3-fold). Interestingly, the ARGs abundance was generally similar in all final composts, which was contributed to the similar bacterial community in final composts. In particular, sulfonamide and ß-lactam resistant genes removed (100%) in PM, while sulfonamide in KC (38-fold) and tetracycline in SG (5-fold) increased the most. Additionally, ARGs abundance rebounded during the maturation period in all treatments. Firmicutes, Proteobacteria, and Actinobacteria were the main ARGs hosts. Several persistent and high-risk genes included tetW, aadA, aadE, tetX, strB, tetA, mefA, intl1, and intl2. The structural equation models showed ARGs removal was mainly affected by physicochemical parameters and bacterial communities in PM, the ARGs enrichment in KC composting correlated with increased mobile genetic elements (MGEs). In general, thermophilic aerobic composting can inhibit the vertical gene transfer (VGT) of pig manure and horizontal gene transfer (HGT) of sludge, but it increases the HGT of kitchen waste, resulting in a dramatic increase of ARGs in KC compost. More attention should be paid to the ARGs risk of kitchen waste composting.


Assuntos
Antibacterianos , Compostagem , Animais , Suínos , Antibacterianos/farmacologia , Esgotos , Tetraciclina , Esterco/microbiologia , Genes Bacterianos , Farmacorresistência Bacteriana , Macrolídeos , Bactérias , Sulfanilamida
18.
Eat Weight Disord ; 28(1): 91, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37899387

RESUMO

PURPOSE: Bulimia nervosa (BN) is characterized by recurrent binge-eating episodes and inappropriate compensatory behaviors. This study investigated alterations in resting-state surface-based neural activity in BN patients and explored correlations between brain activity and eating behavior. METHODS: A total of 26 BN patients and 28 healthy controls were enrolled. Indirect measurement of cerebral cortical activity and functional connectivity (FC) analyses were performed in Surfstat. A principal component analysis (PCA) model was used to capture the commonalities within the behavioral questionnaires from the BN group. RESULTS: Compared with the healthy control group, the BN group showed decreased surface-based two-dimensional regional homogeneity in the right superior parietal lobule (SPL). Additionally, the BN group showed decreased FC between the right SPL and the bilateral lingual gyrus and increased FC between the right SPL and the left caudate nucleus and right putamen. In the FC-behavior association analysis, the second principal component (PC2) was negatively correlated with FC between the right SPL and the left caudate nucleus. The third principal component (PC3) was negatively correlated with FC between the right SPL and the left lingual gyrus and positively correlated with FC between the right SPL and the right lingual gyrus. CONCLUSION: We revealed that the right SPL undergoes reorganization with respect to specific brain regions at the whole-brain level in BN. In addition, our results suggest a correlation between brain reorganization and maladaptive eating behavior. These findings may provide useful information to better understand the neural mechanisms of BN. LEVEL OF EVIDENCE: V, descriptive study.


Assuntos
Bulimia Nervosa , Humanos , Bulimia Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Comportamento Alimentar
19.
Plant Cell Environ ; 45(9): 2827-2840, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35538611

RESUMO

The pathway mediated by jasmonic acid (JA), biosynthesized via 13-lipoxygenases (LOX), plays a central role in both plant development and defense. In rice, there are at least fourteen 13-LOXs. Yet, only two 13-LOXs have been known to be involved in the biosynthesis of JA and plant defenses in rice. Here we cloned a chloroplast-localized 13-LOX gene from rice, OsRCI-1, whose transcripts were upregulated following infestation by brown planthopper (BPH, Nilaparvata lugens), one of the most important pests in rice. Overexpression of OsRCI-1 (oeRCI lines) increased levels of BPH-induced JA, jasmonate-isoleucine, trypsin protease inhibitors and three volatile compounds, 2-heptanone, 2-heptanol and α-thujene. BPHs showed a decreased colonization, fecundity and mass, and developed slowly on oeRCI plants compared with wild-type (WT) plants. Moreover, BPH-infested oeRCI plants were more attractive to the egg parasitoid of BPH, Anagrus nilaparvatae than equally treated WT plants. The decreased attractiveness to BPH and enhanced attractiveness to the parasitoid of oeRCI plants correlated with higher levels of BPH-induced 2-heptanone and 2-heptanol, and 2-heptanone, respectively. Compared with oeRCI plants, WT plants had higher plant height and 1000-grain weight. These results indicate that OsRCI-1 is involved in herbivore-induced JA bursts and plays a role in plant defense and growth.


Assuntos
Hemípteros , Oryza , Animais , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Hemípteros/fisiologia , Heptanol/metabolismo , Herbivoria , Oryza/metabolismo , Oxilipinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo
20.
Int J Med Sci ; 18(6): 1484-1491, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628106

RESUMO

Background: Cathepsin B (CTSB) was well documented in solid tumors, up-regulated of CTSB expression is linked with progression of tumors. However, the study of CTSB in adult leukemia has not been reported. Methods: Total RNA was isolated from PBMC (peripheral blood mononuclear cell) of AML patients and healthy donors. qRT-PCR was performed to detect the expression of CTSB. The association of CTSB expression with the patients' overall survival (OS) and disease-free survival (DFS) were analyzed. Stable HL-60 CTSB-shRNA cell lines were established by retrovirus infection and puromycin selection. Cell proliferation was detected by CCK-8 analysis. Tumorigenesis ability was analyzed by soft agar and xenograft nude mice model. Western blot was performed to detect the expression of CTSB and the proteins of cell signaling pathway. Results: The mRNA expression level of CTSB was up-regulated in AML patients compared to healthy control (p<0.001), and CTSB expression was significantly higher in M1, M2, M4 and M5 AML samples than healthy control. The CTSB expression in AML was associated with WBC count (p=0.037). Patients with high CTSB expression had a relatively poor OS (p=0.007) and a shorter DFS (p=0.018). Moreover, the expression level of CTSB may act as an independent prognostic factor for both OS (p=0.011) and DFS (p=0.004). Knockdown CTSB expression in HL-60 cells could inhibit the cells' proliferation and tumorigeneses in vitro and in vivo. Further study showed knockdown CTSB expression in HL-60 cells could inactive the AKT signaling pathway. Conclusions: CTSB mRNA was upregulated in AML patients. CTSB overexpression was correlated with poor prognosis and may serve as an independent prognostic factor for both OS and DFS in AML patients. Knockdown CTSB expression in HL-60 cells could inhibit the cells' proliferation and tumorigenesis. The underlying mechanism may be the inhibition of the AKT signaling pathway.


Assuntos
Carcinogênese/genética , Catepsina B/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Recidiva Local de Neoplasia/epidemiologia , Carcinogênese/patologia , Estudos de Casos e Controles , Catepsina B/sangue , Catepsina B/metabolismo , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Técnicas de Silenciamento de Genes , Células HL-60 , Voluntários Saudáveis , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
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