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1.
Am J Cardiovasc Dis ; 14(4): 208-219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39309114

RESUMO

BACKGROUND: In this study, we aimed to construct a robust diagnostic model that can predict the early onset of heart failure in patients with ST-elevation myocardial infarction (STEMI) following a primary percutaneous coronary intervention (PCI). This diagnostic model can facilitate the early stratification of high-risk patients, thereby optimizing therapeutic management. METHODS: We performed a retrospective analysis of 664 patients with STEMI who underwent their inaugural PCI. We performed logistic regression along with optimal subset regression and identified important risk factors associated with the early onset of heart failure during the time of admission. Based on these determinants, we constructed a predictive model and confirmed its diagnostic precision using a receiver operating characteristic (ROC) curve. RESULTS: The logistic and optimal subset regression analyses revealed the following three salient risk factors crucial for the early onset of heart failure: the Killip classification, the presence of renal insufficiency, and increased troponin T levels. The constructed prognostic model exhibited excellent discriminative ability, which was indicated by an area under the curve value of 0.847. The model's 95% confidence interval following 200 Bootstrap iterations was found to be between 0.767 and 0.925. The Hosmer-Lemeshow test revealed a chi-square value of 3.553 and a p-value of 0.938. Notably, the calibration of the model remained stable even after 500 Bootstrap evaluations. Furthermore, decision curve analysis revealed a substantial net benefit of the model. CONCLUSION: We have successfully constructed a diagnostic prediction model to predict the incipient stages of heart failure in patients with STEMI following primary PCI. This diagnostic model can revolutionize patient care, allowing clinicians to quickly identify and create individualized interventions for patients at a higher risk.

2.
Adv Sci (Weinh) ; : e2402065, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39106974

RESUMO

The highly oriented 2D perovskite templates of n = 1 have typically been created to attain controllable and oriented crystallization of 3D α-phase formamidinium lead triiodide (α-FAPbI3) perovskites. However, the role of methylammonium iodide (MAI), a widely used α-FAPbI3 phase stabilizer, in regulating the growth dynamics of 2D/3D perovskites is generally ignored. Herein, Ruddlesden-Popper type n = 1 2D octylammonium lead iodide (OA2PbI4) perovskites are added into FAPbI3 precursor solution. The template of n = 2 (OA2MAPb2I7), which is spontaneously constructed by the mixture of n = 1 2D and methylammonium chloride (MACl), acts as a skeleton to template the epitaxial growth of α-FAPbI3. However, the volatilization of MACl inevitably causes damage to the 2D structure during thermal annealing. This study reveals that small amounts of less volatile MAI additive enables the creation of stable 2D template, leading to more controlled vertical orientation crystallization. Consequently, the high-quality mixed-dimensional perovskite film delivers a high efficiency of 24.19% together with improved intrinsic stability. This work provides an in-depth understanding of 2D-assisted controlled epitaxial growth of α-FAPbI3.

3.
J Exp Clin Cancer Res ; 43(1): 218, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39103871

RESUMO

INTRODUCTION: Glioblastoma (GBM) poses a significant challenge in oncology, with median survival times barely extending beyond a year due to resistance to standard therapies like temozolomide (TMZ). This study introduces a novel therapeutic strategy combining progesterone (Prog) and abiraterone (Abi) aimed at enhancing GBM treatment efficacy by modulating the tumor microenvironment and augmenting NK cell-mediated immunity. METHODS: We employed in vitro and in vivo GBM models to assess the effects of Prog and Abi on cell viability, proliferation, apoptosis, and the immune microenvironment. Techniques included cell viability assays, Glo-caspase 3/7 apoptosis assays, RNA-seq and qPCR for gene expression, Seahorse analysis for mitochondrial function, HPLC-MS for metabolomics analysis, and immune analysis by flow cytometry to quantify NK cell infiltration. RESULTS: Prog significantly reduced the IC50 of Abi in TMZ-resistant GBM cell, suggesting the enhanced cytotoxicity. Treatment induced greater apoptosis than either agent alone, suppressed tumor growth, and prolonged survival in mouse models. Notably, there was an increase in CD3-/CD19-/CD56+/NK1.1+ NK cell infiltration in treated tumors, indicating a shift towards an anti-tumor immune microenvironment. The combination therapy also resulted in a reduction of MGMT expression and a suppression of mitochondrial respiration and glycolysis in GBM cells. CONCLUSION: The combination of Prog and Abi represents a promising therapeutic approach for GBM, showing potential in suppressing tumor growth, extending survival, and modulating the immune microenvironment. These findings warrant further exploration into the clinical applicability of this strategy to improve outcomes for GBM patients.


Assuntos
Glioblastoma , Células Matadoras Naturais , Progesterona , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/imunologia , Humanos , Camundongos , Animais , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Progesterona/farmacologia , Androstenos/farmacologia , Androstenos/uso terapêutico , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Apoptose/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Modelos Animais de Doenças
4.
Sensors (Basel) ; 24(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39001108

RESUMO

Scene graphs can enhance the understanding capability of intelligent ships in navigation scenes. However, the complex entity relationships and the presence of significant noise in contextual information within navigation scenes pose challenges for navigation scene graph generation (NSGG). To address these issues, this paper proposes a novel NSGG network named SGK-Net. This network comprises three innovative modules. The Semantic-Guided Multimodal Fusion (SGMF) module utilizes prior information on relationship semantics to fuse multimodal information and construct relationship features, thereby elucidating the relationships between entities and reducing semantic ambiguity caused by complex relationships. The Graph Structure Learning-based Structure Evolution (GSLSE) module, based on graph structure learning, reduces redundancy in relationship features and optimizes the computational complexity in subsequent contextual message passing. The Key Entity Message Passing (KEMP) module takes full advantage of contextual information to refine relationship features, thereby reducing noise interference from non-key nodes. Furthermore, this paper constructs the first Ship Navigation Scene Graph Simulation dataset, named SNSG-Sim, which provides a foundational dataset for the research on ship navigation SGG. Experimental results on the SNSG-sim dataset demonstrate that our method achieves an improvement of 8.31% (R@50) in the PredCls task and 7.94% (R@50) in the SGCls task compared to the baseline method, validating the effectiveness of our method in navigation scene graph generation.

5.
Cell Death Dis ; 15(6): 434, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898023

RESUMO

The interaction between glioblastoma cells and glioblastoma-associated macrophages (GAMs) influences the immunosuppressive tumor microenvironment, leading to ineffective immunotherapies. We hypothesized that disrupting the communication between tumors and macrophages would enhance the efficacy of immunotherapies. Transcriptomic analysis of recurrent glioblastoma specimens indicated an enhanced neuroinflammatory pathway, with CXCL12 emerging as the top-ranked gene in secretory molecules. Single-cell transcriptome profiling of naïve glioblastoma specimens revealed CXCL12 expression in tumor and myeloid clusters. An analysis of public glioblastoma datasets has confirmed the association of CXCL12 with disease and PD-L1 expression. In vitro studies have demonstrated that exogenous CXCL12 induces pro-tumorigenic characteristics in macrophage-like cells and upregulated PD-L1 expression through NF-κB signaling. We identified CXCR7, an atypical receptor for CXCL12 predominantly present in tumor cells, as a negative regulator of CXCL12 expression by interfering with extracellular signal-regulated kinase activation. CXCR7 knockdown in a glioblastoma mouse model resulted in worse survival outcomes, increased PD-L1 expression in GAMs, and reduced CD8+ T-cell infiltration compared with the control group. Ex vivo T-cell experiments demonstrated enhanced cytotoxicity against tumor cells with a selective CXCR7 agonist, VUF11207, reversing GAM-induced immunosuppression in a glioblastoma cell-macrophage-T-cell co-culture system. Notably, VUF11207 prolonged survival and potentiated the anti-tumor effect of the anti-PD-L1 antibody in glioblastoma-bearing mice. This effect was mitigated by an anti-CD8ß antibody, indicating the synergistic effect of VUF11207. In conclusion, CXCL12 conferred immunosuppression mediated by pro-tumorigenic and PD-L1-expressing GAMs in glioblastoma. Targeted activation of glioblastoma-derived CXCR7 inhibits CXCL12, thereby eliciting anti-tumor immunity and enhancing the efficacy of anti-PD-L1 antibodies.


Assuntos
Antígeno B7-H1 , Quimiocina CXCL12 , Glioblastoma , Receptores CXCR , Glioblastoma/patologia , Glioblastoma/imunologia , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Animais , Receptores CXCR/metabolismo , Receptores CXCR/genética , Quimiocina CXCL12/metabolismo , Camundongos , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
BMC Gastroenterol ; 24(1): 146, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689244

RESUMO

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.


Assuntos
Neoplasias da Vesícula Biliar , Pólipos , Ultrassonografia , Humanos , Pessoa de Meia-Idade , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pólipos/diagnóstico por imagem , Pólipos/patologia , Fatores Etários , Idoso , Fatores de Risco , Colecistectomia , China/epidemiologia , Período Pré-Operatório , Adulto Jovem , Cuidados Pré-Operatórios
7.
Plants (Basel) ; 13(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38475440

RESUMO

What represents a water source for the ecological restoration of a plant in an arid region is still up to debate. To address this issue, we conducted an in situ experiment in the Ulan Buh Desert of China, to study desert plants absorbing atmospheric water vapor. We selected Tamarisk, a common drought-salt-tolerant species in the desert, for ecological restoration as our research subject, used a newly designed lysimeter to monitor precipitation infiltration, and a sap flow system to track reverse sap flow that occurred in the shoot, branch, and stem during the precipitation event, and observed the precipitation redistribution process of the Tamarisk plot. The results showed that Tamarisk indeed directly absorbs precipitation water: when precipitation occurs, the main stem, lateral branch, and shoot all show the signs of reversed sap flow, and the reversed sap flow accounted for 21.5% of the annual sap flow in the shoot and branch, and 13.6% in the stem. The precipitation event in the desert was dominated by light precipitation events, which accounted for 81% of the annual precipitation events. It was found that light precipitation can be directly absorbed by the Tamarisk leaves, especially during nighttime or cloudy days. Even when the precipitation is absent, it was found that desert plants can still absorb water from the unsaturated atmospheric vapor; even the absorbed atmospheric water vapor was transported from the leaves to the stem, forming a reversed sap flow, as a reversed sap flow was observed when the atmospheric relative humidity reached 75%. This study indicated that the effect of light precipitation on desert plants was significant and should not be overlooked in terms of managing the ecological and hydrological systems in arid regions.

8.
J Cardiothorac Surg ; 19(1): 163, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555468

RESUMO

BACKGROUND: Accurately predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remains a complex and critical challenge. The primary objective of this study was to develop and validate a robust risk prediction model to assess the 12-month and 24-month mortality risk in STEMI patients after hospital discharge. METHODS: A retrospective study was conducted on 664 STEMI patients who underwent PPCI at Xiangtan Central Hospital Chest Pain Center between 2020 and 2022. The dataset was randomly divided into a training cohort (n = 464) and a validation cohort (n = 200) using a 7:3 ratio. The primary outcome was all-cause mortality following hospital discharge. The least absolute shrinkage and selection operator (LASSO) regression model was employed to identify the optimal predictive variables. Based on these variables, a regression model was constructed to determine the significant predictors of mortality. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: The prognostic model was developed based on the LASSO regression results and further validated using the independent validation cohort. LASSO regression identified five important predictors: age, Killip classification, B-type natriuretic peptide precursor (NTpro-BNP), left ventricular ejection fraction (LVEF), and the usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEI/ARB/ARNI). The Harrell's concordance index (C-index) for the training and validation cohorts were 0.863 (95% CI: 0.792-0.934) and 0.888 (95% CI: 0.821-0.955), respectively. The area under the curve (AUC) for the training cohort at 12 months and 24 months was 0.785 (95% CI: 0.771-0.948) and 0.812 (95% CI: 0.772-0.940), respectively, while the corresponding values for the validation cohort were 0.864 (95% CI: 0.604-0.965) and 0.845 (95% CI: 0.705-0.951). These results confirm the stability and predictive accuracy of our model, demonstrating its reliable discriminative ability for post-discharge all-cause mortality risk. DCA analysis exhibited favorable net benefit of the nomogram. CONCLUSION: The developed nomogram shows potential as a tool for predicting post-discharge mortality in STEMI patients undergoing PPCI. However, its full utility awaits confirmation through broader external and temporal validation.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Alta do Paciente , Estudos Retrospectivos , Volume Sistólico , Antagonistas de Receptores de Angiotensina , Assistência ao Convalescente , Função Ventricular Esquerda , Inibidores da Enzima Conversora de Angiotensina , Intervenção Coronária Percutânea/efeitos adversos , Peptídeo Natriurético Encefálico
9.
Bone ; 181: 117038, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316337

RESUMO

Osteoblast polarity, proliferation, differentiation, and migration are essential for maintaining normal bone structure and function. While the microtubule-associated protein Map1b has been extensively studied in nerve cells, its role in bone cells is less known. We investigated the functional significance of Map1b in mouse bone marrow stromal cells (ST2) and elucidated its relationship and influence on cytoskeletal polarity and Golgi organization. Our results suggest that Map1b, as a microtubule regulatory protein, can also regulate the expression of cyclin PCNA, p-H3(S10) and migration-related protein integrin ß1, thereby affecting the proliferation and migration of osteoblasts. The downstream target gene Rgc32 was screened by RNA sequencing. Furthermore, Map1b, as a downstream mediator, regulates the Wnt5a signaling pathway. This study expands our understanding of the involvement of Map1b in bone biology and highlights its crucial role in governing osteoblast polarity, proliferation, and migration, thereby providing a basis for developing novel therapeutic strategies targeting Map1b in orthopedic medicine and promoting precision treatment modalities. Further investigations on the precise mechanisms underlying Map1b's influence on bone cell function and disease progression are needed.


Assuntos
Osso e Ossos , Proteínas Associadas aos Microtúbulos , Camundongos , Animais , Proteínas Associadas aos Microtúbulos/metabolismo , Diferenciação Celular , Osso e Ossos/metabolismo , Osteoblastos/metabolismo , Proliferação de Células
10.
Int J Biol Macromol ; 263(Pt 1): 130102, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342270

RESUMO

Replacing nonbiodegradable plastics with environmentally friendly cellulose materials has emerged as a key trend in environmental protection. This study highlights the development of a strong and hydrophobic micro-nano fibrillated cellulose paper (MNP) through the incorporation of micro-nano fibrillated cellulose fiber (MNF) and chitin nanocrystal (Ch), followed by the impregnation of polymethylsiloxane (PMHS). A low-acid, heat-assisted colloidal grinding strategy was employed to prepare MNF with a high aspect ratio effectively. Ch was incorporated as a reinforcing matrix into the cellulose fiber scaffold through straightforward mechanical mixing and mechanical hot-pressing treatments. Compared to pure MNP, the 5Ch-MNP exhibited a 25 % improvement in tensile strength, reaching 170 MPa, and showed enhanced barrier properties against oxygen and water vapor. The impregnation of PMHS rapidly confers environmentally resistant hydrophobic properties to 1 % PMHS-5Ch-MNP, leading to a water contact angle exceeding 112°, and a 290 % increase in tensile strength under wet conditions. Additionally, the paper demonstrated excellent antibacterial adhesion properties, with the adhesion rates for E. coli and S. aureus exceeding 98 %. This study successfully produced functional cellulose paper with remarkable mechanical properties and barrier properties, as well as hydrophobicity, using a simple, efficient, and environmentally friendly method, making it a promising substitute for petroleum-based plastics.


Assuntos
Celulose , Escherichia coli , Humanos , Celulose/química , Staphylococcus aureus , Resistência à Tração , Cadáver
11.
Cancer Lett ; 586: 216666, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38311053

RESUMO

Glioblastoma (GBM) is a highly aggressive and treatment-resistant brain tumor, necessitating novel therapeutic strategies. In this study, we present a mechanistic breakthrough by designing and evaluating a series of abiraterone-installed hydroxamic acids as potential dual inhibitors of CYP17A1 and HDAC6 for GBM treatment. We established the correlation of CYP17A1/HDAC6 overexpression with tumor recurrence and temozolomide resistance in GBM patients. Compound 12, a dual inhibitor, demonstrated significant anti-GBM activity in vitro, particularly against TMZ-resistant cell lines. Mechanistically, compound 12 induced apoptosis, suppressed recurrence-associated genes, induced oxidative stress and initiated DNA damage response. Furthermore, molecular modeling studies confirmed its potent inhibitory activity against CYP17A1 and HDAC6. In vivo studies revealed that compound 12 effectively suppressed tumor growth in xenograft and orthotopic mouse models without inducing significant adverse effects. These findings highlight the potential of dual CYP17A1 and HDAC6 inhibition as a promising strategy for overcoming treatment resistance in GBM and offer new hope for improved therapeutic outcomes.


Assuntos
Androstenos , Neoplasias Encefálicas , Glioblastoma , Esteroide 17-alfa-Hidroxilase , Animais , Humanos , Camundongos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/patologia , Desacetilase 6 de Histona/genética , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Estresse Oxidativo , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Med Chem ; 67(4): 2963-2985, 2024 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-38285511

RESUMO

Structural analysis of tazemetostat, an FDA-approved EZH2 inhibitor, led us to pinpoint a suitable site for appendage with a pharmacophoric fragment of second-generation HSP90 inhibitors. Resultantly, a magnificent dual EZH2/HSP90 inhibitor was pinpointed that exerted striking cell growth inhibitory efficacy against TMZ-resistant Glioblastoma (GBM) cell lines. Exhaustive explorations of chemical probe 7 led to several revelations such as (i) compound 7 increased apoptosis/necrosis-related gene expression, whereas decreased M phase/kinetochore/spindle-related gene expression as well as CENPs protein expression in Pt3R cells; (ii) dual inhibitor 7 induced cell cycle arrest at the M phase; (iii) compound 7 suppressed reactive oxygen species (ROS) catabolism pathway, causing the death of TMZ-resistant GBM cells; and (iv) compound 7 elicited substantial in vivo anti-GBM efficacy in experimental mice xenografted with TMZ-resistant Pt3R cells. Collectively, the study results confirm the potential of dual EZH2-HSP90 inhibitor 7 as a tractable anti-GBM agent.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Animais , Camundongos , Temozolomida/farmacologia , Apoptose , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Glioblastoma/metabolismo , Inibidores Enzimáticos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico
13.
Carbohydr Polym ; 327: 121688, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38171695

RESUMO

Micro- and nano-hybrid cellulose fiber (MNCF) stands out as a versatile cellulosic nanomaterial with promising applications in various fields owing to its excellent intrinsic nature and outstanding characteristics. However, the inefficiency in preparing MNCF, attributed to a complex multi-step processing, hinders its widespread adoption. In this study, a straightforward and highly efficient method for MNCF preparation was developed via a hot water soaking-assisted colloid grinding strategy. Active water molecules in hot water facilitating stronger transverse shrinkage and longitudinal expansion in fiber crystallized region, and thus improving the fibrillation degree of cellulose fibers. As a result, MNCFs with a mean diameter of 37.5 ± 22.2 nm and high concentration (2 wt%) were successfully achieved though pure mechanical method. The micro and nano-hybrid structure leads to the corresponding resulting cellulose paper with micro- and nano-hybrid structure possesses a compact stacking and fewer defects, leading to extraordinary mechanical properties including tensile strength of 204.5 MPa, Young's modulus of 6.3 GPa and elongation of 10.1 %. This work achieves significant progress towards straightforward and highly efficient production of MNCFs, offering an appreciable prospect for the development of multifunctional MNCF-based materials.

14.
Sci Rep ; 14(1): 2228, 2024 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278989

RESUMO

This study aimed to clarify the existence of the mild obesity paradox in patients with ST-segment elevation myocardial infarction (STEMI) and assess the impact of mild obesity on the prognosis of STEMI. A retrospective cohort study was conducted on STEMI patients who underwent percutaneous coronary intervention at Xiangtan Central Hospital from January 1, 2020 to July 31, 2022. After excluding individuals with a body mass index (BMI) of no less than 35 kg/m2, subjects were divided into the mildly obese group (BMI, 30-35 kg/m2) and non-obese group (BMI < 30 kg/m2). The cardiovascular events and death were deemed the composite endpoints and were employed as the outcome event. The study recruited 664 patients with STEMI, including 515 males and 149 females. The mildly obese group of male patients exhibited a lower incidence of composite endpoints than the non-obese group (22.4% vs. 41.3%, P < 0.001). For female patients, no significant difference was observed in the incidence of composite endpoints between the two groups (43.6% vs. 43.8%, P = 0.987). After adjusting for confounding factors, the multivariable Cox regression analysis revealed mild obesity as an independent protective factor for male patients [hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.32-0.69; P < 0.001]. Nevertheless, mild obesity was not associated with the prognosis of female patients (HR 0.96; 95% CI 0.47-1.94; P = 0.9). In male STEMI patients, mild obesity presented a paradoxical effect in improving the prognosis and functioned as an independent protective factor for the prognosis of STEMI. However, no association between mild obesity and prognosis was found in female patients, possibly due to distinct physiological and metabolic characteristics between male and female patients, which deserved further investigation and validation.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Estudos Retrospectivos , Prognóstico , Obesidade/complicações , Índice de Massa Corporal , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Fatores de Risco
15.
Int J Biol Macromol ; 254(Pt 1): 127621, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37890750

RESUMO

The CONSTANS-like (COL) genes, as a core transcription factor in the photoperiod regulation pathway, play a key role in plant reproduction development. However, their molecular characterization has rarely been studied in Pinus tabuliformis. Here, 10 PtCOL genes were identified in the P. tabuliformis genome and multiple sequence alignments have indicated that the PtCOL proteins contained highly conserved B-BOX1 and CCT domains. Sequence similarity analysis showed that PtCOL1 and PtCOL3 had the higher similarity with Norway spruce COLs (PaCOL2 and PaCOL1) and Arabidopsis COLs (AtCOL3, 4 and 5), respectively. Phylogeny and gene structure analyses revealed that PtCOLs were divided into three subgroups, each with identical or similar distributions of exons, introns, and motifs. Moreover, 10 PtCOLs were distributed on 6 chromosomes and PtCOL9 has syntenic gene pairs in both Ginkgo biloba and Sequoiadendron giganteum. Interestingly, in transcriptome profiles, most PtCOLs exhibited a diurnal oscillation pattern under both long (LD) and short (SD) day conditions. Additionally, PtCOLs were highly expressed in needles and female cones, and showed different spatial expression patterns. Among the ten PtCOLs, PtCOL1/3 heterologous overexpression Arabidopsis displayed a delayed-flowering phenotype under SD, indicating that they are likely to play a crucial role in the reproductive development. Additionally, PtCOL1 and PtCOL3 were not only capable of interacting with each other, but they were each capable of interacting with themselves. Furthermore, PtCOL1 and PtCOL3 were also involved in the MADS-box protein-protein interaction (PPI) network in P. tabuliformis cone development. Direct interactions of PtDAL11 with PtCOL1/3 impeded PtCOL1/3 translocation into the nucleus. In summary, this study provided comprehensive understanding for the functions of the PtCOL gene family and revealed their biological roles in the photoperiod-dependent P. tabuliformis cone development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Pinus , Arabidopsis/genética , Proteínas de Plantas/metabolismo , Pinus/genética , Fatores de Transcrição/genética , Proteínas de Arabidopsis/metabolismo , Filogenia , Regulação da Expressão Gênica de Plantas , Flores/genética , Proteínas de Ligação a DNA/metabolismo
16.
Sci Total Environ ; 912: 169121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38070552

RESUMO

The response of vegetation to climate change and human activities has attracted considerable attention. However, quantitative studies on the effects of climate change and human activities on dryland vegetation in different seasons remain unclear. This study investigated the impacts of precipitation, temperature, soil water storage (SWS) (top [0-7 cm], shallow [7-28 cm], and middle [28-100 cm] layers), vapor pressure deficit (VPD), and afforestation on vegetation as well as their relative contribution rates during the rainy season ([RS], June to September), dry season ([DS], November to April), transition season ([TS], May and October), and all year period (AY) in China's drylands from 2001 to 2020 using the first-difference method. Areas with precipitation and SWS showing significant positive correlation with dryland vegetation (p < 0.05) were found to be larger in RS than in DS and TS, and the positive effect of SWS increased with soil depth in the 0-28 cm interval. Increasing VPD induced a significant negative effect on vgetation during RS but it was not predominant in DS and TS. Afforestation showed an extremely significant positive correlated with dryland vegetation across >60 % of China's dryland areas (p < 0.01), but this improvement was found to be limited to regions with the highest afforestation area. Moreover, dryland vegetation dynamics were driven by afforestation in all seasons, with contribution rates of 64.23 %-71.46 %. The effects of SWS and VPD on vegetation driven by precipitation and temperature exceeded the direct effects of precipitation and temperature. Among climatic factors, VPD showed a major regulating effect on dryland vegetation at the top and shallow soil layers in almost all seasons, whereas the relative contribution rate of SWS increased with soil layer. The findings can provide a scientific reference for the sustainable development and protection of drylands under global warming.


Assuntos
Mudança Climática , Ecossistema , Humanos , Solo , Chuva , China
17.
BMJ Open Qual ; 12(4)2023 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-38160021

RESUMO

BACKGROUND: Medical error (ME) is a serious public health problem and a leading cause of death. The reported adverse incidents in China were much less than western countries, and the research on patient safety in rural China's primary care institutions was scarce. This study aims to identify the factors contributing to the under-reporting of ME among general practitioners in township health centres (THCs). METHODS: A qualitative semi-structured interview study was conducted with 31 general practitioners working in 30 THCs across 6 provinces. Thematic analysis was conducted using a grounded theory approach. RESULTS: The understanding of ME was not unified, from only mild consequence to only almost equivalent to medical malpractice. Common coping strategies for THCs after ME occurs included concealing and punishment. None of the participants reported adverse events through the National Clinical Improvement System website since they worked in THCs. Discussions about ME always focused on physicians rather than the system. CONCLUSIONS: The low reported incidence of ME could be explained by unclear concept, unawareness and blame culture. It is imperative to provide supportive environment, patient safety training and good examples of error-based improvements to rural primary care institutions so that ME could be fully discussed, and systemic factors of ME could be recognised and improved there in the future.


Assuntos
Clínicos Gerais , Humanos , Pesquisa Qualitativa , Erros Médicos , Segurança do Paciente , China
18.
BMC Oral Health ; 23(1): 929, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38008723

RESUMO

BACKGROUND: The injury of the inferior alveolar nerve (IAN) is one of the most serious complications of impacted mandibular third molars (IMTMs) extraction. The influence of the root orientation of IMTMs on IAN injury is still controversial. A deeper understanding of the risk factors of IAN injury conduces to better prevention of IAN injury. This study aims to explore whether root orientation is an independent risk factor of IAN injury during IMTMs extraction using the statistical strategy of propensity score matching (PSM). METHODS: This retrospective cohort study included 379 patients with 539 cases of high-risk IMTMs screened by panoramic radiography and cone beam computed tomography. The IAN injury incidence after extraction of different groups of IMTMs was analyzed using the chi-square test or Fisher's exact test. The correlation between third molar root orientation and impaction depth/contact degree with IAN was evaluated by the Lambda coefficient. Based on PSM for balancing confounding factors including age, sex, impaction depth, and contact degree, the effect of root orientation on the incidence of IAN injury was further analyzed using Fisher's exact test. RESULTS: There were significant group differences in IAN injury incidence in impaction depth, root orientation, and contact degree of root-IAC before PSM. Root orientation was correlated with impaction depth and contact degree of root-IAC. After PSM, there were 9 cases with IAN injury and 257 cases without IAN injury. There were significant group differences between the buccal and non-buccal groups after PSM, and the risk of IAN injury was higher when the root was located on the buccal side of IAC (OR = 8.448, RR = 8). CONCLUSIONS: Root orientation is an independent risk factor of IAN injury, and the risk is higher when the root is located on the buccal side of IAC. These findings could help better evaluate the risk of inferior alveolar nerve injury before the extraction of IMTMs.


Assuntos
Dente Impactado , Traumatismos do Nervo Trigêmeo , Humanos , Dente Serotino/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Traumatismos do Nervo Trigêmeo/epidemiologia , Traumatismos do Nervo Trigêmeo/etiologia , Tomografia Computadorizada de Feixe Cônico/métodos , Dente Impactado/cirurgia , Nervo Mandibular , Mandíbula , Extração Dentária/efeitos adversos , Radiografia Panorâmica/métodos
19.
PLoS Negl Trop Dis ; 17(10): e0011625, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37788409

RESUMO

INTRODUCTION: Excretory/secretory products (ESPs) derived from helminths have been reported to effectively control allergic inflammation, which have better therapeutic prospects than live parasite infections. However, it remains unknown whether ESPs from schistosome eggs can protect against allergies, despite reports alleging that schistosome infection could alleviate disordered allergic inflammation. METHOD: In the present study, we investigated the protective effects of ESPs from Schistosoma japonicum eggs (ESP-SJE) on asthmatic inflammation. Firstly, we successfully established an allergic airway inflammation model in mice by alum-adjuvanted ovalbumin (OVA) sensitization and challenge. ESP-SJE were administered intraperitoneally on days -1 and 13 (before sensitization), on day 20 (before challenge), and on days 21-24 (challenge phase). RESULTS: The results showed that ESP-SJE treatment significantly reduced the infiltration of inflammatory cells, especially eosinophils into the lung tissue, inhibited the production of the total and OVA-specific IgE during OVA-sensitized and -challenged phases, respectively, and suppressed the secretion of Th2-type inflammatory cytokines (IL-4). Additionally, ESP-SJE treatment significantly upregulated the regulatory T cells (Tregs) in the lung tissue during OVA challenge. Furthermore, using liquid chromatography-mass spectrometry analysis and Treg induction experiments in vitro, we might identify nine potential therapeutic proteins against allergic inflammation in ESP-SJE. The targets of these candidate proteins included glutathione S-transferase, egg protein CP422 precursor, tubulin alpha-2/alpha-4 chain, actin-2, T-complex protein 1 subunit beta, histone H4, whey acidic protein core region, and molecular chaperone HtpG. CONCLUSION: Taken together, the results discussed herein demonstrated that ESP-SJE could significantly alleviate OVA-induced asthmatic inflammation in a murine model, which might be mediated by the upregulation of Treg in lung tissues that may be induced by the potential modulatory proteins. Therefore, potential proteins in ESP-SJE might be the best candidates to be tested for therapeutic application of asthma, thus pointing out to a possible new therapy for allergic airway inflammation.


Assuntos
Asma , Hipersensibilidade a Ovo , Schistosoma japonicum , Animais , Camundongos , Ovalbumina/farmacologia , Ovalbumina/uso terapêutico , Asma/induzido quimicamente , Asma/tratamento farmacológico , Pulmão , Citocinas , Inflamação/tratamento farmacológico , Camundongos Endogâmicos BALB C , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças
20.
Lipids Health Dis ; 22(1): 114, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537607

RESUMO

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with limited treatment options, such as the chemotherapeutic agent, temozolomide (TMZ). However, many GBM tumors develop resistance to TMZ, which is a major obstacle to effective therapy. Recently, dysregulated lipid metabolism has emerged as an important factor contributing to TMZ resistance in GBM. The dysregulation of lipid metabolism is a hallmark of cancer and alterations in lipid metabolism have been linked to multiple aspects of tumor biology, including proliferation, migration, and resistance to therapy. In this review, we aimed to summarize current knowledge on lipid metabolism in TMZ-resistant GBM, including key metabolites and proteins involved in lipid synthesis, uptake, and utilization, and recent advances in the application of metabolomics to study lipid metabolism in GBM. We also discussed the potential of lipid metabolism as a target for novel therapeutic interventions. Finally, we highlighted the challenges and opportunities associated with developing these interventions for clinical use, and the need for further research to fully understand the role of lipid metabolism in TMZ resistance in GBM. Our review suggests that targeting dysregulated lipid metabolism may be a promising approach to overcome TMZ resistance and improve outcomes in patients with GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Metabolismo dos Lipídeos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
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