Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 310
Filtrar
1.
J Investig Med ; : 10815589241252356, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644377

RESUMO

Recent studies have introduced the weight-adjusted waist circumference index (WWI) as a viable obesity indicator that may better reflect centripetal obesity and its associated risks. In examining the connection between WWI and prostate-specific antigen (PSA), this study leveraged data from the National Health and Nutrition Examination Survey (NHANES) 2003-2010, including 5732 participants. Our initial analysis indicated a significant positive association between WWI and PSA levels. However, subsequent models that adjusted for covariates such as age, race, and a range of metabolic and cardiovascular health-related factors revealed that the strength and significance of this relationship were attenuated. Model 1 showed a highly significant correlation (P < 0.0001). Yet, in Model 2, which accounted for age and race, the association softened (P = 0.0520). Moreover, when a full spectrum of health covariates was included in Model 3, the association was no longer significant (P = 0.9775). These findings suggest that while an unadjusted correlation exists, its potential use as a diagnostic predictor is limited without considering the broader health context. Therefore, it is crucial to review such data with multiple considerations in mind, and extensive attention should be paid to the evaluation of covariates.

3.
Cell Mol Life Sci ; 81(1): 187, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635081

RESUMO

Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-ß1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease.


Assuntos
Fibrose Pulmonar Idiopática , Macrófagos , Canal de Cátion TRPA1 , Animais , Camundongos , Acetanilidas , Bleomicina , Colágeno , Proteínas do Citoesqueleto , Camundongos Endogâmicos C57BL , Purinas , Canal de Cátion TRPA1/metabolismo
4.
Chem Sci ; 15(15): 5633-5641, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638231

RESUMO

Encapsulating metal nanoparticles inside carbon layers is a promising approach to simultaneously improving the activity and stability of electrocatalysts. The role of carbon layer shells, however, is not fully understood. Herein, we report a study of boron doped carbon layers coated on nickel nanoparticles (Ni@BC), which were used as a model catalyst to understand the role of a bridging oxygen in a carbon shell coated Ni interface for the improvement of the hydrogen oxidation reaction (HOR) activity using an alkaline electrolyte. Combining experimental results and density functional theory (DFT) calculations, we find that the electronic structure of Ni can be precisely tailored by Ni-O-C and Ni-O-B coordinated environments, leading to a volcano type correlation between the binding ability of the OH* adsorbate and HOR activity. The obtained Ni@BC with a optimized d-band center displays a remarkable HOR performance with a mass activity of 34.91 mA mgNi-1, as well as superior stability and CO tolerance. The findings reported in this work not only highlight the role of the OH* binding strength in alkaline HOR but also provide guidelines for the rational design of advanced carbon layers used to coat metal electrocatalysts.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 389-394, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660841

RESUMO

OBJECTIVE: To investigate the effects of elesclomol-Cu (ES-Cu) on the proliferation and cuproptosis of human acute myeloid leukemia (AML) cells. METHODS: The effects of ES-Cu on the proliferation of AML cells and the AML cells pre-treated with ammonium tetrathiomolybdate (TTM) were examined by CCK-8 assay. The Calcein/PI kit was used to detected the changes in activity and cytotoxicity of AML cells induced by ES-Cu. Flow cytometry and Cytation3 fully automated cell imaging multifunctional detection system were used to analyze DCFH-DA fluorescence intensity, so as to determine the level of reactive oxygen species (ROS). The GSH and GSSG detection kits were used to measure the intracellular GSH content. Western blot was used to detected the expression of cuproptosis-related proteins ATP7B, FDX1, DLAT and DPYD. RESULTS: ES-Cu inhibited the proliferation of Kasumi-1 and HL-60 cells in a concentration-dependent manner (r Kasumi-1=-0.99, r HL-60=-0.98). As the concentration of ES-Cu increased, the level of intracellular ROS also increased (P <0.01-0.001). TTM could significantly reverse the inhibitory effect of ES-Cu on cell proliferation and its promoting effect on ROS. With the increase of ES-Cu concentration, the content of GSH was decreased (r =-0.98), and Western blot showed that the protein expressions of ATP7B, FDX1, DLAT and DPYD were significantly reduced (P <0.05). CONCLUSION: ES-Cu can induce cuproptosis in AML cells, which provides a new idea for the treatment of AML.


Assuntos
Proliferação de Células , Hidrazinas , Leucemia Mieloide Aguda , Molibdênio , Espécies Reativas de Oxigênio , Humanos , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células HL-60 , Linhagem Celular Tumoral , Cobre/farmacologia
6.
Anal Chem ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661330

RESUMO

In light of deep tissue penetration and ultralow background, near-infrared (NIR) persistent luminescence (PersL) bioprobes have become powerful tools for bioapplications. However, the inhomogeneous signal attenuation may significantly limit its application for precise biosensing owing to tissue absorption and scattering. In this work, a PersL lifetime-based nanoplatform via deep learning was proposed for high-fidelity bioimaging and biosensing in vivo. The persistent luminescence imaging network (PLI-Net), which consisted of a 3D-deep convolutional neural network (3D-CNN) and the PersL imaging system, was logically constructed to accurately extract the lifetime feature from the profile of PersL intensity-based decay images. Significantly, the NIR PersL nanomaterials represented by Zn1+xGa2-2xSnxO4: 0.4 % Cr (ZGSO) were precisely adjusted over their lifetime, enabling the PersL lifetime-based imaging with high-contrast signals. Inspired by the adjustable and reliable PersL lifetime imaging of ZGSO NPs, a proof-of-concept PersL nanoplatform was further developed and showed exceptional analytical performance for hypochlorite detection via a luminescence resonance energy transfer process. Remarkably, on the merits of the dependable and anti-interference PersL lifetimes, this PersL lifetime-based nanoprobe provided highly sensitive and accurate imaging of both endogenous and exogenous hypochlorite. This breakthrough opened up a new way for the development of high-fidelity biosensing in complex matrix systems.

7.
Adv Mater ; : e2403281, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661081

RESUMO

Interpenetrated metal-organic frameworks (MOFs) with non-aromatic ligands provide a unique platform for adsorption, catalysis, and sensing applications. However, non-emission and the lack of optical property tailoring make it challenging to fabricate smart responsive devices with non-aromatic interpenetrated MOFs based on ligand-centered emission. In this paper, we introduce the pressure-induced aggregation effect in non-aromatic interpenetrated Zn4O(ADC)4(Et3N)6 (IRMOF-0) nanocrystals (NCs), where carbonyl groups aggregation results in O-O distances smaller than the sum of the van der Waals radii (3.04 Å), triggering the photoluminescence turn-on behavior. It is noteworthy that the IRMOF-0 NCs display an ultra-broad emission tunability of 130 nm from deep blue (440 nm) to yellow (570 nm) upon release to ambient conditions at different pressures. The eventual retention of through-space n-π* interactions in different degrees via pressure treatment is primarily responsible for achieving a controllable multi-color emission behavior in initially non-emissive IRMOF-0 NCs. The fabricated multi-color phosphor-converted light-emitting diodes based on the pressure-treated IRMOF-0 NCs exhibit excellent thermal, chromaticity, and fatigue stability. Our proposed strategy not only imparts new vitality to non-aromatic interpenetrated MOFs but also offers new perspectives for advancements in the field of multi-color displays and daylight illumination. This article is protected by copyright. All rights reserved.

8.
Front Microbiol ; 15: 1301204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38591032

RESUMO

Introduction: Mycobacterium tuberculosis (Mtb), the main cause of tuberculosis (TB), has brought a great burden to the world's public health. With the widespread use of Mtb drug-resistant strains, the pressure on anti-TB treatment is increasing. Anti-TB drugs with novel structures and targets are urgently needed. Previous studies have revealed a series of CYPs with important roles in the survival and metabolism of Mtb. However, there is little research on the structure and function of CYP138. Methods: In our study, to discover the function and targetability of CYP138, a cyp138-knockout strain was built, and the function of CYP138 was speculated by the comparison between cyp138-knockout and wild-type strains through growth curves, growth status under different carbon sources, infection curves, SEM, MIC tests, quantitative proteomics, and lipidomics. Results and discussion: The knockout of cyp138 was proven to affect the Mtb's macrophage infection, antibiotics susceptibility, and the levels of fatty acid metabolism, membrane-related proteins, and lipids such as triacylglycerol. We proposed that CYP138 plays an important role in the synthesis and decomposition of lipids related to the cell membrane structure as a new potential anti-tuberculosis drug target.

9.
Heliyon ; 10(7): e28117, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586319

RESUMO

With the swift advancement of cloud computing and the Internet of Things (IoT), to address the issue of massive data storage, IoT devices opt to offload their data to cloud servers so as to alleviate the pressure of resident storage and computation. However, storing local data in an outsourced database is bound to face the danger of tampering. To handle the above problem, a verifiable database (VDB), which was initially suggested in 2011, has garnered sustained interest from researchers. The concept of VDB enables resource-limited clients to securely outsource extremely large databases to untrusted servers, where users can retrieve database records and modify them by allocating new values, and any attempts at tampering will be detected. This paper provides a systematic summary of VDB. First, a definition of VDB is given, along with correctness and security proofs. And the VDB based on commitment constructions is introduced separately, mainly divided into vector commitments and polynomial commitments. Then VDB schemes based on delegated polynomial functions are introduced, mainly in combination with Merkle trees and forward-secure symmetric searchable encryption. We then classify the current VDB schemes relying on four different assumptions. Besides, we classify the established VDB schemes built upon two different groups. Finally, we introduce the applications and future development of VDB. To our knowledge, this is the first VDB review paper to date.

10.
Bioengineering (Basel) ; 11(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38534501

RESUMO

Deep learning (DL) algorithms used for DOTATATE PET lesion detection typically require large, well-annotated training datasets. These are difficult to obtain due to low incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and the high cost of manual annotation. Furthermore, networks trained and tested with data acquired from site specific PET/CT instrumentation, acquisition and processing protocols have reduced performance when tested with offsite data. This lack of generalizability requires even larger, more diverse training datasets. The objective of this study is to investigate the feasibility of improving DL algorithm performance by better matching the background noise in training datasets to higher noise, out-of-domain testing datasets. 68Ga-DOTATATE PET/CT datasets were obtained from two scanners: Scanner1, a state-of-the-art digital PET/CT (GE DMI PET/CT; n = 83 subjects), and Scanner2, an older-generation analog PET/CT (GE STE; n = 123 subjects). Set1, the data set from Scanner1, was reconstructed with standard clinical parameters (5 min; Q.Clear) and list-mode reconstructions (VPFXS 2, 3, 4, and 5-min). Set2, data from Scanner2 representing out-of-domain clinical scans, used standard iterative reconstruction (5 min; OSEM). A deep neural network was trained with each dataset: Network1 for Scanner1 and Network2 for Scanner2. DL performance (Network1) was tested with out-of-domain test data (Set2). To evaluate the effect of training sample size, we tested DL model performance using a fraction (25%, 50% and 75%) of Set1 for training. Scanner1, list-mode 2-min reconstructed data demonstrated the most similar noise level compared that of Set2, resulting in the best performance (F1 = 0.713). This was not significantly different compared to the highest performance, upper-bound limit using in-domain training for Network2 (F1 = 0.755; p-value = 0.103). Regarding sample size, the F1 score significantly increased from 25% training data (F1 = 0.478) to 100% training data (F1 = 0.713; p < 0.001). List-mode data from modern PET scanners can be reconstructed to better match the noise properties of older scanners. Using existing data and their associated annotations dramatically reduces the cost and effort in generating these datasets and significantly improves the performance of existing DL algorithms. List-mode reconstructions can provide an efficient, low-cost method to improve DL algorithm generalizability.

11.
J Alzheimers Dis ; 98(3): 741-754, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38489182

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by progressive memory loss and cognitive impairment due to excessive accumulation of extracellular amyloid-ß plaques and intracellular neurofibrillary tangles. Although decades of research efforts have been put into developing disease-modifying therapies for AD, no "curative" drug has been identified. As a central player in neuro-inflammation, microglia play a key role inbrain homeostasis by phagocytosing debris and regulating the balance between neurotoxic and neuroprotective events. Typically, the neurotoxic phenotype of activated microglia is predominant in the impaired microenvironment of AD. Accordingly, transitioning the activity state of microglia from pro-inflammatory to anti-inflammatory can restore the disrupted homeostatic microenvironment. Recently, stem cell therapy holds great promise as a treatment for AD; however, the diminished survival of transplanted stem cells has resulted in a disappointing long-term outcome for this treatment. This article reviews the functional changes of microglia through the course of AD-associated homeostatic deterioration. We summarize the possible microglia-associated therapeutic targets including TREM2, IL-3Rα, CD22, C5aR1, CX3CR1, P2X7R, CD33, Nrf2, PPAR-γ, CSF1R, and NLRP3, each of which has been discussed in detail. The goal of this review is to put forth the notion that microglia could be targeted by either small molecules or biologics to make the brain microenvironment more amenable to stem cell implantation and propose a novel treatment strategy for future stem cell interventions in AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/genética , Sobrevivência Celular , Peptídeos beta-Amiloides/uso terapêutico , Inflamação/tratamento farmacológico , Microglia
12.
Biomed Pharmacother ; 173: 116386, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492438

RESUMO

Diffuse large B-cell lymphoma (DLBCL), a heterogeneous lymphoid malignancy, poses a significant threat to human health. The standard therapeutic regimen for patients with DLBCL is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), with a typical cure rate of 50-70%. However, some patients either relapse after complete remission (CR) or exhibit resistance to R-CHOP treatment. Therefore, novel therapeutic approaches are imperative for managing high-risk or refractory DLBCL. Ferroptosis is driven by iron-dependent phospholipid peroxidation, a process that relies on the transition metal iron, reactive oxygen species (ROS), and phospholipids containing polyunsaturated fatty acids-containing phospholipids (PUFA-PLs). Research indicates that ferroptosis is implicated in various carcinogenic and anticancer pathways. Several hematological disorders exhibit heightened sensitivity to cell death induced by ferroptosis. DLBCL cells, in particular, demonstrate an increased demand for iron and an upregulation in the expression of fatty acid synthase. Additionally, there exists a correlation between ferroptosis-associated genes and the prognosis of DLBCL. Therefore, ferroptosis may be a promising novel target for DLBCL therapy. In this review, we elucidate ferroptosis mechanisms, its role in DLBCL, and the potential therapeutic targets in DLBCL. This review offers novel insights into the application of ferroptosis in treatment strategies for DLBCL.


Assuntos
Ferroptose , Linfoma Difuso de Grandes Células B , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Rituximab , Vincristina , Ciclofosfamida/uso terapêutico , Prednisona/uso terapêutico , Doxorrubicina , Linfoma Difuso de Grandes Células B/metabolismo , Ferro , Protocolos de Quimioterapia Combinada Antineoplásica , Resultado do Tratamento
13.
BMC Public Health ; 24(1): 740, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454384

RESUMO

BACKGROUND: Despite the growing interest in hospital rehabilitation services for communities, studies on existing community-based rehabilitation (CBR) services remain scarce owing to limitations in the development of community health services and regional cultural diversity. As a guaranteed measure for ensuring the quality of rehabilitation services and achieving the desired service outcomes, clear roles and responsibilities in multidisciplinary teams and effective service delivery are particularly important. OBJECTIVE: This scoping review aimed to determine the scope of community stroke rehabilitation programs involving existing multidisciplinary teams and to analyze the implementation content and implementers' functional roles to provide guidance for future CBR programs. METHODS: The scoping review design followed the methodology of the Joanna Briggs Institute and was based on the normative scoping review framework proposed by Arksey and O'Malley. The comprehensive CBR framework was proposed by World Health Organization-guided data charting and analysis. RESULTS: Of the 22,849 identified citations, 74 studies were included, consisting of 6,809 patients with stroke and 49 primary caregivers, most of whom were from China. The most common working mode in CBR programs was a dual approach involving both healthcare professionals in medical institutions and community healthcare professionals. The number of programs in each discipline was in the following descending order: nursing, medical care, rehabilitation, psychology, nutrition, and public health. Among these, multidisciplinary teams comprising medical, nursing, and rehabilitation disciplines were the most common, with a total of 29 programs. Disciplinary members were mainly responsible for implementing their respective disciplinary content, with physicians providing guidance for the programs. More than 82.4% of the studies reported 2-4 intervention strategies. The intervention forms of rehabilitation content were the most diverse, whereas preventive interventions were more homogeneous than others. Physical function and socio-psychological measurements were the most commonly reported outcomes. CONCLUSION: CBR services implemented by multidisciplinary teams can effectively achieve functional and emotional improvement in patients with stroke, and nurses are the most involved in implementation, especially in community settings. The results further emphasize the importance of strengthening the exploration of nurses' maximum potential to implement CBR plans in future practice. TRIAL REGISTRATION: The registration information for this scoping review can be found at osf.io/pv7tg.


Assuntos
Serviços de Saúde Comunitária , Acidente Vascular Cerebral , Adulto , Humanos , Grupos Populacionais , Hospitais , Equipe de Assistência ao Paciente , Acidente Vascular Cerebral/terapia
14.
Sci Rep ; 14(1): 5923, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467667

RESUMO

Uric acid (UA) is associated with non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether UA plays a predictive role in NAFLD prognosis. This study aimed to explore the relationship between UA levels and mortality in NAFLD patients without severe renal disease. Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES). Time-dependent Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for mortality. Overall, 2493 individuals with NAFLD and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 were included in this study. The median follow-up period was 26.58 years. Patients were divided into high and low-UA groups according to UA levels. Time-independent Cox regression showed that UA level was not an independent risk factor for mortality in NAFLD patients without decreased eGFR (P > 0.05). After matching for age and sex using the propensity score matching method, UA remained not independently associated with death in NAFLD patients (P > 0.05). Similar results were found for cardiovascular-related and cancer-related deaths. Although UA is closely related to NAFLD, UA levels are not independently associated with the long-term survival of patients with NAFLD without decreased eGFR.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Ácido Úrico , Inquéritos Nutricionais , Prognóstico , Fatores de Risco
15.
Data Brief ; 53: 110141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38406254

RESUMO

A benchmark histopathological Hematoxylin and Eosin (H&E) image dataset for Cervical Adenocarcinoma in Situ (CAISHI), containing 2240 histopathological images of Cervical Adenocarcinoma in Situ (AIS), is established to fill the current data gap, of which 1010 are images of normal cervical glands and another 1230 are images of cervical AIS. The sampling method is endoscope biopsy. Pathological sections are obtained by H&E staining from Shengjing Hospital, China Medical University. These images have a magnification of 100 and are captured by the Axio Scope. A1 microscope. The size of the image is 3840 × 2160 pixels, and the format is ".png". The collection of CAISHI is subject to an ethical review by China Medical University with approval number 2022PS841K. These images are analyzed at multiple levels, including classification tasks and image retrieval tasks. A variety of computer vision and machine learning methods are used to evaluate the performance of the data. For classification tasks, a variety of classical machine learning classifiers such as k-means, support vector machines (SVM), and random forests (RF), as well as convolutional neural network classifiers such as Residual Network 50 (ResNet50), Vision Transformer (ViT), Inception version 3 (Inception-V3), and Visual Geometry Group Network 16 (VGG-16), are used. In addition, the Siamese network is used to evaluate few-shot learning tasks. In terms of image retrieval functions, color features, texture features, and deep learning features are extracted, and their performances are tested. CAISHI can help with the early diagnosis and screening of cervical cancer. Researchers can use this dataset to develop new computer-aided diagnostic tools that could improve the accuracy and efficiency of cervical cancer screening and advance the development of automated diagnostic algorithms.

16.
Expert Rev Gastroenterol Hepatol ; 18(1-3): 121-128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38362663

RESUMO

BACKGROUND: Liaoning score has been developed and validated to predict the risk of esophageal varices in liver cirrhosis. This study aimed to further modify the Liaoning score by combining clinical and laboratory parameters to predict the long-term outcome of cirrhotic patients. METHODS: First, 474 cirrhotic patients were retrospectively enrolled from Shenyang, China as the training cohort. Independent predictors for death were identified by competing risk analyses, and then a new prognostic model, called as modified Liaoning score, was developed. Its performance was externally validated at three centers from Fuzhou, China (n = 1944), Jinan, China (n = 485), and São Paulo, Brazil (n = 221). RESULTS: Age, total bilirubin (TBIL), albumin (ALB), serum creatinine (SCr), and Liaoning score were independently associated with death in the training cohort. Modified Liaoning score = 0.159×Liaoning score + 0.010×TBIL(µmol/L)+0.029×age(years)+0.011×SCr(µmol/L)-0.037×ALB(g/L). The area under curve of modified Liaoning score was 0.714 (95%CI = 0.655-0.773), which was higher than that of Child-Pugh score (0.707, 95%CI = 0.645-0.770), MELD score (0.687, 95%CI = 0.623-0.751), and Liaoning score (0.583, 95%CI = 0.513-0.654). A modified Liaoning score of ≥ 1.296 suggested a higher cumulative incidence of death in liver cirrhosis (p < 0.001). Modified Liaoning score still had the highest prognostic performance in Chinese and Brazilian validation cohorts. CONCLUSIONS: Modified Liaoning score can be considered for predicting the long-term outcome of cirrhotic patients.


Assuntos
Cirrose Hepática , Humanos , Estudos Retrospectivos , Brasil , Cirrose Hepática/complicações , Prognóstico , Índice de Gravidade de Doença
17.
Signal Transduct Target Ther ; 9(1): 42, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355848

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells. To address this question, we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1 (ASGR1) promoted SARS-CoV-2 pseudovirus infection of HeLa cells. In Huh-7 cells, simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells, both of which barely expressed ACE2, SARS-CoV-2 pseudovirus could successfully establish an infection. However, after treatment with ASGR1 antibody or siRNA targeting ASGR1, the infection rate significantly dropped, suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent mechanism. We confirmed that ASGR1 could interact with Spike protein, which depends on receptor binding domain (RBD) and N-terminal domain (NTD). Finally, we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal cells. After inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA, the infection efficiency of the live virus decreased significantly. Collectively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.


Assuntos
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2/fisiologia , Receptor de Asialoglicoproteína/genética , Células HeLa , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/química , Hepatócitos , RNA Interferente Pequeno
18.
Nat Commun ; 15(1): 1005, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307899

RESUMO

Potassium-sulfur batteries attract tremendous attention as high-energy and low-cost energy storage system, but achieving high utilization and long-term cycling of sulfur remains challenging. Here we show a strategy of optimizing potassium polysulfides for building high-performance potassium-sulfur batteries. We design the composite of tungsten single atom and tungsten carbide possessing potassium polysulfide migration/conversion bi-functionality by theoretical screening. We create two ligand environments for tungsten in the metal-organic framework, which respectively transmute into tungsten single atom and tungsten carbide nanocrystals during pyrolysis. Tungsten carbide provide catalytic sites for potassium polysulfides conversion, while tungsten single atoms facilitate sulfides migration thereby significantly alleviating the insulating sulfides accumulation and the associated catalytic poisoning. Resultantly, highly efficient potassium-sulfur electrochemistry is achieved under high-rate and long-cycling conditions. The batteries deliver 89.8% sulfur utilization (1504 mAh g-1), superior rate capability (1059 mAh g-1 at 1675 mA g-1) and long lifespan of 200 cycles at 25 °C. These advances enlighten direction for future KSBs development.

19.
Biomark Res ; 12(1): 16, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308374

RESUMO

Abnormal alterations in human epidermal growth factor receptor 2 (HER2, neu, and erbB2) are associated with the development of many tumors. It is currently a crucial treatment for multiple cancers. Advanced in molecular biology and further exploration of the HER2-mediated pathway have promoted the development of medicine design and combination drug regimens. An increasing number of HER2-targeted drugs including specific monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs) have been approved by the U.S. Food and Drug Administration. The emergence of ADCs, has significantly transformed the treatment landscape for various tumors, such as breast, gastric, and bladder cancer. Classic monoclonal antibodies and novel TKIs have not only demonstrated remarkable efficacy, but also expanded their indications, with ADCs in particular exhibiting profound clinical applications. Moreover the concept of low HER2 expression signifies a breakthrough in HER2-targeted therapy, indicating that an increasing number of tumors and patients will benefit from this approach. This article, provides a comprehensive review of the underlying mechanism of action, representative drugs, corresponding clinical trials, recent advancements, and future research directions pertaining to HER2-targeted therapy.

20.
J Sci Food Agric ; 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308571

RESUMO

BACKGROUND: Adding ZaoShao liquor (high-concentration liquor) is one of the most important steps in the brewing process of Shaoxing Jiafan wine, a product protected by Chinese geographical indications. The focus of this study is the effect of different additive amounts of liquor on the flavor of end products. RESULTS: In this study, four kinds of Shaoxing Jiafan wine were brewed by changing the amount of ZaoShao liquor. Headspace solid-phase microextraction and gas chromatography-mass spectrometry were used to detect the flavor substances of four kinds of Jiafan wine. The difference in flavor of four kinds of Jiafan wine was evaluated by electronic nose analysis technology and verified by sensory evaluation. Finally, the reliability of the experimental results was verified through an aroma reconstruction experiment of rice wine. In this study, the differences in flavoring substances under different amounts of ZaoShao liquor were verified from various angles. The results showed that the flavors of the four kinds of wines were significantly different. CONCLUSION: The composition of flavor substances in Shaoxing rice wine varies with the amount of ZaoShao liquor. This study provided a scientific basis for the improvement of production technology of Shaoxing wine. © 2024 Society of Chemical Industry.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...