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2.
Mol Neurobiol ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831169

RESUMO

Mutations or loss of function of DJ-1 and Toxoplasma gondii (T. gondii) infection has been linked to neurodegenerative diseases, which are often caused by oxidative stress. However, the relationship between DJ-1 and T. gondii infection is not yet fully understood. Therefore, this study aimed to investigate the expression of DJ-1 in the hippocampus tissue of mice or in HT22 infected with T. gondii Chinese 1 genotype Wh3 strain (TgCtwh3) and the effect of DJ-1 knockdown on neuronal apoptosis induced by TgCtwh3 tachyzoite, as well as the underlying mechanism at the cellular and molecular level. Firstly, we detected DJ-1 protein expression and cell apoptosis in the hippocampal tissue of mice infected by TgCtwh3. Then, we examined DJ-1 expression and apoptosis in HT22 challenged with TgCtwh3. Finally, we evaluated the apoptosis in HT22 with DJ-1 knockdown which was infected with TgCtwh3 and assayed the expression of NF-κBp65 and p-NF-κBp65. Our results showed that DJ-1 expression was reduced and neurons underwent apoptosis in the hippocampus of mice infected with TgCtwh3 tachyzoites. Additionally, the knockdown of DJ-1 followed by infection with TgCtwh3 tachyzoites led to increased apoptosis in HT22 cells through the NF-κB signaling pathway. Therefore, this study suggests that DJ-1 is an important target for preventing apoptosis caused by T. gondii TgCtwh3.

3.
PLoS One ; 19(6): e0305249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861562

RESUMO

This paper aims to explore the impact of China's value-added tax (VAT) credit refunds policy on the enterprises' labor demand through a paradigm combining ex-ante analysis and ex-post test. By introducing the VAT credit refunds into the production-decision model of the enterprise, calibrating the parameters and conducting the dynamic effects tests using the data of Chinese A-share listed enterprises, this paper finds that the labor employment of the pilot enterprises exhibits a V-shaped fluctuation trend. In the initial implementation of the policy, due to the existence of layoff costs, iso-cost line of the enterprise bends, which results in that the enterprise with a capital-labor substitution elasticity greater than 1 will not reduce labor hiring, as it has already deployed labor force before the implementation of the policy. When the enterprise enter the next production cycle where the labor force can be freely allocated, the labor employment of the enterprise with a capital-labor elasticity of substitution greater than 1 will decline compared to that without the policy. In the long run, as output increases, the labor demand will recover. The results of ex-post test are consistent with that of the ex-ante analysis. Additionally, heterogeneity test reveals that the greater the elasticity of capital-labor substitution of the sub-industry is, the more severe the degree of the V-shaped fluctuation is. Following the implementation of the policy, the continuous increase in enterprise output and capital stock verifies the relevant transmission mechanism. This study provides a more detailed perspective for comprehensively understanding the impact of VAT credit refunds policy on employment.


Assuntos
Emprego , Impostos , China , Impostos/economia , Emprego/economia , Humanos , Modelos Econômicos
4.
Int J Biol Macromol ; 272(Pt 1): 132816, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38825273

RESUMO

Modulating the interactions between biopolymer matrix and nanofillers highly determined the mechanical performances of composite packaging materials. Herein, we innovatively proposed a sort of eco-friendly and mechanically robust carboxymethyl cellulose/graphene oxide/tannic acid/polyetherimide (CMC/GO/TA/PEI, CGTP) composite by employing PEI as cross-linker and TA as proton donor. The amidation reaction between -NH2 and -COOH chemically connected the CMC/GO, CMC/CMC and GO/GO and the physical interaction (e.g. hydrogen bonds and molecular entanglements) was beneficial to form dense structures. The chemical/physical bonds among polymers and nanofillers contributed to dissipate the external energy. The toughness was effectively reinforced from 1.68 MJ/m3 for CGTP0 to 4.63 MJ/m3 for CGTP1.0. Furthermore, the CGTP1.0 composite film also delivered improved gas (moisture and oxygen) barriers, UV protection and antimicrobial features. Originating from these merits, the shelf life of fresh fruits (e.g. strawberries, blueberries and cherry tomatoes) was prolonged at least 5 days under ambient conditions when the packaging box was covered by the fabricated CGTP1.0 film. Our findings not only provided a facial strategy to reinforce the interactions between biopolymer matrix and nanofillers, but also boosted the development of eco-friendly packaging materials with robust structures in the area of food packaging.


Assuntos
Carboximetilcelulose Sódica , Embalagem de Alimentos , Frutas , Grafite , Polímeros , Grafite/química , Embalagem de Alimentos/métodos , Carboximetilcelulose Sódica/química , Polímeros/química , Frutas/química , Conservação de Alimentos/métodos , Nanocompostos/química
5.
Vaccines (Basel) ; 12(6)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38932305

RESUMO

With the widespread use of the 13-valent pneumonia vaccine (PCV13) in China, monitoring adverse events following immunization (AEFIs) is critical. We conducted a descriptive analysis of the AEFI occurrences reported within Hangzhou between the years 2020 and 2023, including the temporal trend of case reports and variables such as sex, age, type of PCV13, dose number, type of reporter, cause-specific classification, severity, and onset from vaccination. Vaccine safety signals were analyzed using reporting odds ratios (RORs). Over the 4 years analyzed in the study, 2564 AEFI cases were reported, including seven severe cases. Most AEFIs occurred within 0-1 days after vaccination (2398, 93.53%), with over half affecting infants aged 1.5-6 months of age. No statistically significant difference was observed between PCV13-TT and PCV-CRM197. Seasonal differences in AEFI reports were noted. Positive signals were detected for fever (ROR-1.96SE: 1.64) and persistent crying (ROR-1.96SE: 1.61). Four serious AEFI cases were coincidental events, while three others were considered vaccine-related cases (including one case each of allergic reaction, febrile seizure, and thrombocytopenia). The safety and tolerability of PCV13 are good, and attention should be paid to severe AEFIs, as well as long-term safety disparities between different types of PCV13.

6.
Can J Infect Dis Med Microbiol ; 2024: 8675248, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38938548

RESUMO

This study aims to explore the interaction of glycemic control and statin use on the treatment outcomes of pulmonary tuberculosis-diabetes comorbidity (PTB-DM) patients. A nested case-control study was conducted in a tuberculosis patients' cohort. We defined cases as patients who experienced unfavorable outcomes. Glycemic control was estimated at the baseline. Statin use was obtained from medical records. The multivariate logistic regression models were developed, and the interaction table invented by Andersson was adopted to analyze the interaction of glycemic control and statin use on treatment outcomes. A total of 2,047 patients were included in this study. There was a significant interaction between glycemic control and statin use on the treatment outcomes. Patients with good glycemic control and no statin use (OR = 0.464, 95% CI: 0.360-0.623) had a lower risk of unfavorable outcomes than those with poor glycemic control and statin use (OR = 0.604, 95% CI: 0.401-0.734). Patients with good glycemic control and statin use had the lowest risk of unfavorable outcomes (OR = 0.394, 95% CI: 0.264-0.521). Glycemic control in diabetes-tuberculosis treatment should be paid considerable attention. Patients can benefit from statin use even if they have poor glycemic control. Patients with good glycemic control and statin use can have the best outcomes.

7.
Tissue Eng Part A ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38818810

RESUMO

Therapy with mesenchymal stem cells (MSCs) is considered an attractive strategy for the repair or regeneration of damaged tissues. However, low survival of MSCs limits their applications clinically. Oxidized low-density lipoprotein (ox-LDL) is significantly increased in patients with hyperlipidemia and decreases the survival of MSCs. Bcl-2 is critically involved in important cell functions, including cell membrane integrity and cell survival. The present study was designed to test the hypothesis that ox-LDL attenuates the survival of MSCs through suppression of Bcl-2 expression. Bone marrow MSCs from C57BL/6 mice were cultured with ox-LDL at different concentrations (0-140 µg/mL) for 24 h with native LDL as control. Ox-LDL treatment substantially decreased the survival of MSCs dose-dependently and enhanced the release of intracellular lactate dehydrogenase (LDH) in association with a significant decrease in Bcl-2 protein level without change in BAX protein expression in MSCs. Bcl-2 overexpression effectively protected MSCs against ox-LDL-induced damages with preserved cell numbers without significant increase in LDH release. Treatment with N-acetylcysteine (NAC) (1 mM) effectively preserved Bcl-2 protein expression in MSCs and significantly attenuated ox-LDL-induced decrease of cell number and increase in the release of intracellular LDH. These data indicated that ox-LDL treatment resulted in a significant damage of cell membrane and dramatically decreased the survival of MSCs dose-dependently through inhibition of Bcl-2 expression. NAC treatment significantly protected MSCs against the damage of cell membrane by ox-LDL and promoted the survival of MSCs in association with preserved Bcl-2 expression.

8.
Cardiovasc Diabetol ; 23(1): 177, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783270

RESUMO

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.


Assuntos
Biomarcadores , Glicemia , Estudos Observacionais como Assunto , Triglicerídeos , Feminino , Humanos , Masculino , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Metanálise como Assunto , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Revisões Sistemáticas como Assunto , Triglicerídeos/sangue
9.
J Am Med Inform Assoc ; 31(7): 1551-1560, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38758667

RESUMO

OBJECTIVE: Synthesizing and evaluating inconsistent medical evidence is essential in evidence-based medicine. This study aimed to employ ChatGPT as a sophisticated scientific reasoning engine to identify conflicting clinical evidence and summarize unresolved questions to inform further research. MATERIALS AND METHODS: We evaluated ChatGPT's effectiveness in identifying conflicting evidence and investigated its principles of logical reasoning. An automated framework was developed to generate a PubMed dataset focused on controversial clinical topics. ChatGPT analyzed this dataset to identify consensus and controversy, and to formulate unsolved research questions. Expert evaluations were conducted 1) on the consensus and controversy for factual consistency, comprehensiveness, and potential harm and, 2) on the research questions for relevance, innovation, clarity, and specificity. RESULTS: The gpt-4-1106-preview model achieved a 90% recall rate in detecting inconsistent claim pairs within a ternary assertions setup. Notably, without explicit reasoning prompts, ChatGPT provided sound reasoning for the assertions between claims and hypotheses, based on an analysis grounded in relevance, specificity, and certainty. ChatGPT's conclusions of consensus and controversies in clinical literature were comprehensive and factually consistent. The research questions proposed by ChatGPT received high expert ratings. DISCUSSION: Our experiment implies that, in evaluating the relationship between evidence and claims, ChatGPT considered more detailed information beyond a straightforward assessment of sentimental orientation. This ability to process intricate information and conduct scientific reasoning regarding sentiment is noteworthy, particularly as this pattern emerged without explicit guidance or directives in prompts, highlighting ChatGPT's inherent logical reasoning capabilities. CONCLUSION: This study demonstrated ChatGPT's capacity to evaluate and interpret scientific claims. Such proficiency can be generalized to broader clinical research literature. ChatGPT effectively aids in facilitating clinical studies by proposing unresolved challenges based on analysis of existing studies. However, caution is advised as ChatGPT's outputs are inferences drawn from the input literature and could be harmful to clinical practice.


Assuntos
Medicina Baseada em Evidências , Humanos , PubMed
10.
Transplantation ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38725107

RESUMO

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is a major cause of complications in clinical liver surgery. AXL receptor tyrosine kinase (AXL) is a member of the TAM receptor tyrosine kinase family (TYRO3, AXL, and MERTK). Our previous study has shown that AXL expression was markedly upregulated in liver transplantation patients. However, the underlying mechanism of AXL in hepatic I/R injury remains unclear. METHODS: A mouse liver warm I/R model and a primary hepatocyte hypoxia/reoxygenation model were established to investigate the role of AXL activation and ferroptosis in hepatic I/R injury by pretreating with recombinant mouse growth arrest-specific protein 6 (AXL activator) or R428 (AXL inhibitor). Moreover, we used LY294002 (phosphatidylinositol 3-kinase [PI3K] inhibitor) to evaluate the relationship between the PI3K/AKT (the Ser and Thr kinase AKT) pathway and ferroptosis in hepatic I/R injury. RESULTS: Hepatic I/R injury decreased phosphorylation AXL expression and enhanced ferroptosis in liver transplantation patients and hepatic I/R-subjected mice. AXL activation attenuated lipid peroxidation and ferroptosis in hepatic I/R injury in vivo and in vitro. Inhibition of AXL activation exacerbated liver pathological damage and liver dysfunction, as well as iron accumulation and lipid peroxidation in hepatic I/R injury. Mechanistically, activated growth arrest-specific protein 6/AXL and its downstream PI3K/AKT signaling pathway inhibited ferroptosis during hepatic I/R injury. CONCLUSIONS: AXL activation protects against hepatic I/R injury by preventing ferroptosis through the PI3K/AKT pathway. This study is the first investigation on the AXL receptor and ferroptosis, and activating AXL to mitigate ferroptosis may be an innovative therapeutic strategy to combat hepatic I/R injury.

11.
Sensors (Basel) ; 24(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38794051

RESUMO

In recent years, the incidence of thyroid cancer has rapidly increased. To address the issue of the inefficient diagnosis of thyroid cancer during surgery, we propose a rapid method for the diagnosis of benign and malignant thyroid nodules based on hyperspectral technology. Firstly, using our self-developed thyroid nodule hyperspectral acquisition system, data for a large number of diverse thyroid nodule samples were obtained, providing a foundation for subsequent diagnosis. Secondly, to better meet clinical practical needs, we address the current situation of medical hyperspectral image classification research being mainly focused on pixel-based region segmentation, by proposing a method for nodule classification as benign or malignant based on thyroid nodule hyperspectral data blocks. Using 3D CNN and VGG16 networks as a basis, we designed a neural network algorithm (V3Dnet) for classification based on three-dimensional hyperspectral data blocks. In the case of a dataset with a block size of 50 × 50 × 196, the classification accuracy for benign and malignant samples reaches 84.63%. We also investigated the impact of data block size on the classification performance and constructed a classification model that includes thyroid nodule sample acquisition, hyperspectral data preprocessing, and an algorithm for thyroid nodule classification as benign and malignant based on hyperspectral data blocks. The proposed model for thyroid nodule classification is expected to be applied in thyroid surgery, thereby improving surgical accuracy and providing strong support for scientific research in related fields.


Assuntos
Algoritmos , Redes Neurais de Computação , Nódulo da Glândula Tireoide , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/classificação , Nódulo da Glândula Tireoide/diagnóstico , Humanos , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Imageamento Hiperespectral/métodos , Processamento de Imagem Assistida por Computador/métodos
12.
J Evid Based Med ; 17(2): 307-316, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38556728

RESUMO

AIM: It is essential for health researchers to have a systematic understanding of third-party variables that influence both the exposure and outcome under investigation, as shown by a directed acyclic graph (DAG). The traditional construction of DAGs through literature review and expert knowledge often needs to be more systematic and consistent, leading to potential biases. We try to introduce an automatic approach to building network linking variables of interest. METHODS: Large-scale text mining from medical literature was utilized to construct a conceptual network based on the Semantic MEDLINE Database (SemMedDB). SemMedDB is a PubMed-scale repository of the "concept-relation-concept" triple format. Relations between concepts are categorized as Excitatory, Inhibitory, or General. RESULTS: To facilitate the use of large-scale triple sets in SemMedDB, we have developed a computable biomedical knowledge (CBK) system (https://cbk.bjmu.edu.cn/), a website that enables direct retrieval of related publications and their corresponding triples without the necessity of writing SQL statements. Three case studies were elaborated to demonstrate the applications of the CBK system. CONCLUSIONS: The CBK system is openly available and user-friendly for rapidly capturing a set of influencing factors for a phenotype and building candidate DAGs between exposure-outcome variables. It could be a valuable tool to reduce the exploration time in considering relationships between variables, and constructing a DAG. A reliable and standardized DAG could significantly improve the design and interpretation of observational health research.


Assuntos
Mineração de Dados , Mineração de Dados/métodos , Humanos , Bases de Conhecimento , MEDLINE
13.
Trials ; 25(1): 227, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561815

RESUMO

INTRODUCTION: The lack of safe, effective, and simple short-course regimens (SCRs) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment has significantly impeded TB control efforts in China. METHODS: This phase 4, randomized, open-label, controlled, non-inferiority trial aims to assess the efficacy and safety of a 9-month all-oral SCR containing bedaquiline (BDQ) versus an all-oral SCR without BDQ for adult MDR-TB patients (18-65 years) in China. The trial design mainly mirrors that of the "Evaluation of a Standardized Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB" (STREAM) stage 2 study, while also incorporating programmatic data from South Africa and the 2019 consensus recommendations of Chinese MDR/RR-TB treatment experts. Experimental arm participants will receive a modified STREAM regimen C that replaces three group C drugs, ethambutol (EMB), pyrazinamide (PZA), and prothionamide (PTO), with two group B drugs, linezolid (LZD) and cycloserine (CS), while omitting high-dose isoniazid (INH) for confirmed INH-resistant cases. BDQ duration will be extended from 6 to 9 months for participants with Mycobacterium tuberculosis-positive sputum cultures at week 16. The control arm will receive a modified STREAM regimen B without high-dose INH and injectable kanamycin (KM) that incorporates experimental arm LZD and CS dosages, treatment durations, and administration methods. LZD (600 mg) will be given daily for ≥ 24 weeks as guided by observed benefits and harm. The primary outcome measures the proportion of participants with favorable treatment outcomes at treatment completion (week 40), while the same measurement taken at 48 weeks post-treatment completion is the secondary outcome. Assuming an α = 0.025 significance level (one-sided test), 80% power, 15% non-inferiority margin, and 10% lost to follow-up rate, each arm requires 106 participants (212 total) to demonstrate non-inferiority. DISCUSSION: PROSPECT aims to assess the safety and efficacy of a BDQ-containing SCR MDR-TB treatment at seventeen sites across China, while also providing high-quality data to guide SCRs administration under the direction of the China National Tuberculosis Program for MDR-TB. Additionally, PROSPECT will explore the potential benefits of extending the administration of the 9-month BDQ-containing SCR for participants without sputum conversion by week 16. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022 at https://clinicaltrials.gov/ct2/show/NCT05306223?term=NCT05306223&draw=1&rank=1 {2}.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Adulto , Humanos , Antituberculosos , Ensaios Clínicos Fase IV como Assunto , Diarilquinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
14.
Health Data Sci ; 4: 0125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586197

RESUMO

Objective: The aim of this study is to construct a curated bibliographic dataset for a landscape analysis on Health Artificial Intelligence (HAI) research. Data Source: We integrated HAI-related bibliographic records, including publications, open research datasets, patents, research grants, and clinical trials from Medline and Dimensions. Methods: Searching: Relevant documents were identified using Medical Subject Headings (MeSH) and Field of Research (FoR) indexed by 2 bibliographic databases, Medline and Dimensions. Extracting: MeSH terms annotated from the aforementioned bibliographic databases served as the primary information for our processing. For document records lacking MeSH terms, we re-extracted them using the Medical Text Indexer (MTI). Mapping: In order to enhance interoperability, HAI multi-documents were organized using a mapping system incorporating MeSH, FoR, The International Classification of Diseases (ICD-10), and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT). Integrating: All documents were curated based on a pre-defined ontology of health problems and AI technologies from the MeSH hierarchy. Results: We collected 96,332 HAI documents (publications: 75,820, open research datasets: 638, patents: 11,226, grants: 6,113, and clinical trials: 2,535) during 2009 to 2021. On average, 75.12% of the documents were tagged with at least one label related to either health problems or AI technologies (with 92.9% of publications tagged). Summary: This study presents a comprehensive pipeline for processing and curating HAI bibliographic documents following the FAIR (Findable, Accessible, Interoperable, Reusable) standard, offering a valuable multidimensional collection for the community. This dataset serves as a crucial resource for horizontally scanning the funding, research, clinical assessments, and innovations within the HAI field.

15.
MedComm (2020) ; 5(4): e527, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576457

RESUMO

Gastric cancer (GC) is among the most lethal human malignancies, yet it remains hampered by challenges in fronter of molecular-guided targeted therapy to direct clinical treatment strategies. The protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP2) is involved in the malignant progression of GC. However, the detailed mechanisms of the posttranslational modifications of SHP2 remain poorly understood. Herein, we demonstrated that an allosteric SHP2 inhibitor, SHP099, was able to block tumor proliferation and migration of GC by dephosphorylating the pyruvate kinase M2 type (PKM2) protein. Mechanistically, we found that PKM2 is a bona fide target of SHP2. The dephosphorylation and activation of PKM2 by SHP2 are necessary to exacerbate tumor progression and GC glycolysis. Moreover, we demonstrated a strong correlation between the phosphorylation level of PKM2 and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in GC cells. Notably, the low phosphorylation expression of AMPK was negatively correlated with activated SHP2. Besides, we proved that cisplatin could activate SHP2 and SHP099 increased sensitivity to cisplatin in GC. Taken together, our results provide evidence that the SHP2/PKM2/AMPK axis exerts a key role in GC progression and glycolysis and could be a viable therapeutic approach for the therapy of GC.

16.
Pain Ther ; 13(3): 577-588, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38592611

RESUMO

INTRODUCTION: Ultrasound-guided thoracic paravertebral block (UTPB) is widely used for postoperative analgesia in thoracic surgery. However, it has many disadvantages. Thoracoscopy-guided thoracic paravertebral block (TTPB) is a new technique for thoracic paravertebral block (TPB). In this study, we compared the use of TTPB and UTPB for pain management after thoracoscopic radical surgery for lung cancer. METHODS: In total, 80 patients were randomly divided 1:1 into the UTPB group and the TTPB group. The surgical time of TPB, the success rate of the first puncture, block segment range, visual analog scale (VAS) scores at 2, 6, 12, 24, and 48 h post operation, and the incidence of postoperative adverse reactions were compared between the two groups. RESULTS: The surgical time of TPB was significantly shorter in the TTPB group than in the UTPB group (2.2 ± 0.3 vs. 5.7 ± 1.7 min, t = - 12.411, P < 0.001). The success rate of the first puncture and the sensory block segment were significantly higher in the TTPB group than in the UTPB group (100% vs. 76.9%, χ2 = 8.309, P < 0.001; 6.5 ± 1.2 vs. 5.1 ± 1.3 levels, t = - 5.306, P < 0.001, respectively). The VAS scores were significantly higher during rest and coughing at 48 h post operation than at 2, 6, 12, and 24 h post operation in the TTPB group. The VAS scores were significantly lower during rest and coughing at 12 and 24 h post operation in the TTPB group than in the UTPB group (rest: 2.5 ± 0.4 vs. 3.4 ± 0.6, t = 7.325, P < 0.001; 2.5 ± 0.5 vs. 3.5 ± 0.6, t = 7.885, P < 0.001; coughing: 3.4 ± 0.6 vs. 4.2 ± 0.7, t = 5.057, P < 0.001; 3.4 ± 0.6 vs. 4.2 ± 0.8, t = 4.625, P < 0.001, respectively). No significant difference was observed in terms of postoperative adverse reactions between the two groups. CONCLUSIONS: Compared with UTPB, TTPB shows advantages, such as simpler and more convenient surgery, shorter surgical time, a higher success rate of the first puncture, wider block segments, and superior analgesic effect. TTPB can effectively reduce postoperative pain due to thoracoscopic lung cancer radical surgery. TRIAL REGISTRATION: https://www.chictr.org.cn , identifier ChiCTR2300072005, prospectively registered on 31/05/2023.

17.
Int J Biol Sci ; 20(6): 2219-2235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617542

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Metabolismo dos Lipídeos/genética , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Receptores de Quimiocinas , Inflamação
18.
J Hazard Mater ; 470: 134180, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38569342

RESUMO

Obtaining suitable adsorbents for selective separation of SO2 from flue gas still remains an important issue. A stable Zr(IV)-MOF (Zr-PTBA) can be conveniently synthesized through the self-assembly of a tetracarboxylic acid ligand (H4L = 4,4',4'',4'''-(1,4-phenylenebis(azanetriyl))tetrabenzoic acid) and ZrCl4 in the presence of trace water. It exhibits a three-dimensional porous structure. The BET surface area is 1112.72 m2/g and the average pore size distribution focus on 5.9, 8.0 and 9.3 Å. Interestingly, Zr-PTBA shows selective adsorption of SO2. The maximum uptake reaches 223.21 cm3/g at ambient condition. While it exhibits lower adsorption uptake of CO2 (30.50 cm3/g) and hardly adsorbs O2 (2.57 cm3/g) and N2 (1.31 cm3/g). Higher IAST selectivities of SO2/CO2 (21.9), SO2/N2 (912.7), SO2/O2 (2269.9) and SO2/CH4 (85.0) have been obtained, which reveal its' excellent gas separation performance. Breakthrough experiment further confirms its application for flue gas deep desulfurization both in dry and humid conditions. Furthermore, the gas adsorption results and mechanisms have also been studied by theoretical calculations.

19.
Int J Biol Macromol ; 265(Pt 2): 130981, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38513894

RESUMO

High-value utilization of bleached lignin has been widely used in different fields, whereas the investigation on darkened lignin in composite materials was often ignored. In this work, a sort of eco-friendly and structurally robust sodium carboxymethyl cellulose (CMC)/polyvinyl alcohol (PVA)/sodium lignosulfonate (SLS) black composite mulch film was elaborately designed. The chelation and redox reaction effect between Fe ions and SLS lead to the formation of a more quinones structure on lignin, darkening both lignin and the mulch films. The chelation effect between Fe ions and biopolymer formed three-dimensional structures, which can be used as sacrifice bonds to dissipate energy and improve the mechanical properties of the composite films. In particular, the maximum elongation at break and toughness increased from 48.4 % and 1141 kJ/m3 for the CMC/PVA film to 210.9 % and 1426 kJ/m3 for the optimized CMC/PVA/SLS/Fe black mulch film, respectively. In addition, the optimized black mulch film also possesses good soil water retention, thermal preservation effect, controlled urea release, and well biodegradability. This work offered a novel strategy for designing eco-friendly black mulch with reinforced mechanical strength, slow-release urea, soil moisture retention, and heat preservation performances.


Assuntos
Ferro , Lignina , Agricultura/métodos , Solo , Álcool de Polivinil/química , Ureia , Sódio
20.
Int J Biol Macromol ; 266(Pt 1): 131024, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513907

RESUMO

Improving electron transfer rate of Co species and inhibiting aggregation of metal-organic frameworks (MOFs) particles are essential prerequisites for activating advanced oxidation process in wastewater treatment field. Here, we exploit Cu species with variable valence states to accelerate electron transfer of Co species and then to boost the unsatisfactory degradation efficiency for refractory pharmaceuticals via in-situ growth of copper and cobalt species on l-lysine functionalized carboxylated cellulose nanofibers. Utilizing the synergistic interplay of Co sites and deliberately exposed Cu0/Cu1+ atoms, the subtly designed catalyst exhibited a surprising degradation efficiency (~100 %) toward tetracycline hydrochloride within 10 min (corresponding to a catalytic capacity of 267.71 mg/g) without adjusting temperature and pH. Meanwhile, the catalyst displays good recyclability, well tolerance for coexisting ions and excellent antibacterial performance derived from the intrinsic antibacterial property of Cu-MOF. This research provided a novel strategy to construct MOFs-cellulose materials toward degrading various stubborn antibiotic pollutants.


Assuntos
Antibacterianos , Celulose , Cobalto , Cobre , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Celulose/química , Cobre/química , Antibacterianos/química , Antibacterianos/farmacologia , Cobalto/química , Catálise , Tetraciclina/química , Poluentes Químicos da Água/química
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